1. CARDIOVASCULAR DRUGS Chapter

2. ANTIARRHYTHMIC DRUGS

3. Sodium influx inhibitors These drugs decrease the rate of sodium movement into the cell Allow SA node to regain control of heart rate and re-establish sinus rhythm

4. Lidocaine Only comes in injectable form and is given IV MAJOR DRUG OF CHOICE FOR TREATMENT OF VPCS AND VENTRICULAR ARRHYTHMIAS Caution in cats. AV blocks will worsen. Large boluses can produce sinus arrest. Signs of toxicity: sedation, ataxia, drowsiness, excitement, short-lived seizures DO NOT USE IV IF BOTTLE ALSO CONTAINS EPINEPHRINE (intended for use as a local anesthetic-keep this bottle in separate area). Heart rate and contractility will increase while sodium movement is reduced. Sudden collapse and death is possible. Mexiletine-Oral drug for long term maintenance on dogs who respond to lidocaine

5. Quinidine Increase length of the refractory period PO drug, used for long-term maintenance Known to cause GI upset. Can cause digoxin toxicity if given simultaneously Procainamide Increase length of the refractory period PO drug, used for long-term maintenance Regular release or sustained-release tablets

6. Beta Blockers Beta Antagonists. Can block only Beta ones, only Beta twos (called selective) or both (nonselective). Beta blockers decrease sympathetic stimulation of the heart, allowing the parasympathetic system to control the heart. Conduction of impulses and heart rate will slow down. Also called Negative Inotropic drugs as the heart will contract with less force. Will see a prolonged interval between P wave and QRS complex (slowed conduction through AV node) called 1 st Degree AV Block. Atropine can reverse Beta blockers if overdose occurs.

7. Beta Blockers Increased numbers of Beta receptors (upregulation) may occur if an animal has been taking a Beta blocker regularly. This may make it difficult for the Beta blockers to be effective, so the dose may need to be increased. In addition, more receptors makes the tissues more sensitive to epinephrine and norepinephrine. DO NOT suddenly stop administering Beta blockers since a release of epi/norepi by the body will result in extreme tachycardia and arrhythmias. Slowly taper off of meds to allow the body to downregulate its receptors.

8. Propranolol Prototype for this category Blocks Beta one receptors on the SA node and the AV node, slowing the speed of the depolarization. Used in cats with tachycardia due to hyperthyroidism, systemic hypertension, HCM. May also block Beta two receptors, causing broncoconstriction and vasoconstriction of blood vessels to the heart and skeletal muscle.

9. ATENOLOL More selective for Beta ones than propranolol. Safer to use in animals with bronchospasm. Also used with cats that have HCM. CARVEDILOL Newer med, more selective for Beta one receptors. SOTOLOL Nonselective for receptors like propranolol.

10. Calcium Channel Blockers Diltiazem, Verapamil Not used as frequently in veterinary medicine as the other Antiarrhythmic drugs. Block calcium channels which decreases conduction of depolarization waves and decreases automaticity throughout the heart. Negatively effects the contractile mechanism of cardiac muscle. Negative inotropes Amlodipine is used more as a treatment for hypertension than arrhythmias.

11. POSITIVE INOTROPIC DRUGS Increase strength of contraction of weak heart Most work by making more Calcium available to the contractile proteins of the muscle cell.

12. Adrenergic drugs/Sympathomimetics Catecholamines are the body’s natural positive inotropes that are released when the body is stimulated by the sympathetic nervous system. Synthetic versions are called adrenergic or sympathomimetic drugs. Stimulate Beta one receptors in cardiac muscle. Improvement in contractility is short-lived. Not meant to be long-term drugs. Mainly used for short-term treatment of CHF.

13. EPINEPHRINE Preferred drug for stimulating contractions post cardiac arrest and for anaphylaxis. Can be given Intracardiac, Intratracheal, or IV. 1:10,000 solution is preferred. Can be achieved by using a 1:10 dilution of a 1:1000 solution. Store in refrigerator. DOPAMINE Used for treatment of acute heart failure, oliguric renal failure, and treatment of shock. Increases blood pressure and cardiac contractility.

14. Cardiac Glycosides Obtained from the dried leaves of the Digitalis purpurea (foxglove) plant which improve contractility, decrease heart rate, decrease arrhythmias, decrease signs of dyspnea.

15. Digoxin Makes more calcium available to the contractile proteins in cardiac cells. Contractions occur with more force, but with a decreased rate. Dose is often calculated by using the surface area of the animal as opposed to the weight. Small therapeutic index, so toxicities are common. Signs: V/D, anorexia, severe bradycardia, AV block. STOP MEDS. Reverse with Atropine. Digoxin has a half-life of up to 50 hours and is eliminated via the kidneys. Dehydration will prolong the half-life.

16. Pimobendan *VETMEDIN Newer drug Increases sensitivity of cardiac myofilaments to Calcium Used to treat DCM

17. VASODILATORS Vasoconstriction is a response to decreased arterial blood pressure. It results in increased resistance to blood flow and increased force to push blood through the vessels, making the heart work harder. Vasodilators decrease resistance to blood flow, making it easier for the heart to pump blood through the vessels. Hypertension unrelated to heart disease is seen in hyperthyroidism, chronic renal disease, diabetes mellitus, etc. If uncontrolled, retinal issues or stroke can occur. Vasodilators can work by blocking the renin-angiotensin system, directly relaxing the smooth muscle in vessel walls, or blocking Alpha one receptors. Monitor for weakness, syncope, or lethargy when beginning medication.

18. Ace Inhibitors Animals with CHF have decreased cardiac output and decreased blood pressure. Alpha one receptors are stimulated so arterioles become vasoconstricted. Less blood enters the nephron, so less urine is made. The renal tubules detect this and release RENIN in response. Renin converts ANGIOTENSINOGEN to ANGIOTENSIN I. Angiotensin I is converted to ANGIOTENSEN II by ANGIOTENSINOGEN CONVERTING ENZYME. Angiotensin II causing the release of ALDOSTERONE from the adrenal glands. This causes sodium reabsorption and water retention. The end result is increased blood volume, pressure, and work load for the heart.

19. ACE Inhibitors- Enalapril, Captopril, Lisinopril, Benazepril Block ACE, preventing formation of Angiotensin II and Aldosterone. Treating with ACE inhibitors is common. Will not have an effect on normal animals. Also have positive inotropic effect.

20. Hydralazine Drug of choice before ACE inhibitors were invented. Directly causes smooth muscle relaxation in arterioles. Most likely through Calcium inhibition. Dilates pulmonary arterioles more than any other vessel. Slight activity as a positive inotrope. Prazosin Alpha one blocker that causes vasodilation in both arteries and veins. Give to patients with CHF that are not responding to other vasodilators. Not used in small animals as it is too hard to measure out a small enough dose.

21. Nitroglycerin Causes venodilation and coronary arteriole dilation. Well absorbed through skin and mucous membranes. Animals use cream or patch. Cream is applied to hairless part of pinna. Change site of application with each dose. Wear gloves when applying and don’t pet the animal where the cream or patch is applied. Improves cardiac output and reduces pulmonary edema and ascites. No explosions will occur.

22. DIURETICS Increase urine production and promote water loss. Used in the following situations: edema/ascites, removal of drugs excreted by the kidney, reducing arterial blood pressure, decreasing workload on a CHF heart Use with caution in anyone with hypovolemia or hypotension Give animals access to water

23. Loop Diuretic-Furosemide*LASIX Most commonly used diuretic in veterinary medicine. Inhibits Na reabsorption in the LOH. Na stays in urine and so does water. DCT exchanges the Na for K, water stays in urine and potassium ions are lost in it. Diet may need to be supplemented with potassium. Decrease reabsorption of sodium and chloride at the initial segment of the DCT. Like loop diuretics, sodium is exchanged for potassium and hypokalemia may develop. Does not diurese as much water as furosemide. Thiazide Diuretics- Chlorothiazide,Hydrochlorothiazide

24. Potassium-Sparing Diuretic- Spironolactone Cause sodium excretion and potassium conservation. Competitive antagonists of Aldosterone, so it reduces the amount of sodium reabsorbed. Sodium remains in the tubules and water follows it. Osmotic Diuretic- Mannitol Not used for Cardiac-related diuresis, mainly for reducing cerebral edema and for flushing toxins. The molecules of Mannitol are excreted into the urine where they cause additional water to be excreted in the urine via osmosis.