1

Clinical Pharmacy - I
1 - ‫الصيدلة السريرية‬
Dr. Ahmed Al- Akydy
Assoc. Prof. Pharmacology
&
Therapeutics
 Learning objectives

 Upon completion of the chapter, the reader will be able to:

1. Classify blood pressure (BP) levels and treatment goals.
2. Recognize underlying causes and contributing factors in the development
of hypertension (HTN)
3. Describe the appropriate measurement of BP.
4. Recommend appropriate lifestyle modifications & pharmacotherapy for
patients with hypertension.
5. Identify populations requiring special consideration when designing a
treatment plan.
6. Construct an appropriate monitoring plan to assess HTN treatment.
 Case study

 An elderly patient comes to you with a prescription for

the following medications: salbutamol inhaler 200mcg
as required, beclometasone inhaler 200mcg twice daily,
bendroflumethiazide 2.5mg daily, diltiazem 180mg
once daily, and atenolol 50mg daily. The atenolol was
being started by the patient’s primary care , apparently
because of inadequate BP control.
 Question: What action should the pharmacist take?
 Introduction
Blood Pressure (BP)
 Bp is the pressure exerted by circulating
blood on the walls of blood vessels
 BP = SBP/DBP = < 120 /80 mmHg
 BP = CO × TPR
o CO is the major determinant of SBP: ↑CO
→ ↑ SBP →↑BP
o TPR largely determines DBP: ↑ TPR →↑
DBP → ↑BP
 Normal BP
o Fluctuates throughout the day, under
normal physiologic conditions
o ↑ acutely during physical activity or
emotional stress.
o Depends also on age (↑ with age) and sex
 Mechanisms for controlling BP
A (SANS)

B (RAAS)
 Hypertension (HTN)
 Definition of HTN: A persistent elevation in systolic BP (SBP) ≥ 140 mmHg/or
diastolic BP ≥ 90mmHg/or both SBP/DBP ≥ 140/90 mm Hg
 Notes
1) Isolated systolic hypertension (ISH): SPB>140/ DBP 90 mmHg (not benign), a
common in the elderly.
2) Hypertension crisis (BP >180/120 mm Hg):
A.A hypertensive urgency: severe BP elevation without acute/or progressing
target organ damage.
B.A hypertensive emergency: extreme BP elevation with acute/or progressing
target organ damage.
3) Pseudohypertension: a falsely elevated BP measurement that is seen in elderly
with a rigid, calcified brachial artery.
4) An auscultatory gap: either underestimated SBP or overestimated DBP
measurements.
5) White coat hypertension: ↑BP values in a clinical setting but return to normal in
nonclinical environments using ambulatory BP monitoring (ABPM)/ or home BP
monitoring (HBPM)
 Types & etiology of HTN
A. Primary/or essential HTN (90-95%): A sustained high BP with unknown precise
underlying medical illness.
 Risk factors of essential HTN
 Age: > 55 (men)/or > 65 (woman)
 Gender
 Genetic factors: ⅓ - ½ with FH/o HTN
 Diabetes mellitus (DM)
 Hyperlipidaemia
 Obesity (BMI ≥ 30 kg/m2)
 Renal disease: e.g., CKD.
 Smoking & excess alcohol intake (> 400 mL)
 Stress
 Physical inactivity/or sedentary life.
 Dietary: high NaCl intake, low K intake,
saturated fat & animal products
 Ethnicity: more common in patients of black
(e.g., African/Caribbean descent)
 Hyperuricemia (uric acid ≥ 6 mg/dL) in
adolescents.
B. Secondary HTN (5-10%): a specific cause can be identified
Causes of the secondary HTN.

1) Intrinsic renal disease: the most (Phaeochromocytoma)

common (e.g. glomerulonephritis,  Growth hormone excess (acromegaly)
chronic pyelonephritis, polycystic  Hyperthyroidism.
kidneys) 4) Diabetes mellitus (DM)
2) Vascular causes
5) Drugs: corticosteroids, oral
 Renal artery stenosis d/t contraceptives (OCs), NSAIDs,
fibromuscular hyperplasia, atheroma decongestants, 5-HT1 receptor
 Coarctation of the aorta agonists (e.g. sumatriptan, rizatriptan ),
3) Endocrine diseases Ciclosporin, Erythropoietin,
 Steroid excess: recreational drugs (e.g. cocaine,
o Hyperglucocorticoidism (Cushing’s amphetamines, ecstasy), ergotamine,
syndrome) antidepressants.
6) Pregnancy: pre- eclampsia (↑BP by
o Hyperaldosteronism (Conn’s

syndrome) 30/15 mmHg/or DBP>110mmHg +

 Catecholamine excess
proteinuria), treated if BP > 150/100
mmHg/or 140/90mmHg)
 Epidemiology:
 Prevalence: very common, highest in adult (25%) & older (50%) patients,
 Incidence: before 45 years (men > women)/between 45 & 64 years (equal),
thereafter (women > men)
 Clinical manifestations (signs & symptoms)
 HTN is usually asymptomatic (the silent killer) unless the BP reaches very high
levels (malignant HTN), which manifests with end –organ damage
o Eye: fundoscopic changes (papilledema, hemorrhages &/or exudates)
o Renal damage: haematuria, proteinuria & impaired renal function
o Hypertensive encephalopathy: confusion, headache, visual loss, seizures,
coma
 How should BP be measured?
 Preparing of patient:
o Sitting comfortably with his/her back supported & legs uncrossed & feet flat on
the floor for 5 min before the 1st- reading
o Avoid exercise, alcohol, caffeine/or nicotine consumption & empty of bladder
— all 30 min before BP measurement
o Arm should be free of constrictive clothing & supported on a table at heart level
 Devices: sphygmomanometer (manual + stethoscope)/or automated
 Procedure:
 Initially, BP should be measured in both arms & in both sitting & standing
positions (1-2 minutes) → if > 20 mmHg difference → repeat the measurements
(1- 2 minutes apart) → if remains → should be taken from the arm with the
higher reading.
o When the clinic BP ≥ 140/90 mmHg on at least 2 separate visits (1-4 Wks) →
use ABPM/or HBPM for 24h→ if the average readings > 135/85 mmHg →
diagnosis of HTN is confirmed → the treatment should be initiated.
o When the clinic BP ≥ 160/100 mmHg on 1st- visit → diagnosed is conformed
& no need ABPM/or HBPM → the treatment should be initiated immediately
 Investigations
A.General investigations: CBC, electrolytes, urea, creatinine(Cr), glucose, lipid
profile, urinalysis (protein, glucose, cells), CXR, ECG, CT
B.In certain patients:
– Renal disease: RFTs, ultrasound of the abdomen/or isotope renogram
– Hyperaldosteronism: renin/angiotensin ratio
– Phaeochromocytoma: Serum and urinary catecholamine metabolites
(metanephrine & normrtanephrine), CT scan, MRI
 When HTN is not diagnosed → clinic BP should be checked at least every
5years /or annually if BP at high normal values in the range 135-139/85-
89 mmHg.
  HTN complications

3) Hypertensive nephropathy
4) Retinopathy
[chronic kidney disease (CKD)]

HTN
Complications 5)  Morbidity,  Disability

1) CVS complications
o IHD: angina, MI
o PVD: atherosclerosis,
arteriosclerosis &
2) Stroke, transient ischemic dissecting aortic
attack (TIA), hypertensive aneurysm
encephalopathy o CHF: d/t LVH
 Classification of HTN

Category SBP mmHg DBP mmHg

Normal < 120 < 80
Prehypertension 120 -139 80-89
HTN ≥ 140 ≥ 90
Stages of HTN
Stage 1 (Mild) 140 - 159 90 - 99
Stage 2 ≥ 160 ≥ 100
Moderate 160 - 179 100 - 109
Severe 180 – 209 110 – 119
Malignant/
≥ 210 ≥120
emergency
  Treatment of HTN

 Goals of treatment
1) Short-term goal: to ↓ BP
2) Long- term goal: to ↓ mortality by ↓ HTN-induced complications
A. Non- pharmacological approaches:
 Should be provided to all patients with any degree of HTN.
1) Lifestyle modifications:
 Healthy diet: high in fruits/vegetables/K/fish/ whole grains/& low-fat dairy
produce, with ↓saturated fat /red meat/& NaCl
 ↓excessive of caffeine-rich products
 Smoking & alcohol cessation/or↓ consumption
 Weight reduction →↓ SBP by 0.5–2 mmHg/kg (2.5/1.5 mmHg/kg
 Regular physical activity: moderate-intensity aerobic activity, 30- 40 min for
most days of the week (e.g. 3-4d /Wk)
 ↓Stress & relaxation therapies: relaxation techniques, yoga, meditation
2) Risk factors & secondary causes should be controlled & treated
3) Renal denervation: ↓ BP in patients with resistant HTN (recent trials)
B. Pharmacotherapy
 Treatment thresholds & Target BP

A. Uncomplicated HTN
Patient Start drug therapy Clinic BP target ABPM/HBPM target
(years) (mmHg) (mmHg) (mmHg)
 < 60
≥140/90 < 140/90 <135/85

 ≥ 60
150/90 < 150/90 <145/85

B. HTN with comorbidities

Co-morbidity Start drug therapy Clinic BP target without Clinic BP target
(mmHg) complications (mmHg) with complications
(mmHg)
 Type 1 DM 135/85
 Type 2 DM ≥140/90 mmHg 140/80 130/80
 CKD ± DM 140/90
Age ≥ 60 years Age < 60 years DM CKD ±
DM

Black/or Non-black
Non-black Black

ACEI/or ARB (alone/

Thiazide/ACEI/ARB/ in combination
Thiazide/or CCB (alone/
or CCB (alone/ in w/another class)
in combination)
combination)

 Select drug treatment titration strategy

 Strategy A: Start one drug, titrate to maximum dose, & then  Initial
add a second drug. combination
 Strategy B: Start one drug, then add a second drug before therapy: if BP
> 20/10 mmHg
achieving max dose of first. > BP target
 Strategy C: Begin 2 drugs at same time, as separate pills/or
as fixed- dose combination pill.
  In general, wait 2-3 Wks or 1
month to achieve BP target
 If BP target is not achieved,
↑ dose of the initial
medication/or add 2nd – agent
from the other recommended
classes,
 If the BP target cannot be
achieved with 2 medications,
add 3rd - medication

2 medications

3 medications

4 medications
 Malignant hypertension:

 A medical emergency uncommon condition characterized by greatly ↑BP( >210/120

mmHg) associated with evidence of ongoing small vessel damage (e.g., retinopathy,
nephropathy &/or hypertensive encephalopathy).
o Retinopathy: fundoscopic changes (papilledema, hemorrhages &/or exudates)
o Renal damage: haematuria, proteinuria & impaired renal function
o Hypertensive encephalopathy: confusion, headache, visual loss, seizures, coma
 Required hospital admission, & rapid control of BP over12-24 h towards normal
levels
 Therapy
 Parenteral
 IV infusion: Na –Nitroprusside, nitroglycerine, trimethaphan
 IV injection: Furosemide, phentolamine, esmolol, labetalol, fenoldopam,
hydralazine, enalapril
o The BP should be ↓ by not > 25% within minutes to 2 h, & then to 160/100 mmHg
within 2 – 6 h to prevent occurring stroke/or MI
 Orally(large doses), after disappearance of complications (pulmonary edema &
encephalopathy)
 HTN with comorbidities
Indication Treatment choice
 HF  ACEI/or ARB/β blocker/ diuretic/Aldosterone
antagonist
 CAD  β blocker/CCB/ACEI/diuretic
 Post –MI  β-Blocker/ACEI/ or ARB
 Type 1 &2 DM  ACEI/or ARB(1st-line), thiazide diuretic/CCB/or α-
blocker
 CKD  ACEI/or ARB + thiazide/or loop diuretic
 Recurrent stroke prevention  ACEI + thiazide diuretic
 BPH  Selective α1 – blocker
 Dyslipidaemia  α – blocker/CCB/ACEI/or ARB
 Asthma, COPD  CCB
 Pregnancy  Methyldopa (DOC), labetalol (1st - line),)/CCBs
(nifedipine)/hydralazine/β-Blocker (atenolol, less use)
/clonidine
 ISH (elderly)  Diuretic/CCB
 African Americans with HF  ISDN/hydralazine
 Ancillary drug treatment
1) Aspirin

 Should be restricted to patients who have no contraindications & either:

A. Have evidence of established vascular disease or

B. Have no evident CVD but who > 50 years & have either evidence of target
organ damage/or a 10-yr CVD risk >20%.

 BP should be controlled (<150/90 mmHg) before aspirin is instituted.

2) Statins

 Should be prescribed to patients < 80 years, with a TC >3.5 mmol/L who

either have pre-existing vascular disease/or a 10-yr CVD risk >10%.
ACE inhibitors and hypertension

 Recommended as 1st- line treatment of all degree of HTN (step 1):

1) No postural hypotension/or electrolyte imbalance (no fatigue/or weakness)

2) Safe in asthmatic & diabetic patients

3) Prevention of secondary hyperaldosteronism & K+ loss

4) Renal perfusion well maintained

5) Reverse the ventricular hypertrophy & ↑lumen size of vessel

6) No rebound HTN, hyperuricaemia/or deleterious effect on plasma lipid

profile

7) Minimal worsening of quality of life (general wellbeing, sleep & work

performance).
Thiazide diuretics & hypertension

 JNC recommendations:
 Low dose of thiazide diuretic (12.5 – 25 mg/d) in essential HTN + a K+ ─
sparing diuretic as 1st - choice in elderly
 If thiazide therapy fails, not ↑ its dose but add another antihypertensive
 A thiazide +ACEI + →↓ K+ loss by thiazide & ↑ antihypertensive effect
 Thiazide-like diuretics are preference to the thiazide diuretics d/t better
clinical evidence of benefit.
 Effects of low dose:
 No significant hypokalemia
 Low incidence of hyperglycemia, hyperlipidemia, hyperuricaemia,
arrhythmia
 ↓ in MI incidence & in mortality & morbidity
CCBs and hypertension

 The 1st -line antihypertensive agents in patients aged ≥ 60 years

 Treatment HTN in patients with asthma, diabetes, PVD, hyperlipidaemia &

renal dysfunction.

o DHP CCBs: preferred for treatment of HTN (have greater selectivity for the
vascular muscles)

o Non-DHPCCBs: used in patients with HTN & concurrent angina/or certain

arrhythmias (e.g. AF), d/t their additional effects on the myocardium & HR.