Dipiro X New - Removed - Removed - Removed

705
TABLE 48-4 Stepwise Approach to Adjust Drug Dosage TABLE 48-5 GFR Categories Based on KDIGO
Regimens for Patients with Renal Insufficiency Classification
Step 1 Obtain history Ask/obtain patient medical history GFR (mL/min/1.73 m2
and relevant including: GFR Categorya [mL/s/m2]) Terms
demographic/ Prescription medication 1 >90 (>0.87) Normal or high
clinical information
Over-the-counter medication
CHAPTER
2 60-89 (0.58-0.86) Mildly decreased
Recreational drugs
3a 45-59 (0.43-0.57) Mildly to moderately
Tobacco and alcohol use decreased
History of renal disease 3b 30-44 (0.29-0.42) Moderately to severely
Height decreased

Weight 4 15-29 (0.14-0.28) Severely decreased
Step 2 Determine the Measure serum creatinine and/or 5 <15 (<0.14) Kidney failure 48
degree of renal cystatin C
insufficiency GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes.
Determine eGFR or CLcr for drug
Drug Therapy Individualization for Patients with Chronic Kidney Disease

a
To meet criteria for CKD there must be a significant reduction in GFR (categories
dosing based best available
3a-5) or there must also be evidence of kidney damage (categories 1 & 2) for
methodology 3 months or greater. Adapted from reference 96.
Order 24-hour urine collection for
measured CLcr if necessary
Step 3 Review the medication Ensure medications are all indicated
list resulted in some clinicians cautioning against their routine clinical
Evaluate for potential drug
interactions use104,105 (Table 48-6). In addition, none of these sources consistently
provide the explicit relationships of the kinetic parameters of inter-
Identify drugs which need to dosage
regimen adjusted est (total body clearance [CL], elimination rate constant [k], and VD)
Step 4 Individualize Ascertain best initial dosage regimen
with a continuous index of renal function, such as eCLcr or eGFR. To
treatment regimen from FDA- or EMA-approved find this information, one may need to identify the original research
for identified product labelling study that assessed the drug’s disposition or a comprehensive review
medications For narrow therapeutic range article on the class of drugs of interest. This is a time-consuming
drugs—calculate dosage regimen process that may be difficult to carry out for each drug and patient
based on pharmacokinetic combination in real time.
characteristics of the drug and the
Dr. Luzius Dettli is often credited for being the first to system-
patient’s renal function
atically approach the issue of drug dosing for those with impaired
Titrate the dose of drugs to patient
effect, if applicable
kidney function.106 The “Dettli Method” is a graphic means to gener-
ate drug dosing recommendations based on the linear relationship
Step 5 Avoid nephrotoxic Discontinue or avoid prescription
drugs of nephrotoxic medications if
between the elimination rate constant of a given renally cleared drug
possible and a patient’s creatinine clearance:
Step 6 Monitor Monitor drug serum concentrations
(if available) to guide further k = kNR + (α × CLcr)
therapy
where k is the elimination rate constant of the drug based on a first-
Monitor parameters of drug order one compartment model, kNR is the nonrenal elimination rate
response and toxicity
Monitor renal function every 3-5 constant, and α is a constant relating the renal drug elimination rate
days for acute therapies and constant to the patient’s creatinine clearance (CLcr). This approach
monthly or quarterly for chronic assumes that the overall elimination rate constant (or clearance)
medications declines linearly with CLcr, and that the nonrenal elimination rate
Step 7 Reassess Reassess the patient to evaluate drug constant (or CLNR) remains constant as kidney function declines.
efficacy and safety While the first assumption generally holds true for drugs that are
Revise regimen based on drug mainly renally cleared, the second assumption is flawed, as the func-
response or change in patient tional expression of many drug metabolizing enzymes and drug
condition (including renal
function) transporters is reduced in patients with kidney disease.36,37
Ideally, one should be able to identify a relationship between
CLcr, creatinine clearance; eGFR, estimated glomerular filtration rate; EMA, European CL or k with an estimated GFR or CLcr, such as those depicted in
Medicine Agency; FDA, Food and Drug Administration.
Table 48-7. This information, along with the patient’s estimated
CLcr or GFR, is the foundation upon which one can formulate a
therapeutic regimen to attain the desired drug concentration time
defined as a CLcr of less than 10 mL/min (0.17 mL/s). Each of these profile and ultimately the therapeutic outcome when approved
categories encompasses a broad range in renal function, and thus product labeling information is not available.
the recommended drug regimen may not be optimal for all patients If specific literature recommendations and/or the relationship
whose renal function lies within the given category of renal function. of kinetic parameters to estimated GFR or CLcr are not available, then
5 FDA-approved drug labels, and commonly used drug infor- one can estimate the CL or k of the CKD patient with the method of
mation sources such as American Hospital Formulary Service Drug Rowland and Tozer,8 provided the fraction of the drug that is elimi-
Information,97 Goodman and Gilman’s the Pharmacological Basis nated renally unchanged (fe) in subjects with normal renal function
of Therapeutics,17,103 the British National Formulary,98 and Drug is known.107 This approach assumes that the change in CL and k
Prescribing in Renal Failure,99 are excellent sources of information are proportional to eCLcr, that the renal disease does not alter the
about a drugs’ pharmacokinetic characteristics. In some cases, how- drug’s metabolism, that the metabolites, if formed, are inactive and
ever, they yield marked variation in recommendations and the pau- nontoxic, that the drug obeys first-order (linear) kinetic principles,
city of details of the methods used to generate the dosing advice have and that it is adequately described by a one-compartment model.
Dipiro Ch048_p0699_0718.indd 705 10/7/16 10:17 PM

706
TABLE 48-6 Comparison of Secondary References Used for Drug Dosing in CKD
Resource Pros Cons
Aronoff’s Drug - Exclusive focus on drug dosing in renal dysfunction - Hard copy only
Prescribing in Renal - Information provided for IHD, PD, CRRT - Updated every few years; information may not be most
Failure99 - Tables include drug PK and dosage adjustment based on CrCl current, newer drugs may not be included
(>50, 10-50, <10 mL/min [>0.83, 0.17-0.83, <0.17 mL/s]) - Some dosage recommendations are not feasible for
- Tables for both adult and pediatric dosing provided dialysis patients (ie, q 36 hours dosing interval)
SECTION
- Concise, easy to use

- References to primary literature provided
The Renal Drug - Contains information on clinical use of drugs, drug PK, dose in - Updated every few years information may not be most
Handbook100 normal renal function, dose adjustment in CKD, drug interactions and current, newer drugs may not be included
administration - References not provided

- Specific to CKD patients

5 Lexicomp101 - Easy to access with a subscription - Difficult to navigate at first
- Accessible via mobile device - No specific focus on CKD patients
- Easy to navigate - References to primary literature for dosing not provided
Renal Disorders
- Concise information
- Dose adjustment in CKD provided (HD and PD)
Micromedex102 - Easy to access with a subscription - Difficult to navigate
- Accessible via mobile device - Can be slow
- Comprehensive, detailed information (both “in-depth” and “quick”) - No specific focus on CKD patients
- Dose adjustment in CKD provided (both HD and PD) - References to primary literature for dosing not provided
American Hospital - Detailed drug monographs - Hard copy version can be difficult to navigate,
Formulary Service - “Dosage in Renal and Hepatic Impairment/Special Populations” section cumbersome
(AHFS)97 for each drug listed - Information on dose adjustment in CKD is minimal
- Available online with a subscription - No specific focus on CKD patients
- Online version updated regularly, print version updated yearly - References to primary literature for dosing not provided
CKD, chronic kidney disease; CrCl, creatinine clearance; CRRT, continuous renal replacement therapy; HD, hemodialysis; IHD, intermittent hemodialysis; PD, peritoneal dialysis;
PK, pharmacokinetics.
Data from references 97, 99, 100 to 105.
If these assumptions are true, which is rarely the case, then the kinetic The best method for dosage regimen adjustment must then be
parameter/dosage-adjustment factor (Q) can be calculated as: selected. Specifically, one must determine whether the desired goal
Q = 1–[fe (1-KF)] is the maintenance of a similar peak, trough, or average steady-state
drug concentration or if there is a clearly defined pharmacodynamic
where KF is the ratio of the patient’s eCLcr or eGFR to the assumed endpoint such as the time above the MIC (eg, cephalosporins) or
normal value of 120 mL/min (equivalent to 2 mL/s). Thus for a drug the ratio of the AUC relative to the MIC (eg, fluoroquinolones).108
that is 85% eliminated renally unchanged in a patient who has an If there is a significant relationship between peak concentration and
eCLcr of 10 mL/min (0.17 mL/s), the Q factor would be: clinical response (eg, aminoglycosides)109 or toxicity107 (eg, pheno-
Q = 1–[0.85[1–(10/120)]] barbital and phenytoin), then attainment of the specific target values
= 1–[0.85(0.85(0.92)] is critical. If, however, no specific target values for peak or trough
concentrations have been reported (eg, antihypertensive agents and
= 1–0.78
benzodiazepines), then a regimen goal of attaining the same average
= 0.22
steady-state concentration is likely to be appropriate.
The principal choices to attain the desired average steady-state
concentration profile are to decrease the dose or prolong the dosing
TABLE 48-7 Relationship Between CLcr and CL of interval. If the size of the dose is reduced while the dosing interval
Selected Drugs remains unchanged, the desired average steady-state concentration
Drug Total Body Clearancea will be similar; however, the peak will be lower and the trough higher
Acyclovir CL = 3.37 (CLcr) + 0.41 (Fig. 48-1). Alternatively, if the dosing interval is increased and the
Amikacin CL = 0.6 (CLcr) + 9.6 dose size remains unchanged, the peak and trough concentrations
Aztreonam CL = 0.8 (CLcr) + 26.6 in the patient with reduced renal function will be similar to those
Cefazolin CL = 0.34 (CLcr) + 6.6 in the patient with normal renal function. This dosage adjustment
Ceftazidime CL = 1.15 (CLcr) + 10.6 method is often recommended because it is likely to yield cost sav-
Ciprofloxacin CL = 2.83 (CLcr) + 363 ings as a result of a reduction in nursing and pharmacy time, as well
Digoxin CL = 0.88 (CLcr) + 23 as a reduction in the supplies associated with frequent drug admin-
Ganciclovir CL = 1.24 (CLcr) + 8.57 istration. Finally, the dose and dosing interval may both need to be
Gentamicin CL = 0.983 (CLcr) changed to allow the administration of a clinically feasible dose (500
Imipenem CL = 1.42 (CLcr) + 54 mg vs a calculated value of 487 mg) or a practical dosing interval, for
Lithium CL = 0.20 (CLcr)
example, 12 hours instead of 17 hours.
If the relationship between the pharmacokinetic parameters of
Ofloxacin CL = 1.04 (CLcr) + 38.7
the drug and renal function are known, the first step in the process
Piperacillin CL = 1.36 (CLcr) + 1.50
is to estimate the drug disposition parameters in the patient with
Tobramycin CL = 0.801 (CLcr)
renal insufficiency. The dosage-adjustment factor (Q) calculated as
Vancomycin CL = 0.69 (CLcr) + 3.7
the ratio of the estimated k or CL of the patient relative to subjects
CL, total body clearance; CLcr, creatinine clearance. with normal renal function is then used to determine the dose or
Clearance in mL/min can be converted to mL/s through multiplication by 0.0167.
a
dosing interval alterations necessary for the patient.

707
10
Scenario Dose τ Cmax Cmin Cave
A 0.67 12 3.6 2.6 3.1
B 5 90 7.2 0.8 3.1
8 C 2.66 48 5.2 1.6 3.1
CHAPTER
Serum Concentration (mcg/mL)
Scenario B
Scenario C
6
Cave

4
48

2
Scenario A
0
0 100 200
Time (hours)
FIGURE 48-1 Although the average steady-state concentrations (Cave) are identical regardless of which dosage-adjustment strategy one
decides to implement, the concentration–time profile will be markedly different if one changes the dose and maintains the dosing interval
(τ) constant (Scenario A), versus changing the dosing interval and maintaining the dose constant (Scenario B) or changing both (Scenario C).
First, the relationship between drug clearance and CLcr TABLE 48-8 Stepwise Approach to Calculating a Dosage
(expressed in conventional units of mL/min) is required; these rela- Regimen Based on Drug’s Pharmacokinetic
tionship equations have been reported for several drugs (Table 48-7). Characteristics and Patient’s Renal Function
How one can apply the relationship between a patient’s renal function Calculation Examples
and pharmacokinetic characteristics of ciprofloxacin, a commonly Steps with Ciprofloxacin
used antibiotic for the treatment of infections in CKD and dialysis Step 1 Calculate total body clearance CLnorm = [2.83 (CLcr)] + 363
patients to develop and individualized dosage recommendation are of drug in a subject with CLnorm = [2.83(120)] + 363
normal renal function (CLnorm); CLnorm = 702.6 mL/min per
illustrated in Table 48-8 and briefly highlighted here. The first step
CLcr = 120 mL/min 1.73 m2
is to calculate the CL of ciprofloxacin for a subject with normal renal
Step 2 Calculate total body clearance In patient with CLcr
function (CLnorm) and CL for the patient with CKD (CLCKD) to obtain
of drug in a subject with renal = 15 mL/min
the ratio of the predicted clearance values (Q) which can be used to insufficiency (CLfail) CLfail = [2.83(CLcr)] + 363
calculate the new dosing regimen. CLfail = [2.83(15)] + 363
It is also important to consider other characteristics of antibiot- CLfail = 405.5 mL/min per
ics, such as the most relevant MICs and concentrations associated with 1.73 m2
toxicities and adverse events, before modifying a dosage regimen.110 Step 3 Calculate the quotient (Q) Q = CLfail/CLnorm
Ciprofloxacin, a concentration-dependent antibiotic has an associated for a subject with renal Q = 702.6/405.5
insufficiency Q = 0.58
concentration-dependent post antibiotic effect, in which bactericidal
Step 4 Calculate the maintenance Dn = 500 mg; τn = 12 h
action continues for a period of time after the antibiotic concentration
dose (Df ) or adjusted dosing Df = Dn × Q
falls below the MIC. The peak concentration and AUC determine effi- interval (τf ) in a subject with Df = 500 mg × 0.58
cacy of these antibiotics. Therefore extending the interval but keeping renal insufficiency; Df = 290 mg
the same dose allows for this pharmacodynamic action. Furthermore, Dn = normal dose; τn = normal τf = τn/Q
extending the interval without increasing the dose will achieve high dosing interval τf = 12/0.58
τf = 20.7 h
concentrations of ciprofloxacin without an accumulation of drug that
could cause dose-dependent toxicities such as seizures.110 Step 5 Choose dosing adjustment: Dosing adjustments:
1. Maintain Dn and use τf 1. 500 mg every 21 h
If the VD of a drug is significantly altered in CKD patients or if 2. Maintain τn and use Df 2. 290 mg every 12 h
one desires to attain a specific maximum or minimum concentra-
Step 6 Calculate Df based on practical Dn = 500 mg; τf = 21 h;
tion, the estimation of a dosage regimen becomes more complex. If dosing interval (τp), which is τ = 24 h (selected to limit
the relationship between VD and CLcr has been characterized, then selected missed doses)
VD may be estimated. If one assumes that a one-compartment linear Df = (Dn × Q × τp)/τn
model can describe the drug, the predicted VD may then be used with Df = (500 mg × 0.58 ×
24)/12
the predicted k of the drug to yield an adjusted-dosing interval and Df = 580 mg
IV dose.
Step 7 Recommend dosing regimen 500 mg every 24 h
For orally administered drugs, the τf can be calculated and the (dependent on product
dose can be approximated from the following equations as: availability and limited risk of
missed doses)
τf =[(–1/kf )[ln(Cmin/Cmax)]]+tpeak CLcr, creatinine clearance.
Creatinine clearance in mL/min can be converted to mL/s through multiplication
Dose po = [F C VD (ka – k)] / [ka (e– /1 – e– )(e– /1 – e– )]
t
p
kt kτ kat kaτ
by 0.0167. Clearance in mL/min per 1.73 m2 can be converted to mL/s/m2 through
multiplication by 0.00963.

708
where F equals bioavailability, Ctp equals the desired plasma concen- peritoneal drug clearance and molecular weight, protein binding,
tration at time t, and ka is the absorption rate constant. Although, this and VD. In addition, drug compounds that are ionized at physiologic
approach allows for the individualization of an oral dosage regimen pH will diffuse across the membrane more slowly than unionized
for attainment of specific peak and trough serum concentrations it compounds. Detailed reviews of the disposition of several drugs
is rarely used in clinical practice. This is in part due to the paucity in chronic peritoneal dialysis patients are reported elsewhere.120,121
of data on the absorption rate constant of individual drug formula- Anti-infective agents are the most commonly studied drugs because
tions. Thus many assume that the drug is absorbed extremely rap- of their primary role in the treatment of peritonitis.120,122 The treat-
SECTION
idly, in which case one can approximate the τf and the dose using ment priorities for peritoneal dialysis peritonitis and the recom-
equations originally proposed for IV dosing as: mended drug regimens are presented in detail in Chapter 45.
Peritoneal dialysis, in current practice, is often prescribed to
τf = (–1/kf )[ln (Cmin/Cmax)]
attain a urea clearance of approximately 10 mL/min (0.17 mL/s), so

Dose po = VD × (Cmax – Cmin) it is unlikely to significantly impact the CL of any drug.96 In addi-
5 These principles have been used by several investigators to derive
tion, since most medications have a larger molecular size than urea,
their resultant CL will likely be even lower: probably between 5 and
dosage recommendations for many commonly used drugs for CKD 7.5 mL/min (0.08-0.13 mL/s). Therefore, drug dosing recommen-
Renal Disorders
patients (Tables 48-9 and 48-10).99-102,111-114 dations for the management of conditions other than peritonitis,
It should be noted, however, that in most dosing guidelines, the reported for patients with estimated CLcr or GFR of 10 to 15 mL/min
“usual” dose or dose for “normal renal function” represents eGFR (0.17-0.25 mL/s), are likely suitable for patients receiving peritoneal
greater than 50 mL/min/1.73 m2. This assumption, however, could dialysis.99
lead to dosing errors for patients with eGFRs of 60 mL/min/1.73 m2
versus 90 mL/min/1.73 m2 versus 130 mL/min/1.73 m2. In fact, Hemodialysis
augmented renal clearance (ARC) defined as CLcr greater than 130 Although many hemodialyzers have been introduced in the
mL/min/1.73 m2 has been associated with subtherapeutic antibiotic past 20 years and more than 100 different ones were available
concentrations and patient outcomes when standard doses of anti- in North America in 2015, the effect of HD on drug disposi-
biotics were administered.115-117 Although more research has been tion is rarely reevaluated after it is initially reported. Thus,
performed in the past 10 years in the critically ill, clinicians need most of the literature, especially for older medications, probably
to be aware of the potential to under dose these patients because of represents an underestimation of the impact of HD on a drug’s
their augmented renal function and thus need to consider the use of disposition.123
higher doses especially for antibiotics and antivirals. 6 The impact of HD on a patient’s drug therapy is dependent
on several factors, including the physicochemical characteristics of
DRUG DOSAGE REGIMEN DESIGN the drug, the dialysis conditions, and the clinical situation for which
dialysis is performed. Drug-related factors that affect dialyzability
FOR PATIENTS RECEIVING RENAL include the molecular weight or size, degree of protein binding, and
REPLACEMENT THERAPY VD.6 The vast majority of dialysis filters in use in North America up
until the mid-1990s were composed of cellulose, cellulose acetate,
Continuous renal replacement therapies are used for the man- or regenerated cellulose (cuprophane), and they were generally
agement of fluid overload and the removal of uremic toxins in impermeable to drugs with a molecular weight greater than 1,000
patients with AKI and other conditions. Several forms of continu- Da.123 Dialysis membranes in the 21st century are predominantly
ous renal replacement therapy in clinical use today are extensively composed of semisynthetic or synthetic materials (eg, polysulfone,
described in Chapter 43 and several dosage regimen individualiza- polymethylmethacrylate, or polyacrylonitrile). These high-flux
tion approaches are also presented in that chapter. Which of these dialysis membranes have larger pore sizes and more closely mimic
therapies will be optimal for a given patient is dependent on several the filtration characteristics of the human kidney. This allows the
factors, including bleeding risk, degree of hypercatabolism, acid– passage of most solutes, including drugs (eg, vancomycin) that have
base balance, and experience of the healthcare provider team. The a molecular weight of 20,000 Da or less.123,124 Therefore drugs such
rationale and approaches for delivery of renal replacement therapy as vancomycin (1,450 Da) will be more easily removed with high
for those with ESRD are described in Chapter 45. flux dialyzers. An increase in removal has also been reported with
This next section will describe drug dosing regimens for several other drugs that have lower molecular weights such as ceft-
patients on peritoneal dialysis and HD, including short-daily hemo- zadine.123 Some drugs that are cleared in high-flux dialysis but not
dialysis (SDHD) and nocturnal hemodialysis (NHD). through conventional dialysis include: carbamazepine, cisplatin,
enoxaparin, ranitidine, valproic acid, sorafenib, and tramadol.96
Peritoneal Dialysis Therefore, it is likely that many dosing recommendations for HD
Peritoneal dialysis, like other dialysis modalities, has the potential to patients made prior to this change underestimate the impact of HD
affect drug disposition; however, drug therapy individualization is on drug removal. If this is the case some have suggested that the
often less complicated in these patients as a result of the limited drug dosage of many of these older drugs may need to be increased by
clearances achieved with the variants of this procedure (see Chapter as much as 25% to 50% due to enhanced dialytic clearance.96 There-
45). In general, HD is more effective in removing drugs than perito- fore therapeutic drug monitoring for drugs such as aminoglycosides
neal dialysis such that if a drug is not removed by HD, it is unlikely to and vancomycin should be performed to ensure adequate dosing for
be significantly removed by peritoneal dialysis. Many of the factors patients on HD.
that are important in determining drug dialyzability for other treat- Drugs that are small but highly protein bound (ie, greater than
ment modalities pertain to peritoneal dialysis as well.118,119 Factors 90%) are not well dialyzed because both of the principal binding
that influence drug dialyzability by peritoneal dialysis include drug- proteins, α1-acid glycoprotein and albumin, have a very high molec-
specific characteristics such as molecular weight, solubility, degree of ular weight. For example, the molecular weight of albumin is 60,000
ionization, protein binding, and VD. The intrinsic properties of the Da; thus a drug such as apixaban which is 90% bound to plasma
peritoneal membrane that affect drug removal include blood flow proteins would not be removed by HD. Finally, those drugs that are
and peritoneal membrane surface area, which is approximately equal widely distributed, with VD greater than 2 L/kg such as ciprofloxacin,
to the body surface area. There is an inverse relationship between are poorly removed by HD.

709
TABLE 48-9 Drug Dosing Guidelines for Nonantibiotics Commonly Used by CKD Patients
Regimen for Normal Glomerular Filtration Rate (mL/min)a
Drug Renal Function 30-50 10-30 <10 IHD Dosing
Amlodipine 5 mg daily No Adjustment Necessary
Apixaban Indication dependent; 50-25 mL/min: 100% <25 mL/min: Not Not Recommended 5 mg BID
2.5-10 mg BID Recommended 2.5 mg BID if age >
CHAPTER
79 years or body
weight <61 kg3
Aripiprazole 2-5 mg daily No Adjustment Necessary
Atenolol 50-100 mg daily 100% 50 mg q 24 h 25 mg q 24 h 25-50 mg three times
weekly

Atorvastatin 10 mg daily No Adjustment Necessary
Bumetanide 0.5-2 mg q 8-12 h No Adjustment Necessary 48
Canagliflozin 100-300 mg daily Not Recommended Avoid1 Avoid1 Avoid1
Dabigatran Indication dependent; 50-15 mL/min: 75 mg Not Recommended Not Recommended Not Recommended

Starting Dose: 75-110 mg BID
MD: 150-220 mg daily
Digoxin Indication: dependent; LD: 100%, MD: 25%-50% LD: 100%, MD: 25%- LD: 50%, MD: 10%- LD: 50%, MD: 10%-25%
LD: 1-1.5 mg q 24 h 75% q 24 h 25% q 48 h q 48 h
MD: 0.125-0.5 mg q 24 h
Diltiazem 30 mg q 6-8 h (oral regular) No Adjustment Necessary
Duloxetine 30-60 mg daily 100% Avoid Avoid Avoid
Esomeprazole 20-40 mg daily No Adjustment Necessary
Exenatide (immediate 5-10 mcg q 12 h 100%b Avoid Avoid Avoid
release)
Famotidine 20-40 mg daily 50% daily 50% daily 25%-50% daily 25%-50% daily or 20-40
mg q 48-72 h
Furosemide Individualize No Adjustment Necessary
Gabapentin 300-600 mg q 8 h 200-700 mg q 12 h 200-700 mg q 24 100-300 mg q 24 LD: 300 mg, MD:
100-300 mg q 24
Post-HD: 100-300 mg
Glipizide 5-10 mg daily 50% 50% 50% 50%
Glyburide 2.5-5 mg daily Use with caution Use with caution Use with caution Not recommended
Hydralazine (oral) 25-50 mg q 6 h q8h q8h q 8-12 h q 8-12 h
Hydrochlorothiazide 25-50 mg daily 100% 100% Avoidc Avoidc
Insulin Variable 75% 75% 50% 50%
Lansoprazole 15-60 mg daily No Adjustment Necessary
Linagliptin 5 mg daily No Adjustment Necessary
Lisinopril 10 mg daily 50%-75% 50% 25% 25%
Metformin 0.5-1 g q 12 h 25%-50% 25% Avoid Avoid
Metoprolol 25-200 mg q 12 h No Adjustment Necessary
Olmesartan 20-40 mg daily No Adjustment Necessary
Pantoprazole (oral) 40 mg q 12 h No Adjustment Necessary
Pravastatin 10-40 mg daily 100% 10 mg q 24 h 10 mg q 24 10 mg q 24
Pregabalin 300 mg/day 50% 25% 10%-25% 10%-25% Post-HD:
50-75 mg
Ramipril 2.5-10 mg daily 50% 50% 25% 25%
Ranitidine 150-300 mg daily (oral) 150 mg q 24 h 150 mg q 24 h 75 mg q 24 h 75 mg q 24 h
Rivaroxaban Treatment dependent; 15-50 mL/min: 15 mg daily <15 mL/min: Avoid Avoid Avoid
10-20 mg daily
Rosuvastatin 5-40 mg daily 100% 5–10 mg dailyd 5-10 mg dailyd 5-10 mg dailyd
Simvastatin 10-40 mg daily 100% 100% 5 mg q 24 h 5 mg q 24
Sitagliptin 100 mg daily 50% 25% 25% 25%
Spironolactone 50-100 mg/daily Usual dose, q 12-24 h Usual dose, q 12-24 h Not Recommended Not Recommended
Venlafaxine 75 mg daily 25%-50% 25%-50% 25%-50% 50%
Zopiclone 5-7.5 mg daily 3.75-5 mg daily 3.75-5 mg daily 3.75-5 mg daily 3.75-5 mg daily
IHD, intermittent hemodialysis; LD, loading dose; MD, maintenance dosing.
% = percentage of usual dose.
a
The range following glomerular filtration rate (GFR) indicates the use of the dose that corresponds to that range of GFR in patients not on dialysis. GFR in mL/min can be
converted to mL/s through multiplication by 0.0167.
b
Caution should be used when initiating or escalating dose.
c
Should not be used with CLcr <30 mL/min (<0.5 mL/s), but are effective with loop diuretics.
d
Initial dose should be 5 mg daily and titrate as needed to a maximum dose of 10 mg daily.
Data from references 9, 26, 97, 99, 100 to 102.

710
TABLE 48-10 Antibiotic and Antifungal Drug Dosing Recommendations
Regimen for Normal Glomerular Filtration Rate (mL/min)a
Drug Renal Function 30-50 10-30 <10 IHD Dosing
Amoxicillin 0.5-1.0 g q 8 q 8-12 h q 12 h q 24 h 0.25-0.5 g q 24 h
Amoxicillin/clavulanate 500/125 mg q 8 h q 8-12 h q 12 hb q 12 hb q 12-24 hb
Ampicillin 1-2 g q 6 h q 6-12 q 6-12 q 12-24 1 g q 12 h
SECTION
Ampicillin/sulbactam 1.5-3 g q 6-8 h q8h q 12 h q 12-24 h q 12-24 h

Azithromycin 250-500 mg q 24 h 100% 100% 100% 100%
Caspofungin 50-70 mg IV q 24 h 100% 100% 100% 100%
Cefazolin 1-2 g q 8 h q 8-12 h 0.5-1 g q 12 h 0.5-1 g q 24 h 15-20 mg/kg q 48-72

Cefepime 2 g q 8-12 h q 12-24 h 1-2 g q 24 h 0.5-1 g q 24 h 1-2 g q 48-72 h

5 Ceftriaxone 1 g q 24 h 100% 100% 100% 100%
Ceftazidime 1-2 g q 8-12h q 12-24 h q 12-24 h q 24-48 h 1 g after dialysis
Cefuroxime 750 mg-1.5 g q 6-8 h q8h q 8-12 h q 12-24 h Dose after dialysis
Renal Disorders
Cephalexin 250-1,000 mg q 6 h 500 mg q 8–12 h 500 mg q 8–12 h 250-500 mg q 12-24 h 250 mg q 12-24 h
Ciprofloxacin 400 mg q 8-12 h (IV) q 8-12 h q 24 h q 24 h 200-400 q 24
500-750 mg q 12 h (oral) 50%-75% 50%-75% 50% 50%
Clarithromycin 250-500 mg q 12 h 100% 100% 100% No data on
supplemental dosing.
Dose after dialysis.
Clindamycin 150-450 mg q 6 h 100% 100% 100% No supplement for
dialysis
Doripenem 500 mg q 8 h 250 mg q 8 h 250 mg q 12 h 250 mg q 12 h 250 mg q 24 hc
Ertapenem 1 g q 24 h 100% 50% 50% 50%
Fidaxomicin 200 mg po bid 100% 100% 100% No dose adjustment
in IHD
Imipenem 0.5 g q 6 h 0.5 g q 8 h 0.5 g q 12 h 0.25 g q 12 h 0.25-0.5 g q 12 h
Itraconazole 100-400 mg q 24 h Limited data. Consider Limited data. Limited data. Consider dose Limited data; not
dose adjustment. Consider dose adjustment. removed by dialysis
adjustment.
Levofloxacin 500-750 mg q 24 h 50% 50% 25%-50% 25%-50%
q 24 h q 24-48 h q 48 h q 48-72 h
Linezolid 600 mg q 12 h 100% 100% 100% No adjustment in IHD
Meropenem 1gq8h 1 g q 12 h 0.5-1 g q 12 h 0.5 g q 24 h 1 g q 48-72 h
Metronidazole 250-500 mg q 8-12 h 100% 100% 100% Dose after dialysis
Moxifloxacin 400 mg q 24 h 100% 100% 100% 100%
Penicillin G 1-4 million U q 4-6 h 75% 75% 25%-50% LD: usual dose
MD: 25%-50% q 4-6 h or
50%-100% q 8-12 h
Piperacillin/tazobactamd 3.375-4.5 g q 6 h 2.25-3.375 g q 6 h 2.25-3.375 g q 2.25 g q 8-12 125 g q 8-12 h
8-12 h
Tobramycine 5-7 mg/kg q 24 h 5-7 mg/kg q 36-48 h IND IND 1.5-2 mg/kg q 48-72 h
and then IND
Trimethoprim/ 2.5-5 mg/kg q 6-12 h q 6-12 h q 12-24 h q 24 h 2.5-10 mg/kg/day or
sulfamethoxazolef 5-20 mg/kg three
times weekly
Vancomycine,g 15-20 mg/kg q 8-12 h q 24 h IND IND LD: 15-25 mg/kg
MD: 5-10 mg/kg (after
IHD)
Voriconazoleh Weight <40 kg: 100 mg 100% 100% 100% 100%
PO q 12 h
Weight >40 kg: 200 mg
PO q 12 h
IND, individualize based on concentration monitoring; IHD, intermittent hemodialysis; LD, loading dose; MD, maintenance dosing; MU, million units; NC, no change.
a
The range following glomerular filtration rate (GFR) indicates the use of the dose that corresponds to that range of GFR in patients not on dialysis. GFR in mL/min can be
converted to mL/s through multiplication by 0.0167.
b
Extended release and 875 mg tablets are not recommended.
c
For infection caused by Pseudomonas aeruginosa, should be dosed 500 mg IV q 12 h on day 1, then 500 mg IV q 24 h.
d
First dosage modification should be made at a GFR of ≤40 mL/min (≤0.67 mL/s). Second dosage modification should be made at a GFR of <20 mL/min (<0.33 mL/s).
e
Dosing in critically ill patients should be individualized based on pharmacokinetic monitoring.
Dosed based on trimethoprim component.
f
g
A vancomycin loading dose of 25-30 mg/kg (based on actual body weight) should be considered for all patients. In patients with a GFR ≤ 30 mL/min (≤0.5 mL/s), subsequent doses
of 15 to 20 mg/kg should be given when the serum concentration falls below 10 mg/L or 20 mg/L (6.9 or 14 μmol/L) (depending on the site of infection and MIC of organism).
h
Intravenous formulation of voriconazole not recommended, as the vehicle it is prepared in can be nephrotoxic.
Data from references 9,97,99,100 to 102,107,108,114,120 to 123.

711
The HD procedure, be it acute for the management of AKI, readily partition into and out of erythrocytes, this equation would
intermittent three times a week or daily for an extended period likely underestimate HD clearance. Furthermore, one must keep in
or some combination thereof for the management of category G5 mind that venous plasma concentrations may be artificially high
CKD patients can dramatically affect the total body clearance of a and CLpD will be low if plasma water is removed from the blood
medication.123 The primary factors that vary between patients are the at a faster rate than the drug. This tends to occur when extensive
composition of the dialysis filter, the filter surface area, the blood, ultrafiltration is performed simultaneously with diffusion during
CHAPTER
dialysate and ultrafiltration flow rates, and whether or not the dialy- dialysis.96
sis unit reuses the dialysis filter. The following principles may be used to generate a drug dos-
Overall, the impact of HD on drug therapy is highly variable age regimen recommendation for HD patients, if none is available
and thus one cannot assume that a certain percentage of a drug is in FDA or EMA product labeling, by using a value of CLD that is
removed with each dialysis session; neither should a “yes” or “no” reported in the literature.6,17,123 Because clearance terms are additive,

answer regarding the dialyzability of a drug be considered sufficient the total clearance during dialysis can be calculated as the sum of the
information to make therapeutic decisions, since this provides no patient’s residual renal and nonrenal clearance during the interdia- 48
quantification of the impact of HD. Characteristics of the dialysis lytic period (CLRES) and dialyzer clearance (CLD):
procedure that was utilized in the drug study, such as membrane
CLT = CLRES + CLD

composition and surface area and blood and dialysis flow rates, are
thus critical data that should be known before one uses the pub- The half-life during the period between dialysis treatments and
lished HD clearance data to prospectively design a drug dosing regi- during dialysis can then be calculated from the following relation-
men for a HD patient. ships using an estimate of the drug’s VD, which can be obtained from
If drug concentrations can be measured in the clinical setting the literature:6,107
the quantitative impact of HD on drug disposition can be calcu-
lated in one of several ways.6 The most commonly utilized means t1/2,off HD = 0.693(VD/CLRES)
for assessing the effect of HD is to calculate the dialyzer clearance
t1/2,on HD = 0.693(VD/CLRES + CLD)
(CLD) of the drug. The CLpD from blood can be calculated as CLpD =
Qp [(Ap – Vp)/Ap], where Qb is the blood flow through the dialyzer Once the key pharmacokinetic parameters have been esti-
and Qp is the plasma flow, which equals Qb (1 – hematocrit) and, mated/calculated, they may be used to simulate the plasma concen-
Ap is the plasma concentration of drug entering the dialyzer, and tration–time profile of the drug for the individual patient and then
Vp is the plasma concentration of the drug leaving the dialyzer. one can ascertain how much drug to administer and when. This
This clearance calculation most accurately reflects dialysis drug approach to drug therapy individualization can be accomplished in
clearance as most drugs do not significantly penetrate red blood a stepwise fashion assuming first-order elimination of the drug and
cells or bind to formed blood elements. However, for drugs that a one-compartment model.
CLINICAL CASE EXAMPLE Dosage Regimen Calculation for a Hemodialysis patient

A 54-year-old critically ill woman with ESRD was infusion time for the drug (t′) was 1 hour. The concentration
transferred to a medical intensive care unit from the at the end of the 1-hour infusion (Cmax) would be:
general medical unit, where she was febrile with a
temperature of 39°C (102.2°F). Her weight was 64 kg (Dose /t' )(1− e − kt ′ )
Cmax =
(141 lb) and her height was 65 in (165 cm). She had a CL RES
residual CLcr of 5 mL/min (0.083 mL/s), and was receiving
high-flux dialysis (F80 polysulfone dialyzer) for 4 hours (1,000 mg/h)(1− e −(0.0079)1 )
=
on Mondays, Wednesdays, and Fridays. She was started 0.43 L/h
on vancomycin for a methicillin-resistant Staphylococcus
= (2,325.58 mg/L)(0.0078)
aureus (MRSA) catheter-associated bacteremia and her
first dose of 1,000 mg was administered at the end of her = 18.1 mg/L
HD treatment. The first step is to estimate this patient’s The plasma concentration prior to the next dialysis
pharmacokinetic parameters of vancomycin on the basis session (CbD), which is 44 hours away can be calculated as:
of published population data.125 The VD in this patient
can be estimated to be 54.4 L (0.85 L/kg × 64 kg), and CbD = Cmax × e–(CLRES/VD) × t
her residual total body clearance (CLRES) estimated from
= 18.1 × e–0.0079 × 44
the relationship between CL and CLcr [CLRES = (0.69 × CLcr)
= 12.8 mg/L
+3.7] is 7.15 mL/min (0.12 mL/s) or 0.43 L/h. The k can be
approximated as: and the concentration 4 hours later after dialysis (CaD)
k = CLRES/VD can be calculated as:
= 0.43 L/h/54.4 L CaD = CbD × e–[(CLRES + CLD)/VD] × t
= 0.0079 h–1 = 12.8 × e–[(0.43 + 7.2)/54.4] × 4
The HD clearance of vancomycin (CLD) is dependent on = 12.8 × e–0.14 × 4
the dialyzer and a value of 120 mL/min (2 mL/s; 7.2 L/h) is = 7.3 mg/L
a reasonable estimate for this dialyzer.125,126 On the basis of these data, the second dose which
One now can predict what the plasma concentrations of should be administered after the second dialysis session
vancomycin will be over the next 24 to 48 hours, assuming the should be increased as one generally desires to maintain
(Continued)

712
CLINICAL CASE EXAMPLE Dosage Regimen Calculation for a Hemodialysis

patient (Continued)
vancomycin trough concentrations between 15 and 20 dialysis session (CbD), which is 40 hours away can be
mg/L (10-14 μmol/L) for a MRSA catheter-associated estimated as:
SECTION
bacteremia.111,127 The patient received a vancomycin dose

of 1,500 mg 4 hours after the end of the second dialysis CbD = Cmax × e–(CLRES/VD) × t
session. The increase in serum concentration at the end
of this 1-hour infusion (Cchange) can thus be estimated: = 34 mg/L × e–0.0079 × 40
= 24.8 mg/L

(Dose/t' )(1− e − kt' ) and the concentration 4 hours later after the third dialysis
5 C change = (CaD) can be estimated as:
CL RES
(1,500 mg/h)(1− e −(0.0079)1 ) CaD = CbD × e–[(CLRES + CLD)/VD] × t
Renal Disorders
=
0.43 L/h = 24.8 × e–[(0.43 + 7.2)/54.4] × 4
= (3,488.4 mg/L)(0.0078) = 27.2 mg/L = 24.8 × e–0.14 × 4
= 14.2 mg/L
Thus the Cmax would be approximately 34 mg/L This higher dose would be considered by many to have
(24 μmol/L), the sum of the residual concentration from achieved too high of concentrations since the lowest
the first dose of approximately 7 mg/L (5 μmol/L) and value during the majority of the dosing interval exceeded
the Cchange. The plasma concentration prior to the third 24.8 mg/L (17.1 μmol/L).
For medications with a narrow therapeutic index (eg, vancomy- observed when the same dose was administered postdialysis; conse-
cin, phenytoin, and gentamicin), therapeutic drug monitoring (eg, quently, higher dosage regimens are usually necessary to compen-
plasma concentration measurements and dialyzer clearance estima- sate for the additional loss of drug during the dialysis procedure.
tion) should be utilized to guide drug dosing.6 The ultimate reason Furthermore, emerging pharmacokinetic and pharmacodynamic
for measuring the plasma concentrations of antibacterial agents is considerations suggest that it may be optimal approach to adminis-
to individualize the patient’s dosage regimen to achieve a bacterio- ter some drugs, such as aminoglycosides128,129 and vancomycin dur-
logic cure while preventing adverse effects and preserving residual ing or immediately prior to the start of a dialysis treatment.130,131 Two
renal function. Thus there remains one important step in the case evaluations of predialysis and one of intradialytic dosing of amino-
above: the calculation of the dose the patient should receive after the glycosides indicate that similar peak concentrations, a prime indica-
second dialysis session. Vancomycin dosing is primarily based on tor of efficacy, can be obtained in these scenarios relative to those
attaining desired trough concentrations, usually between 15 and 20 observed with postdialysis dosing.128 The AUC during the dosing
mg/L (10-14 μmol/L). Peak concentrations are rarely used and not interval and the subsequent predialysis concentrations were noted to
recommended to derive dosing recommendations and adjustments; be significantly reduced and thus the risk of ototoxicity and further
however, for this patient example, a desired peak concentration of renal injury may be minimized. The best dosing schedule, a dose
30 mg/L (21 μmol/L), the midpoint of the recommended range of roughly twice that traditionally employed for postdialysis adminis-
20 to 40 mg/L (14-28 μmol/L) could be utilized to calculate a dose.111 tration, in the 26 patients evaluated by Teigen et al, resulted in the
Assuming the desired peak concentration of 30 mg/L achievement of the desired peak and AUC in approximately 90% of
(21 μmol/L) and trough concentration was 15 mg/L (10 μmol/L), patients.128
the postdialysis dose this patient would need can then be calculated Performing HD immediately after dosing might also be a good
using the simplified approach below, because the t1/2 is extremely option for several anticancer drugs. The predialysis administration
prolonged relative to the infusion time, and thus minimal drug is of a normal dose makes sense when the patient undergoes HD 2 to
eliminated during the post HD infusion period: 12 hours later. This strategy delivers the desired maximum plasma
concentration effect while minimizing patient exposure to the toxic
Dose = VD × (Cmax – Cmin) drug or metabolite effects.132-135
= 40 L × (30 – 15)
Alternative Hemodialysis Modalities
= 600 mg
Short-daily and nocturnal HD are two alternative HD techniques.
7 It is common practice in most HD units to administer Both modalities are administered 6 to 7 days a week but differ pri-
drugs after the patient has received dialysis on the premise that it marily in the duration of the treatment and blood-flow rate. SDHD
is desirable to minimize the loss of drug that would result from the is typically for 2 hours per session; nocturnal HD occurs overnight
additional clearance during HD. Certainly, administration of anti- for 6 to 8 hours but at lower blood and dialysate flow rates.136
hypertensive agents and vasoactive drugs should be avoided in the
hours prior to a HD session to minimize the likelihood of hypo- Nocturnal Hemodialysis
tension. In some cases, medications for pain are given on a precise NHD use is increasing since there is increased evidence of benefits
schedule and thus the medication would be given to the patient irre- over conventional thrice-weekly HD137-139 (Chapter 45). NHD has
spective of the time on dialysis. The administration of traditional demonstrated improvements in hypertension, left ventricular hyper-
doses of tobramycin (1.5 mg/kg) or vancomycin (1,000 mg) during trophy, quality of life related to burden and effects of kidney disease,
dialysis has been associated with markedly lower AUCs than those and malnutrition compared to conventional HD.137,138 In addition,

713
North American studies suggest that survival is significantly better been quantified but warrant future investigations. The utilization
in NHD than conventional HD and possibly similar to survival after of FDA or EMA drug dosage recommendations in official prescrib-
kidney transplantation.140,141 ing information should be used for the initiation of therapy in most
NHD is performed over 5 to 8 hours on 3 to 7 nights per week clinical situations. However, critically ill individuals especially those
thus receive between 24 and 45 hours of dialysis per week, versus with preexisting CKD likely have marked pharmacokinetic vari-
12 hours with conventional HD.136 The longer dialysis duration ability and may require the use of pharmacokinetic principles in
CHAPTER
removes a higher quantity of solute and fluid, more closely mim- conjunction with reliable population pharmacokinetic estimates to
icking the human physiological state when compared with conven- determine the optimal drug dosage regimen design. Individualiza-
tional HD.136 There is a paucity of data when it comes to drug dosing tion of all drugs with a narrow therapeutic index for AKI and CKD
with this modality; however, the principles of drug dosing discussed patients should be undertaken whenever clinical therapeutic moni-
above with intermittent HD can also be applied here. Although there toring tools are available. The key action step is to use the knowledge

is an increase in dialysis hours, which would suggest an increase in we have to improve patient outcomes. The lack of dosage adjustment
drug removal, the blood and dialysate flow rates are slower and thus for CKD patients in ambulatory and hospital environments is an 48
drug clearance per unit of time will be less. This has been shown in unfortunate reminder of how far we still have to go to optimize the
a study with cefazolin where the cefazolin clearance during NHD therapy of CKD patients.10-14,145

was slightly lower (CL = 1.65 L/h) than during high-flux intermittent Clinicians should therefore be aware of all the possible alterna-
HD (CL = 1.85 L/h );141 however, a greater percentage of cefazolin tions in pharmacokinetics of drug, what processes are likely to be
was removed in 8 hours of NHD (80%) than conventional 4-hour altered in renal failure and tailor pharmacotherapy accordingly to
high-flux HD (60%). The investigators concluded that a dosing regi- ensure that CKD patients receive maximal benefits from their drug
men of a 2-g loading dose followed by 1g IV after each NHD was suf- therapy while minimizing potential adverse outcomes.
ficient to achieve concentrations 6 × MIC for Staphylococcus species
for at least 70% of the dosing interval.141
ABBREVIATIONS
Short-Daily Hemodialysis
SDHD involves 2 hours of dialysis, 6 days of the week, and has been Ab concentration of drug in blood going into the
associated with improved control of blood pressure and phospho- dialyzer (arterial side)
rus, decreased medication requirements, decrease in left ventricular AKI acute kidney injury
mass, and improved quality of life.142,143 It has also shown a trend Ap concentration of drug in plasma going into the
toward prolonged survival because of these improvements in clini- dialyzer (arterial side)
cal outcomes. As in the case with NHD, there is also limited data on AUC0-t the area under the predialyzer plasma
drug dosing with this modality; however, the general principles of concentration–time curve during hemodialysis
drug dosing for HD also apply here. In SDHD, the number of dialy-
sis sessions per week and blood and dialysate flow rates are similar to ARC augmented renal clearance
intermittent HD, which may suggest similar drug removal. However, BSA body surface area
for certain medications (smaller size and decreased VD, and protein CaD plasma concentration after dialysis
binding) drug removal may be increased. CbD plasma concentration prior to the next dialysis
This has been shown in a study with cefazolin where the cefazo- session
lin clearance rate in SDHD was slightly higher than the value observed
CG Cockcroft–Gault
during high-flux intermittent HD; in fact the amount of cefazolin
removed in 2 hours of SDHD was similar to that after 4 hours of CKD chronic kidney disease
high-flux HD.144 The investigators concluded that a dosing regimen CKD-EPI Chronic Kidney Disease Epidemiology
of 1 g after each SDHD was sufficient to achieve concentrations 8 × Collaboration Equation
MIC for Staphylococcus species for at least 90% of the dosing inter- CL total body clearance
val.144 Therefore, it appears that the same amount of medication given CLbD dialyzer clearance from blood
over the entire week for patients on intermittent HD could also be
CLcr creatinine clearance
given to patients on SDHD but in smaller amounts administered
more frequently. For instance, in intermittent HD, the cefazolin dose CLD dialyzer clearance
is typically 2 g IV after each HD for a total of 6 g per week; whereas in CLfail clearance of a drug in patients with impaired renal
SDHD, the dose would be 1 g IV daily (ie, for 6 days) after each HD. function
Overall small solute removal is more efficient if the frequency CLnorm clearance of a drug in patients with normal renal
of HD is increased. Therefore, SDHD and NHD therapies yield dif- function
ferent clearance values compared to intermittent three times per CLNR clearance nonrenal
week HD. Furthermore, prolonged HD such as in the case of NHD,
CLpD dialyzer clearance from plasma
results in less rebound of drug concentrations after the termination
of dialysis. This likely occurs because the rate of transfer from the CLR net renal excretion
peripheral to central compartment relative to the rate of diffusive CLrD recovery clearance of dialyzer
removal is lower. Therefore, careful monitoring of drug therapy is CLreabsorption tubular reabsorption
necessary when these newer modalities are used to avoid potential
CLRES residual drug clearance in a dialysis patient
errors in designing drug dosing regimens.
CLsecretion tubular secretion
CLT total clearance during dialysis
CONCLUSION Cmax peak drug concentration
Subtherapeutic responses to drugs in patients with renal insuf- Cmin trough drug concentration
ficiency are often misinterpreted and not recognized. The adverse Css average steady-state plasma concentration
outcomes associated with inappropriate drug dosing have rarely CYP cytochrome P450

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2454
Pain management (Cont.): for chronic disease cryptosporidiosis, e377–e378
pharmacologic diagnosis of, 554–557 giardiasis, e375–e377
coanalgesics, 922 general approach to, 554 trypanosomiasis, American (Chagas disease),
multimodal therapy, 922 nonpharmacologic, 554 e378–e379
nonopioid agents, 913, 914t outcomes of, desired, 554 Parasitic disease treatment
opioid agents, 913, 915t–916t, 916–922 pharmacologic, 554–557, 556t ectoparasites
patient selection in, 913 abdominal pain relief in, 554–555 lice, e384
regional analgesia, 922–923 analgesics in, 554–555 scabies, e384
Painless thyroiditis, 1187 clinical controversies in, 556b helminthic, nematodes, e382–e383
Palbociclib, 2043t, 2104t enzyme therapy adjuncts in, 557 cysticercosis, e383
Paliperidone palmitate, 1020, 1033t. See also malabsorption treatment in, 556 neurocysticercosis, e383, e383t
Antipsychotics pancreatic enzymes, 555, 556 strongyloidiasis, e382, e383t
INDEX
for schizophrenia, 1018t recommendations, 554, 554f, toxocariasis, e383, e383t

Palivizumab, 424 555f, 555t malaria, e380–e382, e380t–e381t
Palliative care, e109–e113 personalized pharmacotherapy in, 557 protozoan
definition of, e109 Paneth cells, e300 amebiasis, e378
end-of-life care in, e112 Panhypopituitarism, e291–e292 cryptosporidiosis, e377–e378
goals of care in, e112–e113 Panic disorder (attack). See also Anxiety giardiasis, e376–e377
hospice in, e109 disorders trypanosomiasis, American (Chagas disease),
medication management in, e112 clinical presentation of, 1081–1082, 1082b e379
spiritual considerations in, e113 epidemiology of, 1079 Parasitism, e375
symptoms management in, e109–e112 etiology of, 1079–1080, 1080t Parasomnias, 1120
anxiety in, e111–e112 pathophysiology of, 1080–1081 Parasympathomimetic agents, 1515–1516
constipation, e111 Panic disorder (attack) treatment, 1090–1093 Parathion, e125
delirium in, e112 in elderly, 1093 Parathyroid hormone, 626, 627t, 1458–1460
dyspnea, e110–e111 general approach to, 1090 Parathyroidectomy, 627
nausea and vomiting in, e111, e111t nonpharmacologic, 1090 Paregoric, 514, 516t
pain, e109–e110 outcomes of Parental Health Literacy Activities Test
Pamidronate, 2273 desired, 1090 (PHLAT), e8
p-Aminosalicylic acid (PAS), 1788t, 1790t therapeutic, evaluation of, 1093 Parenteral iron therapy, 1599–1600
adverse effects and monitoring of, 1794t personalized pharmacotherapy in, 1093 Parenteral nutrition, 2343–2361
for tuberculosis, 1790–1792 pharmacologic, 1090–1093 assessment for (See Nutrition assessment)
Pancolitis, 481 algorithm for, 1092f complications of, 2357–2359
Pancreas alternative drugs, 1090 mechanical and technical, 2357
exocrine physiology of, 545–546, 546f antidepressants in, 1090–1093 metabolic and nutritional, 2357–2359
proteolytic enzymes in, 546 benzodiazepines, 1091 essential fatty acid deficiency, 2359
Pancreatic polypeptide, 2366t selective serotonin reuptake inhibitors, hyperglycemia, 2358
Pancreatitis, 545–549 1091 hypertriglyceridemia, 2358
acute, 546–549 serotonin-norepinephrine reuptake liver disease, 2358
clinical presentation of, 545, 548–549, 549t inhibitors (SNRIs), 1091 with long-term use, 2359
complications of, 549 tricyclic antidepressants, 1090–1091 metabolic bone disease, 2359
diagnosis of, 548, 549t phases of therapy in, 1092 refeeding syndrome, 2358–2359
etiology of, 546, 546t acute, 1092 of trace elements and vitamins, 2359
incidence of, 545 discontinuation, 1092 components of, 2345–2349, 2345t
medications in, 547, 547t maintenance, 1092 amino acids, 2345–2346
pathophysiology of, 548, 548f resistance to, 1092 dextrose, 2346
prevalence of, 545 in pregnancy, 1093 electrolytes, 2349
prognosis of, 548–549 Panitumumab, e78t, 2047t, 2156 intravenous fat emulsion, 2347–2348
signs and symptoms, 548 Pannus, 1437 trace elements, 2348–2349, 2349t
chronic, 552–553 Panobinostat, 2044t, 2057, 2269–2270 vitamins, 2348
clinical course and prognosis of, 553 Pantoprazole, 445–446, 463t, 466–468, 472t compounding of, 2354–2356
clinical presentation of, 545, 553, 553t Pantothenic acid, 2332t home, 2359–2360
diagnosis of, 553, 553t Papaverine, 1328–1329 indications for, 2344
etiology of, 552t Papillary necrosis, 670–671 in adults, 2344t
incidence of, 545 Papillary renal cell carcinoma types 1 and 2, in children, 2345t
pathophysiology of, 552–553 e421–e422 infection control in, 2354–2356
prevalence of, 545 Papules, e334f initiating and advancing, 2352–2354
risk factors for, 552, 552t Para-aminophenol, 914t in adults, 2352
stages of, 552 Para-aminosalicylic acid, e209 in children, 2352–2354
definition of, 545 Paraquat, e210–e211 continuous vs. cyclic, 2354
epidemiology of, 545 Parasitic disease, e375–e388. See also specific outcomes of
postERCP, 552 types desired, 2343–2344
Pancreatitis treatment ectoparasites, e383–e384 therapeutic, evaluation of, 2354, 2355f
for acute disease, 549–552 definition of, e383 personalized pharmacotherapy in,
abdominal pain relief in, 551 lice, e383–e384 2360–2361
antimicrobials in, 551–552 scabies, e384 pharmacoeconomic considerations in, 2360
clinical controversies in, 551 epidemiology of, e375 regimen design in, 2349–2352
fluid resuscitation in, 551 helminthic, nematodes, e382–e383 construction of, 2350–2352
general approach to, 550 cysticercosis, e382–e383 administration in, 2352
nonpharmacologic, 550 neurocysticercosis, e383 for adults, 2350–2352
nutrition and probiotics in, 550 strongyloidiasis, e382–e383 for children, 2352
outcomes of, desired, 549, 549ff toxocariasis, e383 routes, 2349–2350
pancreatic necrosis prevention in, 551 host-parasitic relationship in, e375 central, 2350
pharmacologic, 551 malaria, e379–e382 peripheral, 2349–2350, 2350t
systemic complication limitation protozoan, e375–e379 stability and compatibility of, 2356–2357
in, 551 amebiasis, e378 storage in, 2354–2356
Dipiro Index_p2403_2478.indd 2454 10/7/16 10:13 PM

2455
timing of initiation, 2368 elimination in, e87 bismuth preparations, 469
vs. enteral, 2367–2368 infant mortality in, e85 H2-receptor antagonists in, 468, 468t
Paricalcitol, 629–631, 630t metabolism in, e87 prostaglandins, 469
Paritaprevir, 573–574 poisonings in, e115, e116t proton pump inhibitors, 466–468
Parity, 1227 Pediculus humanus capitis, e383 sucralfate, 468–469
Parkinson disease, 895–898 Pediculus humanus corporis, e383 for H. pylori–positive ulcers, 460–464, 461t,
clinical presentation of, 897–898, 897b, 898f, Peeling agents (exfoliants), 1544–1545 462t, 464
898t adverse effects and monitoring of, 1552t bismuth-based four-drug regimens,
definition of, 895 resorcinol, 1544 462–463, 462t
epidemiology of, 895 retinoids, topical, 1545 eradication after initial treatment failure,
etiology of, 895, 896f salicylic acid, 1544 464
nonmotor symptoms of, 899t sulfur, 1544–1545 non-bismuth quadruple therapy, 462t,
INDEX
pathophysiology of, 896–897, 896f Pegloticase, 1490t, 1491t, 1495–1496 464
Parkinson disease treatment, 898–906 Pegvisomant, e284–e285 PPI-based three-drug regimens, 462t
general approach to, 898–899, 900f, 902t Pegylated interferon, 575 probiotics, 464
dosing and administration of, 901t Pegylated interferon-b1a, 823t sequential therapy, 462t, 463
nonpharmacologic (surgical), 899–900 Peliosis hepatitis, e234 long-term maintenance of ulcer healing
outcomes of Pelvic inflammatory disease (PID), 1845 in, 466
desired, 898 Pembrolizumab, 2048t, 2064, 2294–2295 for non–H. pylori, non-NSAID ulcers, 466
therapeutic, evaluation of, 906 Pemetrexed, 2039t, 2051 for NSAID-induced ulcers, 464–466,
personalized pharmacotherapy in, 905–906 Pemphigoid gestationis (PG), e342 465–466
pharmacologic, 900–905 Penicillin G, 1672 COX-2 inhibitors vs. NSAID plus PPI,
adverse effects of, monitoring for, 902t dosing by age group, 1670t 465
amantadine, 901 Penicillins. See also specific types cyclooxygenase-2 Inhibitors, 465
anticholinergics, 900–901 adverse effects and monitoring of, 1655t gastrointestinal and cardiovascular safety
carbidopa/L-Dopa, 901–904 allergic reactions to, e319 issues in, 465–466
COMT inhibitors, 905 drug interactions, 1653t H2 receptor antagonist cotherapy, 465
dopamine agonists, 905 for sickle cell disease, 1634 misoprostol cotherapy, 465
monoamine oxidase B inhibitors, 904 for syphilis, 1849, 1850t proton pump inhibitor cotherapy, 465
Paromomycin, e376, e377t for UTIs, 1833t risk-reducing strategies, 464–465, 465t
Paroxetine. See also Selective serotonin reuptake Penile prostheses, 1329, 1329f personalized pharmacotherapy in, 469
inhibitors (SSRIs) Penis recommendations, 460
for major depressive disorder, 1053t hormonal system of, 1309 for refractory ulcers, 466
in menopause and perimenopausal/post- nervous system and psychogenic stimuli for refractory ulcers, 466
menopausal hormone therapy, 1296t of, 1309 Peptic ulcer-related bleeding, 470–471
for OCD, 1105 vascular system of, 1308–1309, 1308f clinical presentation of, 470
Paroxysmal supraventricular tachycardia Pentaerythritol tetranitrate, 150t diagnosis of, 470
(PSVT), 212–215 Pentamidine, 1161t treatment of, 471
antidromic, 213 Pentazocine, dosing and administration of, 918t Peptide nucleic acid fluorescence in situ hybrid-
management, 213–215, 213f, 215f Pentobarbital, for refractory GCSE, 877 ization (PNA-FISH) assay, e364
mechanisms of, 212–213, 212f, 213f Pentostatin, 2050, 2315t Peptide/nucleoside transporters, e240, e242t
orthodromic, 213 Pentoxifylline, e192 Perampanel
PARP inhibitor, 2045t, 2059 Pepsin, 456 advantages and disadvantages of, 859
Partial mastectomy, 2088 Pepsinogen, 456, 2366t adverse effects of, 853t, 859
Pasireotide, e284, 1211t, 1212t Peptic ulcer disease (PUD), 453–473, 470 dosing and administration of, 859
Patient Explanatory Model, e22–e23, e23b, e23t clinical course of, 460 drug interactions, 859
Patient Health Questionnaire (PHQ-9), e275t clinical presentation of, 458, 458t for epilepsy, 859
Patient information leaflets, e5–e6 common forms of, 454t monitoring of, 853t
Patiromer, 766, 767 complications of, 458 pharmacokinetics of, 859
Pazopanib, e427–e429, e427t, e430t, 2045t, 2058 diagnosis of, 459–460 Percentage transferrin situation, 1596
PD-1 checkpoint inhibitors, 2294–2295 endoscopy in, 458–459 Percutaneous coronary intervention, 154–157
PD-L1 checkpoint inhibitors, 2294–2295 imaging in, 458–459 pharmacotherapy with, 156–157
Peak expiratory flow (PEF), e196 epidemiology of, 453–454 primary, for STEMIs, 169–172
Pediatrics, e85–e94 H. pylori, 453–454 vs coronary artery bypass graft surgery,
absorption in, e86–e87 NSAIDs, 454 158–159
distribution, e86–e87 etiology and risk factors for, 454t vs medical therapy, 155–156
gastrointestinal tract, e86 cigarette smoking, 456 Percutaneous transluminal coronary angioplasty
intramuscular sites, e86 dietary factors, 456 (PTA), e190
skin, e86 H. pylori, 454, 454t, 455f Perforin system, e301
drug therapy in NSAIDs, 454–456, 454t, 455t Pergolide, e283
efficacy and toxicity, e87–e88 psychological stress, 456 Perhexiline, e70
factors affecting, e89–e90 pathophysiology of, 456–458 Perianal warts, 1858t
cystic fibrosis, e90 H. pylori, 456–457 Periengraftment respiratory distress syndrome,
hepatic disease, e89 NSAIDs, 457–458, 457f 2311
obesity, e90 Pediculus humanus corporis, 458–460 Perimenopausal/postmenopausal hormone
renal disease, e89–e90 prognosis of, 460 therapy
issues in, e91–e94 vs. gastritis and erosions, 453 benefits and risks of, 1289–1290, 1289t
complementary and alternative therapy, Peptic ulcer disease (PUD) treatment body weight effects, 1292
e93 general approach to, 460, 461f breast cancer, 1291
dosage form alteration, e92–e93 nonpharmacologic, 460 cardiovascular disease, 1290
dose requirements, e93 outcomes of diabetes, 1292
drug administration, e91–e92 desired, 460 endometrial cancer, 1291
drug interactions, e93 therapeutic, evaluation of, 469, 470t gallbladder disease, 1292
medication adherence, e93 pharmacologic, 460–469, 462t lung cancer, 1291
medication safety, e93–e94 antiulcer agents in, 466–469 mood, cognition, and dementia, 1291–1292
pain management, e91, e91t, e92t antacids, 469 osteoporosis, 1291

2456
Perimenopausal/postmenopausal hormone Peripheral blood smear, 1596 factor V Leiden, prothrombin genes, and
therapy, benefits and risks of (Cont.): Peripheral vascular disease, 1175 oral contraception, e76
ovarian cancer, 1291 Peritoneal dialysis, 647–654 HLA gene and hypersensitivity to antiepi-
venous thromboembolism, 1290–1291 access in, 648, 648f leptic drugs and abacavir, e76
bioidentical hormones, compounded, 1295 adequacy of, 649 drug development and, novel sites for, e77
clinical trials on, 1289t advantages and disadvantages of, 641t drug labeling and guidelines in, e77, e78t–79t
combined estrogen-progestogens, 1294–1295, complications of, 649–650 ethical considerations in, e80
1295t catheter-site infections, 650, 653, 653f gene therapy in, e77–e79, e79 (See also
complementary and alternative medicine in, peritonitis, 649–650, 650–653, 650t Gene therapy)
1297–1298 antibiotic therapy for, 650–652, 652t genetic concepts in, e68
phytoestrogens, 1297 fungal, 652–653 genetic variations in, e68–e69
estrogens in, 1292–1294 prevention of, 653–654 goals of, e67
INDEX
adverse effects of, 1292 recommendations, 651f Human Genome Project in, e68
dosage and administration of, 1292, 1293t drug dosage regimen in renal replacement in poison prevention strategies, e117–e118,
oral, 1292 therapy, 708 e118t
other routes of administration in, 1294 history of, 647 polymorphisms in, e69–e73
evidence-based, 1300t peritonitis in, complications of, 650t cytochrome P450 enzymes, e69–e73, e70t,
indications and contraindications for, 1287t principles of, 647–648 e71–e72
other treatments in, 1295–1298, 1296t procedures of, 648–649 CYP2B6, e72
androgens, 1295–1296 automated peritoneal dialysis, 648–649 CYP2C19, e71–e72
selective estrogen receptor modulators, continuous ambulatory peritoneal dialysis, CYP2C9, e72
1296–1297 648 CYP2D6, e70–e71
tibolone, 1297 solutions, 649 CYP3A4/5, e72
personalized pharmacotherapy in, 1298 Peritonitis. See also Intra-abdominal infection in drug target genes
progestogens in, 1294 bacterial enzyme genes and drug response,
therapeutic outcomes of, evaluation of, causes of, 1812t e74–e75
1298–1299, 1299t spontaneous, 1811 genes for intracellular signaling proteins,
Perimenopause, 1285–1287 clinical presentation of, 1814–1815, 1815t ion channels, and drug response,
clinical presentation of, 1286–1287, 1286b complications in hemodialysis, 650, 650t e75–e76, e75f
epidemiology of, 1285 definition of, 1811 receptor genotypes and drug response,
etiology of, 1285 primary, 1811 e74
genitourinary symptoms of, 1288–1289 secondary, 1811 in drug transporter genes, e73–e74
pathophysiology of, 1285–1286 treatment of, 536–537 (See also Intra-abdomi- phase II and nucleotide-base metabolizing
vasomotor symptoms of, 1288 nal infection treatment) enzymes, e72–e73
Perimenopause treatment, 1287–1299 Perphenazine, e70, 505. See also Antipsychotics Pharmacogenomics, e67. See also
general approach to, 1287, 1287t, 1288f pharmacokinetics of, 1023 Pharmacogenetics
nonpharmacologic, 1287 Perseveration, e271 Pharmacogenomics Research Network
outcomes of, desired, 1287 Persistent depressive disorder, 1064t (PGRN), e68
for perimenopausal women, 1288 Pertussis, e152–e155 Pharmacokinetics, clinical, e43–e65. See also
pharmacologic clinical presentation of, e152–e153, e155b Pharmacodynamics, clinical; specific
first choice, 1287 definition of, e152 agents and disorders
guidelines for, 1287 epidemiology of, e152 abbreviations in, e45t
Periodic limb movements of sleep, 1120 etiology of, e152 autoinduction, e48
Perioral dermatitis, 1537 pathophysiology of, e152 bioavailability in, e45–e46, e46f
Peripheral arterial disease (PAD), e187–e192 treatment of, e153–e155 bioequivalence in, e45–e46, e46f
clinical presentation of, e188–e189, e188t postexposure prophylaxis in, e153, e153t clearance in, e46
definition of, e187 preexposure prophylaxis in, e153 elimination route and metabolic pathway
diagnosis of, e188–e189 for suspected or confirmed cases, in, e47
epidemiology of, e187, e187f e153–e155 intrinsic, e46–e47
etiology of, e188 Pertuzumab, 2047t, 2063, 2100–2102 computer programs for, e54–e55
hypertension treatment and, 62–63 Pervasive developmental disorders (PDDs), 1127 definition of, e44
pathophysiology of, e188 Pestivirus, 1798t half-life in, e47
risk factors for, e187 Petasin, 1529 for individualizing pharmacotherapy, e51–e52
Peripheral arterial disease (PAD) treatment, Petasites, 933t initial drug doses in, e52–e53, e53t
e189–e192 Petasites hybridus, 938 linear, e45, e45f
antiplatelet therapy in, e190–e192 Petechiae, 455, 1761 measurement of parameters of, e54, e54f
aspirin, e190–e191 P-glycoprotein (P-gp), e52, 153 models and equations for, e49–e51
aspirin+dipyridamole ER, e191 pH, e243 multicompartment model in, e49–e50,
clopidogrel, e191 Phagocytosis, e298, e298f, e298t e50f
ticlopidine, e191–e192 Pharmaceutical excipients and additives, e322 volume of distribution in, e50
general approach to, e189 Pharmacists, electronic resources for, e12t one-compartment model in, e49, e49f
goals of, e189 Pharmacodynamics, clinical, e62–e65. See also multiple dosing and steady-state equations in,
intermittent claudication, e192 Pharmacokinetics, clinical e50–e51
cilostazol, e192 baseline effects in, e64 nonlinear, e48
pentoxifylline, e192 definition of, e63 Michaelis-Menten kinetics, e48
nonpharmacologic therapy in, e189–e190 Emax and sigmoid Emax models in, e63 protein binding in, e48
exercise in, e189–e190 hysteresis in, e64–e65, e65f of specific drugs
interventional procedures in, e190 linear models, e63–e64, e64f aminoglycosides, e55–e58, e56t, e57f
percutaneous transluminal coronary Pharmacogenetics, e67–e82 cyclosporine, e62
angioplasty in, e190 clinician role in, e81 digoxin, e60
smoking cessation in, e189 definition of, e67 phenytoin, e61–e62, e61–e62f
outcomes of, therapeutic, e192 in disease management, applications theophylline, e60–e61
pharmacologic therapy in, e190, e191t of, e81f vancomycin, e58–e60, e58t
in diabetes mellitus, e190 diseases-associated genes in, e76 steady-state drug concentrations in, e53–e54
in hyperlipidemia, e190 congenital long-QT syndrome and therapeutic ranges in, e44, e44t
in hypertension, e190 drug-induced torsade de pointes, e76 volume of distribution in, e47

2457
Pharmacologic stress testing, e177–e178 dosing and administration of, 1319 tuberculosis (Mycoplasma tuberculosis),
dobutamine stress testing, 178 drug interactions, 1320, 1323 1696–1697
vasodilator stress testing, e177–e178, e178f efficacy of, 1316–1318 viral pneumonia, 1696–1697
Pharyngitis, acute, 1713–1716, 1845t mechanism of, 1316, 1317f, 1318t classification of, 1693t
clinical presentation of, 1713, 1714b monitoring for, 1321t–1323t clinical presentation of, 1692t, 1693
definition of, 1713 pharmacodynamics and pharmacokinetics community-acquired, 1693
epidemiology of, 1713 of, 1319 health-care associated, 1694
etiology of, 1713 selectivity of, 1318–1323 hospital-acquired, 1693–1694
pathophysiology of, 1713 for multiple sclerosis, 830 ventilator-associated, 1694
treatment of, 1713–1716 Phospholipidosis, e233 common pathogens of, 1697
general approach to, 1714 Phospholipids, 271 anaerobic bacteria, 1697
nonpharmacologic, 1714 Phosphoribosyl pyrophosphate (PRPP), gram-negative bacteria, 1697
INDEX
outcomes of 1484, 1484f enteric, 1697
desired, 1713 Phosphorus homeostasis disorders, 750–755. nonenteric, 1697
therapeutic, evaluation of, 1716 See also specific disorders gram-positive bacteria, 1697
personalized pharmacotherapy in, 1716 hyperphosphatemia, 751–752 epidemiology of, 1692
pharmacologic, 1714–1716, 1715t hypophosphatemia, 752–755 in HIV patients, 1694, 1694t
Phenanthrenes, 915t Photochemotherapy, 1565 in neutropenic host, 1694
Phendimetrazine, 2392t, 2394t Photosensitivity, e338 pathogenesis of, 1692
Phenobarbital, 153 Phototherapy, 1565, 1584 prevention of, 1702, 1702t
advantages and disadvantages of, 860 Phthirus pubis, e383 risk factors for, 1693t
adverse effects of, 853t, 859 Physical dependence, 974 Pneumonia treatment, 1697–1703
allergic reactions to, e323 Phytoestrogens, 1297, 1465 clinical controversies in, 1697b, 1698b
dosing and administration of, 860 Phytotherapy, 1346 desired outcome in, 1697
drug interactions, 859–860 P-i concept, e314 general approach to, 1697
for epilepsy, 859–860 PI3K inhibitor, 2045t, 2059 outcome evaluation for, therapeutic,
mechanism of action, 859 PI3K signaling pathway, 2036 1702–1703
monitoring of, 853t Picornaviridae, 562 pharmacologic, 1698–1702
pharmacokinetics of, 859 Pilocarpine, 1513t, 1515 antibiotic concentrations in, 1698–1699
for status epilepticus, 874 Pioglitazone, 1164t antimicrobial agents in, 1699–1700
therapeutic range of, e44t Piperazines, 981 in adults, 1699t
Phenothiazines, 501t, 502, 1029 Piroxicam, 1426t, 1489t in children, 1700t
Phenotype, e68 Pituitary adenomas, TSH-secreting, 1184 dosing of, 1701t
Phentermine, 2392t, 2394t, 2396–2397 Pituitary gland, e279 for atypical pneumonia, 1702
Phentermine–topiramate ER, 2392t, 2393–2395, anatomy of, e279–e280, e280f for community-acquired pneumonia,
2393t, 2394t physiology of, e279–e280, e280f 1700–1701
Phentolamine, 1329 Pituitary gland disorders, e279–e292 for healthcare-associated pneumonia, 1701
Phenylephrine, 1526t, 1639 growth hormone deficiency, e285–e289 for ventilator-associated pneumonia, 1701
for septic shock, 314–315, 1883t, 1884 growth hormone excess (acromegaly), The Pocket Guide to the DSM-5 Diagnostic Exam,
for shock, 310 e280–e285 e268
for ventricular fibrillation/pulseless hyperprolactinemia, e289–e291 Podagra. See Gout and hyperuricemia
ventricular tachycardia, 29 panhypopituitarism, e291–e292 Podocytes, 675
Phenylpiperidines, 915t, 920 Pituitary hormones, e281t Poikilothermia, 1028
Phenytoin, e72, 153, 1161t Pityriasis versicolor, 1901t Poison Prevention Packaging Act (PPPA) of
advantages and disadvantages of, 860 Plague, e145–e146 1970, e116
adverse effects of, 853t, 860 biologic agents in, plague, e145–e146 Poisoning
allergic reactions to, e323 as a bioweapon, e145 with acetaminophen, e121–e123
for arrhythmias, 197 clinical presentation of, e145, e154b causative agents, e122
dosing and administration of, 860 epidemiology of, e145 clinical presentation, e121, e121t
drug interactions, 860 etiology of, e145 incidence of, e122
for epilepsy, 860 pathophysiology of, e145 management of toxicity, e122–e123, e123t
hepatotoxicity of, e229 treatment of, e145–e146 mechanism of toxicity, e121–e122, e122b
monitoring of, 853t postexposure prophylaxis in, monitoring and prevention, e123
pharmacogenetics of, e79t e145–e146, e146t risk assessment, e122
pharmacokinetics of, e61–e62, e61f, 860 preexposure prophylaxis in, e145 with acute iron, e129–e131
for status epilepticus, 873–874, 873t for suspected or confirmed cases, e146 causative agents, e129–e130
therapeutic range of, e44t Plaque, e335f clinical presentation, e129, e129b
Philadelphia chromosome positive ALL, 2230 Plasma-derived factor VIII products, incidence of, e130
Phobias, specific, 1082–1083, 1096. See also 1615–1616 management of toxicity, e130–e131
Anxiety disorders Plasmodium falciparum, e379–e382, 1627 mechanism of toxicity, e129, e130f
Phosphate, 750–751 Plasmodium malariae, e379 monitoring and prevention, e131
Phosphate nephropathy, acute, 667 Plasmodium ovale, e379 risk assessment, e130
Phosphate-binding agents, 627–629, 628t. Plasmodium vivax, e379 with anticholinesterase, e123–e126
See also specific agents Plateau iris, 1508 causative agents, e124–e125
adverse effects of, 629 Platelet aggregation, 1612t clinical presentation, e123–e124,
dosing and administration of, 629 Platelet count, 1612t e124b, e125f
drug-drug interactions, 629 Platelet function analyzer, 1612t incidence of, e125
drug-food interactions, 629 Platelet-activating factors, e314–e315 management of toxicity, e126, e126t
efficacy of, 629 Platelet-derived growth factor (PDGF), 275 mechanism of toxicity, e124, e125f
pharmacology and mechanism of action, 627 Platinum analogs, 2053–2054 monitoring and prevention, e126
Phosphodiesterase 4 inhibitors (PDE-4), 1688 Pneumocystis jiroveci, 1944, 2020t, 2021t with calcium channel blockers, e126–e129
Phosphodiesterase inhibitors, 411, 1341t, Pneumonia, 1692–1697 causative agents, e127
1344–1345 atypical, 1695–1697 clinical presentation, e126–e127, e127b
for benign prostatic hyperplasia, 1341t–1342t Chlamydia pneumoniae, 1698 incidence of, e128
for erectile dysfunction, 1316–1323 Legionella pneumophila, 1697–1698 management of toxicity, e128–e129
adverse effects of, 1319–1320, 1320t, 1321 Mycoplasma pneumoniae, 1686, 1715 mechanism of toxicity, e127t

2458
Poisoning, with calcium channel blockers Positive and Negative Syndrome Scale (PANSS), Pregnancy, 1227–1241
(Cont.): e274t acute care issues in, 1232–1235
monitoring and prevention, e129 Positron emission tomography (PET) bacterial vaginosis and trichomoniasis,
risk assessment, e128 in neurological evaluation, e266 1234
mass chemical, e133–e135 positron emission tomography in, e180, e181f chlamydia, 1234
categories of, e134t Postantibiotic effect, e369, e369f genital herpes, 1234
causative agents, e134 PostERCP pancreatitis, 552 gonorrhea, 1234
clinical presentation, e133–e134, e134t Postinjection delirium/sedation syndrome headaches, 1234–1235
incidence of, e134 (PDSS), 1020, 1036t sexually-transmitted infections, 1233–1234,
management of toxicity, e134 Postoperative nausea and vomiting (PONV), 1233t
mechanism of toxicity, e134 505–506 syphilis, 1234
monitoring and prevention, e134–e135 prophylaxis of, 505 urinary tract infections, 1232–1233, 1838
INDEX
risk assessment, e134 risk factors for, 507t antiemetics in, 507–508
with opioids, e131–e133 treatment of, 505–506, 507t bipolar disorder treatment in, 1074
causative agents, e131–e132 Postpartum depression, 1241 cardiac arrest treatment in, 35–36
clinical presentation, e131, e132b Postpartum thyroiditis (PPT), 1187, 1232 characteristics of, 1228
incidence of, e132 Poststreptococcal glomerulonephritis, 695–696 chronic illnesses in, 1235–1237, 1235t
management of toxicity, e132–e133, e133t clinical presentation of, 695–696 allergic rhinitis, 1235–1236
mechanism of toxicity, e131 epidemiology of, 695 ashthma, 1235–1236
monitoring and prevention, e133 etiology of, 695 diabetes, 1236
risk assessment, e132 prognosis of, 696 epilepsy, 1236
Poliovirus, vaccines, 1997 treatment of, 696 HIV infection, 1236
Poly(adenosine diphosphate [ADP]-ribose) Posttraumatic stress disorder (PTSD), hypertension, 1236–1237
polymerase, 2219 1099–1101 mental health conditions, 1237
Polybromo 1 (PBRM 1), 1012 clinical presentation of, 1100–1101, 1101b thyroid disorders, 1237
Polycarbophil, 516t, 520 definition of, 1099 cystic fibrosis and, 425
Polycystic ovarian syndrome (POS), 1221 epidemiology of, 1099 drug safety in, 1228–1229
in adolescents, 1271b etiology of, 1099 drug selection during, 1228–1229
progesterone in, 1271b pathophysiology of, 1099–1100 epilepsy treatment in, 850, 850–851
Polycythemia, 395 neurochemical theories, 1100 hepatitis B treatment in, 570
Polydipsia, 1067 neuroendocrine theories, 1100 hypothyroidism treatment in, 1200
Polydisperse colloids, 331 neuroimaging studies, 1100 immunization in, 1991–1992
Polyethylene glycol, 520–521 Posttraumatic stress disorder (PTSD) treatment, inflammatory bowel disease and, 490
Polyhexanide, 654 1102–1104 influenza prevention in, 1726–1727
Polymerase chain reaction (PCR), e368, 1667 general approach to, 1102 influenza treatment in, 1728
Polymorphisms, e68–e69 nonpharmacologic, 1102 issues in, 1229–1232
in drug target genes outcomes of gastrointestinal tract, 1229–1230
enzyme genes and drug response, e74–e75 desired, 1102 gestational diabetes, 1230–1231 (See also
genes for intracellular signaling proteins, therapeutic, evaluation of, 1104 Diabetes mellitus (DM))
ion channels, and drug response, personalized pharmacotherapy in, 1103–1104 hypertensive disorders of pregnancy, 1232
e75–e76, e75f pharmacologic, 1102–1103, 1102t, 1103t, thromboembolism, 1232
receptor genotypes and drug response, e74 1104f thyroid abnormalities, 1232
in drug transporter genes, e73–e74 alternative drugs, 1103 labor and delivery in, 1238–1240
in genes for drug-metabolizing enzymes antidepressants in, 1102–1103 antenatal corticosteroids, 1239
cytochrome P450 enzymes, e69–e73, e70t, in children, 1103 cervical ripening, 1239–1240
e71–e72 dosage and administration of, 1103 drug therapies, 1238–1239
CYP2B6, e72 Potassium, 759 group B Streptococcus infection, 1239
CYP2C19, e71–e72 in foods, 762 labor analgesia, 1240
CYP2C9, e72 Potassium homeostasis, 759–760 labor induction, 1239–1240
CYP2D6, e70–e71 Potassium homeostasis disorders postpartum hemorrhage, 1240
CYP3A4/5, e72 hyperkalemia, 763–768 (See also preterm labor, 1238
phase II and nucleotide-base metabolizing Hyperkalemia) tocolytic therapy, 1238
enzymes, e72–e73 hypokalemia, 760–763 (See also nausea and vomiting in, 507–508
insertion-deletion, e69 Hypokalemia) pharmacokinetic changes during, 1228
in pharmacogenetics, e69–e73 Pralatrexate, 2051 physiology of, 1227–1228
phase II and nucleotide-base metabolizing Pralidoxime, for anticholinesterase poisoning, postpartum issues in, 1240–1241
enzymes, e72–e73 e126t depression, 1241
premature stop codon, e69 Pramipexole, 902t, 905 drug use in lactation, 1240–1241
single-nucleotide, e69 Pramlintide, 1169t, 1173 mastitis, 1241
Polymorphonuclear leukocytes (PMNs), 1829 Prasugrel, 173t, 178–181, 188t preconception planning for, 1229, 1230t
Polymyxins Prazosin, 1103, 1341t psoriasis treatment in, 1571
adverse effects and monitoring of, 1656t Prealbumin, 2328 schizophrenia treatment in, 1029–1030
dosing by age group, 1670t Prednisolone, 1490t. See also Corticosteroids sickle cell disease in, 1633
Polyphenols, 807 Prednisone, 489, 490, 682, 1403–1404, 1490t, skin disorders in, e342
Pomalidomide, 2046t, 2059, 2268–2269 2183–2185, 2315t. See also systemic lupus erythematosus (SLE)
Ponatinib, 2043t, 2056, 2249t, 2251t, 2252 Corticosteroids treatment, 1384
Popliteal cyst, 1440f Preeclampsia, 62 thyrotoxicosis treatment in, 1193
Portal hypertension, 528 Pregabalin, 1083 transplacental drug transfer, 1228
clinical features of, 528 advantages and disadvantages of, 860 Pregnenolone, 2167
treatment of, 532 adverse effects of, 853t, 860 Premature babies, e85
Posaconazole, 1935 dosing and administration of, 860 Premature ovarian failure, 1299
for CNS infection, 1675 for epilepsy, 860–861 Premature stop codon polymorphisms, e69
dosing by age group, 1670t mechanism of action, 860 Premature ventricular complexes,
for febrile neutropenia, 1956 monitoring of, 853t 215–216
for HSCT infections, 1963 for multiple sclerosis, 830 Premenstrual dysphoric disorder, 1265t,
for oropharyngeal candidiasis, 1896 pharmacokinetics of, 860 1274–1275, 1274b

2459
Premenstrual syndrome, 1274–1275 Proctitis, 481, 1845t radiation therapy in, 2170
epidemiology of, 1274 Proctocolectomy, 483 radical prostatectomy in, 2170–2171
etiology of, 1274 Proctosigmoiditis, 481 outcomes of
pathophysiology of, 1274 Progesterone desired, 2168
treatment of, 1274–1275 for dysmenorrhea, 1273 therapeutic, evaluation of, 2177
general approach to, desired, 1274 for polycystic ovarian syndrome, 1271b personalized pharmacotherapy in, 2176
nonpharmacologic, 1274 Progestin, 1249, 2104t, 2105t pharmacologic, 2171–2176
outcomes of for amenorrhea, 1264 alternative
desired, 1274 for endometriosis, 1280t, 1282 immunotherapy, 2176
therapeutic, evaluation of, 1275 injectable, 1257 nuclear medicine, 2176
pharmacologic, 1274–1275 subdermal implants, 1257–1258 alternative drugs, 2174–2176
drug class in, 1275 Progestogens, 1294, 1294t. See also specific types chemotherapy, 2176
INDEX
GnRH agonist, 1275 Programmed cell death. See Apoptosis secondary hormonal manipulations,
monophasic OCs, 1275 Progressive multifocal leukoencephalopathy 2174, 2174–2176
selective serotonin reuptake inhibitors, (PML), 826 first-choice, 2171–2174
1274–1275 Prohaptens, e314 antiandrogens, 2171–2174, 2172t–2173t,
venlafaxine, 1275 Prolactin, e281t, e289 2175t
Prescribing error, e40t Prolactinomas, e289 combined androgen blockade, 2174
Pressure sores, 1732t, 1751–1753 Proliferation signal inhibitors, 1405–1406 gonadotropin-releasing hormone
classification of, 1751t adverse effects of, 1406 antagonists, 2171
clinical presentation of, 1752b, 1752f dosing and administration of, 1406 luteinizing hormone-releasing hormone
complications of, 1751 drug-drug interactions, 1406 agonists, 2171
etiology of, 1751 drug-food interactions, 1406 Prostate gland, 2166, 2166f
pathophysiology of, 1751 efficacy of, 1406 Prostatism, 1335
treatment of, 1752–1753 pharmacokinetics of, 1406 Prostatitis, 1839–1840
nonpharmacologic, 1752–1753 pharmacology and mechanism of action, clinical presentation of, 1839–1840, 1839b,
outcomes of 1405–1406 1840f
desired, 1752 Promethazine, e88, 501t etiology of, 1839
therapeutic, evaluation of, 1753 Promotility agents, 446–447. See also specific pathogenesis of, 1839
pharmacologic, 1753 agents treatment of, 1840
Pressured speech, e271 bethanechol, 447 antibiotic therapy in, 1840
Priapism, 1029, 1631–1632, 1639 metoclopramide, 447 evidence-based, 1834t
Primaquine, e78t, e380t, e381t, e388t other investigative, 447 goals of, 1840
Primary immunodeficiency states, 2001 Promyelocytic leukemia, acute personalized pharmacotherapy in,
Primary ovarian insufficiency (POI), 1299–1302 patient monitoring in, 2238 1840–1841
clinical presentation of, 1300–1301, 1301, relapsed, 2237–2238 Prosthetic valve endocarditis. See Endocarditis,
1302b treatment of, 2236–2237 infective
definition of, 1299 phases of, 2236–2237 Prosthetic valve endocarditis (PVE)
epidemiology of, 1299 consolidation therapy in, 2237 definition of, 1759
etiology of, 1299, 1300t induction, 2237 epidemiology of, 1759
pathophysiology of, 1300 postconsolidation therapy in, 2237 etiology of, 1759
treatment of, 1301–1302, 1301t for relapsed APL, 2237–2238 pathophysiology of, 1760
general approach to, 1302 Propafenone, e70, 198, 200t, 202t, 210 Protease inhibitors, 153, 1161t
outcomes of Propionibacterium acnes, 1534, 1535 Proteasome inhibitors, 2046t, 2059
desired, 1302 Propionic acid, 914t bortezomib, 2059
therapeutic, evaluation of, 1302 Propofol, for refractory GCSE, 877 carfilzomib, 2059
premenopausal hormone replacement Propofol infusion syndrome, 886 ixazomib, 2059
therapy in, 1301t Propranolol, 933t Protein
Primary resistance, 1910 Propylthiouracil, 1190–1191 daily requirements, 2335–2336
Primary-angle closure glaucoma, 1503 Prostacyclin and prostacyclin analogs, in enteral nutrition, 2371
clinical presentation of, 1508 409–410 Protein binding, linear, e48
epidemiology of, 1508 Prostaglandin analogs, 1509–1511, 1512, 1514t Proteinuria, e244, 612, 667, 682, 1830
etiology of, 1508 Prostaglandin E1. See Alprostadil in chronic kidney disease, 611
pathophysiology of, 1508 Prostaglandins, e314–e315, 469 treatment of, 617
with pupillary block, 1508 Prostate, physiology of, 1334–1335, 1334f Protestant Christians, beliefs and values, e29t
without pupillary block, 1508 Prostate cancer, 2163–2168 Prothrombin, e76
Primidone chemoprevention of, 2164–2165 Prothrombin time, 530, 1612t
adverse effects of, 853t clinical presentation of, 2167b Proton pump inhibitors, 444, 445–446, 445t,
monitoring of, 853t diagnosis and staging workup for, 2167–2168, 447–448, 449t, 464, 465, 467t, 471.
therapeutic range of, e44t 2167t, 2168t See also specific agents
Prinzmetal’s angina, 139, 160 epidemiology of, 2163 drug interactions, 467–468
Probenecid, 1490t, 1491t, 1495 etiology of, 2163–2164, 2164t long-term safety issues, 468, 468t
Probiotics. See also specific types benign prostatic hyperplasia in, 2164 potential risks, 468, 468t
for allergic rhinitis, 1529 diet in, 2164 Prucalopride, 522
for atopic dermatitis, 1585 family history in, 2164 Pruritic urticarial papules and plaques of
for colorectal cancer, 2139t race and ethnicity in, 2163–2164 pregnancy (PUPPP), e342
for constipation, 522 smoking in, 2164 Pruritus, 1580–1581
for diarrhea, 516, 516b, 516t pathophysiology of, 2166–2167, 2166f, 2167t Pseudoaddiction, 921–922
for gastrointestinal infections, 1804 risk factors for, 2164t Pseudoallergy, e313. See also Allergic drug
for pancreatitis, 550 screening for, 2165 reactions
for peptic ulcer disease, 464 survival rates, 2168 Pseudobulbar palsy, 831
Procainamide, 200t, 202t Prostate cancer treatment, 2168–2177 Pseudodementia, 1028
therapeutic range of, e44t general approach to, 2168–2170, 2169t, 2170f Pseudoephedrine, 1526t
Procalcitonin, e361, 1667 nonpharmacologic, 2170–2171 Pseudohypertension, 51
Procarbazine, e213, 2041t, 2183–2185 observation in, 2170 Pseudomonas aeruginosa, 423, 1672–1673, 1695,
Prochlorperazine, 501t, 932t, 935 orchiectomy in, 2170 1944

2460
Pseudonatremia, 721 social history in, e270–e271 gold salts, e213
Pseudoparkinsonism, 1027 techniques in, e269, e270t mitomycin, e212
Pseudopolyps, 479 DSM, e267–e268 nitrosoureas, e211–e212
Pseudotumor cerebri, e288 DSM-5, e268 noncytotoxic drugs, e213
Psilocybin, 973, 981 laboratory assessment in, e273 pulmonary toxicity, e213
Psoriasis, 1559–1561 physical assessment in, e272–e273 therapeutic outcomes of, monitoring,
clinical presentation of, 1561t psychological testing in, e275–e276 e213–e214
comorbidities in, 1560 symptom and cognitive function measures in, Pulmonary edema
definition of, 1559–1561 e273–e275 drug-induced, e208–e209, e208t
diagnosis of, 1561 neuropsychiatric rating scales in, narcotic-induced, e208–e209
epidemiology of, 1559 e274–e275 other drugs, e209
etiology of, 1559–1560 psychiatric rating scales in, e273, e274t, Pulmonary embolism
INDEX
genetic factors in, 1559–1560 e275t clinical presentation of, 242b

pathophysiology of, 1560 WHO-ICD 10, e268 diagnosis of, 231, 236f
plaque in, 1560 Psychiatric rating scales, e273, e274t treatment of
precipitating factors in, 1560 Psychological testing, e275–e276 guidelines for, 241t
predisposing factors in, 1560 Psychosis. See also Antipsychotics outpatient, 243t
types of, 1560, 1560t in Parkinson disease, 899t Pulmonary eosinophilia, drug-induced,
Psoriasis treatment, 1561–1572 rating scales, e274t e209–e210, e209t
algorithm for, 1562f schizophrenia (See Schizophrenia) Pulmonary fibrosis
in children, 1571 Psyllium hydrophilic colloids, 520 causes of, e211t
combination therapies in, 1569–1570 Pulmonary arterial hypertension, e167, 401–415 drug-induced, e210–e213, e211, e211t
in elderly, 1571 classification of, 401, 402t, 404t alkylating agents, e212
general approach to, 1561–1562 clinical presentation of, 404b amiodarone, e213
goals of, 1561 definition of, 401 antineoplastics, e211
nonpharmacologic, 1562 diagnosis of, 404–406, 405f, 406t biological agents, e213
outcomes of epidemiology of, 401–402 bleomycin, e212
desired, 1561 etiology of, 402 gold salts, e213
therapeutic, evaluation of, 1561 pathophysiology of, 402–406 mitomycin, e212
personalized pharmacotherapy in, 1570–1571 signs and symptoms of, 403–404 nitrosoureas, e211–e212
pharmacoeconomic considerations in, Pulmonary arterial hypertension treatment, noncytotoxic drugs, e213
1571–1572 406–415 Pulmonary function tests (PFTs), e195–e201
pharmacologic general approach to, 406–427 for airway hyperreactivity, e198–e199
alternative drugs, 1570 nonpharmacologic therapy in, 407 carbon monoxide diffusing capacity in, e197
complementary and alternative outcomes of for exercise testing, e200–202, e201t
medicines, 1570 desired, 406 lung volumes in, e196f, e197
hydroxyurea, 1570 therapeutic, evaluation of, 414–415 for pulmonary gas exchange, e200
mycophenolate mofetil, 1570 pharmacologic therapy in, 408–415, 408f for upper airway obstruction, e199, e199f
first choice, 1562f calcium channel blockers, 411, 412t, 413t, uses of, e195
guidelines on, 1562f 414t Pulmonary gas exchange, e200
topical therapies in, 1562–1565 combination therapy, 411–414 Pulmonary hypertension
anthralin, 1564–1565 conventional, 408–409, 408f in sickle cell disease, 1632, 1632t
calcineurin inhibitors, 1565 endothelin receptor antagonists, 410–411 targeted therapy for, 395
coal tar, 1565 guanylate cyclase agonist, 411 Pulse pressure, 46–47
corticosteroids, 1563–1564, 1563t phosphodiesterase inhibitors, 411 Pulseless electrical activity (PEA), 32–33
retinoids, 1564 prostacyclin and prostacyclin analogs, causes of, 33t
salicylic acid, 1565 409–410 nonpharmacologic therapy in, 32–33
Vitamin D3 analogs, 1564 specific, 409, 409f pharmacologic therapy in, 33
photochemotherapy in, 1565 risk assessment in, 406, 407t Pulseless ventricular tachycardia, 27–32
phototherapy in, 1565 Pulmonary artery catheter, 304 antiarrhythmics for, 30t, 32
in pregnancy, 1571 Pulmonary disease, 62–63 magnesium for, 30t, 32
with solid tumor theory, 1571 Pulmonary diseases, drug-induced, e203–e214 nonpharmacologic therapy in, 27–28
systemic therapies in, 1565–1567 ACE inhibitor–induced cough, e207–e208 pharmacologic therapy in, 28–32, 30t
acitretin, 1566 adverse drug reactions, e203 sympathomimetics for, 28–29
cyclosporine, 1566 apnea, e203–e204, e204t thrombolytics for, 30t, 32
methotrexate, 1566–1567 asthma, e204 vasopressin for, 29–32, 30t, 31t
systemic therapy with biologic response bronchospasm, e204, e205t Punitive culture, e41
modifiers, 1567–1569 aspirin-induced, e204–e206, e205t Purine analogs, 2050
alefacept, 1569 cross-sensitivity with food, drug cladribine, 2050
secukinumab, 1569 additives and other agents, e206 fludarabine, 2050
tumor necrosis factor-a inhibitors, desensitization in, e206 mercaptopurine, 2050
1567–1568 pathogenesis of, e205 pentostatin, 2050
adalimumab, 1567–1568 incidence of, e203 thioguanine, 2050
etanercept, 1567–1568 natural rubber latex allergy, e207 Purnell model, e22
infliximab, 1567–1568 from oxygen toxicity, 210, 210f Purulent cellulitis, 1742–1743
ustekinumab, 1569 pulmonary edema, e208–e209, e208t Pyelonephritis, acute, 1836
Psychiatric disorders evaluation, e267–e276 narcotic-induced, e208–e209 Pyranocarboxylic acid, 914t
clinical controversies in, e269b other drugs, e209 Pyrazinamide
clinical interview in, e269–e272 pulmonary eosinophilia, e209–e210, e209t adverse effects and monitoring of, 1794t
for challenging patient, e270 pulmonary fibrosis, e210–e213, e211, e211t for CNS infection, 1677
medication history in, e271 alkylating agents, e212 dosing by age group, 1670t, 1788t
mental status examination in, amiodarone, e213 for tuberculosis, 1786t, 1790, 1790t
e271–e272 antimetabolites, e212–e213 Pyrazoles, 914t
psychiatric history in, e270 antineoplastics, e211 Pyridoxine, 2332t
questions in, e269, e270t biological agents, e213 Pyrimethamine, e246, e388t, 1677
release of information in, e269 bleomycin, e212 Pyrimidine analogs, 2037, 2049

2461
cytarabine, 2037, 2049 pathophysiology of, 694 targeted therapy in, e426–e431, e427t, e428f
fluoropyrimidines, 2050 prognosis of, 695 axitinib, e427t, e429, e430t
gemcitabine, 2050 treatment of, 694–695 bevacizumab, e427t, e429–e431
tipiracil, 2050 for antiglomerular basement membrane cabozantinib, e429
trifluridine, 2050 glomerulonephritis (type I), 694–695 everolimus, e427t, e430t, e431
Pyrovalerone, 980 for antineutrophil cytoplasmic pazopanib, e427–e429, e427t, e430t
Pyrrolizine carboxylic acid, 914t autoantibody- associated sorafenib, e426–e427, e427t, e430t
Pyschiatric rating scales, e274t, e275t glomerulonephritis (type III), 695 sunitinib, e426, e427t, e430t
Pyuria, 1830 general approach to, 694 temsirolimus, e430t, e431
for immune-complex-mediated Renal disease
Q glomerulonephritis (type II), 695 in children, e89–e90
Quadrivalent influenza vaccine, 1723 renal transplantation in, 695 end-stage (See Chronic kidney disease
INDEX
Quaternary ammonium compounds, 1550 types of, 694 (CKD))
Quercetin, 2139t Rasagiline, 902t, 904 Renal osteodystrophy, 613
Quetiapine. See also Antipsychotics Rasburicase, e78t, e79t Renal replacement therapy, 589, 598, 600, 600t.
for ADHD, 953 Rash, 2070 See also specific types
adverse effects of, 953t Raxibacumab, e144t for acute kidney injury, 600, 600t
for bipolar disorder, 1074 Reabsorption, e240 drug dosage regimen in, 708–713
dosing, 953t Rebound headache, 931 hemodialysis, 708–713, 711b–712b
mechanism of action, 1023 Rebound vasodilation, 1527 peritoneal dialysis, 708
for schizophrenia, 1033t Recombinant factor IX, 1614t Renal solute load, 2372–2373
Quick Inventory of Depressive Symptomatology Recombinant factor VIII, 1614, 1614t Renal tubular acidosis, 780
(QIDS-C [Clinician] and QIDS-SR Recombinant interferon, for atopic dermatitis, Renal ultrasonography, e256–e257
[Patient]), e275t 1585 Renal vasculitis, 671
Quinacrine, e376, e388t Recommended dietary allowances, 2333 Renin-angiotensin-aldosterone system (RAAS),
Quinagolide, e283 Red blood cells 47–48, 48f, 83, 767
Quinidine, 197, 202t, e388t, 831 distribution width, 1596 Repaglinide, 1164t
side effects of, 200t erythropoiesis stimulation in, 1592–1593, Replacement therapy, complications of,
therapeutic range of, e44t 1593f 1623–1624
Quinidine gluconate, e381t hemoglobin synthesis in, 1593 Reserpine, 68–69
Quinine, 645 indices, 1595–1596 Residual volume (RV), e196
Quinine sulfate, e381t, e388t mean cell hemoglobin, 1595 Resistant hypertension, 71–73
Quinolones, 1792 mean cell hemoglobin concentration, causes of, 72t
drug interactions, 1653t 1595–1596 diuretic therapy in, 72–73
mean cell volume, 1595 hypertensive emergency in, 73, 74t
R iron incorporation into heme in, 1593 hypertensive urgency in, 73
Rabbit anti-thymocyte globulin (ATG), normal destruction of, 1593, 1593f Resorcinol, 1544, 1552t
1407–1408, 2315t total reticulocyte count, 1596 Respiratory acidosis, 790–791
Rabeprazole, 445–446, 463t, 466–468 5a-reductase inhibitors, 1341t, 1342–1344 causes of, 790
Rabies, e395, 1755 Reed–Sternberg cell, 2180 clinical presentation of, 790, 790b
vaccines, 1997–1998 Refeeding syndrome, 2358–2359 compensation in, 790–791
Radiation-induced nausea and vomiting Reflex incontinence, 1355 pathophysiology of, 790
(RINV), 506–507 Reflexology, 831t treatment of, 791
incidence of, 506 Regadenoson, e177–e178 for acute respiratory acidosis, 791
prophylaxis of, 507 Regional analgesia, 922–923 in compensated chronic respiratory
risk groups, 506 Regional perfusion monitoring, 306–307 acidotic patients, 791
Radioactive iodine, 1192–1193 Regorafenib, 2045t, 2058, 2156 Respiratory alkalosis, 788–790
Radiocontrast media, e320–e321 Regulatory regions, e68 causes of, 788t
Radiofrequency ablation, 444 Rehydration therapy, 1801–1802, 1802t clinical presentation of, 789, 789b
Radiographic contrast media nephrotoxicity, Renal cancer carcinoma (RCC), e419–e424 compensation in, 789
660–662 clinical presentation of, e422–e423, e422b definition of, 788
clinical presentation of, 660 definition of, e419 pathophysiology of, 788–789
pathogenesis of, 660 diagnosis of, e422–e423 treatment of, 789–790
prevention of, 661–662, 661t epidemiology of, e419–e420 Respiratory tract infections, lower, 1683–1703.
risk factors for, 660–661 etiology of, e420 See also specific infections
Radioimmunoconjugates, e402 staging and prognosis in, e423–e424, e423t, bronchiolitis, 1690–1692
Radioimmunotherapy, 2197 e424t bronchitis, 1684–1690
Radionuclide imaging, in gastrointestinal tract subtypes and pathophysiology of, pneumonia, 1692–1702
evaluation, e224 e420–e422 Respiratory tract infections, upper, 1707–1716.
Radionuclide ventriculography, e176–e177 chromophore and oncocytoma RCC, e422 See also specific infections
Radium-223, 2054–2055, 2176 clear cell RCC and VHL gene, e420–e421, acute bacterial rhinosinusitis,
Raloxifene, 1297, 1472–1473, 2079 e421f, e422f 1710–1713
Raltegravir, 1791t, 2011t, 2013t, 2015 papillary renal cell carcinoma types 1 and acute otitis media, 1707–1710
Ramelteon, 1113 2, e421–e422 acute pharyngitis, 1713–1716
Ramucirumab, 2047t, 2063, 2156–2157 survival rate, e419–e420 Resting membrane potential (RMP), 194
Ranitidine, e246, 444, 446, 463t, 471, 472t, 501t Renal cancer carcinoma (RCC) treatment, Restless leg syndrome, in Parkinson disease,
Ranolazine, 153–154, 1161t e424–e432 899t
Rapamycin inhibitors, 685 chemotherapy, e425 Restless legs syndrome, 1119, 1120t
Rapid diagnostic tests, e363 clinical controversies in, e425 Restrictive lung disease, e199–e200. See also
Rapid Estimate of Adult Literacy in Medicine immunotherapy in, e425–e426 specific types
(REALM), e8 outcomes of causes of, e200t
Rapidly progressive glomerulonephritis, desired, e424 pulmonary function tests for, e199–e200
693–695 therapeutic, evaluation of, e432 Resveratrol, 807, 2139t
clinical presentation of, 694 personalized pharmacotherapy in, Reteplase, 646
epidemiology of, 693–694 e431–e432 Reticulocytes, 1596
etiology of, 693–694 surgery in, e424–e425 Retinoic acid, 1545, 1552t

2462
Retinoids, 2054, 2055 Rheumatoid factors, 1437 Riociguat, 411
for acne vulgaris, 1545 Rheumatoid nodules, 1440–1441 Risperidone. See also Antipsychotics
adverse effects and monitoring of, 1552t Rhinitis, allergic, 1519–1530 for ADHD, 953–954
monitoring of, 2042t allergens in, 1519–1520 adverse effects of, 953t
for psoriasis, 1564 clinical presentation of, 1521–1522 for autism spectrum disorder, 1131
Retinopathies, 52 complications of, 1521–1522 dosing, 953t
Retinopathy, 1174 definition of, 1519 mechanism of action, 1023
Retroviral gene delivery, e79–e80 diagnosis of, 1521 pharmacokinetics of, 1023
Rett syndrome, 1132–1134 epidemiology of, 1519 for schizophrenia, 1018t
clinical controversies in, 1133b etiology of, 1519–1520 Ristocetin cofactor activity (RCo), 1620t
clinical presentation of, 1132b, 1133–1134, pathophysiology of, 1520–1521, 1520f, 1521t Ritodrine, 1238
1133t treatment of, 1522–1530 Ritonavir, 573–574, 2011t, 2014, 2014t
INDEX
diagnosis of, 1128t, 1133–1134 algorithm for, 1523f Rituximab, 679, 683, 687, 1382, 1409, 1449,
epidemiology of, 1132 general approach to, 1522 1622–1623, 2046t, 2060
etiology of, 1132–1133 nonpharmacologic, 1522–1523, 1524t Rivaroxaban, 208–210
history of, 1132 outcomes of Rivastigmine, 803, 804t
pathophysiology of, 1132–1133 desired, 1522 Rizatriptan, 932t
treatment of, 1134 therapeutic, evaluation of, 1530 Rockall Score, 470
general approach to, 1134 personalized pharmacotherapy in, Rolapitant, 501t, 502–503
nonpharmacologic, 1134 1529–1530, 1529t Romidepsin, 2044t, 2057
outcomes of pharmacologic, 1522t, 1523–1530 Ropinirole, 902t
desired, 1134 alternative treatment, 1529 Rosiglitazone, 808
therapeutic, evaluation of, 1134 anticholinergics, intranasal, 1522t Rosuvastatin, 148
personalized pharmacotherapy in, 1134 antihistamines, 1522t, 1523–1525 Rotavirus, 1798t
pharmacologic, 1134 combination products, 1527 Roth’s spots, 1761
Reverse cholesterol transport, 274 corticosteroids, intranasal, 1522t Rotigotine, 902t
Rheumatoid arthritis, 1437–1442 cromolyn sodium, 1528 Rubella vaccine, 1998
clinical presentation of, 1438b decongestants, 1522t, 1525–1527 Rufinamide
definition of, 1437 dosing for, 1526t advantages and disadvantages of, 861
diagnostic criteria, 1442 immunotherapy in, 1528 adverse effects of, 853t, 861
epidemiology of, 1437 ipratropium bromide, 1528 dosing and administration of, 861
extra-articular involvement in, 1440–1441 leukotriene receptor antagonists, 1522t drug interactions, 861
amyloidosis, 1441 mast cell stabilizers, 1522t for epilepsy, 861
Felty syndrome, 1441 nasal steroids, 1527 mechanism of action, 861
laboratory findings in, 1441–1442 Rhinitis medicamentosa, 1527 monitoring of, 853t
lymphadenopathy, 1441 Rhinosinusitis, acute bacterial, 1710–1713 pharmacokinetics of, 861
ocular manifestations, 1441 clinical presentation of, 1710–1711, 1710b Ruxolitinib, 2044t, 2057–2058
pulmonary complications, 1441 epidemiology of, 1710 rVSV- Ebola, e148t
rheumatoid nodules, 1440–1441 etiology of, 1710
vasculitis, 1441 pathophysiology of, 1710 S
joint involvement in, 1439–1440, 1439f, 1440f treatment of Saccharomyces boulardii, 483
pathophysiology of, 1437–1439, 1438f general approach to, 1711 Sacubitril, 102
seronegative inflammatory arthritis, 1442 nonpharmacologic, 1711 S-adenosyl-l-methionine (SAMe), 1054
Rheumatoid arthritis treatment, 1442–1451 outcomes of Safflower oil, 2347
general approach to, desired, 1442 desired, 1711 Salicylanilides, 1550
nonpharmacologic, 1442 therapeutic, evaluation of, 1713 Salicylates, 455t, 914t, 1161t
outcomes of personalized pharmacotherapy in, Salicylic acid, 1544, 1547, 1552t, 1565
desired, 1442 1712–1713 Salmeterol, 389
therapeutic, evaluation of, 1451 pharmacologic, 1711–1712 Salmonella enterica, 1799
personalized pharmacotherapy in, 1450–1451, Rhinosinusitis, chronic, 351 Salmonella infection, 1808t, 2020t. See also
1450t Rho(D) immunoglobulin, 2001–2002 Gastrointestinal infection
pharmacologic, 1443 Rhodnius prolixus, e379 Salpingitis, 1845t
abatacept, 1449 Ribavirin, 575, 1691 Salsalate, 1426t
adalimumab, 1449 Riboflavin, 933t, 2332t Santeros (mediums), e26
anakinra, 1450 Rifabutin Saphenous vein graft, 158
biologic agents, 1448 adverse effects and monitoring of, 1794t Saquinavir, 2014, 2014t
non-TNF, 1449–1450 for stable ischemic heart disease, 153 Sarcoptes scabiei, e384
suboptimal response, 1450 for tuberculosis, 1790 Sargramostim, e407
TNF-a inhibitors, 1448 Rifampin, 1254, 1789–1790, 1791t Saxagliptin, 1166t
certolizumab, 1449 adverse effects and monitoring of, 1794t Scabies, e384
clinical monitoring in, 1446t for CNS infection, 1677 clinical presentation of, e384
corticosteroids, 1444–1446 dosing by age group, 1670t, 1788t epidemiology of, e384
DMARDs, 1443–1444, 1443f drug interactions, 1653t etiology of, e384
doses in, 1445t for stable ischemic heart disease, 153 pathophysiology of, e384
etanercept, 1448–1449 for tuberculosis, 1786t, 1790t treatment of, e384
golimumab, 1449 Rifamycin Scedosporium, 1932
hydroxychloroquine, 1447 adverse effects and monitoring of, 1655t Schilling test, 1597
infliximab, 1449 for tuberculosis, 1790 Schizoaffective disorder, 1064–1065
leflunomide, 1447 Rifapentine Schizoid, 1013
methotrexate, 1446–1447 adverse effects and monitoring of, 1794t Schizophrenia, 1011–1014
nonsteroidal anti-inflammatory drugs, for stable ischemic heart disease, 153 chronic phase of, 1013
1444 for tuberculosis, 1790 clinical presentation of, 1013–1014
rituximab, 1449 Rifaximin, 524, 539, 540t epidemiology of, 1011
sulfasalazine, 1447–1448 Right-sided heart, 335 etiology of, 1011–1012
tocilizumab, 1449–1450 Rilonacept, 1490t maternal stress in, 1011
tofacitinib, 1448 Rilpivirine, e246, 2011t, 2013t, 2014 pathophysiology of, 1012–1013

2463
prodromal phase of, 1013 Selective serotonin reuptake inhibitors (SSRIs), pathogen identification in, 1650
symptoms of, 1014, 1014t 1046, 1048, 1053t, 1118 radiologic and laboratory tests in, 1867
violence in, 1022–1023 for Alzheimer disease, 809 Septic emboli, 1760
Schizophrenia treatment, 1014–1035 for bulimia nervosa, 966 Septic shock, 1876t
adverse effects of, 1023–1029 in children, e89b Serious cutaneous adverse reactions (SCARs),
guidelines, 1015–1016 for chronic pancreatitis, 555 e316, e318
mechanism of action of, 1023 for menstruation-related disorders, 1267 Seronegative inflammatory arthritis, 1442
nonpharmacologic, 1014, 1015t for OCD, 1105 Serotonergic agents, 2397
active community treatment in, 1014 for panic disorder (attack), 1091 Serotonergic antidepressants, 1106
cognitive remediation in, 1014 pharmacogenetics of, e79t Serotonin, 960
recovery-based system of care in, 1014 for premenstrual dysphoric disorder, Serotonin agonists, 932t, 933t
social media in, 1014 1274–1275 Serotonin and a2-adrenergic antagonists,
INDEX
outcomes of for PTSD, 1102–1103 1046–1048, 1049, 1053t, 1058t
desired, 1014 for schizophrenia, 1022 Serotonin receptor agonists, 935–936t, 935–937
evaluation of, 1034–1036, 1035t, 1036t Selegiline, 902t, 904. See also Monoamine Serotonin syndrome, 1049–1050
personalized pharmacotherapy in, 1031, oxidase inhibitors Serotonin-norepinephrine reuptake inhibitors
1034 Selenium, 2329t, 2330 (SNRIs), 1046, 1048–1049, 1053t,
pharmacokinetics of, 1023 Self-assessment, e29–e31, e31t 1091, 1103, 1118. See also Tricyclic
pharmacologic, 1014–1031 (See also Self-Rating Anxiety Scale (Zung SAS), e275t antidepressants (TCAs)
Antipsychotics) Self-tolerance, e297–e298 Sertraline, 645, 966, 1053t, 1105
algorithm for, 1017t Sella turcica, e279 Serum immunoglobulin A (SIgA), 581
clinical controversies in, 1019 Senna, 523 Serum sickness, e317
drug interactions, 1030–1031, 1031t–1034t Sensorium, e272 Serum sickness-like disease, e317
first- vs. second-generation antipsychotics Separation, e25 Serum sickness-like reactions, e337
in, 1015, 1016t Sepsis and septic shock, 1875–1879 Setraline. See also Selective serotonin reuptake
initial treatment of acute psychotic episode clinical presentation of, 1878, 1878t inhibitors (SSRIs); Serotonin and
in, 1017–1019, 1018t complications of, 1877–1878 a2-adrenergic antagonists
in lactation, 1029–1030 acute renal failure, 1878 for Alzheimer disease, 809
long-injectable antipsychotics in, 1020, acute respiratory distress syndrome, 1878 for binge-eating disorder, 960
1021t disseminated intravascular coagulation, for depression, 967f
maintenance therapy in, 1019–1020 1877–1878 in children, 1054
patient adherence in, 1020–1021 hemodynamic effects, 1878 in pregnancy, 1054–1055
predictors of response to, 1016–1017 definitions of, 1875, 1876f, 1876t dosing of, 1047t
in pregnancy, 1029–1030 infection sites in, 1875 drug interactions of, 1034t, 1053t
stabilization therapy in, 1019 pathogens in for generalized anxiety disorders, 1083t, 1089,
toxicity with overdose in, 1029 in anaerobic and misc. bacterial sepsis, 1090
for treatment-resistant disease, 1021–1022 1876 half-life of, 1050
augmentation and combination diagnosis and identfiication of, 1879 for hypotension, 644t, 645
strategies in, 1022 in fungal sepsis, 1876 for night eating syndrome, 960
clozapine, 1021–1022 gram-negative bacterial sepsis, 1876 for obsessive-compulsive disorder, 1105–1107
for violent patients, 1022–1023 in gram-positive bacterial sepsis, 1875 for panic disorder (attack), 1091t
Schizophrenic lesion, 1011 pathophysiology of, 1877 in pediatrics, e89b
Sclerotherapy, 534 cellular components for initiating pharmacogenetics of, ee51, e70
Scopolamine, 500t, 505, 507 inflammatory process in, 1877 pharmacokinetics of, 1050, 1051t
Screening Tool of Older Persons’ Potentially pro- and antiinflammatory mediators in, for postpartum depression, 1241
Inappropriate Prescriptions 1877 for psoriasis, 1566
(STOPP), e102 prognosis of, 1878–1879, 1879f for psychotic disorders, 1034t
Seborrheic eczema, definition of, 1578t Sepsis and septic shock treatment, for PTSD, 1102–1103, 1104t
Secondary hypertension, 46, 46t 1879–1885 side effects of, 1048t
Secondary malignancies, 2071 adjunctive therapies in, 1884–1885 for social anxiety disorder, 1094, 1094t
Secondary resistance, 1910 antifungals, 1881–1882 for vasovagal syncope, 224
Secondhand smoke, 376 antimicrobials, 1879–1881, 1880t Sevelamer, 629
Secretin, 2366t duration of treatment, 1882 Severe sepsis, 1875, 1876t. See also Sepsis and
Secukinumab, 1569 empiric regimen, 1881t septic shock treatment
Sedation, 1028, 1035t pharmacokinetics of, in critically ill, Sexual dysfunction, 1035t
Sedative-hypnotics, 977, 978t. See also 1879–1880 in multiple sclerosis, 830
specific agents selection of, 1880–1881 Sexually transmitted diseases (STDs),
Segmental mastectomy, 2088 antivirals, 1882 1843–1859. See also specific diseases
Seizures, 1028 clinical controversies in, 1882 age-specific rates of, 1843
alcohol withdrawal, 996 definition of, 1876t Chlamydia trachomatis, 1851–1852
antipsychotics and, 889–890 eliminating source of infection in, 1879 combined hormonal contraceptives and, 1249
epileptic evidence-based, 303t genital herpes, 1855–1858
classification of, 839–840 hemodynamic support gonorrhea, 1844–1847, 1846t
focal onset, 839, 841 fluid therapy, 1882–1883 human papillomavirus in, 1858–1859
generalized onset, 839–840, 841–842 vasopressor and inotropic therapy, pathogens, 1844
triggers of, 838 1883–1884, 1883t in pregnancy, 1233–1234, 1233t
posttraumatic, 889–890 initial resuscitation in, 1884, 1885t prevalence of, 1843
Selective estrogen receptor degrader (SERD), personalized pharmacotherapy in, 1885 prevention of, 1844
2104t, 2105t resuscitation goals in, 311–312 risk factors for, 1843
Selective estrogen receptor modulators, Septic arthritis syndromes, associated, 1845t
1296–1297 animal bites and, 1753 syphilis, 1847–1851
adverse effects of, 1297 differential diagnosis of, 1486–1487, treatment of, 1858t
dose and administration of, 1297 1486t–1487t trichomoniasis, 1856–1858
efficacy of, 1297 epidemiology of, 1864 Sheehan Panic and Anticipatory Anxiety Scale
Selective estrogen receptor modulators (SERMs), etiology of, 1864 (SPAAS), e275t
2104t, 2105t incidence of, 1864 Shift work sleep disorder, 1119

2464
Shigella, 1800, 1803t, 1808t, 2020t chronic, 1632–1633 Skin
Shigellosis, 1799 cardiac diseases, 1633 age-related changes in, e332
Shock growth and development, 1633 structure and functions of, e331–e332
definition of, 302 hepatobiliary diseases, 1633 Skin and soft-tissue infections (SSTIs), 1731–
septic (See Sepsis and septic shock) ocular manifestations, 1633 1755, 1732t. See also specific infections
Shock liver, 335 pregnancy and, 1633 animal and human bite wounds, 1753–1755
Shock treatment. See also Sepsis and septic psychiatric, 1633 carbuncles, 1733–1734
shock treatment pulmonary, 1632, 1632t cellulitis, 1741–1745 (See also Cellulitis)
desired outcomes and clinical applications in, renal diseases, 1633 classification of, bacterial, 1732
311–317 skeletal and skin diseases, 1632–1633 diabetic foot infections, 1746–1749
catecholamine vasopressors, comparative definition of, 1627 epidemiology of, 1732
studies, 312 epidemiology of, 1627–1628 erysipelas, 1732t, 1734
INDEX
corticosteroids, 313, 317 etiology of, 1628, 1628f etiology of, 1732–1733
dobutamine, 316 incidence of, 1627 folliculitis, 1733–1734
dopamine, 315–316 pathophysiology of, 1628–1629, 1629f furuncles, 1733–1734
epinephrine, 315 prevalence of, 1627–1628 impetigo, 1734, 1740
hemodynamic considerations and adverse Sickle cell disease (SCD) treatment, 1633–1642 lymphangitis, 1741
effects, 313–314 allogeneic hematopoietic stem cell necrotizing soft-tissue infections, 1745–1746
norepinephrine, 314 transplantation in, 1638 pathophysiology of, 1733
phenylephrine, 314–315 for complications, 1638–1641 pressure sores, 1751–1753
resuscitation goals, septic shock, 311–312 acute chest syndrome, 1639 Sepsis and septic shock in, 1881
vasopressin, 312–313, 316–317 aplastic crisis, 1639 treatment of
experimental therapies in, 317–318 cerebrovascular accidents, 1639 drug dosing in, 1737t–1739t
esmolol, 317–318 infection and fever, 1638–1639 drug monitoring in, 1740t
levosimendan, 317 priapism, 1639 evidence-based recommendations,
methylene blue, 317 sickle cell pain, acute, 1640–1641, 1640t 1735t–1736t
nitric oxide inhibitors, 317 sickle cell pain, chronic, 1641 oral drugs in, 1737t
terlipressin, 317 fetal hemoglobin inducers in, 1635–1636 personalized pharmacotherapy in, 1755
monitoring in, 302–306 hydroxyurea, 1635–1636, 1636t, 1637f Skin cancers, e341
global perfusion, 302–306 (See also Global outcomes of age in, 2283
perfusion monitoring) desired, 1633 basal cell carcinoma, e341, e341f
regional perfusion, 306–307 therapeutic, evaluation of, 1641–1642 malignant melanoma, e341, e342f
gastrointestinal tonometry, 306 personalized pharmacotherapy in, 1641 squamous cell carcinoma, e341, e341f
myocardial dysfunction, 306–307 routine health maintenance in, 1633–1635, types of, 2283
personalized pharmacotherapy in, 320t 1634t Skin conditions
recommendations in, 318–320, 319f, 320t immunizations in, 1633–1634 patient assessment in, e332–e336
vasopressors and inotropes in, 307–317 penicillin prophylaxis, 1634 lesion assessment in, e333–e336, e333f–e336f
adrenoceptor function in critically ill transfusion therapy in, chronic, 1636–1638 patient history questions in, e332–e333
patients, 309 Sickle cell hemoglobin, clinical presentation of, Skin disorders, common, e339–e341
catecholamine receptor pharmacology in, 1630t in children, e342
307–309, 307t, 308f Sickle cell syndromes, 1627 contact dermatitis, e339–e340
clinical pharmacology of, 309–310, Sickle cell trait, 1627, 1628f diaper dermatitis, e340–e341
310–311, 310t clinical presentation of, 1630t in pregnancy, e342
vasopressin and cortisol deficiencies and, Sigmoid Emax model, e63 skin cancers, e341
309–310 Sigmoidoscopy, e225, e225f Skin reactions, drug-induced, e336–e339
Short stature (growth hormone deficiency), Significant abacteriuria, 1828 management and prevention of, e338–e339
e285–e289. See also Growth hormone Significant bacteriuria, 1828, 1828t types of, e338
deficiency (GHD) Sildenafil, 1313t, 1321t acneiform, e338
clinical presentation of, e285, e286t Silodosin, 1341t, 1347 acute generalized exanthematous
definition of, e285 Siltuximab, 2048t, 2064 pustulosis, e338
diagnosis of, e286 Simeprevir, 575 allergic, e336
etiology of, e285 Simvastatin, e79t, 148 angioedema, e336–e337, e337t
treatment of, e287–e288 Single-nucleotide polymorphisms (SNPs), e69, drug hypersensitivity reactions, e336
personalized pharmacotherapy in, e288 1012. See also Polymorphisms fixed drug eruptions, e337
pharmacologic, e287–e288 nonsynonymous, e69 hyperpigmentation, e337f, e338
recombinant growth hormone, e287 synonymous, e69 irritant, e336
recombinant insulin-like growth Single-photon emission computed tomography maculopapular, e336
factor-1, e288 (SPECT), e176, e177f photosensitivity, e338
therapeutic outcomes of, evaluation of, in neurological evaluation, e266 serum sickness-like reactions, e337
e288 Sinistrin, e248 Stevens-Johnson syndrome, e337–e338
Short-acting insulin secretagogues, 1173 Sinoatrial (SA) node, 194–195 toxic epidermal necrolysis, e337–e338
Short-daily hemodialysis, 713 Sinus bradycardia, 223–224 urticaria, e336–e337
Sialorrhea, 1029, 1036t Sinusitis Sleep
Sickle cell anemia, clinical presentation of, 1630t allergic rhinitis and, 1521–1522 circadian rhythm, 1111
Sickle cell b-thalassemia, clinical presentation in asthma, 351 cycles, 1111
of, 1630t chronic, 351 neurochemistry of, 1111
Sickle cell disease (SCD), 1627–1633 in cystic fibrosis, 420f polysomnography of, 1111
clinical presentation of, 1629–1630, 1630t definition of, 1710 Sleep apnea, 1115–1116
complications of NSAID allergy and, e321 central, 1116
acute, 1630–1632, 1631t Sinusoidal obstruction syndrome, definition of, 1115
acute chest syndrome, 1631 2311–2312 obstructive, 1115–1116
fever and infection, 1630–1631 Sipuleucel-T, 2048t, 2064–2065, 2175t, Sleep-wake disorders, 1111–1120. See also
neurologic, 1631 2176 specific types
priapism, 1631–1632 Sirolimus, 679, 685, 1405–1406, 2314–2315, apnea
sickle cell pain, 1632 2315t central, 1116
splenic sequestration, 1632 Sitagliptin, 1166t obstructive, 1115–1116

2465
circadian rhythm disorders, 1118–1120 Sodium homeostasis disorders, 721–737. mycophenolic acid derivatives,
classification of, 1112 See also specific disorders 1404–1405
insomnia, 1112–1115 (See also Insomnia) edema, 734–737 nondepleting antibodies, 1408–1409
narcolepsy, 1117–1118 hypernatremia, 729–734 proliferation signal inhibitors, 1405–1406
parasomnias, 1120 hyponatremia, 721–729 outcomes of
personalization of therapy in, 1120 Sodium nitroprusside, 74t desired, 1399
prevalence of, 1111 Sodium overload, 732, 733–734. See also therapeutic, evaluation of, 1409–1410
sleep apnea, 1115–1116 Hypernatremia personalized pharmacotherapy in,
Slow-reacting substances of anaphylaxis, Sodium oxybate, 1118 1410–1411
e314–e315 Sodium polystyrene sulfonate, 765, 766, 767 Solifenacin, 1342t, 1345, 1362–1363
Small bowel follow-through, e222 Sodium valproate, 1070 Soluble transferrin receptor, 1596
Small cell lung cancer, 2116–2117. See also Lung Sodium zirconium cyclosilicate, 766, 768 Somatic mutation, 2138t
INDEX
cancer; Non-small cell lung cancer Sodium-glucose cotransporter-2 inhibitors, Somatomedins, e280
screening and prevention of, 2119–2120 1170–1171 Somatostatin, 533
treatment of, 2126–2127 Sodium-glucose cotransporters, 1144 Somatostatin analogs, e283. See also specific
extensive disease in, 2127 Sofosbuvir, 574 agents
limited disease in, 2127 Soft-tissue infections. See Skin and soft-tissue Somatotropin, e280
outcome evaluation for, therapeutic, 2127 infections (SSTIs) Sonidegib, 2044t
personalized pharmacotherapy in, 2127 Solanezumab, 808 Sorafenib, e426–e427, e427t, e430t, 2045t, 2058
recurrent disease in, 2127 Solid-organ transplant recipients Sorbitol, 520–521, 523, 766
Small molecule inhibitors, 2046t immunization in, 1992 Sotalol, 199, 200t, 202t, 211
Smoking infections in, 1963–1967 South Asians/East Indians, beliefs and values,
cessation, 149, 383–384, 384t, 385t, clinical presentation of, 1965, 1965b e28t
1001–1002 etiology of, 1964 Southern blotting, e364
chronic kidney disease and, 611 prevention of, 1966 Soybean oil, 2347–2348
chronic obstructive pulmonary disease and, risk factors for, 1964 Space of Disse, e229
376 timing of, 1964–1965 Spanish influenza of 1918, 1720
colorectal cancer and, 2134 treatment of, 1965–1967 Specific gravity, urine, e244
combined hormonal contraceptives and, 1249 outcomes of, desired, 1965–1966 Spermicides, 1247t, 1248
economic impact of, 999 personalized pharmacotherapy in, 1967 Spice (synthetic marijuana), e234
epidemiology of, 999 types of, 1965 Spirochetes, 1661
health risks of, 999 Solid-organ transplantation (SOT), 1393–1413 Spirometry, e196, e197f
osteoporosis and, 1465 epidemiology and etiology of, 1394 Spironolactone, 540t, 763, 1549, 1553t
peptic ulcer disease and, 456 heart, 1394 Spleen, e297
prostate cancer and, 2164 kidney, 1394 Splenic flexure, 481
systemic lupus erythematosus and, 1374 liver, 1394 Splenic sequestration, 1632, 1639–1640
Smooth muscle tissue, 1334 lung, 1394 Splenomegaly, 1761
Social anxiety disorder. See also Anxiety physiologic consequences of, 1395–1396 Splinter hemorrhages, 1761
disorders in heart transplantation, 1395–1396, 1396t Sponge (contraception), 1247t
clinical presentation of, 1082, 1082b in kidney transplantation, 1395 Spontaneous bacterial peritonitis, treatment of,
epidemiology of, 1079 in liver transplantation, 1395, 1395t 536–537
etiology of, 1079–1080, 1080t in lung transplantation, 1396 Sprue, celiac. See Celiac disease
pathophysiology of, 1080–1081 rejection pathophysiology in, 1396–1399 Squamous cell carcinoma, e341, e341f
Social anxiety disorder treatment, 1093–1096 acute cellular rejection, 1397–1398 Squamous cell carcinoma (SCC), 2116–2117
in adolescents, 1095 antibody-mediated rejection, 1398 St . Anthony’s fire. See Erysipelas
in alcohol use disorder, 1096 chronic rejection in, 1398–1399 St. John’s wort, 153, 1052–1054
in children, 1095–1096 general concepts of, 1396–1397, 1397f Stable ischemic heart disease (SIHD), 135–160
general approach to, 1093 hyperacute rejection, 1397 biomarkers of, 142–143
nonpharmacologic, 1094 statistics on, 1393–1413 clinical presentation of, 139–140, 139t
outcomes of survival rates, 1394, 1394t coronary vasospasm, 139
desired, 1093 treatment of rejection in, 1399–1409 death rate of, 135–136
therapeutic, evaluation of, 1096 bottom line, clinical, 1412–1413 diagnostic and prognostic testing of, 140–142,
personalized pharmacotherapy in, 1096 general approach to, 1399, 1400f 141f, 142f
pharmacologic, 1094–1096 in acute rejection, 1399 epidemiology of, 135–136
alternative drugs, 1095 induction therapy in, 1399 etiology and pathophysiology of, 136–139
anticonvulsants, 1095 generic substitution in, 1410–1411 management of angina episodes, 159–160
betab-blockers, 1095 immunosuppression-related complications myocardial oxygen demand in, 136
benzodiazepines, 1095 in, 1411–1413 myocardial oxygen supply in, 136–138
antidepressants, 1094–1095, 1094t, 1095f cardiovascular disease, 1411 coronary blood flow, 136–138, 137f, 138
selective serotonin reuptake inhibitors, diabetes, new-onset, 1411 coronary collateral circulation, 138
1094 infection, 1411–1412 heart rate and systole, 138
venlafaxine, 1094–1095 malignancy, 1412 oxygen extraction and oxygen carrying
resistance to, 1095 maintenance therapy in, 1399–1409 capacity, 138
Social identity, e24 alemtuzumab, 1408 nonpharmacologic therapy (revascularization)
Social workers, 426 antibody agents, 1407–1409 coronary artery bypass graft surgery,
Sodium bicarbonate, 34, 463t, 767, 784–785 antimetabolites, 1404–1405 157–158
Sodium chloride-resistant disorders, 788 antithymocyte globulin, 1407–1408 percutaneous coronary intervention,
Sodium chloride-responsive disorders azathioprine, 1405 154–157
ammonium chloride for, 788 calcineurin inhibitors, 1399–1403 pharmacotherapy with, 156–157
arginine monochloride for, 788 corticosteroids, 1403–1404 vs medical therapy, 155–156
definition of, 787 co-stimulatory signal inhibitor, Prinzmetal’s angina, 139
hydrochloric acid for, 787–788 1406–1407 treatment of, 143–154, 144f
Sodium ferric gluconate, 622t depleting antibodies, 1407–1408 guideline-directed medical therapy
Sodium glucose cotransporter-2 inhibitors, interleukin-2 receptor antagonists, angiotensin-converting enzyme
1165t 1408–1409 inhibitors, 147–148
Sodium homeostasis, 719–720 investigational agents, 1409 antiplatelet therapy, 143–147

2466
Stable ischemic heart disease (SIHD), treatment allogeneic, 2234–2235, 2273 Streptococcus gallolyticus, 1763
of (Cont.): autologous, 2235, 2271–2272 Streptococcus mutans, 1763
guideline-directed medical therapy in, for chronic lymphocytic leukemia, 2258 Streptococcus oralis, 1763
143–148, 145t for chronic myelogenous leukemia, Streptococcus pneumoniae, 1630, 1668–1671,
medical therapy in, 149–154 2253–2254 1688, 1708–1709, 1763, 2021t
b-blockers, 150 complications of, 2311–2317 clinical presentation of, 1692t
calcium channel blockers, 150–151 graft failure, 2312–2313 Streptococcus pyogenes, 1733, 1973
nitrates, 150t, 151–153 graft-versus-host disease, 2313–2317 Streptococcus salivarius, 1763
ranolazine, 153–154 infections, 2317 Streptococcus sanguinis, 1763
outcome of, 143 late, 2317 Streptococcus thermophilus, 483
outcomes of, 160 pulmonary, 2312 Streptomycin
risk factor modification in, 148–149 sinusoidal obstruction syndrome, adverse effects and monitoring of, 1794t
INDEX
blood pressure management, 148–149 2311–2312 for tuberculosis, 1788t, 1790–1792, 1790t
diabetes management, 149 definition of, 2303 Stress, peptic ulcer disease and, 456
lipid management, 148–149 donor selection in, 2304–2305 Stress urinary incontinence, 1352–1353. See also
smoking cessation, 149 hematopoietic stem cells in, 2305–2307 Urinary continence
Staphylococcal endocarditis, 1766–1769 histocompatibility testing in, 2304–2305 clinical presentation of, 1354b
IV drug abuser, 1770–1771 immunization in, 1992 pharmacologic treatment of, 1365–1366
prosthetic valves, 1769 infections in, 1960–1963 a-adrenergic receptor agonists, 1347
Staphylococcus aureus infections, 423, 1630, etiology and clinical presentation of, duloxetine, 1366
1692, 1732–1733, 1875 1960–1961, 1961f estrogens, 1365
atopic dermatitis in, 1579, 1581 prophylaxis of, 1961–1963, 1963 venlafaxine, 1366
enterotoxigenic poisonings, 1808t bacterial infections, 1962 Stress-related mucosal bleeding, 471–472
osteomyelitis in, 1863 fungal infections, 1963 epidemiology of, 471
surgical site infections, 1973 viral infections, 1962–1963 prevention of, 471–472
Staphylococcus epidermidis, 1875, 1973 treatment of, 1961–1963 risk factors for, 471
Staphylococcus pneumoniae infections, 1880 outcome evaluation for, therapeutic, treatment of, 471–472
Stargazing (divination), e26 1963 Stress-related mucosal damage (SRMD), 470
Stasis dermatitis, definition of, 1578t outcomes of, desired, 1961 Stroke, 261–268
Statins, 680–681 malignant cell eradication in, 2307–2311 clinical presentation of, 263, 263b, 263f, 264b
for acute coronary syndromes, 183, 188t conditioning regimens, 2307–2310 definition of, 263
in chronic kidney disease, 634 myeloablative, 2308, 2308t epidemiology of, 261
for ischemic stroke, 266–267 reduced-intensity, 2308–2310, 2309f etiology of, 261
myocardial infarction and, 187 in myelodysplastic syndromes (MDS) mortality rate, 261
pharmacokinetics of, 284t treatment, e412 pathophysiology of
Status epilepticus (SE), 867–878 posttransplant therapy in, 2310–2311 in hemorrhagic stroke, 262–263
classification of, 867, 868t chemotherapy in, 2310–2311 in ischemic stroke, 262, 262f
clinical presentation of, 870–871, 870b donor lymphocyte infusion, 2310 risk factors for, 261–262, 262t
definition of, 867 immunotherapy in, 2310 Stroke treatment
diagnosis of, 870 monoclonal antibodies, 2310 general approach to, 264
epidemiology of, 867 targeted therapy in, 2311 nonpharmacologic therapy in
etiology of, 869t Stenosis, fluid mechanics of, 137f for hemorrhagic stroke, 264–265
morbidity and mortality in, 868–869, 868t Stenotrophomonas, 424 for ischemic stroke, 264, 264t
pathogenesis of, 869 Stenotrophomonas maltophilia, 1944 outcomes of
pathophysiology of, 869–870 Stereotypes, e24 desired, 264
Status epilepticus (SE) treatment, 871–878 Steroid resistant nephritic syndrome, 684 therapeutic, 268
hypothermia in, 878 Steroidogenesis inhibitors, 1211–1212 pharmacologic therapy in
ketogenic diet in, 878 Steroids, 505, 682 for hemorrhagic stroke, 267–268
nonpharmacologic, 871, 872f for focal segmental glomerulosclerosis, for ischemic stroke, 265–267, 265t
outcomes of 684–685 alternative drugs, 267
desired, 871 for immunoglobulin A nephropathy, 690 antiplatelet agents, 266
therapeutic, evaluation of, 878 intralesional, 1548–1549 ASA plus clopidogrel, 267
personalized pharmacotherapy in, 878 for membranoproliferative aspirin, 266, 267
pharmacologic, 871–878, 872f glomerulonephritis, 688 blood pressure lowering, 266
benzodiazepines, 871–874, 873t for membranous nephropathy, 686 clopidogrel, 267
fosphenytoin, 874 nasal, 1527 extended-release dipyridamole plus ASA,
phenytoin, 873–874, 873t Stevens–Johnson’s syndrome (SJS), e76, e318, 267
for refractory GCSE, 875–878, 876t e337–e338 heparin, 267
benzodiazepines, 875 Stimulant laxatives, 521 oral anticoagulants, 266
immunomodulating therapies, 878 Stimulants, 948–952. See also specific agents statins, 266–267
inhaled anesthetics, 877–878 for ADHD, 948–952 tissue plasminogen activator, 265–266
ketamine, 877 adverse effects of, 951–952, 951t personalized, 268
lacosamide, 876–877 cardiac, 951–952 Stromal tissue, 1334
levetiracetam, 876–877 on growth, 952 Strongyloides stercoralis, e382
lidocaine, 877 psychiatric, 951 Strongyloidiasis, e382
pentobarbital, 877 clinical controversies in, 949b clinical presentation of, e382
propofol, 877 dosing and administration of, 950t epidemiology of, e382
topiramate, 877 Stool DNA screening tests, 2141 etiology of, e382
valproate, 875–876 Stratum basale (basal layer), e331 pathophysiology of, e382
vagus nerve stimulation in, 878 Stratum corneum (horny layer), e331 treatment of, e382, e383t
Stavudine, 2013t Stratum granulosum (granular layer), e331 Struma ovarii, 1187
Steady-state equations, in clinical Stratum spinosum (prickle cell layer), e331 ST-segment elevation myocardial infarction
pharmacokinetics, e50–e51 Streptococcal endocarditis, 1763–1766, 1765t, (STEMI)
stem cell transplantation, hematopoietic, 1766t. See also Endocarditis, infective nonpharmacologic therapy in, primary PCI,
1960–1963, 2198, 2293–2294, Streptococcal gangrene, 1745 169–172
2303–2317, 2304f Streptococcus agalactiae, 1672 pharmacotherapy for

2467
anticoagulants, 182 Succinimide, 855t latent, 1848
antiplatelet therapy, 172, 173t–176t Sucralfate, 463t, 468–469, 471 neurosyphilis, 1848
aspirin, 177–178 Sucroferric oxyhydroxide, 629 primary, 1848
beta-blockers, 183 Sudden cardiac death, 215–216, 219, 1025 secondary, 1848
clopidogrel, 178–181 Suicide risk, 1044–1045 tertiary, 1848
fibrinolytic therapy, 177 Sulfadiazine, 1677 treatment of, 1849–1851, 1850t
glycoprotein IIb/IIIa receptor inhibitors, Sulfamethoxazole, e229 Systemic adjuvant therapy, 2089–2099
182 Sulfasalazine, 483, 490, 491t, 1443, 1447–1448 benefits, 2090, 2090t
nitrates, 183 Sulfites, e207 biologic therapy, 2094–2096, 2095t
P2Y12 receptor, 178–181, 179t–180t, 181f Sulfonamides, e209, e322 dose density and intensity in, 2093–2094
prasugrel, 178–181 adverse effects and monitoring of, 1656t endocrine therapy, 2096–2099, 2098f
statins, 183 drug interactions, 1653t guidelines, 2090, 2090f
INDEX
ticagrelor, 178–181 Sulfonylureas, 1155, 1168–1170 neoadjuvant (primary), preoperative, 2090
Subacute thyroiditis, 1186–1187 Sulfur, 1544–1545, 1552t Systemic lupus erythematosus (SLE), 1373–1387
Subdermal progestin implants, 1257–1258 Sulindac, 1489t cigarette smoking and, 1374
Substance P, 501t Sumatriptan, 932t, 935–936 from combined hormonal contraceptives,
Substance-related disorders, 973–988 Sunitinib, e426, e427t, e430t, 2045t, 2058 1251–1252
acute vs. chronic, 975 Superficial spreading melanoma (SSM), 2286 definition of, 1373
addiction in, 974 Supraventricular arrhythmias, 202–215 environmental triggers of, 1374
alcohol, 993–999 atrial fibrillation and atrial flutter, 202–212 epidemiology of, 1373
caffeine, 1005–1007 (See also Atrial fibrillation and atrial ethnicity factor in, 1373
in children, 974 flutter) etiology of, 1373–1374
CNS depressants, 975–978 paroxysmal supraventricular tachycardia, incidence of, 1373
benzodiazepines, 977, 977b, 978t reentry, 212–215 pathophysiology of, 1374–1376, 1374f
carisoprodol, 978 antidromic, 213 prevalence of, 1373
dextromethorphan, 978 management, 213–215, 213f, 215f in women, 1374
fentanyl, 977 mechanisms of, 212–213, 212f, 213f Systemic lupus erythematosus (SLE) treatment,
heroin, 976–977 orthodromic, 213 1376–1387
methadone, 976 Surgical site infections (SSIs), 1971–1982 algorithm for, 1377f
opiates and opioids, 975–976 antimicrobial prophylaxis in with drug-induced lupus, 1384–1385
sedative-hypnotics, 977, 978t choice in, 1975 general approach to, 1376–1377
CNS stimulants, 978–981 scheduling in, 1974–1975 immunizations, 1386
amphetamine, 979–980, 979b for specific surgery types, 1975–1981, nonpharmacologic, 1377, 1378f
cathinones, synthetic (bath salts), 980–981 1977t–1978t outcomes of
cocaine, 978–979 appendectomy, 1976 desired, 1376
ecstasy and methamphetamine analogs, 980 cardiothoracic surgery, 1980–1981 therapeutic, evaluation of, 1381t, 1387
methamphetamine, 979–980 cesarean section, 1979–1980 personalized pharmacotherapy in, 1386–1387
drug abuse in, 974 colorectal surgery, 1976–1979 pharmacologic, 1377–1383, 1380t, 1381t
economic impact of, 975 gastroduodenal surgery, 1976 antimalarials, 1379–1382
epidemiology of, 974 gastrointestinal endoscopy, 1979 biologic agents, 1382
Drug Abuse Warning Network, 977 gastrointestinal surgery, 1976 corticosteroids, 1379
Monitoring the Future Study, 974 head and neck surgery, 1980 cyclophosphamide, 1382–1383
National Survey on Drug Use and Health, hepatobiliary surgery, 1976 dehydroepiandrosterone, 1383
974 hysterectomy, 1980 immunosuppressive agents, 1382
hallucinogens, 981 neurosurgery, 1981 nonsteroidal anti-inflammatory drugs, 1379
designer drugs, 981 obstetric and gynecologic surgeries, vitamin D supplements, 1383
LSD, 981 1979–1980 pregnancy and contraception in, 1384
history of, 973 orthopedic surgery, 1981 with SLE–antiphospholipid syndrome overlap,
inhalants, 983 urologic surgery, 1979 1384–1385, 1385t
marijuana, 981–983 vascular surgery, 1981 Systemic vascular resistance (SVR), 120
nicotine, 999–1005 antimicrobial resistance in, 1974 Systolic blood pressure, 46–47
physical dependence in, 974 bacteriology of, 1973–1974 Systolic murmurs, e162, e164t
prevalence rates, 974 categories of, 1971
terminology, 974 epidemiology of, 1971 T
tolerance in, 974 risk factors for, 1971–1973, 1972t T lymphocytes, e299, e300–e301, e360
Substance-related disorders, treatment of, identification of, 1972–1973, 1973t Tachyarrhythmias, mechanisms of, 195
983–988 inherent patient, 1972, 1972t Tachycardia, e170
for acute drug intoxications and withdrawals, Sustained low-efficiency dialysis (SLED), 601, automatic, 195
983–985, 985t 601f reentrant, 195–196, 195–197
barbiturates, 985t Suvorexant, 1113 Tacrolimus
benzodiazepines, 978t, 985t Swan-Ganz catheter, 120, 335 for celiac disease, 584
cocaine, 978t, 985b Swine influenza, 1721 chronic interstitial nephritis and, 670
hallucinogens, 978t Symbiosis, e375 for focal segmental glomerulosclerosis, 685
inhalants, 978t Sympathomimetics, 1161t. See also for graft-versus-host disease, 2314–2315,
marijuana, 978t specific agents 2315t
opiates, 978t, 985t Symptomatic abacteriuria, 1836 for minimal-change nephropathy, 682
opioids, 984b, 984t Symptom-triggered therapy, 997t nephrotoxicity of, 666, 670
sedative-hypnotics, 978t Synonymous SNPs, e69 pharmacogenetics of, e79t
for CNS depressant withdrawal, 985–988 Synthetic marijuana, e234 Tadalafil, 1313t, 1321t, 1341t
benzodiazepines, 985 Syphilis, 1234, 1847–1851 Taenia solium, e383
opiates, 985–986 clinical presentation of, 1847, 1847–1848, Tafluprost, 1514t
buprenorphine, use of, 986–988, 987f 1848t Talimogene laherparepvec, 2048t, 2065, 2296
outcomes of, desired, 988 congenital, 1848 TALKDOC, e8
personalized pharmacotherapy in, 988 diagnosis of, 1848–1849 Tamm–Horsfall protein, e244–e245, 1829
substance dependence in, 988 epidemiology of, 1847 Tamoxifen, 1297, 2079, 2096–2099, 2104t, 2105
Substantial nigra, 896 etiology of, 1847 Tamsulosin, 1341t, 1347

2468
Tanacetum parthenium, 938 Temozolomide, 2042t, 2053 Thought blocking, e271
Tandem repeats, e69 Temsirolimus, e430t, e431, 2045t, 2058 Thought broadcasting, e271
TandemHeart, 130–131 Tenecteplase, 646 Thrombin time, 1612t
Tangential speech, e271 Tenofovir, 569, 1791t, 2011t, 2012, 2013t Thrombocytopenia
Tapentadol, 921 Tension-type headache, 938–939 in cancer patients, 2068
dosing and administration of, 918t clinical presentation of, 939 in cirrhosis, 530, 531
Tardive dyskinesia, 1027, 1035t epidemiology of, 938–939 drug-induced, e352–e355
Targeted drugs, for cancer, 2036–2037, 2048t. pathophysiology of, 939 causative agents, e354, e354t
See also specific agents treatment of, 939 clinical presentation of, e352
ALK Inhibitors, 2055 general approach to, 939 epidemiology of, e352
alectinib, 2055 nonpharmacologic, 939 mechanism of, e352–e354
ceritinib, 2055 pharmacologic, 939 drug-dependent antibody, e353–e354
INDEX
crizotinib, 2055 Terazosin, 1341t hapten-type, e353

BCR-ABL inhibitors, 2055–2056 Terbinafine, 1904–1905 immune-mediated, e354
bosutinib, 2056 Terbutaline, e209, 1238, 1639 platelet-specific antibody, e354
dasatinib, 2056 Terconazole, for vulvovaginal candidiasis, 1891, treatment of, e354–e355
imatinib, 2055–2056 1891t heparin-induced, 182, e352, e353f
nilotinib, 2056 Teriflunomide, 823t, 824t, 827 Thrombocytosis, 1441
ponatinib, 2056 Teriparatide, 1473–1474 Thromboembolism
BRAF inhibitors, 2056 Terlipressin, 317 from combined hormonal contraceptives,
BTK inhibitor, 2056 Test Of Functional Health Literacy in Adults 1251
DNA methyltransferase inhibitors, 2056 (TOFHLA), e8 in pregnancy, 1232
EGFR pathway inhibitors, 2056–2057 Testosterone, 1309, 1314t–1315t, 1322t–1323t, venous (See Venous thromboembolism
afatinib, 2057 1334f, 2166 (VTE))
erlotinib, 2056–2057 for erectile dysfunction, 1323–1325 Thrombolytics, 30t, 32. See also specific agents
gefitinib, 2057 adverse effects of, 1325 Thrombotic microangiopathy, 671
lapatinib, 2057 dosing and administration of, 1325 Thromboxane A, 347
osimertinib, 2057 efficacy of, 1324, 1324t Thromboxanes, e314–e315
HDAC inhibitors indications for, 1323–1324 Thrush. See Esophageal candidiasis
belinostat, 2057 mechanism, 1323 Thymus, e296
panobinostat, 2057 pharmacokinetics of, 1324–1325 Thyroglobulin, 1181–1182
romidepsin, 2057 for osteoporosis, 1473 Thyroid cancer, 1187
vorinostat, 2057 Tetanus, 1754 Thyroid disorders, 1181–1200
Hedgehog pathway inhibitors, 2057 immunoglobulin, 1998–1999 hypothyroidism, 1194–1210
JAK inhibitor, 2057–2058 vaccines, 1998–1999, 1998t in pregnancy, 1237
lanreotide, 2059–2060 Tetanus toxoid adsorbed, 1998–1999 thyrotoxicosis, 1183–1194
lenalidomide, 2059 Tetracosactide, 687 Thyroid hormones, 1181
MEK inhibitor, 2058 Tetracyclines, e88 coupling reactions, 1181, 1182f
mTOR pathway inhibitors, 2058 for acne vulgaris, 1547, 1553t exogenous, 1187
everolimus, 2058 adverse effects and monitoring of, 1655t pituitary resistance to, 1184
temsirolimus, 2058 drug interactions, 1653t regulation and action of, 1183
multikinase inhibitors, 2058–2059 nonalcoholic steatohepatitis and, e233 structure of, 1182
axitinib, 2058 for peptic ulcer disease, 462–463 synthesis of, 1181–1182, 1182f, 1182t, 1183t
cabozantinib, 2058 for syphilis, 1850t Thyroid storm, 1193–1194, 1193t
lenvatinib, 2058 Tetrahydrocannabinol (THC), 831t Thyroiditis
pazopanib, 2058 Tetrofosmin-99m, e176 autoimmune, 1194–1195
regorafenib, 2058 Th1 and Th2 cell imbalance, 345–346 painless, 1187
sorafenib, 2058 Thalidomide, e85, 2046t, 2059, 2267–2268 postpartum, 1187
sunitinib, 2058 T-helper type 1 or 2 responses, e299 subacute, 1186–1187
vandetanib, 2058–2059 Theophylline Thyroid-stimulating hormone (TSH), e280,
PARP inhibitor, 2059 pharmacokinetics of, e60–e61 e281t
PI3K inhibitor, 2059 therapeutic range of, e44t Thyrotoxicosis, 1183–1188
pomalidomide, 2059 Therapeutic range, e44, e44t clinical presentation of, 1188b
proteasome inhibitors, 2059 Thermogenic effect of food, 2386 differential diagnosis of, 1183t
bortezomib, 2059 Thermoregulation, 1028 in elderly, 1188
carfilzomib, 2059 Thiacetazone, 1792 epidemiology of, 1183–1194
ixazomib, 2059 Thiamine, 2332t etiology of, 1183
thalidomide, 2059 Thiazides, 56, 619b etiology of, with elevated RAIU, 1184–1186
Tau oligomers, 808 for edema, 734–737 Graves’ disease, 1184–1185, 1185f, 1185t
Taxanes, 2051, 2107, 2214–2220. See also for heart failure with preserved ejection multinodular goiters, 1186
specific agents fraction, 94 pituitary resistance to thyroid hormone,
Tazarotene, 1552t, 1564 for hypertension, 57t, 66 1184
Tazobactam, 1949 Thiazolidinediones, 1155, 1164t, 1172 toxic adenoma, 1186, 1186f
T-cell lymphomas, 2190 Thioguanine, e79t, 489, 2050 trophoblastic diseases, 1185
T-cell receptors, e299 Thionamide drugs, 1190–1191 TSH-induced hyperthyroidism, 1184
Technetium scanning, e176–e177 adverse effects of, 1190–1191 TSH-secreting pituitary adenomas, 1184
Technetium sestamibi, e176 dosing and administration of, 1190 etiology of, with suppressed RAIU,
Technology mechanism of action, 1190 1186–1188, 1187
in health literacy and medication use, e12t, pharmacokinetics of, 1190 exogenous thyroid hormone, 1187
e13, e13f Thiopurine methyltransferase (TPMT), e69, medications containing iodine,
medical adherence in, e13–e14, e14t 491, 1383 1187–1188
Tedizolid, 1743 Thioridazine. See also Antipsychotics painless thyroiditis, 1187
Tegafur, e79t dosing of, 1016t subacute thyroiditis, 1186–1187
Tegaserod, 523 drug interactions, 1053t thyroid cancer, 1187
Telavancin, 1743 for schizophrenia, 1025 pathophysiology of, 1183
Telbivudine, 569 Thiotepa, 2042t, 2308t Thyrotoxicosis factitia, 1187

2469
Thyrotoxicosis treatment, 1188–1194, 1189t Tolvaptan, 126 management of toxicity, e132–e133,
in children, 1193 Tonic seizure, 842. See also Epilepsy e133t
general approach to, 1188 Tonic-clonic seizure, 842. See also Epilepsy mechanism of toxicity, e131
in Graves’ disease, 1193 Tophaceous gout, 1487, 1487f monitoring and prevention, e133
nonpharmacologic, 1188–1189 Topiramate, 937, 968, 2392t risk assessment, e132
outcomes of advantages and disadvantages of, 861–862 weapons of mass chemical poisoning,
desired, 1188 adverse effects of, 853t, 861 e133–e135
therapeutic, evaluation of, 1194 for bipolar disorder, 1074 categories of, e134t
pharmacologic, 1190–1193 dosing and administration of, 861, 933t causative agents, e134
adrenergic blockers, 1191–1192 drug interactions, 861 clinical presentation, e133–e134, e134t
antithyroid medications, 1190–1193 for epilepsy, 861–862 incidence of, e134
iodides, 1191 mechanism of action, 861 management of toxicity, e134
INDEX
methimazole, 1190–1191 monitoring of, 853t mechanism of toxicity, e134
propylthiouracil, 1190–1191 pharmacokinetics of, 861 monitoring and prevention, e134–e135
radioactive iodine, 1192–1193 for refractory GCSE, 877 risk assessment, e134
thionamide drugs, 1190–1191 Topoisomerase II inhibitors, e402 databases, e115, e116t
in pregnancy, 1193 Topoisomerase inhibitors, 2052 death rates, e115
for thyroid storm, 1193–1194, 1193t anthracyclines, 2052 epidemiology of, e115, e116t
Thyrotropin, 1182 camptothecins, 2052 poison prevention strategies, e116–e118,
Thyroxine, 1181 etoposide, 2052 e116t
Tiagabine monitoring of, 2040t pharmacogenetics in, e117–e118, e118t
advantages and disadvantages of, 861 teniposide, 2052 psychosocial patient characteristics in,
adverse effects of, 853t, 861 Topotecan, 2040t, 2218 e117t
for bipolar disorder, 1074 Toremifene, 2104t, 2105 recognition and assessment in, e116–e117,
dosing and administration of, 861 Torsade de pointes, e76, 221–222, 222f, 223t e117t
drug interactions, 861 Tositumomab, 2046t, 2061 poisoning in, e115
for epilepsy, 861 Total iron-binding capacity, 1596 treatment approaches in
mechanism of action, 861 Total peripheral resistance, 46–47 activated charcoal in, e119, e120
monitoring of, 853t Total reticulocyte count, 1596 antidotes in, e120t
for multiple sclerosis, 829–830 Tourette disorder, 955 cathartics in, e119
pharmacokinetics of, 861 Toxic adenoma, 1186, 1186f diuresis in, e119–e120
Tibolone, 1296t Toxic cirrhosis, e233–234 enhanced elimination in, e119
Ticagrelor, 173t, 178–181, 188t Toxic epidermal necrolysis (TEN), e76, e316, gastric decontamination in, e119
Tick-borne infections, e395 e337–e338 gastric lavage in, e119
Ticlopidine, e191–e192 Toxic megacolon, 479–480, 489 hemodialysis in, e120
Ticonazole, for vulvovaginal candidiasis, 1891, Toxicology, clinical, e115–e135 hospital treatment in, e118
1891t clinical spectrum of, e121–e135 ipecac syrup in, e118
Timed-kill curve tests, e368–e369, e369f acetaminophen poisoning, e121–e123 prehospital care in, e118–e121
Timolol, 933t, 1513t, 1514t causative agents, e122 whole-bowel irrigation in, e119
Tinea barbae, 1901t, 1902 clinical presentation, e121, e121t Toxocara canis, e383
Tinea capitis, 1901t, 1902 incidence of, e122 Toxocara cati, e383
Tinea corporis, 1901–1902, 1901t management of toxicity, e122–e123, Toxocariasis, e383
Tinea cruris, 1901, 1901t e123t clinical presentation of, e383
Tinea manuum, 1901, 1901t mechanism of toxicity, e121–122, e122b epidemiology of, e383
Tinea pedis, 1901t monitoring and prevention, e123 etiology of, e383
Tinidazole, e376, e377t risk assessment, e122 pathophysiology of, e383
for amebiasis, e378 acute iron poisoning, e129–e131 treatment of, e383, e383t
for trichomoniasis, 1857 causative agents, e129–e130 Toxoids, 1989
Tiotropium, 389 clinical presentation, e129, e129b Toxoplasma gondii, 1944, 2021t
Tipiracil, 2039t, 2050, 2155t incidence of, e130 Toxoplasmic encephalitis, 2020t
Tipranavir, 2014t management of toxicity, e130–e131 Trabectedin, 2042t, 2054
Tiratricol, 1187 mechanism of toxicity, e129, e130f Trace elements, 2329t. See also specific types
Tirofiban, e353 monitoring and prevention, e131 chromium, 2329t, 2330
Tissue factor pathway inhibitor (TFPI), 233 risk assessment, e130 copper, 2328–2329, 2328–2330, 2329t
Tissue inhibitor of metalloproteinase 2 anticholinesterase insecticide poisoning, deficiencies and toxicities of, 2328–2331
(TIMP-2), 658 e123–e126 iodine, 2329t, 2331
Tissue plasminogen activator (tPA), 265–266 causative agents, e124–e125 iron, 2328, 2329t
Tissue transglutaminase (tTG), 581 clinical presentation, e123–e124, e124b, manganese, 2329t, 2330
Tizanidine, 829 e125f molybdenum, 2329t, 2330
Tobacco use. See Smoking incidence of, e125 in parenteral nutrition, 2348–2349, 2349t
Tobramycin, e371t management of toxicity, e126, e126t parenteral nutrition complications, 2359
for cystic fibrosis, 423 mechanism of toxicity, e124, e125f selenium, 2329t, 2330
dosing by age group, 1670t monitoring and prevention, e126 zinc, 2328, 2329t
for intra-abdominal infection, 1818 calcium channel blocker poisoning, Traditional healers, e26
therapeutic range of, e44t e126–e129 Tramadol, 921, 1430
Tocilizumab, 687, 1449–1450 causative agents, e127 adverse effects of, 1430, 1432t
Tocolytics, 1238 clinical presentation, e126–e127, e127b dosing and administration of, 918t, 1425t,
Tofacitinib, 1443, 1448 incidence of, e128 1430
Tolazamide, 1163t management of toxicity, e128–e129 drug-drug interactions, 1430
Tolbutamide, e72 mechanism of toxicity, e127t for osteoarthritis, 1424, 1426
Tolcapone, 902t, 905 monitoring and prevention, e129 pharmacology and mechanism of action, 1430
Tolerance, 974 risk assessment, e128 Trametinib, 2044t, 2296t, 2297t
Tolterodine opioid poisoning, e131–e133 Tramiprosate, 807, 808
for benign prostatic hyperplasia, 1342t causative agents, e131–e132 Tranexamic acid
immediate release, 1361–1362 clinical presentation, e131, e132b for heavy menstrual bleeding, 1269
long acting, 1362 incidence of, e132 for menstruation-related disorders, 1267

2470
Tranilast, 1497 Trauma. See also specific types Trimester, 1228
Transcapillary refill, 325 cardiac arrest treatment in, 36–37 Trimethobenzamide, 500t
Transdermal contraceptives, 1256 hypovolemic shock treatment in, 333–334 Trimethoprim
Transesophageal echocardiography (TEE), Traumatic brain injury (TBI) adverse effects and monitoring of, 1656t
e174–e175, 207–208, 1761–1762 clinical presentation of, 883b, 883t for prostatitis, 1840
Transferrin, 2327 epidemiology of, 881 Trimethoprim-sulfamethoxazole, e322, 1833t
Transforming growth factors, 275 management of., acute, 881–892 (See also for acne vulgaris, 1547
Transient ischemic attack (TIA). See Stroke Brain injury management, acute) dosing by age group, 1670t
Transjugular intrahepatic portosystemic shunt pathophysiology of, 881–883, 882f for HSCT infections, 1963
(TIPS), 534, 534f primary and secondary, 881–883 Triptans. See also specific agents
Transplant patients, cystic fibrosis in, 425 Travel associated venous thromboembolism for cluster headache, 940
Transplantation, solid-organ, 1393–1413 (TAVTE), e397 for migraine headache, 932t, 933t, 935–936t,
INDEX
epidemiology and etiology of, 1394 Travel health, e389–e398 935–937

heart, 1394 pretravel preparation in, e389–e392 Triptorelin, 2173t
kidney, 1394 in immunocompromised travelers, for breast cancer, 2104t
liver, 1394 e391–e392 for endometriosis, 1280t, 1281t
lung, 1394 medical kits, e390–e391 Trivalent influenza vaccine, 1723–1725
physiologic consequences of, 1395–1396 in pregnant travelers, e391 Tromethamine, 785
in heart transplantation, 1395–1396, 1396t pretravel consultation, e390, e390t Trophoblastic diseases, 1185
in kidney transplantation, 1395 travel-related diseases, e392–e398 (See also Trospium, for benign prostatic hyperplasia,
in liver transplantation, 1395, 1395t Travel-related diseases) 1342t
in lung transplantation, 1396 Traveler’s diarrhea, e392, 1807 Trospium chloride
rejection pathophysiology in, 1396–1399 Traveler’s thrombosis, e397 extended release, 1362
acute cellular rejection, 1397–1398 Travel-related diseases immediate release, 1362
antibody-mediated rejection, 1398 healthcare outreach in, e398 Trypanosoma brucei, e378
chronic rejection in, 1398–1399 global health organizations in, e398 Trypanosoma brucei gambiense, e378
general concepts of, 1396–1397, 1397f medical missions and outreach, e398 Trypanosoma brucei rhodesiense, e378
hyperacute rejection, 1397 non-governmental organizations in, e398 Trypanosomiasis, American (Chagas disease),
statistics on, 1393–1413 incidence of, e392–e398 e378–e379
survival rates, 1394, 1394t infectious, e392–e396 clinical presentation of, e379
treatment of rejection in, 1399–1409 food and water borne infections, e392–e393 epidemiology of, e378–e379
bottom line, clinical, 1412–1413 diarrheal illness, e392 etiology of, e378–e379
general approach to, 1399, 1400f vaccine-preventable food and water born pathophysiology of, e379
in acute rejection, 1399 pathogens, e392–e393 treatment of, e379
induction therapy in, 1399 neglected tropical diseases, e396 Trypsinogen, 2366t
generic substitution in, 1410–1411 respiratory-transmitted infections, Tuberculosis, 1696–1697, 1777–1782, 1780b
immunosuppression-related complications e395–e396 clinical presentation of, 1780–1781
in, 1411–1413 sexually-transmitted infections, e396 in children, 1781
cardiovascular disease, 1411 vector borne infections, e393–e395, e393f in elderly, 1781
diabetes, new-onset, 1411 mosquito-borne infections, e393–e395 HIV in, 1781
infection, 1411–1412 rabies, e395 definition of, 1777
malignancy, 1412 tick-borne infections, e395 diagnosis of, 1781–1782
maintenance therapy in, 1399–1409 miscellaneous travel infections, e396 culture and staining in, 1782
alemtuzumab, 1408 noninfectious, e396–e398 tests in, 1781–1782, 1782t
antibody agents, 1407–1409 altitude sickness, e396–e397 interferon-g release assays (IGRA), 1782
antimetabolites, 1404–1405 jet lag, e397 Mantoux test, 1781–1782
antithymocyte globulin, 1407–1408 mental health, e398 epidemiology of, 1777–1778
azathioprine, 1405 traveler’s thrombosis, e397 etiology of, 1778–1779
calcineurin inhibitors, 1399–1403 Travoprost, 1514t culture and etiology testing in, 1778–1779
(See also Calcineurin inhibitors) Trazodone, e229, 1058t, 1113 transmission in, 1779
corticosteroids, 1403–1404 Treadmill testing, e172 pathophysiology of, 1779–1780
co-stimulatory signal inhibitor, Tremor, in multiple sclerosis, 830 extrapulmonary and miliary tuberculosis
1406–1407 Treponema pallidum, 1677, 1848–1849 in, 1780
depleting antibodies, 1407–1408 Treprostinil, 409–410 HIV infection and, 1780
interleukin-2 receptor antagonists, Tresiba, 1159t immune response in, 1779
1408–1409 Tretinoin, 1545, 1552t, 2042t primary infection in, 1779–1780
investigational agents, 1409 Triamcinolone, 1425t, 1526t reactivated disease in, 1780
mycophenolic acid derivatives, Triatoma infestans, e379 risk factors, 1777–1778
1404–1405 Triazenes, 2042t for disease, 1778
nondepleting antibodies, 1408–1409 Trichomoniasis, 1234–1235, 1856–1858 for infection, 1777–1778
proliferation signal inhibitors, clinical presentation of, 1856, 1856t age in, 1778
1405–1406 diagnosis of, 1856–1857 coinfection with HIV, 1778
outcomes of epidemiology of, 1856 ethnicity in, 1778
desired, 1399 etiology of, 1856 location and place of birth in, 1777–1778
therapeutic, evaluation of, 1409–1410 outcome evaluation for, therapeutic, race in, 1778
personalized pharmacotherapy in, 1857–1858 travel-related, e395–e396
1410–1411 pathophysiology of, 1856 Tuberculosis treatment, 1782–1794
Transthoracic echocardiography (TTE), treatment of, 1857 algorithm for, 1785f
e174–e175, 1761 Trichophyton, 1900 general approaches to, 1783
Transthyretin, 2328 Trichophyton mentagrophytes, 1902 nonpharmacologic, 1783
Transurethral incision of the prostate (TUIP), Trichophyton rubrum, 1902 outcomes of, 1794t
1346 Tricyclic antidepressants (TCAs), e79t, 1046, desired, 1783
Tranylcypromine, 1047t. See also Monoamine 1048–1049, 1090–1091, 1118 therapeutic, evaluation of, 1793–1794
oxidase inhibitors Trifluridine, 2039t, 2050, 2155t personalized pharmacotherapy in, 1793
Trastuzumab, e78t, 2047t, 2062, 2094–2096, Triglycerides, 271 pharmacologic, 1783–1793
2100–2102 Triiodothyronine, 1181 in active disease, 1784–1787, 1785f, 1786t

2471
in children, 1787, 1788t–1789t for acute coronary syndromes, 174t, 182–183, urethral underactivity (stress urinary
drug monitoring in, 1793 188t incontinence), 1352–1353
in extrapulmonary disease, 1787 dosing and administration of, 255 medication-related, 1354t
in hepatic failure, 1787 drug-drug interactions, 255 pathophysiology of, 1351–1354
in HIV patients, 1787 efficacy of, 254 prevalence of, 1351
in latent infection, 1783–1784, 1783–1794, pharmacokinetics of, 254 Urinary incontinence treatment, 1356–1367
1784t pharmacology and mechanism of action, 254 general approach to, 1356
in morbid obesity, 1787–1788 for stable ischemic heart disease, 157 nonpharmacologic, 1356–1359
in pregnancy, 1787 for venous thromboembolism, 245, 247t nonsurgical treatment, 1356–1357,
primary anti-TB drugs in, 1789–1790 United States Pharmacopeia (USP) Center for 1358t–1359t
ethambutol, 1786t, 1788t, 1790, 1790t the Advancement of Patient Safety, e93 surgical treatment, 1357–1359
isoniazid, 1786t, 1788t, 1789, 1790t Upper airway obstruction, e199, e199f. See also outcomes of
INDEX
pyrazinamide, 1786t, 1788t, 1790, 1790t specific types desired, 1356
rifabutin, 1790 Upper gastrointestinal bleeding, 470 therapeutic, evaluation of, 1367
rifampin, 1786t, 1788t, 1789–1790, Upper respiratory tract infections, 1707–1716. personalized pharmacotherapy in, 1366–1367
1790t, 1791t See also specific infections pharmacologic, 1359–1367
rifamycin, 1790 acute bacterial rhinosinusitis, 1710–1713 for urge urinary incontinence, 1359–1365,
rifapentine, 1790 acute otitis media, 1707–1710 1359t, 1360t, 1361t
in renal failure, 1787, 1790t acute pharyngitis, 1713–1716 antimuscarinic agents, 1359, 1360t
secondary anti-TB drugs in, 1790–1793 Uracil mustard, e212 b3-adrenergic agonist, 1359, 1360t
Bacille Calmette-Guérin vaccine, 1793 Urate-lowering agents, 1496 botulinum toxin A, 1364
clofazimine, 1792 Urea nitrogen, e245 catheterization combined with
corticosteroids, 1792, 1793 Urea reduction ratio, 643 medications, 1364–1365
cycloserine, 1788t, 1792 Urethra, 1351–1352 darifenacin, 1363
ethionamide, 1788t, 1792 Urethral meatus warts, 1858t fesoterodine fumarate, 1362
macrolides/azalides, 1792 Urethral underactivity, 1352–1353 mirabegron, 1363
new drugs and delivery systems clinical presentation of, 1354b oxybutynin extended-release, 1360–1361
in, 1792 pharmacologic treatment of, 1365–1366 oxybutynin immediate release, 1360
p-aminosalicylic acid, 1788t, 1790–1792 a-adrenergic receptor agonists, 1347 oxybutynin topical gel, 1361
quinolones, 1792 duloxetine, 1366 solifenacin succinate, 1362–1363
streptomycin, 1788t, 1790–1792, 1790t estrogens, 1365 tolterodine immediate release,
thiacetazone, 1792 venlafaxine, 1366 1361–1362
in tuberculous meningitis, 1787 Urethritis, 1845t tolterodine long acting, 1362
principles for, 1783 Urge urinary incontinence, 1353. See also trospium chloride extended release, 1362
Tuberculous meningitis, 1787 Urinary continence trospium chloride immediate release,
Tubular carcinoma, 2084 clinical presentation of, 1355b 1362
Tubular necrosis, acute, 659–663 pharmacologic treatment of, 1360t, 1361t pharmacologic treatment of
aminoglycoside, 659–660 botulinum toxin A, 1364 for overflow incontinence, 1366
amphotericin B, 662–663 catheterization combined with medications, for urethral underactivity, 1365–1366
cisplatin, 662 1364–1365 a-adrenergic receptor agonists, 1347
radiographic contrast media, 660–662 darifenacin, 1363 duloxetine, 1366
Tumor necrosis factor-a, e361 fesoterodine fumarate, 1362 estrogens, 1365
for Crohn’s disease, 489 mirabegron, 1363 venlafaxine, 1366
for inflammatory bowel disease, 485 oxybutynin extended-release, 1360–1361 Urinary tract infections (UTIs), 1827–1839
inhibitors, 491–492 oxybutynin immediate release, 1360 abacteriuria
for lupus arthritis, 1382 oxybutynin topical gel, 1361 significant, 1828
for rheumatoid arthritis, 1448 solifenacin succinate, 1362–1363 symptomatic, 1836
Tumor suppressor genes, 2029–2030 tolterodine immediate release, 1361–1362 bacteriuria, asymptomatic, 1836
Turmeric, 807 tolterodine long acting, 1362 in catheterized patients, 1838–1839
Turner’s (XO) syndrome, 1374 trospium chloride extended release, 1362 classification of, 1827
Two-dimensional echocardiography, e174 trospium chloride immediate release, 1362 clinical presentation of, 1830–1831, 1831b
Type 1 diabetes. See Diabetes mellitus (DM) Uric acid bacterial count, 1830
Type 2 diabetes. See Diabetes mellitus (DM) cardiovascular risk and, 1497–1498 chemistry in, 1830–1831
Tyrosine kinase inhibitors, 2219, 2252–2253 lowering in absence of gout, 1497 culture in, 1831
overproduction, 1484, 1484f hematuria in, 1830
U underexcretion of, 1484–1485, 1485t infection site in, 1831
Ulcer, decubitus. See Pressure sores Uric acid nephrolithiasis, 1487, 1497 proteinuria in, 1830
Ulcerative colitis, 479–480. See also Uricosurics, 1490t, 1495 pyuria in, 1830
Inflammatory bowel disease (IBD) Uridine triacetate, 2050 urine collection in, 1830
abscesses in, 479 Urinary continence, 1352 complicated, 1827
clinical presentation of, 481, 481t Urinary incontinence, 1029, 1351–1367 acute pyelonephritis, 1836
colonic dysplasia in, 480 clinical presentation of, 1354–1356 recurrent infections, 1837–1838
complications of, 479 with bladder overactivity, 1355b UTI in males, 1836–1837, 1837f
pharmacologic therapy for, 485–486, 486f, with overflow incontinence, 1355f definition of, 1827
487f prior medical or surgical illness in, 1356 in elderly, 1828
toxic megacolon in, 479–480 symptoms in, 1354–1355, 1355t epidemiology of, 1828
Ulipristal, 1259 with urethral underactivity, 1354b etiology of, 1828
Ulodesine, 1497 urine leakage in, 1354 in females, 1828
Ultrafiltration, 126 definition of, 1351 pathophysiology of, 1828–1829
Ultrasonography epidemiology of, 1351 bacterial virulence factors in, 1829
in gastrointestinal tract evaluation, e222, etiology of, 1351–1354 host defenses mechanisms in, 1828–1829
e223f mechanisms of, 1352–1354 infection route in, 1828–1829
in neurological evaluation, e265 bladder overactivity (urge urinary predisposing factors to, 1829–1830
Umeclidinium, 389 incontinence), 1353 in pregnancy, 1232–1233, 1838
Unfractionated heparin (UFH), 254–255, urethral overactivity and/or bladder under- prevalence of, 1828
646, 1232 activity (overflow incontinence), 1353 recurrent, 1827–1828

2472
Urinary tract infections (UTIs) (Cont.): multiple sclerosis, 832 somatostatin, 533
treatment of, 1831–1841 mumps, 1995 vasopressin, 534
clinical controversies in, 1832b pertussis, 1995–1996 Varicella vaccine, 1999
evidence-based, 1834t pneumococcal, 1669, 1996–1997 Varicella zoster virus, 2020t, 2021t
in females, 1835f conjugate, 1996–1997, 1997t Vascular access thrombosis, 646, 646t
for lower tract infections, 1834t polysaccharide, 1996 Vascular cell adhesion molecule 1 (VCAM-1),
management of, 1831, 1831–1832 poliovirus, 1997 275, 826
outcomes of, 1831 rabies, 1997–1998 Vascular endothelial growth factor (VEGF), 275
pharmacologic, 1832b, 1832t–1834t rubella, 1998 Vascular surgery, antimicrobial prophylaxis in,
for acute uncomplicated cystitis, storage of, 1990 1981
1832–1835 tetanus, 1998–1999, 1998t Vasculitis, e318, 1441
uncomplicated, 1827 use of, 1993 Vasoactive inhibitory peptide, 2366t
INDEX
Urine varicella, 1999 Vasoactive intestinal peptide (VIP), 546

chemical analysis of, e243–e244 zoster, 1999–2000 Vasoconstrictors, 1639
glucose, e243 Vaginal rings, 1256–1257, 1280t, 1281t Vasodilator stress testing, e177–e178, e178f
heme, e244 Vaginal warts, 1858t Vasodilators. See also specific agents
ketones, e243 Vaginosis, bacterial, 1234 for acute decompensated heart failure,
leukocyte esterase, e244 Vagus nerve stimulation 124–125, 125t
nitrite, e243–e244 for epilepsy, 844 nesiritide, 125, 125t
pH, e243 in status epilepticus (SE) treatment, 878 nitroglycerin, 124–125, 125t
protein or albumin, e244 Valacyclovir nitroprusside, 125t, 127
specific gravity, e244 for genital herpes, 1855 for priapism, 1639
microscopic analysis of, e244–e245 for HSCT infections, 1962 sodium nitroprusside, 126–127
Urologic surgery, antimicrobial prophylaxis in, Valerian, 1113 Vasopressin, 720
1979 Valganciclovir, for HSCT infections, antagonists, 125–126
Urothelium, 1352 1963 for cardiac arrest, 30t, 37
Urticaria, e336–e337 Valproate for cirrhosis, 540t
Ustekinumab, 1569 for ADHD, 953 for pituitary gland disorders, e279, e281t
Uterine bleeding with ovulatory dysfunction, for refractory GCSE, 875–876 for septic shock, 312–313, 316–317
1269–1272 Valproate sodium, 1070 for variceal hemorrhage, acute, 534
clinical presentation of, 1270b Valproic acid for ventricular fibrillation/pulseless
definition of, 1269 advantages and disadvantages of, 862 ventricular tachycardia, 31t
epidemiology of, 1269 adverse effects of, 853t, 862, 1070 Vasopressors. See also specific types
etiology of, 1269–1270 for bipolar disorder, 1070, 1070–1072, 1074 catecholamine, 312
pathophysiology of, 1270 dosing and administration of, 862, 933t, for sepsis and septic shock treatment,
treatment of, 1270–1272 1070–1072 1883–1884, 1883t
general approach to, 1270 drug interactions, 862 for shock, 307–317
nonpharmacologic, 1271 for epilepsy, 862 Vasovagal syndrome, 224
outcomes of monitoring of, 853t Vector borne infections, e393–e395, e393f
desired, 1270 pharmacokinetics of, 862 mosquito-borne infections, e393–e395
therapeutic, evaluation of, 1272 therapeutic range of, e44t rabies, e395
personalized pharmacotherapy in, 1272 Valsartan, 102 tick-borne infections, e395
pharmacologic, 1271 Valvular stenosis, e183 Vedolizumab, 485, 491t
drug class in, 1272 Vancomycin, e371, e371t VEGF inhibitors, 2063
hormonal contraceptives, 1271 dosage chart, e58t bevacizumab, 2063
in special populations, 1271–1272 dosing by age group, 1670t ramucirumab, 2063
Uveal melanoma, 2286 for intra-abdominal infection, 1818 Vemurafenib, 2043t, 2296, 2297t
pharmacokinetics of, e58–e60 Venlafaxine, 1296t. See also Serotonin-norepi-
V for renal disease in children, e90 nephrine reuptake inhibitors (SNRIs)
Vaccine Adverse Event Reporting System therapeutic range of, e44t dosing and administration of, 933t
(VAERS), 1993 Vancomycin-intermediate-resistant for major depressive disorder, 1053t, 1058t
Vaccines, 1990–2000. See also Immunobiologics Staphylococcus aureus (VISA), e368 for menstruation-related disorders, 1267
administration of, 1990, 1991t Vancomycin-resistant Staphylococcus aureus for PTSD, 1103
components of, 1989–1990 (VRSA), e368 for urinary incontinence, 1366
diarrhea, 517 Vandetanib, 2045t, 2058–2059 Venous thromboembolism (VTE), 231–235, 1885
diphtheria toxoid adsorbed, 1993 Vapreotide, 516 clinical presentation of, 234–235
Haemophilus influenzae type B (Hib), Vardenafil, 1313t, 1321t definition of, 231, 232f
1993–1994 Varenicline, 1003–1004 diagnosis of, 234–235, 236f
hepatitis A, 563 Variant allele, e69 D-dimer in, 235
hepatitis B, 567, 567t Variceal bleeding radiographic contrast in, 235
human papilloma virus, 1994 endoscopic variceal ligation for, 532 epidemiology of, 231
inactivated, 1989 prophylaxis etiology of, 231–232, 233t
influenza, 1723–1725, 1723t, 1724t primary, 532 blood stasis in, 231
for different age groups, 1724t secondary, 535 hypercoagulability in, 231
live-attenuated, 1725 treatment recommendations, 535t vascular injury in, 231
quadrivalent, 1723–1725 Variceal hemorrhage, 533–535 hypercoaulability disorders in, inherited and
rates and goal by patient population, 1723t drug therapy for, 535 acquired, 233–234
trivalent, 1723–1725 prophylaxis, secondary, 535 in menopausal hormone therapy, 1290–1291
information resources, 2002 recommendations, 534–535 pathophysiology of, 232–234, 234f, 235f
live attenuated, 1989 treatment of, 533f prevention of, 235–239
measles, 1994–1995 clinical controversies in, 535 duration of therapy in, 239
meningococcal, 1671 interventional and surgical, 534 general approach to, 237
meningococcal polysaccharide and conjugate, octreotide, 533 guidelines for, 238t
1995 sclerotherapy and bind ligation, nonpharmacologic, 237
meningococcal serogroup B (MenB), 1995 endoscopic, 534 pharmacologic

2473
in medical patients, 237 Verapamil, 188t, 199, 202t, 938, 940, 1073. See oral contraceptives and, 1256
in surgical patients, 237 also Calcium channel blockers pathophysiology of, 497–498
risk factors for, 233t Vertebroplasty, 1466 Vomiting center, 497
Venous thromboembolism (VTE) treatment, Very-low density lipoproteins (VLDL), 271, 678 von Hippel-Lindau gene, e420–e421, e421f,
239–258 Vesicles, e335f e422f
in cancer patients, 249–250 Vibrio cholerae, 1798, 1799–1800, 1803t, 1808t von Willebrand disease, 1620–1623
in children, 248–249 Vibrio parahaemolyticus, 1808t classification of, 1620–1621, 1621t
drug class information, 250–256, 251t Vigabatrin clinical presentation of, 1620–1621
direct oral anticoagulants, 250–252 advantages and disadvantages of, 863 definition of, 1620
fondaparinux, 253–254 adverse effects and monitoring of, 854t diagnosis of, 1621–1622, 1621t
low-molecular-weight heparin, 252–253 adverse effects of, 862 treatment of, 1622–1623
unfractionated heparin, 254–255 dosing and administration of, 863 algorithm for, 1610f
INDEX
warfarin, 255–256 drug interactions, 863 desmopressin, 1622–1623
general approach to, 239–244, 239f, 240f for epilepsy, 862–863 gene therapy in, 1623
guidelines for, 241t mechanism of action, 862 outcome evaluation for, therapeutic, 1623
in invasive procedures, 250 monitoring of, 854t personalized pharmacotherapy in, 1623
personalized pharmacotherapy in, 256–257 pharmacokinetics of, 862 replacement therapy in, 1622
pharmacogenomics in, 257 Vilazodone, 1058t rituximab, 1622–1623
prevention vs. treatment, 256 Vinblastine, e213, 2039t, 2052, 2183–2185, von Willebrand factor antigen (vWF:Ag), 1620t
renal function in, 256 2186–2187 von Willebrand factor (vWF), 529, 1620t
response to previous therapy in, 256–257 Vincristine, 2039t, 2052, 2183–2185 Voodoo doctors, e26
weight in, 256 Vindesine, e213 Voriconazole, e78t
pharmacologic (See also specific agents) Vinorelbine, 2039t, 2052 for aspergillosis, 1931
direct oral anticoagulants, 244 Viral encephalitis, 1675–1677 for CNS infection, 1675
fondaparinux, 245 Viral hepatitis, 561–576 dosing by age group, 1670t
low-molecular-weight heparin, 244–245, hepatitis A, 561–564 for invasive fungal infections, 1934–1935
245t hepatitis B, 564–571 for oropharyngeal candidiasis, 1896
unfractionated heparin, 245, 247t Viral pneumonia, 1696–1697. See also specific Vorinostat, 2044t, 2057
warfarin, 245, 245t types Vulvovaginal candidiasis, 1889–1892
in pregnancy, 247–248, 249t Virilism, adrenal, 1220 antifungal-resistant, 1892
prevention of, desired outcome in, 237 Visceral adipose tissue, 1143–1144 classification of, 1889
in renal insufficiency, 250 Visceral proteins, 2327–2328, 2327t clinical presentation of, 1890
therapeutic outcomes of, evaluation of, Vismodegib, 2044t complicated, 1891
257–258 Visual field, 1505, 1505f, 1505t, 1506f definition of, 1889
treatment of, outpatient, 243t, 246t Vital capacity (VC), e196 epidemiology of, 1889–1890
Ventilator-associated pneumonia, 1694, 1701 Vitamin A acid, 1545 pathophysiology of, 1890
Ventricular arrhythmias, 215–223. See also Vitamin A toxicity, e234, 2332t recurrent, 1892
specific types Vitamin B12, 1596–1597 risk factors for, 1890
CAST trials on, 216–217 Vitamin B12 deficiency anemia, 1600–1602 treatment of, 1890–1892
clinical presentation of, 216 clinical controversies in, 1602b general approaches to, 1890–1891
incessant monomorphic VT, 220–221 etiology of, 1600–1601 goals of, 1890
premature ventricular complexes, 215–216 laboratory evaluation of, 1601 pharmacologic, 1890–1892
sudden cardiac death, prevention of, pathophysiology of, 1601 uncomplicated, 1891, 1891t
215–216 treatment of, 1601–1602, 1601t Vulvovaginitis, 1845t
torsade de pointes, 221–222, 222f, 223t Vitamin C, 645
ventricular fibrillation, 223 Vitamin D, 613f, 630t W
ventricular proarrhythmia, 219–220 administration of, 1470 Warfarin
ventricular tachycardia, 217–219 (See also adverse effects of, 631 for atrial fibrillation and atrial flutter, 208–210
Ventricular tachycardia) for CKD-MBD, 629–631 dosing and administration of, 256
Ventricular assist devices (VAD), 130–131 colorectal cancer and, 2135 drug-drug interactions, 255
Ventricular fibrillation, 27–32, 223 deficiency in, 747–748 drug-food interactions, 255, 255t
antiarrhythmics for, 30t, 32 dosing and administration of, 631 gene polymorphisms in pharmacogenomics
definition of, 223 drug interactions, 1470 of, e72, e74f, e75t
magnesium for, 30t, 32 drug-drug interactions, 631 pharmacogenetics of, e79t
management, 223 drug-food interactions, 631 pharmacogenomic labeling in, e78t
mortality rate, 223 efficacy of, 631, 1470 pharmacokinetics of, 255
nonpharmacologic therapy in, 27–28 osteoporosis and, 1458–1460, 1465 pharmacology and mechanism of action, 255
pharmacologic therapy in, 28–32, 30t pharmacokinetics of, 631 for vascular access thrombosis, 646
prevention of, 223 pharmacology and mechanism of action, 630 for venous thromboembolism, 245, 245t,
sympathomimetics for, 28–29 supplementation, 1469–1470 255–256
thrombolytics for, 30t, 32 for systemic lupus erythematosus, 1383 Water homeostasis, 719–720
vasopressin for, 29–32, 30t, 31t Vitamin D3 analogs, 1564 Water homeostasis disorders, 721–737. See also
Ventricular gallop, e162 Vitamin E, 645, 806, 2332t specific disorders
Ventricular hypertrophy, 82 Vitamin K oxido reductase, e74 edema, 734–737
Ventricular proarrhythmia, 219–220 Vitamins. See also specific types hypernatremia, 729–734
Ventricular remodeling, 82 deficiencies and toxicities of, 2331, 2332t hyponatremia, 721–729
Ventricular tachycardia, 217–219. See also fat soluble, 2332t Weapons of mass chemical poisoning, e133–e135
specific types in parenteral nutrition, 2348 categories of, e134t
incessant monomorphic, 220–221 parenteral nutrition complications, 2359 causative agents, e134
management, 218–219 water soluble, 2332t clinical presentation, e133–e134, e134t
implantable cardioverter-defibrillator in, Vitek system, e367 incidence of, e134
218–219, 218f, 221t Vogel, Friedrich, e67 management of toxicity, e134
sudden cardiac death, prevention of, 219, Vomiting. See also Nausea and vomiting mechanism of toxicity, e134
220f definition of, 497 monitoring and prevention, e134–e135
mechanisms and types of, 217–218, 217t etiology of, 497, 498t risk assessment, e134

2474
Websites, e12t Yeasts, 933t, 1944, 1963 Ziv-aflibercept, 2048t, 2064
Wernicke-Korsakoff syndrome, 996 Candida infections, 1923 ZMapp, e148t
Wernicke’s encephalopathy, 871 isovuconazole for, 1935 Zoledronic acid, 2273
West Nile virus (WNV), 1675–1677 morphology, 1909, 1910f Zollinger-Ellison syndrome, 472–473
Western biomedical model (WBM), e22, e23b susceptibility testing, 1910 clinical presentation of, 472
Wheals, e337f unicellular, 1909, 1910f diagnosis of, 472
White blood cells (WBC) Yellow fever virus, e394–e395 incidence of, 472
agranulocytes, e360 Yersinia enterocolitica, 1798–1799, 1799, 1808t pathophysiology of, 472
granulocytes, e360 Yersinia pestis, e140, e141t, e275t treatment of, 472–473
White blood cells (WBC) count, e305, e360 Yersinia pseudotuberculosis, 1799 Zolmitriptan, 932t
White coat hypertension, 50 Yersinia spp., 1799, 1803t Zolpidem, 977, 1114
WHO Disability Assessment Schedule 2.0 Yodoxin, e387t Zonisamide
INDEX
(WHODAS), e268 Yohimbine, 1328 advantages and disadvantages of, 863

Whole-bowel irrigation, e119 Young Mania Rating Scale (YMRS), e275t adverse effects and monitoring of,
Wild type allele, e69 854t
Wolff-Parkinson- White (WPW) syndrome, 212 Z adverse effects of, 863
Wrong administration-technique error, e40t Zafirlukast, 368–369 for bipolar disorder, 1074
Wrong dosage-form error, e40t Zaleplon, 1114 dosing and administration of, 863
Wrong drug-preparation error, e40t Zidovudine, 1791t, 2013t drug interactions, 863
Wrong time error, e40t Zileuton, 368–369 for eating disorders, 968
Zinc, 539, 1804, 2328, 2329t for epilepsy, 863
X zinc finger protein 804A (ZNF804A), 1012 mechanism of action, 863
Xanthine oxidase, 1405 Ziprasidone. See also Antipsychotics monitoring of, 854t
Xanthine oxidase inhibitors, 1490t, 1493–1495 for ADHD, 953–954 Zoster, vaccines, 2001–2002
adverse effects of, 953t Zotarolimus, 157
Y dosing, 953t Z-tract, e91t
Yale–Brown Obsessive-Compulsive Scale mechanism of action, 1023 Zung Self-Rating Depression Scale (ZSDS),
(YBOCS), e275t for schizophrenia, 1033t e275t

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

Dipiro Ch048_p0699_0718.indd 705 10/7/16 10:17 PM

- Concise, easy to use

- Specific to CKD patients

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8 C 2.66 48 5.2 1.6 3.1

Drug Therapy Individualization for Patients with Chronic Kidney Disease

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

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Ampicillin/sulbactam 1.5-3 g q 6-8 h q8h q 12 h q 12-24 h q 12-24 h

Cefepime 2 g q 8-12 h q 12-24 h 1-2 g q 24 h 0.5-1 g q 24 h 1-2 g q 48-72 h

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

CLINICAL CASE EXAMPLE Dosage Regimen Calculation for a Hemodialysis patient

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CLINICAL CASE EXAMPLE Dosage Regimen Calculation for a Hemodialysis

bacteremia.111,127 The patient received a vancomycin dose

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

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fu fraction of drug unbound to plasma proteins February 1, 2016.

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

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Drug Therapy Individualization for Patients with Chronic Kidney Disease

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for schizophrenia, 1018t recommendations, 554, 554f, toxocariasis, e383, e383t

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genetic factors in, 1559–1560 e275t clinical presentation of, 242b

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crizotinib, 2055 Terazosin, 1341t hapten-type, e353

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epidemiology and etiology of, 1394 Travel health, e389–e398 935–937

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Urine varicella, 1999 Vasoactive intestinal peptide (VIP), 546

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(WHODAS), e268 Yohimbine, 1328 advantages and disadvantages of, 863

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