Pharmacology: Fast and Dirty Board Review

NORTH AMERICAN VETERINARY LICENSING EXAMINATION

Edward Cooper, VMD
Resident in Emergency and Critical Care, The Ohio State University
Check out the "Pharmacology: Fast and Dirty Board Review" slideshow.

GENERAL FORMAT
 Drug (Trade name)
 Mechanism of action
 Uses/applications
 Side effects/toxicities/contraindications
 * = particularly board worthy

CHEMOTHERAPEUTICS
 Doxorubicin (Adriamycin)
 Intercalating agent - DNA fragmentation. Cell-cycle non-specific
 Very broad spectrum - big gun. Single agent or combo for carcinoma, sarcoma, lymphoma, leukemia
 BM suppression, hemorrhagic enterocolitis, dose-dependant cardiomyopathy*. Perivascular sloughing. Metabolized by liver,
caution in liver disease.
 Cyclophosphamide (Cytoxan)
 Alkylating agent - DNA fragmentation and crosslinking. Cell cycle non-specific
 Used in combo protocols for carcinoma, sarcoma, lymphoma, leukemia. Not affected by multi-drug resistance (MDR) gene*.
Orally active.
 BM suppression, GI signs, sterile hemorrhagic cystitis*. Caution in liver and kidney disease
 Melphalan (Alkeran)
 Alkylating agent - same as Cytoxan
 Most commonly used for multiple myeloma*
 Same as Cytoxan
 Vincristine (Oncovin)
 Inhibits microtubule formation, blocks mitotic spindle. Cell cycle specific
 Combination protocols for lymphoma, carcinomas, sarcomas. Single agent for transmissible venereal tumor (TVT)*
 Relatively GI and BM sparing*, peripheral neural toxicity-cumulative. Severe perivascular irritant.
 Vinblastine (Velban)
 Same as vincristine
 Agent of choice for mast cell tumors in some protocols
 Severe BM toxicity (as compared to vincristine)
 Methotrexate
 Dihydrofolate reductase inhibitor blocks nucleotide synthesis. Cell cycle specific.
 Primarily used in combination protocols for lymphoma and leukemia
 Causes GI toxicity and BM suppression. Caution in renal failure.
 Cytosine arabinoside (Cytosar)
 Inhibits DNA synthesis. Cell cycle specific.
 Primarily used in combination protocols for lymphoma and leukemia
 Causes GI toxicity and BM suppression.
 Cisplatin
 Incorporates into DNA strands and inhibits replication
 Single agent or combo for osteosarcoma*, malignant melanoma, squamous cell carcinoma, other carcinomas/sarcomas
 Acute renal toxicity*, nausea/vomiting, peripheral neuropathy, seizures. Extremely toxic to cats causing fulminant pulmonary
edema (CISPLATIN SPLATS CATS)*. Relatively BM sparing.
 Carboplatin
 Same as cisplatin
 Same as cisplatin
 No renal toxicity but more BM and GI. Also risk of hepatotoxicity.
 L-Asparaginase (ELSPAR)
 Degrades intracellular asparagine. Lymphoid cells can't make new amino acid resulting in cell death
 Almost exclusively for lymphoma. Also not affected by MDR.*
 Very little toxicity. Immune mediated reactions and pancreatitis.
 Lomustine (CCNU)
 Mechanism not entirely understood, probably alkylating. Disrupts DNA and RNA synthesis. Cell cycle non-specific
 Used primarily for CNS neoplasia, excellent penetration*. Can be used in combination protocols for lymphoma and other
neoplasia.
 Can cause severe BM suppression, GI signs, renal and hepatic toxicity.
 5-Flurouracil (5FU)
 5-FU inhibits synthesis of thymidine. Interferes with DNA replication.
 Primarily carcinomas, esp. mammary gland but also GI, pancreas, etc
 BM suppression, GI signs. Severe neurotoxicity in cats (5-FU F's Up cats).
 Piroxicam (Feldene)
 NSAID - COX inhibitor
 Believed to be effective in palliating carcinoma, esp. prostatic and TCC
  GI ulceration

ANTIMICROBIALS
 Enrofloxacin (Baytril)
 DNA gyrase inhibitor. Interferes with DNA replication. Bactericidal.
 Moderate spectrum. Especially good with gram-negative bacilli and cocci, few gram positive. NO anaerobic coverage (requires
oxygen to work)*. Uses: pneumonia, UTI, sepsis, prophylaxis for GI translocation.
 Damages articular cartilage in growing animals.* Blindness in cats when used above 5mg/kg/dose.* Neurotoxicity in people,
can cause seizures if given too quickly.
 Metronidazole (Flagyl)
 Mechanism of action unknown - believed to disrupt DNA. Bactericidal.
 Primarily anaerobes and protozoa (especially Giardia*). Also has anti-inflammatory/immune-modulator affects - IBD. Also used
for HE/CLF.*
 Neurological signs (acute high dose or chronic use)*, hepatotoxicity, GI signs. Not to exceed 15mg/kg/dose IV.
 ß-lactams (Penicillin, Amoxicillin, Ampicillin)
 Inhibit cell synthesis by blocking cross-linking of peptidoglycan molecules. Bactericidal.
 Penicillin G - gram + and gram - cocci (staph and strep), gram + bacilli, spirochetes. Inactivated by ß-lactamases.
 Methicillin - used for penicillinase producing staph infections
 Ampicillin - less potent against cocci but have extended spectrum against gram + and - bacilli. Good anaerobic spectrum.
 Clavamox (Amoxicillin + clavulanic acid) - similar spectrum to ampicillin. Clavulanic acid (ß-lactamase inhibitor) potentiates
amoxicillin* and expands spectrum. Used for cat bites, UTIs.
 Ticarcillin/piperacillin - very big guns. Covers pseudomonas infections in addition to spectrum of ampicillin. Ticarcillin +
clavulanic acid = Timentin.*
 Synergistic affects with aminoglycosides.*
 Generally very safe drugs. Very little toxicity associated. Hypersensitivity can occur, can trigger IMHA/ITP. Some GI signs when
given orally.
 Cephalosporins
 Also ß-lactams which inhibit cell wall synthesis. Generally more resistant to ß-lactamases than penicillins.
 1st generation - predominantly G+ with little G-. Good anaerobic. Includes cefazolin and cephalexin (Keflex). Commonly used
for skin infections (Keflex) and intra-op (cefazolin).
 2nd generation - same G+ but expanded G- and anaerobic coverage (including Bacteroides spp.). Very good for pneumonia,
sepsis, GI bacterial translocation. Cefoxitin (Mefoxin) best in this group.
 3rd generation - varying G+ and anaerobic depending on drug but further expanded G-
 Ceftiofur (Naxcel) used commonly in food animals - no withdraw time.
 Ceftazidime (IV) - 3rd gen of choice for pseudomonas
 Ceftriaxone (IV) - excellent CNS penetration
 Cefotaxime (IV) - best 3rd gen for gram +
 Cefpodoxime (PO) - orally active, good staph and strep, no anaerobes.
 Also fairly safe. Side effects similar to penicillins.
 Carbapenems
 Similar to ß-lactams
 Very broad spectrum, very big gun. Covers everything as single agent. Imipenem combined with cilastatin (inhibits
metabolism).
 Can cause GI, CNS, and renal signs if given too rapidly.
 Vancomycin
 Inhibits cell wall synthesis and membrane permeability. Bacteriocidal.
 Spectrum against only gram (+). Most common application against methicillin-resistant staph aureus (MRSA).* Use limited to
documented resistant infections
 Can cause nephrotoxicity and ototoxicity (uncommon).* Must be given as slow injection, can cause severe hypotension or
cardiac arrest
 Aminoglycosides (Gentamicin, Amikacin, Neomycin)
 Binds to 30s ribosomal subunit blocking protein synthesis. Cidal.
 Predominantly G- spectrum. NO anaerobic coverage.* Due to toxicity, reserved for use only in hospitalized patients with severe
infections resistant to other options. Only dosed once a day (post-antibiotic affect). Neomycin only used topically or orally
(TAO/HE/CLF).
 Primarily causes nephrotoxicity and ototoxicity.* Cats more severely affected. Should measure trough blood levels but only
done in LA.
 Erythromycin
 Macrolide - binds to 50s subunit blocking protein synthesis. Generally considered static but cidal at high concentrations.
 Has mostly G+ spectrum similar to Penicillin G. Previously tx of choice for campylobacter infections. Also has prokinetic effects
on GI motility.*
 GI signs when given orally. Should not be given with liver disease.
 Tetracyclines (doxycycline, tetracycline, oxytetracycline)
 Binds 30s subunit blocking protein synthesis. Bacteriostatic.
 Activity against multiple organisms including mycoplasma, Rickettsial organisms (RMSF, Ehrlichia)*, Haemobartonella*,
chlamydia, some G+, G- and spirochetes (Lyme disease and leptospirosis*). Most enteric G- are resistant. Doxycycline also
believed to have some immune-modulatory affects.
 Contraindicated in pregnancy - retard fetal skeletal growth and stain deciduous teeth. Tet and Oxytet cause renal and hepatic
toxicity, doxy does not. Also can cause GI signs (oral), phototoxicity, superinfections (SIBO), and esophageal stricture
(orally in cats). Doxy - CV collapse in horses.
 Clindamycin (Antirobe)
  Lincosamide - binds 50s subunit blocking protein synthesis. Static or cidal, depending on concentration.
 Spectrum includes aerobic G+ cocci, excellent anaerobic, protozoa and mycoplasma. Used for Toxo/Neospora,* abscesses,
osteomyelitis and to treat dental disease.*
 Can cause clostridial overgrowth, gastroenteritis.
 Chloramphenicol
 Binds 50s subunit blocking protein synthesis. Bacteriostatic.
 Broad spectrum of G+, G-, and anaerobes. Also, rickettsia, chlamydia, and mycoplasma. Seldom used because of toxicity.
Frequently used in exotics, esp. rabbits*.
 Bone marrow suppression (reversible) in all species*, aplastic anemia in humans. Prohibited use in food animals*. Caution with
renal, liver dz.
 Sulfonamides (Sulfadiazine, Sulfadimethoxine, Sulfasalazine)
 Inhibit folate synthesis which limits bacterial DNA replication. Bacteriostatic alone, cidal when combined with trimethoprim.
 Good G+ and G- spectrum. Also protozoal organisms. Most commonly used for UTIs. TMS (Trimethoprim/sulfadiazine) most
common. Sulfasalazine used in IBD - alter GI flora and have local anti-inflammatory effects.
 Many side effects associated. KCS,* polyarthritis, immune mediated disease (IMHA,ITP)*, idiosyncratic hepatic necrosis,*
pancreatitis, urticaria, PU/PD, crystalluria, renal tubular destruction, vomiting, diarrhea, anorexia

GRAM + BACTERIA
 S: Staph
 S: Strep
 B: Bacillus
 E: Erysipelothrix
 C: Clostridium
 C: Corynebacterium
 L: Listeria
 A: Actinomyces
 R: Rhodococcus
 D: Dermatophilus
 A: Arcanobacter
 M: Mycobacteria
 N: Nocardia

ANTHELMINTICS
 Benzimidazoles (fenbendazole, febantel)
 Bind to tubulin and inhibit formation of cytoskeleton
 Activity against lung worms, hooks, rounds, tapes (but not Dipylidium*), whips*, and liver flukes. Requires long exposure.
 High margin of safety, may cause vomiting, hypersensitivity.
 Imidazothiazoles (levamisole)
 Neurotoxic - spastic paralysis of nematodes
 Primarily nematodes and lungworms (no tapes or flukes)
 Side-effects related to cholinergic overstimulation - SLUD.
 Tetrahydropyrimidines (pyrantel, morantel)
 Similar to levamisole
 Nematodes (hooks, rounds, strongyles, pinworms)
 Similar to levamisole
 Avermectins (Ivermectin, Selemectin, Moxidectin)
 GABA mediated hyperpolarization leading to paralysis
 Ivermectin - everything except tapes, flukes and adult heartworm. Only labeled for HW prev in dogs and cats. May be
adulticidal at higher doses. Also active against external parasites - mites, ticks, fleas, lice. Selemectin - hooks and rounds in
cats, not dogs.*
 Wide margin of safety. Neuro signs with severe overdose. Collies/herding dogs especially sensitive.*
 Praziquantel (Droncit)
 Interferes ion balance and cell membrane potential.
 Primarily tapeworms (esp. Dipylidium)* in dogs and cats.
 Very wide margin of safety.

ANTIFUNGALS
 Amphotericin B
 Irreversibly binds to ergosterol in fungal cell membrane
 Broad spectrum of activity - Blasto, Histo, Crypto, Coccidioides, Candida, Aspergillus. Does not cross BBB*.
 Severely nephrotoxic.* Need to give fluid diuresis. Severe perivascular irritant,* anemia, GI signs. Significantly decreased
toxicity with liposome encapsulated formulation - $$$$$.
 Flucytosine (5FC)
 Pyrimidine analog - interferes with DNA synthesis
 Crypto and Candida. Not very effective as a single agent, used in combination with amphotericin B. Does cross BBB*.
 Bone marrow toxicity, very toxic to cats (similar to 5FU)
 Ketoconazole (Nizoral)
 Inhibits cytochrome p450, sterol synthesis (ergosterol, cortisol, etc)
  Broad spectrum - similar to Ampho B but also gets Sporothrix and dermatophytes. Also can be used to treat HAC*. P450 affect
decreases amount of other drugs needed (e.g. cyclosporin* Dosed orally, have to be on for a long time. Does not get CNS
or urine.*
 GI signs, hepatitis,* pruritis, alopecia.
 Fluconazole (Diflucan)
 Good CNS penetration - fungal meningitis. Also urinary tract. Less toxic than ketoconazole. Oral or IV.
 Itraconazole (Sporanox)
 Similar spectrum to ketoconazole, less toxicity* but much more expensive. Orally active. Also need to treat for long time.

ANTIVIRALS
 Acyclovir
 Preferentially taken up by viral cells and converted to active triphosphate which inhibits viral DNA replication
 Used to treat herpes, CMV etc. in humans. Relatively little experience in veterinary medicine. Can be used to treat feline
herpesvirus infection.*
 Can cause GI signs and renal failure. Can cause leukopenia and anemia in cats.*
 Interferon 2α
 Exert antiviral, antiproliferative and immunomodulatory affects by affecting DNA, RNA and protein synthesis.
 Also limited experience in vet med. Has been used to treat FELV infected cats as well as ocular herpesvirus infections.*
Documented in treatment of T-cell lymphoma in dogs.
 No adverse affects noted when given orally. Lethargy if given intravenously.
 Zidovudine (AZT)
 Mechanism not entirely understood but thought to be anti-retroviral. Interferes with reverse transcriptase function preventing
RNA viral replication
 May be used in treatment of FeLV or FIV.* Studies show it can decrease viral load and diminish clinical signs but no effect on
disease course.
 Can cause anemia in cats (can see neutropenia and GI affects in people).
 Idoxuridine
 Similar to thymidine it interferes with DNA replication. Virostatic, not virucidal.
 Topically ophthalmic solution used to treat ocular herpes virus infections.* Very well tolerated by cats, minimal irritation. Poor
penetration into the cornea so must be applied frequently.*
 No adverse affects reported.

ANTI-EMETICS
 Metoclopramide
 Local GI effects by increasing sensitivity to Ach - causes increased upper GI motility, relaxes pylorus, increased LES tone.
Central anti-emesis by antagonizing dopamine receptors in CRTZ.
 Used for both local and central anti-emetic effects. Generally mild to moderate vomiting. Also used in ileus, gastroesophageal
reflux* and treatment of nausea associated with chemotherapy.
 Contraindicated with GI perforation*, obstruction*, GI hemorrhage or seizure disorders. CNS affects leading to changes in
mentation and behavior, extrapyramidal signs. Excreted by kidneys, consider dose reduction with renal failure*.
 Phenothiazine derivatives (Chlorpromazine, Prochlorperazine)
 Mechanism similar to acepromazine - exert anti-dopaminergic, cholinergic, histaminergic and α-adrenergic affects having
potent antiemetic effects on the CRTZ and emetic center.*
 More potent anti-emetic effects with less sedation make them better suited than acepromazine for treatment of moderate to
severe vomiting.
 Cause vasodilation/hypotension - caution in unstable or debilitated patients.* Concern for excessive sedation in vomiting
patient - aspiration. Can also cause extrapyramidal effects, esp. in cats - tremors, shivering rigidity.
 5-HT3 Antagonists (Ondansetron, Dolasetron)
 Inhibit serotonin receptors peripherally in GI and in the CRTZ.
 Potent anti-emetic used for nausea associated with chemotherapy or for intractable vomiting.* Very expensive so usually a last
resort
 Relatively few adverse effects. May cause constipation, extrapyramidal signs, or hypotension. Caution in liver failure. Herding
breeds may be more susceptible to side effects.
 Butorphanol
 Mixed opioid agonist (κ), antagonist (μ) acting on the CRTZ.
 Can be used to provide anti-emesis along with (mild) analgesia. Short duration of action so should be given as a CRI.
 Few contraindications - can cause sedation (risk of aspiration).

GASTRIC PROTECTANTS
 H2 Blockers
 Block H2 receptors and histamine-induced release of acid from parietal cells raising gastric pH
 Used to treat gastric ulceration, hyperacidity syndromes, esophageal reflux
 Cimetidine - requires frequent dosing (Q6-Q8), inhibits p450 system (decreased drug metabolism)*
 Ranitidine - less frequent dosing (Q8-Q12), promotility effects*, minimal p450 inhibition
 Famotidine - least frequent (Q12-24), minimal p450 inhibition
 Fairly safe, bradyarrhythmias with rapid IV bolus, intravascular hemolysis with IV administration in cats, tachyphylaxis can develop
with long term use
 Proton pump inhibitors
 Irreversibly binds to H+/K+ ATPase decreasing acid production at the common pathway*
 Same as H2 blockers. Omeprazole oral form, pantoprazole IV form. 24-48 hours until effective.* SID dosing.
 Minimal side affects reported
 Sucralfate
  Preferentially binds to necrotic tissue at ulcer sites forming a protective barrier. Increases local blood flow by stimulating
prostaglandins, cytoprotective
 Most effective in the presence of esophageal, gastric or duodenal ulceration or erosions. Minimal benefit as a preventive
 No major side effects reported

DIURETICS
 Osmotic diuretic (Mannitol)
 Freely filtered but not reabsorbed. Exerts osmotic force in proximal tubule decreasing reabsorption of water. Also has free
radical scavenging properties.
 Used to treat early acute renal failure, cerebral edema, and glaucoma.* Consider volume status before giving.
 Can cause volume depletion, dehydration, hypernatremia (more free water loss than sodium).*
 Carbonic anhydrase inhibitor (Acetazolamide, Methazolamide)
 Decrease reabsorption of HCO3 and Na in the proximal tubule.* Relatively weak diuretic.
 Fallen out of favor. Used for glaucoma or in combination with loop diuretic for synergistic effect.
 Can cause metabolic acidosis (loose HCO3),* hypokalemia
 Loop diuretic - Furosemide (Lasix, Salix)
 Inhibits Na/K/2Cl channel in loop of Henle.* Most potent diuretic.
 Used in management of edematous states: congestive heart failure (pulm. edema, ascites), protein losing nephropathy, liver
disease
 Can cause volume depletion, dehydration,* potassium depletion,* hyponatremia,* metabolic alkalosis and ototoxicity (hair
cells)
 Thiazide diuretic - hydrochlorothiazide
 Reduce Na transport in distal tubule* decreasing water reabsorption. Not very potent, most Na already reabsorbed
 Used in edematous states, also in conjunction with loop diuretic.
 Can cause hypokalemia and alkalosis. Can worsen HE.*
 Potassium sparing diuretics - Spironolactone, Amiloride
 Aldosterone antagonist which blocks translation of Na/K pumps in the collecting duct.* Very weak diuretic.
 Almost always used in conjunction with other diuretics for potassium sparing effects. Used in edematous states (especially
ascites)* or with hypertension.
 Contraindicated in renal failure, diabetes or when using ACE inhibitors (also antagonize aldosterone).* Can cause
hyperkalemia.

CARDIOVASCULAR
 Brief receptor review
 Sympathetic nervous system
 α 1 - post synaptic: vasoconstriction, decrease GI motility
 α 2 - presynaptic: decreased sympathetic outflow
post synaptic: vasoconstriction
 β 1 - postsynaptic: increased heart rate, contraction force
 β 2 - postsynaptic: vasodilation, bronchodilation
 Parasympathetic nervous system
 Muscarinic - postsynaptic: vasodilation, decrease heart rate, force of contraction, increase GI motility, secretions

CARDIOVASCULAR - SYMPATHOMIMETIC
 Epinephrine
 α and β receptor agonist
 Positive chronotrope, inotrope, vasoconstriction, bronchodilator. Used in anaphylaxis, cardiac arrest,* severe asthma
 Ephedrine
 α and β receptor agonist
 Can be used orally. Long-term bronchodilator and decongestant also used for urinary incontinence
 Norepinephrine
 α and β 1 agonist (no beta 2)*
 Used as a pressor in severe cardiogenic or septic shock.
 Dopamine
 Effects are dose dependent (and very animal dependant)*:
 0.5 - 2 mcg/kg/min: dopaminergic causing dilatation of renal, mesenteric, coronary vessels, falling out of favor
 2 - 10 mcg/kg/min: increasing β 1 effect with increased cardiac output (inotropy)
 10-20 mcg/kg/min primarily α 1 effects causing vasoconstriction
 Previously used in oliguric renal failure but strong evidence against,* can be used for heart failure, hypotension
 Phenylephrine
 α 1 selective causing primarily vasoconstriction
 Used to treat hypotension, especially during anesthesia. Also can be used topically for epistaxis.*
 Dobutamine
 Selective β 1 agonist causing increased inotropy with minimal chronotropy. Increased contraction but decreased oxygen
demand.
 Used with hypotension, forward heart failure, and DCM*. Has a very short duration so only given CRI in hospital setting.*
 Terbutaline
 Selective β 2 agonist causing bronchodilation.
 Used in the treatment of both acute and chronic asthma*, other airway disease
 Major side effects of sympathomimetics
  α agonists - hypertension, decreased GI motility, CNS effects
 β agonists - arrhythmias, myocardial damage, GI motility, CNS

CARDIOVASCULAR - INOTROPES
 Digoxin
 Inhibits cardiac Na/K ATPase* leading to increased intracellular Ca concentrations in myocardial cells and increased force of
contraction (+ inotrope). Also slows AV node conduction and prolong refractory period (- chronotrope).
 Most commonly used in the treatment of DCM* in dogs but also used to treat SVTs (especially a. fib. in horses). Rarely used in
cats, much more sensitive to toxic affects.*
 Many side affects associated digoxin administration including arrhythmias, ECG changes, GI upset, anorexia, diarrhea.
 Pimobendan
 Phosphodiesterase III inhibitor leads to increased sensitization of myocytes to calcium resulting in increased contractility.* Also
causes both veno and vasodilation (inodilator).
 CHF secondary to DCM or mitral valve disease.* Increases cardiac output while decreasing both preload and afterload.
 Potentially increases risk of arrhythmias, mild GI signs.

CARDIOVASCULAR - NITRATES
 Nitroglycerin
 Stimulates production of nitric oxide (NO) in vascular endothelium leading to vasodilation primarily on the venous side.*
 Primarily used to treat congestive heart failure and pulmonary edema by decreasing preload.* Applied topically.
 Can cause severe hypotension. Must wear gloves for application.
 Nitroprusside
 Also causes production of NO but has affects on both arterial and venous vasculature.*
 Severe CHF in hospital setting by reducing both preload and afterload. Also used in treatment of acute severe hypertension.
Need to monitor blood pressure constantly.*
 Profound hypotension. Can cause cyanide toxicity, caution with prolonged use.*

CARDIOVASCULAR - ACE INHIBITORS

 Enalapril (Enacard)
 Inhibits conversion of angiotensin I to II and ultimately aldosterone release.* Causes vasodilation and decreased sodium
retention leading to decreased preload and afterload.
 Primarily used for long term treatment of heart failure and hypertension.* Also used to treat PLN due to dilation of efferent
arteriole ( filtration pressure causing protein loss).* Increasing use in treatment of intrinsic renal failure.
 May cause initial worsening of azotemia secondary to decreased GFR*. Can also cause GI upset.
 Benazepril (Lotensin)
 Similar to Enalapril
 Decreased renal metabolism, safer in renal failure?

CARDIOVASCULAR - ANTIHYPERTENSIVES
 Prazosin (Minipress)
 Selective α-1 blocker causing both vasodilation and venodilation
 Potential applications in managing CHF (decrease preload and afterload) and systemic hypertension (especially 2° to CRF)* or
pulmonary hypertension
 Syncope secondary to hypotension, GI signs, tachyphylaxis
 Hydralazine
 Mechanism unclear, interferes with intracellular calcium in smooth muscle resulting in vasodilation
 Used in CHF (decrease afterload) and in systemic hypertension
 Profound hypotension, reflex tachycardia, Na+/fluid retention

CARDIOVASCULAR - ANTIARRHYTHMICS
 Classification system
 Ia: Moderate Na channel blocker - Procainamide
 Ib: Fast Na channel blocker - Lidocaine
 Ic: Slow Na channel blocker - Flecainide
 II: β antagonists - Propanolol
 III: K channel blocker - Sotalol
 IV: Ca channel blocker - Diltiazem

CARDIOVASCULAR - NA CHANNEL BLOCKERS

 Lidocaine
 Class Ib antiarrhythmic agent blocking fast sodium channels
 Primarily used to treat ventricular tachyarrhythmias* (also local anesthetic). Mexiletine orally active form.
 Can cause CNS signs: drowsiness, depression. Cats are extremely sensitive to CNS effects.*
 Procainamide
 Class Ia antiarrhythmic agent which prolongs refractory times.
 Usually the second drug of choice for ventricular tachyarrhythmias.
 Can cause GI signs, hypotension, AV block

CARDIOVASCULAR - ΒBLOCKERS
 Atenolol
 Relatively specific β 1 blocker causing decreased heart rate, cardiac output and slowed AV conduction. Minimal β 2 effects.
 Used to treat HCM in cats by prolonging diastole.* Also used to treat supraventricular tachyarrhythmias and VPCs. Oral only.
  Propranolol
 Non-selective β blocker with effects similar to atenolol but also causing bronchoconstriction (β 2)
 Used primarily to treat arrhythmias (APCs, VPCs, tachyarrhythmias).
 Esmolol
 Fairly selective β 1 blocker. Negative inotrope and chronotrope, slows AV node conduction, prolongs SA recovery.
 IV only, very short acting. Can be used as a test drug to determined if β blocker is going to be effective.* Primarily used to
treat SVTs,* but also VTs.

CARDIOVASCULAR - K CHANNEL BLOCKERS

 Sotalol
 Has primarily class III affects but also some β blocking affects. Prolongs repolarization and refractory period.
 Limited use in vet med but used to treat refractory VTs in humans and in dogs.
 Can have negative inotropic affects, caution in CHF or with DCM.
 Amiodarone
 Mechanism of action not entirely known. Mostly class III but has anti- α and β effects as well*. Prolongs myocardial action
potential and refractory period
 Also used to treat refractory VTs, high toxicity profile makes it a last resort*
 GI effects*, hepatopathy, little experience in dogs. In people, pulmonary fibrosis, CHF, VT, thyroid dysfunction, blue
discoloration of skin

CARDIOVASCULAR - CA CHANNEL BLOCKERS

 Verapamil
 Primarily affects cardiac calcium channels causing slowed AV conduction, increased refractory period, decreased automaticity
 Relatively little use in vet med. Applications with SVT and a. fib.
 Diltiazem
 Mixed affect on both vascular and cardiac calcium channels causing vasodilation and changes in conduction (see verapamil)
 Drug of choice for HCM*, both decreases heart rate (prolonging diastolic filling) and decreases afterload (vasodilation). Also
used to treat hypertension, a fib and SVTs.*
 Amlodipine
 Primarily affects vascular smooth muscle causing vasodilation.
 Drug of choice for treating hypertension (esp. secondary to CRF) in cats*
AUTHOR INFORMATION
(click the author's name to view other papers and abstracts submitted by this author)

Edward Cooper, VMD

Resident in Emergency and Critical Care
The Ohio State University