General Format

• Drug (Trade name)

Pharmacology: – Mechanism of action
Fast and Dirty Board – Uses/applications
– Side effects/toxicities/contraindications
Review – * = particularly board worthy
Edward Cooper, VMD
Emergency Fellow
University of Pennsylvania

Chemotherapeutics Chemotherapeutics
• Doxorubicin (Adriamycin) • Melphalan
– Intercalating agent – DNA fragmentation. Cell-cycle non-specific – Alkylating agent – same as cytoxan
– Very broad spectrum – big gun. Single agent or combo for carcinoma, – Particularly used in multiple myeloma*
sarcoma, lymphoma, leukemia
– Same as cytoxan
– BM suppression, hemorrhagic enterocolitis, dose-dependant
cardiomyopathy*. Perivascular sloughing. Metabolized by liver, • Vincristine (Oncovin)
caution in liver disease. – Inhibits microtubule formation, blocks mitotic spindle. Cell cycle
• Cyclophosphamide (Cytoxan) specific
– Combination protocols for lymphoma, carcinomas, sarcomas.
– Alkylating agent – DNA fragmentation and crosslinking. Cell cycle non-
Single agent for transmissible venereal tumor (TVT)*
specific
– Relatively GI and BM sparing*, peripheral neural toxicity-
– Used in combo protocols for carcinoma, sarcoma, lymphoma, leukemia.
cumulative. Severe perivascular irritant.
Not affected by multi-drug resistance (MDR) gene*. Orally active.
– BM suppression, GI signs, sterile hemorrhagic cystitis*. Caution in liver • Vinblastine
and kidney disease – Same as vincristine
– Agent of choice for mast cell tumors
– Severe BM toxicity (as compared to vincristine)

Chemotherapeutics Chemotherapeutics
• Methotrexate • Cisplatin
– Dihydrofolate reductase inhibitor blocks nucleotide synthesis. Cell cycle – Incorporates into DNA strands and inhibits replication
specific. – Single agent or combo for osteosarcoma*, malignant melanoma, squamous
cell carcinoma, other carcinomas/sarcomas
– Primarily used in combination protocols for lymphoma and leukemia
– Acute renal toxicity*, nausea/vomiting, peripheral neuropathy, seizures.
– Causes GI toxicity and BM suppression. Caution in renal failure. Extremely toxic to cats (CISPLATIN SPLATS CATS)*. BM sparing.
• Cytosine arabinoside (Cytosar) • Carboplatin
– Inhibits DNA synthesis. Cell cycle specific. – Same as cisplatin
– Primarily used in combination protocols for lymphoma and leukemia – Same as cisplatin
– Causes GI toxicity and BM suppression. – No renal toxicity but more BM and GI
• 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 (rarely) pancreatitis.

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 Chemotherapeutics
• 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
• ß-lactams (Penicillin, Amoxicillin, Ampicillin)
– Inhibit cell synthesis by blocking crosslinking 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. Most
commonly used antimicrobial in hospital setting.
– Clavamox (Amoxicillin + clavulanic acid) – similar spectrum to ampicillin.
Clavulanic acid (ß-lacamase inhibitor) potentiates amoxicillin* and
expands spectrum. Used for cat bites, UTIs.
Antimicrobials
• Cephalosporins (con’t)
– 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 – sl. less G+ but further expanded G-. Cefotaxime and
Ceftiofur (Naxcel) most common. Naxcel used commonly in large
animals – no withdraw time.
– Also fairly safe. Side effects similar to penicillins.
• Carbapenems
– Similar to ß-lactams
– Very broad spectrum, very big gun. Covers everything as single agent.
Imipenum combined with cilastatin (inhibits metabolism).
– Can cause GI, CNS, and renal signs if given too rapidly.
Antimicrobials
• Enrofloxacin (Baytril)
– DNA gyrase inhibitor. Interferes with DNA replication. Bactericidal.
– Broad spectrum – big gun. 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 growth plate in growing animals.* Also has been shown to cause
blindness in cats when used above 5mg/kg/dose.*
• Metronidazole
– Mechanism of action unknown – believed to disrupt DNA. Bactericidal.
– Primarily anaerobes and protozoa (especially giardia*). Also has anti-
inflammatory/immune-modulatory 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.
Antimicrobials
• ß-lactams (con’t)
– 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).
Antimicrobials
• 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.
– Primarily causes nephrotoxicity and ototoxicity.* Cats more severely affected.
Should measure peak and trough blood levels.
• 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. Often given for campylobacter
infections. Also has prokinetic effects on GI motility.*
– GI signs when given orally. Should not be given with liver disease.
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 Antimicrobials
• Tetracyclines (doxycycline, oxytetracycline)
– Binds 30s subunit blocking protein synthesis. Bacteriostatic.
– Activity against multiple organisms including mycoplasma,
Rickettsial organisms (RMSF, ehrlichia)*, hemobartonella*,
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 toxicity, doxy
does not. Also can cause phototoxicity, superinfections (SIBO),
and esophageal stricture (cats).
Antimicrobials
• Clindamycin (Antirobe)
– Lincosamide - binds 50s subunit blocking protein synthesis. Static or
cidal, depending on concentration.
– Spectrum includes aerobic G+ cocci, many 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.
– Bone marrow suppression, reversible (aplastic anemia in humans).
Prohibited use in food animals. Caution with renal, liver dz.

Antimicrobials Gram + Bacteria

• Sulfonamides (Sulfadiazine, Sulfadimethoxine, Sulfasalazine) • S: Staph
– Inhibit folate synthesis which limits bacterial DNA replication. • S: Strep
Bacteriostatic alone, cidal when combined with trimethoprim. • B: Bacillis
– Good G+ and G- spectrum. Also protozoal organisms. Most commonly • E: Erysipelothrix
used for UTI’s. TMS (Trimethoprim/sulfadiazine) most common. • C: Clostridium
Sulfasalazine used in IBD – alter GI flora and have local anti-
inflammatory effects. • C: Corynebacterium
– Many side effects associated. KCS,* polyarthritis, immune mediated • L: Listeria
disease (IMHA,ITP)*, idiosyncratic hepatic necrosis,* pancreatitis, • A: Actinomyces
urticaria, PU/PD, crystalluria, renal tubular destruction, vomiting, • R: Rhodococcus
diarrhea, anorexia • D: Dermatophylis
• A: Archanobacter
• M: Mycobacteria
• N: Nocardia

Anthelmintics
• Benzimidazoles (fenbendazole, febental)
– Bind to tubulin and inhibit formation of cytoskeleton
– Activity against metastrongyles (lung worms), strongyles,
trichostrongyles, tapeworms, liver flukes. Requires long exposure.
– High margin of safety. Has teratogenic affects.
• Imidazothiazoles (levamisole)
– Neurotoxic - spastic paralysis of nematodes
– Primarily nematodes and lungworms (no tapes or flukes)
– Side-effects related to cholinergic overstimulation – SLUDGE.
• Tetrahydropyrimidines (pyrantel, morantel)
– Similar to levamisole
– Nematodes (hooks, rounds, strongyles, pinworms)
– Similar to levamisole
Anthelmintics
• Avermectins (Ivermectin, Selemectin, Moxidectin)
– GABA mediated hyperpolarization leading to paralysis
– Everything except tapes, flukes and adult heartworm. Also active
against external parasites – mites, bots, ticks, lice
– 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 in dogs and cats.
– Very wide margin of safety.

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 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.
• 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)
Diuretics
• Osmotic diuretic - Mannitol
– Freely filtered but not reabsorbed. Exerts osmotic force in proximal
tubule decreasing reabsorption of water.
– 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
– 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
Diuretics
• Potassium sparing diuretics – Spironolactone
– 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 or with hypertension.
– Contraindicated in renal failure, diabetes or when using ACE inhibitors
(also antagonize aldosterone). Can cause hyperkalemia.
Antifungals
• Ketoconazole
– Inhibits cytochrome p450, sterol synthesis (ergosterol, cortisol, etc)
– Broad spectrum – similar to Ampho B but also gets sporothrix and
dermatophytes. Also used to to treat Cushing’s. P450 affect decreases
amount of other drugs needed (e.g. cyclosporine). Dosed orally be on
for long time. Does not get CNS or urine.
– GI signs, hepatitis,* pruritus, alopecia.
• Fluconazole
– Good CNS penetration – fungal meningitis. Also urinary tract. Less
toxic than ketoconazole. Oral or IV.
• Itraconazole
– Similar spectrum to Ketoconazole, less toxicity but much more
expensive. Orally active. Also need to treat for long time.
Diuretics
• 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 – hydrochlorthiazide
– Reduce Na transport in distal tubule* decreasing water reabsorption.
Not very potent, most Na already reabsorbed by then
– Used in edematous states, also in conjunction with loop diuretic.
– Can cause hypokalemia and hypernatremia.
Cardiovascular
• Brief receptor review
– Sympathetic nervous system
• α 1 – post synaptic: vasoconstriction, decrease GI motility
• α 2 – presynaptic: decreased sympathetic outflow
post synaptic: vasoconstricion
• 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
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 Cardiovascular - Sympathomimetic Cardiovascular - Sympathomimetic
• Epinephrine • Dopamine
– α and β receptor agonist – Effects are dose dependent:
• 0.5 – 2 mcg/kg/min: dopaminergic causing dilatation of renal, mesenteric,
– Positive chronotrope, ionotrope, vasoconstriction, bronchodilator. Used
coronary vessels.
in anaphylaxis, cardiac arrest, severe asthma • 2 – 10 mcg/kg/min: increasing β 1 effect with increased cardiac output
• Ephedrine (ionotropy)
– α and β receptor agonist • 10-12 mcg/kg/min primarily α 1 effects causing vasoconstriction
– Used in oliguric renal failure, heart failure, hypotension
– Can be used orally. Long-term bronchdilator and decongestant also
used for urinary incontinence • Phenylephrine
– α 1 selective causing primarily vasoconstriction
• Norepinephrine
– Used to treat hypotension, especially during anesthesia
– α and β 1 agonist (no beta 2)*
– (Rarely) used as a pressor in cardiogenic shock.

Cardiovascular - Sympathomimetic Cardiovascular - Sympatholytic

• 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 Sympathomimetic
– α agonists – hypertension, decreased GI motility, CNS effects
– β agonists – arrhythmias, myocardial damage, GI motility, CNS
• Prazosin (Minipress)
– Selective α 1 blocker causing vasodilation
– Used in the treatment of hypertension but rarely applied to veterinary medicine.
• 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.
• Propranolol
– Non-selective β blocker with effects similar to atenolol but also causing
bronchoconstriction (beta 2)
– Used primarily to treat arrhythmias (APCs, VPCs, tachyarrhythmias).

Cardiovascular – Ca Channel
Blockers
Cardiovascular - Nitrates
• Verapamil • Nitroglycerin
– Primarily affects cardiac calcium channels causing slowed AV conduction, – Stimulates production of nitric oxide (NO) in vascular endothelium
increased refractory period, decreased automaticity leading to vasodilation primarily on the venous side.
– Relatively little use in vet med. Applications with SVT and a. fib. – Primarily used to treat congestive heart failure and pulmonary edema by
• Diltiazem decreasing preload. Applied topically.
– Mixed affect on both vascular and cardiac calcium channels causing vasodilation – Can cause severe hypotension.
and changes in conduction (see Verapamil) • Nitroprusside
– Drug of choice for HCM*, both decreases heart rate (prolonging diastolic filling) – Also causes production of NO but has affects on both arterial and
and decreases afterload (vasodilation). Also used to treat hypertension, a fib venous vasculature.
and SVTs.
– Severe CHF in hospital setting by reducing both preload and afterload.
• Amlodipine Need to monitor blood pressure constantly.
– Primarily affects vascular smooth muscle causing vasodilation. – Profound hypotension and cyanide toxicity.
– Drug of choice for treating hypertension (secondary to CRF) in cats*

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Cardiovascular – ACE inhibitors
• Enalapril
– Inhibits conversion of angiotensin I to II and 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 to treat PLN due to dilation of efferent arteriole (↓ filtration
pressure causing ↓ protein loss).
– Caution in animals with renal insufficiency, causes decreased GFR
Cardiovascular – Na Channel
Blockers
• Lidocaine
– Class Ib antiarrhythmic agent blocking fast sodium channels
– Primarily used to treat ventricular tachyarrhythmias* (also local
anesthetic).
– 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 - Digitalis
• Digoxin
– Inhibits 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.
– Many side affects associated digoxin administration including
arrhythmias, ECG changes, GI upset, anorexia, weight loss, diarrhea.
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 – Propanalol
– III: K channel blocker – Bretylium
– IV: Ca channel blocker - Diltiazem