Cardiac Pharmacology Flashcards
Goals of pharmocologic therapy of CHF
Improves quality of life, prognosis, and contractile function*
Drugs used to DECREASE cardiac load
Diuretics (↓blood volume)
Vasodilators (↓ preload and afterload)
Drugs used to INCREASE cardiac pumping efficiency
Catecholamines
Phosphodiesterase inhibitors
Cardiac glycosides
Calcium sensitizers
Why is calcium activation a problem?
Ca2+ release requires more O2/ energy
Cardiac activation
- Sensitizes muscle to the Ca2+ (↑contraction, doesn’t require O2)
- ↑ contractility by ↓ Ca2+ uptake (keeping Ca+ longer)
- Causes more Ca2+ to come in and release more Ca2+
Calcium-tension relation
Too much Ca2+ in and out of the cell = overload
Causes ↓ heart response to Ca2+ and arrhythmias
Catecholamines
B agonists
Stimulation of b1 receptors has both inotropic and chronotropic effects
What does persistant stimulation of B1 receptors by agonists do?
Produces receptor down regulation and rapid ↓ in drug effectiveness (tolerance)
SHORT-TERM DRUGS
Catecholamine drugs
Dobutamine and dopamine
Dobutamine
↓ output failure patients (CHF patients)
Inotropic effects without vasoconstrictive activity (b1)
Vasodilation (b2)
Only available IV (CRI)
Dopamine
Not for CHF patients, for shock patients
IV administration only!
Metabolized in kidney, liver by monoamine oxidase (MAO) and COMT
Cardiac Glycosides (digitalis)
From foxglove
Used in the treatment of dropsy (edema), congestive heart failure, dysrhythmias
Positive inotropic effect
Why don’t vets like to use digitalis glycosides?
Narrow TI
↑ toxicity range
Cardiac Glycoside drug
Digoxin
Digoxin
Most common digitalis
Renally excreted and blood levels rise with ↓ GFR (lower dose if patients has renal insufficiency)
Digitalis MOA
- Inhibits K+ on Na+, K+-ATPase
- Intracellular Na+ ↑
- Na+-Ca++ exchanger : pumps Ca++ in, Na++ out
- Intracellular Ca++ accumulates and complexes with tropinin → contraction
- Effects cardiac and smooth muscles
Digitalization effects
↑ excitability, refractory pd.
Delayed afterdepolarization
↓ conduction velocity (vagal effects), automaticity
Tachyarrhythmias
Heart block with high doses
Digitalis dosing
Emergency situation: loading dose
Non- emergency: slow administration with maintenance dosing
Calcium sensitization
Drugs that ↑ myofilament responsiveness to given Ca
No Ca2+ overload
Pimobendan (Vetmedin)
Positive inotropic and vasodilator effects
Smaller cardiac preload and afterload
MV disease in dogs
Pimobendan MOA
Ca2+ sensitizer and inhibits PDE 3
Peak concentration @ 4 hours, cardio effects 2-4 hrs
Drugs that ↓ cardiac workload
Cause fluid and Na retention in vessels (compensates for ↓ pumping ability)
Excessive retention: overload, pulmonary edema, deoxygenation of blood, peripheral edema
Vasodilators and ACE inhibitors
Vasodilators
Unloads the failing heart
↓ workload = ↓ arterial pressure so left ventricle pumping blood with lower resistance
Arterial vasodilation
Reduction in afterload
Side effects: hypotension, reflex tachycardia
Not used in patients with late stage heart failure, SBP <70
Arterial vasodilators
Amlodipine (Norvasc)
Hydralazine
Amlodipine (Norvsac)
1-4 dihydropyrodine
Peripheral calcium channels blockers with little central effects
Enhances NO-
Hydralazine
Research/ emergency drug
↓ systemic vascular resistance in heart failure
Side effects: reflexive tachycardia, hypotension, GI distress
T/F: hydralazine has an unknown MOA
TRUE
Venodilators
↑ venous capacity reduces preload and relieves congestion
Ex: nitroglycerin
Nitroglycerin
Cats with fluid buildup
2% ointment (gloves) on hairless area
Rapidly develops tolerance (once a day)
Mixed (balance) dilators
Sodium nitroprusside: prototype for acute left CHF, must use saline
Adverse effects: cyanide toxicity, not useful in 2-3 days
With nitroprusside you should avoid _______
Extravasation (bad wound if not in vessel)
Drug tolerance
Depletion of sulfhydryl group
Inactive aldehyde dehydrogenasde
Production of peroxynitrite (blocks GTP-cGMP conversion)
ACE inhibitors
Inhibits angiotensin converting enzyme (ACE) → prevents angiotensin 2 formation → prevents vasoconstriction
Used for CHF
Adverse effects of ACE inhibitors
Possible renal insufficiency
ACE inhibitor drugs
Enalapril and benzepril
Enalapril
Prodrug that undergoes hepatic hydrolysis forming enalaprilat
Distributed in all tissues except CNS, cross placenta, enter milk in traces
Enalapril toxicity is @ ___________
200 mg/ kg
Benazepril (prodrug)
Rapidly metabolized to benazeprilat
Eliminated via hepatic metabolism
Angiotensin Receptor Blockes (ARBs)
Antagonizes angiotensin 2 binding to AT1 subtype receptor in smooth muscle and adrenal gland
Used more for hypertensive cats
Drugs that end in “Sartan”
Temisartan
Only approved drug in vet med
Selectively binds to AT1 subtype receptors
Doesn’t metabolize well in dogs
ARB excretion
Biliary elimination into the feces (86%-100%)
Prazosin HCL
A1 adrenergic antagonist
Mixed arterial and venous dilation
Hepatic metobolism
Prazosin interactions
Displaced by high protein bound drugs like sulfonamides and warfarin
What is significant about loop Acting Diuretics
Only drug that’ll save a patient in respiratory distress due to cardiogenic edema
High ceiling
Loop acting diuretics
Secreted into the tubular lumen
Inhibits Na+, K+, CL- in thick ascending loop of henle
Ex: Furosemid (Lasix) and Torsemide (demadex)
Fursosemid (lasix)
Venodilation occurs with IV administration
Dehydration and hypokalmeia common side-effects + metabolic alkalosis
TORESEMIDE
Used when level D heart failure
Longer duration of action than furosemide
Side effects ↑BUN and creatinine, ↓ collagen and myocardial fibrosis
Thiazide Diuretics
Directly inhibits Na+ CL-/ H2O cotransporter in DCT
Synergist drug
Low ceiling, given 2nd
Induce dehydration and hypokalemia
Examples of thiazide
Hydrocholorothiazide (pure) and chlorthiazide (capsule)
Potassium Sparing Diuretics
Used in early heart failure for antifibrotic effect because weak
Given in combo with other drugs
Reduce loss of K+ from other drug
Potassium Sparing Diuretic drugs
Spironolactone → Canrenone
Potassium Sparing Diuretics MOA
Inhibits Na/H2O resorption in DCT/CT
Antifibrotic properties
