Chapter 146 Cardiovascular Drugs
Pharmacologic interventions allow the veterinarian to impact pathophysiologic processes in animals with cardiovascular (CV) diseases. To effectively use drugs affecting the heart and circulation, the clinician must understand the pathophysiology of the disease and appreciate the relevant pharmacology of the drugs prescribed. This chapter reviews aspects of cardiovascular pharmacology that are particularly applicable to clinical small animal veterinary practice. Most drugs used to treat CV diseases in dogs and in cats prescribed in an extra-label manner and dosages are at best approximate for many of these agents. Specific drugs and commonly recommended dosages are listed in Table 146-1. Drugs used in management of cardiopulmonary-cerebral resuscitation are discussed in Chapter 157. Management of shock is discussed in Chapter 156.
|Amlodipine||Norvasc, 2.5-mg tablet size||DOG: 0.05–0.2 mg/kg q12h–24h|
|CAT: ¼–½ tablet dose, once or twice daily|
|Amiodarone||Cordarone injection, 50 mg/ml||DOG: Loading dose of 10 mg/kg PO q12h for 1 week; thereafter 5 mg/kg PO q12–24h|
|Cordarone and USP scored tablets, 200 mg||For IV use: 3–5 mg/kg over 60 min, followed by 5–10 mcg/kg/min CRI|
|Amrinone||Inocor, 5 mg/ml (20-ml vials)||DOG: 1–3 mg/kg IV followed by 30–100 mcg/kg/min constant rate infusion|
|Atenolol||Tenormin and USP tablets, 25 and 50 mg||DOG: 0.25–1.5 mg/kg PO q12h|
|CAT: 6.25–12.5 mg dosage, once or twice daily (up-titrate dosages for both species)|
|Atropine||USP: 0.4 and 0.5 mg/ml for injection||0.01–0.04 mg/kg, IV, IM, SQ|
|Benazepril hcl||Lotensin tablets, 5, 10, 20, 40 mg||DOG: 0.25–0.5 mg/kg PO q12–24h (initial daily dose typically 0.5 mg/kg daily)|
|CAT: 0.25–0.5 mg/kg PO q12–24h (as per dog)|
|Butorphanol||Torbutrol 0.5 mg/ml for injection||DOG: 0.25–0.5 mg/kg, SQ, IM for sedation|
|Torbutrol tablets, 1, 5, 10 mg||DOG: 0.5 mg/kg PO q6–12h as an antitussive|
|CAT: 0.2–0.3 mg/kg in a cocktail with acepromazine|
|(0.05–0.1 mg/kg), SQ, IM|
|Carvedilol||Coreg tablets, 3.125, 6.25, 12.5 mg||DOG: initiate dosage in canine DCM at 0.05–0.1 mg/kg PO q12h for 2 weeks; up-titrate the dose every 2–4 weeks provided marked lethargy, progressive CHF, or relative bradycardia develop (HR < 100/minute during examination) do not develop. Typical dose target is 0.2–0.4 mg/kg PO q12h for canine DCM.|
|Digoxin||Lanoxin, Cardoxin, USP tablets, 0.125, 0.25 mg||DOG: 0.0055–0.0075 mg/kg q12h, PO|
|Elixirs of 0.05 mg/ml and 0.15 mg/ml||CAT: ¼ of a 0.125 mg Lanoxin tablet q48 to 72 hours|
|Lanoxin for injection, 0.25 mg/ml|
|Dihydrocodone||Hycodan, 5-mg tablets||DOG: 1.25–5.0 mg, PO q8–24h for cough|
|Diltiazem||Cardizem and USP tablets, 30, 60, 90, 120 mg||DOG: 0.5–2.0 mg/kg PO q8h (up-titrate dose)|
|Dilacor XR capsules 120, 180, 240 mg||DOG/CAT: 0.1 mg/kg IV (can repeat every 15 minutes to 0.5 mg/kg while monitoring arterial blood pressure).|
|Cardizem CD capsules 120, 180, 240 mg||CAT: 0.5–2.0 mg/kg PO q8–12h for standard diltiazem; ½ of a 60 mg Dilacor pellet (taken from the capsule) q12–24h|
|Diltiazem for injection 50 mg/ml||PO; or compounded Cardizem CD starting at 30 mg PO q12h|
|Dobutamine||Dobutrex for injection, 250 mg (20 ml vial)||DOG: 2.5–20 mcg/kg/min, constant rate IV infusion.|
|CAT: 2.5–10 mcg/kg/min CRI|
|Dopamine||Intropin, USP for injection, 200 mg, 400 mg vials||2–10 mcg/kg/min, constant rate IV infusion|
|Enalapril||Enacard, USP tablets: 1.25, 2.5, 5, 10, 20 mg||DOG: 0.25–0.5 mg/kg PO q12–24h (initial daily dose typically 0.5 mg/kg daily)|
|CAT: 0.25–0.5 mg/kg PO q12–24h (as per dog)|
|Epinephrine||Adrenaline, USP 1:1000 (1 mg/ml), 1:10,000||DOG, CAT: 0.05–0.2 mg/kg, IV or intratracheal (only for status asthmaticus or cardiopulmonary-cerebral resuscitation)|
|Esmolol||Brevibloc for injection, 100 mg/ml (10-ml vial)||DOG, CAT: Initial IV loading dose of 100 to 500 mcg/kg administered over one minute, followed by a 25–150 mcg/kg/min constant rate infusion.|
|Furosemide||Furosemide for injection, 10 mg/ml and 50 mg/ml||DOG: 2–6 mg/kg q8–12h as needed, IV, IM, SQ, PO|
|Veterinary Lasix tablets, 12.5, 50 mg||CAT: 1–4 mg/kg q12h as needed, IV, IM, SQ, PO|
|Furosemide USP tablets, 20, 40, 50, 80 mg||Following initial bolus, CRI can be used to deliver 24h dose|
|Furosemide 1% oral syrup (10 mg/ml)|
|Heparin USP||Heparin USP for injection||CAT: 150–250 units/kg initial dose, SQ, IV|
|50–200 units/kg q8h, SQ|
|Hydralazine||Apresoline, USP tablets, 10, 25, 50 mg||DOG: 1–3 mg/kg PO, q12h (up-titrate dose to ABP effect)|
|Hydrochlorthiazide||Hydrodiuril, USP tablets, 25, 50 mg||DOG, CAT: 1–4 mg/kg q24–48h, PO|
|Isosorbide dinitrate||Sorbitrate, Isordil, USP tablets, 5, 10 mg||DOG: 2.5–5 mg orally bid|
|Lidocaine||Xylocaine, USP for injection, 2% (20 mg/ml, without epinephrine)||DOG: 2 mg/kg IV bolus, can repeat up to 8 mg/kg over a 10- minute period; 25–75 mcg/kg/minute constant rate IV infusion (check blood potassium concentration if no effect);|
|CAT: 0.25–1.0 mg/kg, slow IV injection over a 3–5-minute period|
|Lisinopril||Prinivil unscored tablets, 2.5, 5, 10, 20, 40 mg||DOG: 0.25–0.5 mg/kg q12–24h, PO|
|Magnesium||20% MgCl2 solution for injection (contains||DOG: 0.75–1 mEq/kg/24h IV infusion (50% of total dose can be given in 2–4 hours if necessary)|
|1.97 mEq of Mg++ per mL)||For ventricular fibrillation: 0.15–0.30 mEq/kg IV over 5–10 min|
|Metoprolol tartrate||Toprol-XL scored tablets, 25 mg||DOG: Start at ¼ of a 25 mg tablet once daily; up-titrate every 2 weeks to 12.5 mg q12h, PO (for a 20–30 kg dog)|
|Mexiletine||Mexitil, USP capsules, 150, 200, 250 mg||DOG: 5–8 mg/kg q8h, PO|
|Mexitil, 250 mg for injection||DOG: 2.5 mg/kg bolus IV given over 10 min, followed by 30 mcg/kg/min for 3 hours CRI, followed by 5–8 mcg/kg/min CRI for 24–48 hours IV (currently available in Europe)|
|Nitroprusside sodium||Nitropress, Nipride 50 mg/vial||Usual dosage range is 2–10 mcg/kg/min CRI|
|Begin at 0.5–1 mcg/kg/minute and uptitrated|
|If possible limit infusion to 24 hours|
|Nitroglycerine ointment (2%)||Nitrol, Nitro-bid, Nitrostat, USP 15 mg per inch||DOG: ¼–1 inch topically q12h; Patch: 2.5–10 mg (small-giant dog)|
|Minitran transderm patches 2.5, 5, 10, 15 mg/24 hr||CAT: ¼ inch topically q12h|
|Pimobendan||Vetmedin capsules, 1.25, 2.5, 5 mg||DOG: 0.3–0.6 mg/kg/day, divided; usual dose is 0.25 mg/kg q12h PO (give 1 hour before feeding)|
|Prazosin||Minipress, 1-, 2-, 5-mg capsules||1 mg/15 kg q8–12h PO|
|Procainamide||Pronestyl, USP for injection, 100 mg/ml; 500 mg/ml||DOG: 2 mg/kg (IV) to a maximum total dose of 20 mg/kg over a 30-minute period; 25–40 mcg/kg/min IV infusion; 8–20 mg/kg, IM or SQ q4–6h; 10–20 mg/kg q8h PO (sustained release preparation)|
|Procainamide SR, USP capsules and tablets, 250, 375, 500 mg||CAT: 3–8 mg/kg q6–8h IM or PO|
|Propranolol||Inderal, USP for injection, 1-mg ampoule||DOG, CAT: 20–60 mcg/kg over 5–10 min, IV|
|Tablets, 10, 20, 40, 60, 80 mg||DOG: 0.5–1.0 mg/kg q8h, PO (use with caution in CHF)|
|Inderal LA capsules, 60, 80, 120, 160 mg||Can up-titrate dose from 0.1 mg/kg q8h, PO|
|CAT: 2.5–5.0 mg dose q8h, PO (use with caution in CHF)|
|Spironolactone||Aldactone, USP tablets, 25 mg||DOG: 0.5 mg/kg–1.0 mg/kg q12–24h, PO|
|Sotalol||Betapace, USP scored tablets, 80, 160, 240 mg||DOG: 1–2 mg/kg q12h, PO|
|Tocainide||Tonocard, USP tablets, 400, 600 mg||DOG: 10–20 mg/kg q8h (rarely prescribed today; available in Europe)|
|Verapamil||Isoptin, 5-, 10-mg ampoules for injection;||DOG: 0.05 mg/kg, IV every 10–30 minutes to a maximum cumulative dose of 0.2 mg/kg|
|Isoptin, Calan, 40-, 80-, 120-mg tablets|
|Warfarin||Coumadin 1-, 2-mg scored tablets||CAT: 0.5 mg PO, initial daily dose; compounding may be needed|
Check dosing information and standard textbooks for specific dosing recommendations.
Prescription of many of these drugs in small animal patients constitutes an extra-label use and vary across different countries; Clients should be so advised. Recommendations are based on current standards of veterinary practice.
Many drugs must be titrated to effect, especially in dogs and cats with congestive heart failure. Consider drug interactions when prescribing multiple drugs.
Diuretics are a standard of chronic congestive heart failure (CHF) therapy and are administered for two main purposes: (1) diuresis of the patient with pulmonary edema or body cavity effusions and (2) prevention of the chronic sodium and water retention that characterizes chronic CHF. Diuretics are also anti-hypertensive agents but do not represent an important treatment approach for high arterial blood pressure (ABP) in dogs and cats. Diuretics should be administered with a sodium-restricted diet that is proportional to the severity of CHF.
Furosemide is the most often used diuretic. It acts by inhibiting the co-transporter of chloride in Henle’s loop with resultant losses of chloride, sodium, water, calcium, magnesium, potassium, and water-soluble vitamins in the urine. Bumetanide and torsemide are related human drugs infrequently used in veterinary practice.
Chronic monotherapy with furosemide leads to sodium and volume depletion and activates homeostatic vasoconstricting (renin-angiotensin) and sodium retaining responses. These effects are deleterious in the heart failure and are countered by co-administration of an angiotensin converting enzyme inhibitor (ACEI) and control of dietary sodium intake.
Spironolactone is a potassium- (and magnesium) sparing diuretic that antagonizes the effects of aldosterone by binding to mineralocorticoid receptors in the distal collecting duct. Though a weak diuretic, it is often added to a comprehensive CHF therapy regimen that includes furosemide, an ACEI, and a positive inotrope. Eplerenone is a related drug that is not widely used in veterinary practice.
Hydrochlorothiazide (HCT) is occasionally used in combination with furosemide and spironolactone for management of refractory fluid retention. HCT primarily blocks the sodium transporter in the distal convoluted tubule and the connecting segment but also has action across the proximal tubule. This effect inhibits sodium, chloride, and water reabsorption. HCT is a moderately potent diuretic, but when used in combination with furosemide, the diuretic impact is greatly magnified as HCT prevents distal sodium reabsorption that escapes the effects of the loop diuretic.
Nesiritide, or synthetic human brain natriuretic factor (h-BNP), has been developed as a “smart diuretic” and this drug may be applicable to veterinary practice. Naturally occurring BNP is released from the heart during volume expansion and leads to natriuresis and vasodilation.
Diuretics contract plasma volume and dosing must be adjusted to control fluid accumulation while preventing hypotension, weakness, dehydration, electrolyte disturbances, and azotemia. In most cases, simple monitoring of ABP along with serum creatinine and BUN are sufficient to ensure the dose is not excessive.
Positive inotropic drugs increase the availability of calcium to cardiomyocytes, thereby enhancing the strength of heart contraction. This class of drugs includes the digitalis glycosides (digoxin, digitoxin), catecholamines (dobutamine, dopamine), phosphodiesterase inhibitors (milrinone), and calcium sensitizers (pimobendan).
Digoxin is the oldest inotropic drug in common use. (Digitoxin is used rarely and will not be discussed.) Digoxin is indicated in therapy of moderate to severe CHF caused by dilated cardiomyopathy, chronic valvular heart disease, or untreated congenital heart disease in dogs. It is rarely prescribed to cats. Digoxin is especially useful when CHF is complicated by atrial fibrillation or frequent premature atrial complexes. The cardiac glycosides have not been shown to prolong survival in CHF.
Digoxin is unlikely to provide satisfactory control of ventricular response rate to atrial fibrillation unless used in combination with diltiazem or a beta-blocker. However, as a positive inotrope, digoxin is the first drug used in treatment of atrial fibrillation in the setting of CHF.
While some veterinarians use the examination heart rate to decide if they will prescribe digoxin, there is no established basis for this approach or for predicting the potential benefit of the drug. Digoxin does little to mitigate heart rate due to high sympathetic tone, stress, or exercise; heart rate benefits of increased vagal tone are most evident in the resting state.
Common adverse effects of digoxin include anorexia, depression, vomiting, diarrhea, and cardiac arrhythmias. Arrhythmias are explained by either increased vagal tone (causing sinus node depression or AV block) or enhanced calcium entry into cells, leading to membrane oscillations, increased automaticity (particularly in the His-Purkinje fibers), and subsequently premature complexes. Ventricular bigeminy and ectopic junctional rhythms also have been observed in dogs with digitalis toxicity.
The catecholamines used most often in emergent management of CHF are dobutamine and dopamine. These drugs stimulate cardiac beta- and alpha–receptors to increase contractility in a dose-dependent manner via the second messenger effect (increased generation of cyclic AMP or IP3for beta- and alpha–receptor stimulation, respectively). In patients with CHF, the heart rate generally increases slightly during infusion of catecholamines. The effects of catecholamines on systemic arterioles are dose dependent but include vasodilation at lower doses (beta2 effect) and vasoconstriction (alpha effects) at higher infusion rates.
Adverse effects of catecholamines are predictable extensions of sympathomimetic stimulation and include sinus tachycardia; premature supraventricular and ventricular complexes; ventricular tachycardia that can progress to ventricular fibrillation; anxiety; tremors; elevated ABP; and seizures (mainly in cats). Simply stopping or lowering the infusion rate controls most adverse effects as the drug is rapidly hydrolyzed within minutes of administration. Life-threatening side effects can be treated with the ultrashort-acting beta-blocker esmolol (100-500 mcg/kg dose infused over 5-10 minutes with HR and ABP monitoring).
The word “inodilator” pertains to positive inotropic drugs that also demonstrate significant vasodilator effects. The combination of increased myocardial contractility and left ventricular afterload reduction result in a potent increase in ventricular stroke volume.
Milrinone and amrinone are PDE-III inhibitors that prevent the degradation of cyclic AMP, the second messenger of the beta-adrenoceptor. This leads to accumulation of the cyclic nucleotide and a potent positive inotropic effect. Cyclic AMP also functions as a peripheral vasodilator, especially in dogs, so that reduced left ventricular afterload further improves cardiac performance.
These drugs are administered by IV infusion, are relatively expensive, and are used infrequently in veterinary practice, though canine studies with oral and IV milrinone showed both acute and chronic benefit of this drug.
Clinical indications for IV milrinone would be the combination of severe systolic dysfunction and tachycardia (as PDE-III inhibitors have relatively little effect on heart rate, even at higher doses) or the patient with acute-on-chronic heart failure, already receiving beta blockade and in need of acute inotropic support that bypasses the beta-receptor.
Pimobendan (Vetmedin) is classified as a calcium sensitizer, as well as a phosphodiesterase inhibitor with vasodilator properties. It is approved for veterinary use in many countries and completing clinical trials in other countries (including the USA). Pimobendan is an inodilator with a novel mode of action on contractility. Whereas digitalis and catecholamines increase the transport of calcium into the cardiomyocyte, pimobendan increases the sensitivity of the actin-myosin contractile apparatus to available calcium.