Drugs for Ischemic Heart Dz

Question 1

Classic angina

Answer 1

(angina of effort, stable angina) occlusion of coronary arteries resulting from the formation of atherosclerotic plaques

Question 2

variant angina

Answer 2

(prinzmental) episodes of vasoconstriction of coronary arteries

Question 3

Two approaches to treat angina pectoris

Answer 3

1) decrease cardiac work to reduce O2 demand

2) increase blood flow through coronary arteries to increase O2 supply

Question 4

Coronary steal phenomenon

Answer 4

vasodilators are not useful in stable/classic angina because of redistribution of blood to non-ischemic areas

Question 5

Determinants of myocardial O2 demand

Answer 5

• heart rate
• contractility
• preload
• afterload

Question 6

mechanism of vasodilator drugs

Answer 6

NTG –> Endothelial cells –> NO –> NO + guanylyl cyclase –> cGMP –> protein kinase G

protein kinase G –> open K+ channel to release K+ –> hyperpolarization and reduced Ca2+ entry

Protein kinase G –> dephosphorylation myosin LC –> smooth muscle relaxation

Question 7

nitrovasodilators

Answer 7

nitroglycerin
isosorbide dinitrate
isosorbide mononitrate

Question 8

What is needed to release NO from nitrates?

Answer 8

thiol compounds

Question 9

Sensitivity of vasculature to nitrate-induced vasodilation

Answer 9

Veins > large arteries > small arteries and arterioles

Question 10

nitrates interaction with platelets

Answer 10

inhibit platelet aggregation

Question 11

Nitrate MOA in angina

Answer 11

decreased myocardial O2 demand; reduce ventricular preload

Question 12

How does tolerance develop with nitrates?

Answer 12

• depletion of thiol compounds
• increased generation of superoxide radicals
• reflex activation SNS
• retention of Na+ and H2O

Question 13

Why are sublingual, buccal, and transdermal routes of administration used for NTG administration as opposed to oral?

Answer 13

Bioavailability of nitrate via oral administration is low. Liver has high nitrate reductase activity. Routes that avoid first-pass metabolism are used.

Question 14

What are short acting (10-90 minutes) formulas of nitrovasodilators?

Answer 14

NTG and isosorbide dinitrate sublinguals and sprays

Question 15

Adverse effects of nitrates

Answer 15

HA, orthostatic hypotension, increased sympathetic contractility (tachycardia, increased contractility), increased renal Na+ and H20 resorption

Question 16

Important nitrate drug interaction

Answer 16

PDE-5 inhibitors, drugs used for erectile dysfunction

Question 17

Non-cardioactive calcium channel blockers used in angina

Answer 17

• amlodipine
• nifedipine
• nicardipine

Question 18

cardioactive calcium channel blockers used in angina

Answer 18

• diltiazem

- verapamil

Question 19

MOA cardioactive CCBs

Answer 19

decrease signaling and conduction of SA node and AV node

Question 20

MOA noncardioactive CCBs

Answer 20

vasodilation

Question 21

How do CCBs operate in atherosclerotic angina?

Answer 21

decreased myocardial O2 demand through dilation of peripheral arterioles and decreased cardiac contractility/heart rate

Question 22

How do CCBs operate in variant/prinzmental angina?

Answer 22

dilation of coronary arteries relieves local spasm

Question 23

What vessels are more affected with CCBs?

Answer 23

arterioles > veins

Question 24

Adverse effect of nifedipine (non-cardioactive CCB)

Answer 24

increase risk of MI in patients with HTN

Question 25

adverse effects of cardioactive CCBs

Answer 25

cardiac depression, cardiac arrest, acute heart failure, bradyarrhythmias, AV block

Question 26

Minor side effects CCBS

Answer 26

flushing, HA, anorexia, dizziness, peripheral edema, constipation

Question 27

How are beta blockers useful in treatment of angina?

Answer 27

decreased myocardial O2 demand due to decreased HR and decreased contractility

Question 28

Adverse effects of beta blockers

Answer 28

reduced cardiac output, bronchoconstriction, impaired liver glucose metabolism, sedation, depression

Question 29

contraindications of beta blockers

Answer 29

asthma, PVD, T1DM on insulin, bradyarrhythmias, severe depression of cardiac function

Question 30

Rationale for using beta-blockers, CCBs, and nitrates in combination therapy of angina pectoris

Answer 30

nitrates with beta-blockers OR cardioactive CCBs can treat angina pectoris while avoiding undesirable side effects (increased HR, increased preload, increased contractility, increased ejection time)