Cardiac Pharmacology

Question 1

Goals of pharmocologic therapy of CHF

Answer 1

Improves quality of life, prognosis, and contractile function*

Question 2

Drugs used to DECREASE cardiac load

Answer 2

Diuretics (↓blood volume)
Vasodilators (↓ preload and afterload)

Question 3

Drugs used to INCREASE cardiac pumping efficiency

Answer 3

Catecholamines
Phosphodiesterase inhibitors
Cardiac glycosides
Calcium sensitizers

Question 4

Why is calcium activation a problem?

Answer 4

Ca2+ release requires more O2/ energy

Question 5

Cardiac activation

Answer 5

1. Sensitizes muscle to the Ca2+ (↑contraction, doesn’t require O2)
2. ↑ contractility by ↓ Ca2+ uptake (keeping Ca+ longer)
3. Causes more Ca2+ to come in and release more Ca2+

Question 6

Calcium-tension relation

Answer 6

Too much Ca2+ in and out of the cell = overload
Causes ↓ heart response to Ca2+ and arrhythmias

Question 7

Catecholamines

Answer 7

B agonists
Stimulation of b1 receptors has both inotropic and chronotropic effects

Question 8

What does persistant stimulation of B1 receptors by agonists do?

Answer 8

Produces receptor down regulation and rapid ↓ in drug effectiveness (tolerance)
SHORT-TERM DRUGS

Question 9

Catecholamine drugs

Answer 9

Dobutamine and dopamine

Question 10

Dobutamine

Answer 10

↓ output failure patients (CHF patients)
Inotropic effects without vasoconstrictive activity (b1)
Vasodilation (b2)
Only available IV (CRI)

Question 11

Dopamine

Answer 11

Not for CHF patients, for shock patients
IV administration only!
Metabolized in kidney, liver by monoamine oxidase (MAO) and COMT

Question 12

Cardiac Glycosides (digitalis)

Answer 12

From foxglove
Used in the treatment of dropsy (edema), congestive heart failure, dysrhythmias
Positive inotropic effect

Question 13

Why don’t vets like to use digitalis glycosides?

Answer 13

Narrow TI
↑ toxicity range

Question 14

Cardiac Glycoside drug

Answer 14

Digoxin

Question 15

Digoxin

Answer 15

Most common digitalis
Renally excreted and blood levels rise with ↓ GFR (lower dose if patients has renal insufficiency)

Question 16

Digitalis MOA

Answer 16

1. Inhibits K+ on Na+, K+-ATPase
2. Intracellular Na+ ↑
3. Na+-Ca++ exchanger : pumps Ca++ in, Na++ out
4. Intracellular Ca++ accumulates and complexes with tropinin → contraction
5. Effects cardiac and smooth muscles

Question 16

Digitalization effects

Answer 16

↑ excitability, refractory pd.
Delayed afterdepolarization
↓ conduction velocity (vagal effects), automaticity
Tachyarrhythmias
Heart block with high doses

Question 17

Digitalis dosing

Answer 17

Emergency situation: loading dose
Non- emergency: slow administration with maintenance dosing

Question 18

Calcium sensitization

Answer 18

Drugs that ↑ myofilament responsiveness to given Ca
No Ca2+ overload

Question 19

Pimobendan (Vetmedin)

Answer 19

Positive inotropic and vasodilator effects
Smaller cardiac preload and afterload
MV disease in dogs

Question 20

Pimobendan MOA

Answer 20

Ca2+ sensitizer and inhibits PDE 3
Peak concentration @ 4 hours, cardio effects 2-4 hrs

Question 21

Drugs that ↓ cardiac workload

Answer 21

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

Question 22

Vasodilators

Answer 22

Unloads the failing heart
↓ workload = ↓ arterial pressure so left ventricle pumping blood with lower resistance

Question 23

Arterial vasodilation

Answer 23

Reduction in afterload
Side effects: hypotension, reflex tachycardia
Not used in patients with late stage heart failure, SBP <70

Question 24

Arterial vasodilators

Answer 24

Amlodipine (Norvasc) Hydralazine

Question 25

Amlodipine (Norvsac)

Answer 25

1-4 dihydropyrodine Peripheral calcium channels blockers with little central effects Enhances NO-

Question 26

Hydralazine

Answer 26

Research/ emergency drug ↓ systemic vascular resistance in heart failure Side effects: reflexive tachycardia, hypotension, GI distress

Question 27

T/F: hydralazine has an unknown MOA

Answer 27

TRUE

Question 28

Venodilators

Answer 28

↑ venous capacity reduces preload and relieves congestion Ex: nitroglycerin

Question 29

Nitroglycerin

Answer 29

Cats with fluid buildup 2% ointment (gloves) on hairless area Rapidly develops tolerance (once a day)

Question 30

Mixed (balance) dilators

Answer 30

Sodium nitroprusside: prototype for acute left CHF, must use saline Adverse effects: cyanide toxicity, not useful in 2-3 days

Question 31

With nitroprusside you should avoid _______

Answer 31

Extravasation (bad wound if not in vessel)

Question 32

Drug tolerance

Answer 32

Depletion of sulfhydryl group Inactive aldehyde dehydrogenasde Production of peroxynitrite (blocks GTP-cGMP conversion)

Question 33

ACE inhibitors

Answer 33

Inhibits angiotensin converting enzyme (ACE) → prevents angiotensin 2 formation → prevents vasoconstriction Used for CHF

Question 34

Adverse effects of ACE inhibitors

Answer 34

Possible renal insufficiency

Question 35

ACE inhibitor drugs

Answer 35

Enalapril and benzepril

Question 36

Enalapril

Answer 36

Prodrug that undergoes hepatic hydrolysis forming enalaprilat Distributed in all tissues except CNS, cross placenta, enter milk in traces

Question 37

Enalapril toxicity is @ ___________

Answer 37

200 mg/ kg

Question 38

Benazepril (prodrug)

Answer 38

Rapidly metabolized to benazeprilat Eliminated via hepatic metabolism

Question 39

Angiotensin Receptor Blockes (ARBs)

Answer 39

Antagonizes angiotensin 2 binding to AT1 subtype receptor in smooth muscle and adrenal gland Used more for hypertensive cats Drugs that end in "Sartan"

Question 40

Temisartan

Answer 40

Only approved drug in vet med Selectively binds to AT1 subtype receptors Doesn't metabolize well in dogs

Question 41

ARB excretion

Answer 41

Biliary elimination into the feces (86%-100%)

Question 42

Prazosin HCL

Answer 42

A1 adrenergic antagonist Mixed arterial and venous dilation Hepatic metobolism

Question 43

Prazosin interactions

Answer 43

Displaced by high protein bound drugs like sulfonamides and warfarin

Question 44

What is significant about loop Acting Diuretics

Answer 44

Only drug that'll save a patient in respiratory distress due to cardiogenic edema High ceiling

Question 45

Loop acting diuretics

Answer 45

Secreted into the tubular lumen Inhibits Na+, K+, CL- in thick ascending loop of henle Ex: Furosemid (Lasix) and Torsemide (demadex)

Question 46

Fursosemid (lasix)

Answer 46

Venodilation occurs with IV administration Dehydration and hypokalmeia common side-effects + metabolic alkalosis

Question 47

TORESEMIDE

Answer 47

Used when level D heart failure Longer duration of action than furosemide Side effects ↑BUN and creatinine, ↓ collagen and myocardial fibrosis

Question 48

Thiazide Diuretics

Answer 48

Directly inhibits Na+ CL-/ H2O cotransporter in DCT Synergist drug Low ceiling, given 2nd Induce dehydration and hypokalemia

Question 49

Examples of thiazide

Answer 49

Hydrocholorothiazide (pure) and chlorthiazide (capsule)

Question 50

Potassium Sparing Diuretics

Answer 50

Used in early heart failure for antifibrotic effect because weak Given in combo with other drugs Reduce loss of K+ from other drug

Question 51

Potassium Sparing Diuretic drugs

Answer 51

Spironolactone → Canrenone

Question 52

Potassium Sparing Diuretics MOA

Answer 52

Inhibits Na/H2O resorption in DCT/CT Antifibrotic properties