CV Drugs (System Specific)

Lectures 2, 3, 4

Classification/Physiologic response: Class III Potassium Channel Blockade

MOA(s): prolong repolarization in action potential duration (do NOT mix with Class Ia)

Side effect(s): hyper/hypothyroidism, liver cholestasis

Indications for use: acute setting to convert AFib, SVTs, VTach

Other: has all arrythmias drug class effects but primary is potassium blocker, will non competitively bind to alpha and beta receptors, works on all levels of heart muscle

Amiodarone

Classification/Physiologic response: Arterial dilators (Vasodilator)

Location of action: arterial trees

MOA(s): peripheral calcium channel blocker to decrease afterload

Side effect(s): hypotension, tachycardia

Indications for use: chronic need for us to lower blood pressure (hypertension patients or patients where we need to unload heart more)

Other: 3-5 days before you reach steady state effect due to 24-36 hour half life

Amlodipine

Classification/Physiologic response: Class II Beta Adrenergic Blockade

MOA(s): selective beta 1 receptor antagonist, beta 2 effects at high doses

Side effect(s): negative inotropic effect, negative chronotropic effect

Indications for use: chronic oral therapy for AFib or SVT

Other: do not use with underlying muscle disease resulting in heart contractility issues

Atenolol

Classification/Physiologic response: Anti-vagolytic (Parasympatholytic)

Side effect(s): GI if used long term

Indications for use: vagally induced bradycardia

Other: can be used to test if we have bradycardia secondary to high vagal tone, effectiveness decreases over time

Atropine

Classification/Physiologic response: Ace inhibitor (Mixed dilator, vasodilator)

MOA(s): Blocks ACE to reduce after/preload

Side effect(s): occasional azotemia

Indications for use: chronic heart failure

Other: longer half life compared to enalapril

Benazepril

Classification/Physiologic response: Digitalis glycosides (Positive inotrope)

Location of action: Cardiac baroreceptors

MOA(s): Blocks K+ side of Na+/K+ ATPase pump in sarcolemma (blocks ability of sodium to be removed after cell has depolarized so sodium partners with calcium instead which causes more calcium to be released from cell resulting in positive inotropic response)

Side effect(s): GI, arrythmia, neurologic, signs of digoxin toxicity if given to hypokalemic patient

Indications for use: additive for controlling supraventricular arrythmias (atrial fibrillation, supraventricular tachycardia)

Other: normalizes baroreceptor function, slows AV node conduction, indirect diuresis, very low/narrow therapeutic to toxic indices (BE CAREFUL AND KNOW WHAT YOU’RE DOING WITH THIS DRUG), 24-36 hours to get to steady state due to long half life, need to monitor drug serum levels 6-8 hours after administration

Digoxin

Classification/Physiologic response: Sympathomimetic (positive inotrope)

Location of action: Cardiac vasculature

MOA(s): B1 >> B2 >>> alpha agonist (interacts mostly with B1 receptors, which are heart muscle receptors, to work on ventricular muscles; B2 results in vasodilation which helps with circulatory efficiency by reducing vascular resistance)

Side effect(s): tachycardia and ventricular arrythmia (VPCs) at high dosing

Indications for use: ER setting

Other: B2 decreased SVR to improve circulation, must give as CRI, can cause excoriation of muscles and surrounding cells if not given in patent IVC

Dobutamine

Classification/Physiologic response: Ace inhibitor (Mixed dilator, vasodilator)

MOA(s): Blocks ACE to reduce after/preload

Side effect(s): occasional azotemia

Indications for use: chronic heart failure

Other: CV protective effects

enalapril

Classification/Physiologic response: Class II Beta Adrenergic Blockade

MOA(s): rapid acting emergent beta blocker  

Side effect(s): negative inotropic effect, negative chronotropic effect, bronchospasm at high doses

Indications for use: emergency arrythmias (SVTs, AFib)

Other: must be given IV, potentially as CRI to maintain effect, be careful with morphine as it will increase serum concentration by 50%

Esmolol

Classification/Physiologic response: Loop diuretic

Location of action: Thick ascending loop of Henle

MOA(s): Blocks Na+/K+/Cl- ATPase

Side effect(s): Dehydration, hypokalemia, hypochloremia, metabolic alkalosis

Indications for use: CHF cardiogenic edema, ascites

Other: venodilation when given IV (good thing because veins now dilate and can hold more volume instead of pushing more into left side of heart which helps decrease pressure going into left side and deload), high ceiling diuretic

Furosemide (Lasix, Salix)

Classification/Physiologic response: Arterial dilator (Vasodilator)

MOA(s): unknown but decreases afterload

Side effect(s): hypotension, tachycardia

Indications for use: hypertension

Other: biotransformation can be affected by renal failure

Hydralazine

Classification/Physiologic response: Thiazide diuretic

Location of action: Distal convoluted tubule

MOA(s): Blocks Na+/Cl- cotransporter

Side effect(s): Dehydration, hypokalemia, azotemia

Indications for use: “stacking diuretic” for synergistic effect, already on furosemide or torsemide and still producing fluid in belly (ascites) or edema, patient will stay on same dose of torsemide and furosemide with this drug, low ceiling (give it and immediately see maximum effects, increasing dose will not increase effect, must give loading dose and wean off), can induce calciuresis

hydrochlorothiazide

Classification/Physiologic response: Class Ib Sodium Channel Blockade

Location of action: activated sodium channels in ventricles

MOA(s): shorten repolarization of action potential

Indications for use: Ventricular arrythmias, Ventricular tachycardia

Other: membrane stabilizers that work best in diseased/damaged tissues, short onset of action and duration, give as IV bolus to get to drug levels then start CRI (HAVE TO BE SPOT ON TO START CRI OR YOU WILL BYPASS THERAPEUTIC LEVELS)

Lidocaine

Classification/Physiologic response: Class Ib Sodium Channel Blockade

Location of action: activated sodium channels in ventricles

MOA(s): shorten repolarization of action potential

Side effect(s): GI (diarrhea)

Indications for use: Chronic ventricular arrythmias, Ventricular tachycardia

Other: very similar to lidocaine but available in oral formulation, Theophylline can reduce circulating ability (be cautious when using with other drugs)

Mexelitine

Classification/Physiologic response: Venous dilator (vasodilator)

MOA(s): nitric oxide production to decrease preload

Side effect(s): builds up tolerance relatively quickly, no side effects generally seen

Other: only topical

Nitroglycerin 2% ointment

Classification/Physiologic response: Phosphodiesterase inhibitor (mixed dilator, vasodilator), Calcium sensitizer (positive inotrope)

Location of action: Cardiac muscle, cardiac vasculature

MOA(s): PDE3 inhibitor, sensitizes myofibrils to calcium concentration, PDE 5 inhibitor?

Side effect(s): minimal, GI sensitivity to beef flavored Vetmedin tabs if patient has beef allergy

Indications for use:

Other: inodilator, positive inotropic response, negligible effect on blood pressure, may see AFib rate speed up in early use of this drug  

pimobendan (Vetmedin)

Classification/Physiologic response: Class Ia Sodium Channel Blockade

Location of action: atrial and ventricular tissues

MOA(s): prolong repolarization phase of action potential duration

Side effect(s): neurologic (seizures),

Indications for use: supraventricular tachycardia (SVT), ventricular tachycardia refractory to lidocaine(VT), atrial fibrillation (AF)

Other: IV only, can decrease myocardial excitability, minimal side effects on ability of heart muscle function, can see decrease in heart rate, do not have antimuscarinic effects like quinidine, very short half life, be ready to give as CRI after loading dose

procainamide

Classification/Physiologic response: Class II Beta Adrenergic Blockade

MOA(s): nonselective beta blocker (blocks B1 and B2) with membrane stabilizing properties

Side effect(s): negative inotropic effect, negative chronotropic effect

Indications for use: heart rate control (slow it down) in supraventricular tachycardia and atrial fibrillation

Other: can cross placenta and enter milk (caution in pregnant patients), hyperthyroidism can result in decreased clearance of drug

Propanolol

Classification/Physiologic response: Class Ia Sodium Channel Blockade

Location of action: atrial and ventricular tissues

MOA(s): prolong repolarization phase of action potential duration

Side effect(s): depress myocardial function (negative inotropic effect), reduce contractility, vasodilation, GI upset, arrythmias, hypotension, laminitis in horses

Indications for use: supraventricular tachycardia (SVT), ventricular tachycardia (VT), atrial fibrillation (AF)

Other: some muscarinic receptor antagonist activity at higher doses (can block discharge of vago nervous system, increase AV nodal conduction rate), good to reduce re-entry phenomenon, when given orally it undergoes first pass effect, highly protein bound, high differences in volume of distribution among species, do NOT give IV to small animals/dogs, use nasogastric tube to give orally in horses

quinidine

Classification/Physiologic response: Phosphodiesterase inhibitor (Mixed dilator, vasodilator)

MOA: PDE 5 inhibitor to decrease pulmonary arterial pressure

Indications for use: Primary pulmonary hypertension, stiff arterioles, vascular changes secondary to heartworm disease

Other: caution in patients with left sided heart disease

Sildenafil (Viagra, Revatio)

Classification/Physiologic response: NO producer (mixed dilator, vasodilator)

MOA(s): produces nitric oxide

Side effect(s): hypotension, tachycardia, cyanide toxicity at high doses

Other: must be given as CRI, ultra short half life (quick onset and quick loss of action), patients develop tolerance at 72 hours, can cause scarring and burning to tissues if IVC is not in vein when administered, can be used prior to Furosemide administration to lower amount of Furosemide needed

Sodium nitroprusside

Classification/Physiologic response: Class III Potassium Channel Blockade

MOA(s): prolong repolarization in action potential duration (do NOT mix with Class Ia)

Side effect(s): minimal

Indications for use: chronic oral therapy for arrythmias

Other: non selective beta blocking activities as well but much more potassium blocking, be careful in inotropic compromise as it can push them into failure

Sotalol

Classification/Physiologic response: Potassium sparing diuretic

Location of action: Late distal convoluted tubule

MOA(s): Aldosterone inhibition

Side effect(s): hyperkalemia, allergic excoriations reported in some cats

Indications for use: patient experiencing hypokalemia, added very early on in heart disease or heart failure (even earlier in DCM patients) because it has an anti-fibrotic effect in heart muscle (mineralocorticoid receptor target in heart)

Spirinolactone

Classification/Physiologic response: Angiotensin II blocker (mixed dilator, vasodilator)

MOA(s): blocks angiotensin II AT2 receptor to decrease afterload and potentially preload

Indications for use: Feline hypertension

Telmisartan

Classification/Physiologic response: Loop diuretic

Location of action: Thick ascending loop of Henle

MOA(s): Blocks Na+/K+/Cl- ATPase plus aldosterone inhibition

Side effect(s): Dehydration, azotemia

Indications for use: Used furosemide for a while and they have built a tolerance for it so switch to torsemide (anti-aldosterone effect protects from tolerance), patient will stay on furosemide, CHF cardiogenic edema, ascites

Torsemide (Demadex)

Classification/Physiologic response: Angiotensin receptor-Neprilysin inhibitor (ARNi)

Location of action:

MOA(s):

—>Valsartan: angiotensin receptor blocker at AT1 receptor

—>Sacubitril: prodrug esterified to active for Sacubitrilat which inhibits Neprilysin (stops breakdown of natriuretic peptides

Side effect(s): hyperkalemia, renal impairment, hypotension

Indications for use: Canine Hypertension

Other: lowers blood pressure in 1-2 hours, protects cardiac remodeling, additive diuretic effect, NOT CURRENTLY APPROVED IN VET MED

Valsartan/Sacubitril (Entresto)

Classification/Physiologic response: Class IV Calcium Channel Blockade (nondihydropyridines)

Location of action: AV node

Indications for use: SVT, AFib

Other: can have negative inotropic effects but tolerated better than beta blockers

Verapamil