Drugs for Ischemic Heart Disease - Konorev

Question 1

2 ways to treat angina pectoris

Answer 1

• Decreased cardiac work (i.e. oxygen demand)

- Increase blood flow through coronary arteries

Question 2

When are vasodilators most useful in treating angina?

Answer 2

Prinzmetal (vasospastic) angina

Question 3

Coronary steal phenomenon

Answer 3

Why NOT to use vasodilators in atherosclerotic angina…

- Dilate un-blocked arterioles –> LESS collateral flow around block to blocked arterioles

Question 4

4 determinants of myocardial oxygen demand (to be altered in angina)

Answer 4

• HR
• Contractility
• Preload
• Afterload

Question 5

3 drug classes used in chronic ischemic heart disease

Answer 5

• Nitrates (vasodilate)
• CCBs (vasodilate, slow HR)
• Beta-blockers (slow HR)

Question 6

3 nitrovasodilator drugs

Answer 6

• Nitroglycerin
• Isosorbide dinitrate
• Isosorbide mononitrate

Question 7

Function of endothelium on vascular relaxation

Answer 7

• Nitric oxide release w/ ACh or bradykinin stimulation

Question 8

Describe N.O. release following stimulation of endothelium

Answer 8

Receptor –> calcium release –> calmodulin –> NOS active –> arginine converted to NO –> released onto SM

Question 9

Molecular pathway of N.O. on muscle cell

Answer 9

Activates guanylyl cyclase –> cGMP –> K+ channel opens and myosin LC dephosphorylation –> hyperpolarization and SM relaxation

Question 10

2 functions of nitrates at low concentration

Answer 10

Dilate VEINS and LARGE arteries, inhibit platelet aggregation

Question 11

Benefit of nitrates vs. other vasodilators in atherosclerotic angina

Answer 11

No coronary steal phenomenon since arterioles not affected

Question 12

MOA of nitrates in treating atherosclerotic angina

Answer 12

• Dilate veins –> reduced preload
• Dilate arteries –> reduced pressure
  EFFECT = DECREASED O2 DEMAND OF HEART

Question 13

MOA of nitrates in treating vasospastic angina

Answer 13

Coronary artery relaxation

Question 14

Most short acting formulation of nitrates

Used for?

Answer 14

Sublingual or spray nitroglycerin (10-30 min)

Relieving current attack

Question 15

Most long acting formulation of nitrates

Used for?

Answer 15

Oral nitroglycerin or isosorbide (4-10 hours)

Prevent future attacks

Question 16

3 ways to generate tolerance to nitrates

Answer 16

• Increased oxygen free radical formation (combines to make H2O2 + O2)
• Reflex sympathetics (tachy, vasoconstriction)
• Na/H2O retention

Question 17

Adverse effects of nitrates

Answer 17

• Headache (vasodilation)
• Hypotension (orthostatic)
• Sympathetic symptoms (tachy, HTN)

Question 18

Dangerous combination when treating elderly man with nitrates

Answer 18

Do NOT combine w/ E.D. drugs…

• Nitrates + alpha-1 inhibitors (-afil) = BP DROP
• Nitrates + alprostadil = cGMP increase –> BP DROP

Question 19

Non-cardioactive (DHP) CCBs

Answer 19

• Amlodipine
• Nifedipine
• Nicardipine

Question 20

Cardioactive (non-DHP) CCBs

Answer 20

• Diltiazem

- Verapamil

Question 21

Long-acting CCB

Answer 21

Amlodipine (30-50 hr half life)

Question 22

CCB MOA

Answer 22

Block L-type calcium flow into SM and cardiac muscle –> decreased myosin LC kinase activation –> decreased LC phosphorylation –> decreased contraction

Question 23

Non-DHP CCB MOAs in treating angina

Answer 23

• Dilate ARTERIOLES + decreased contractility/HR –> decreased O2 demand of myocardium
• Dilate coronary arteries –> vasospastic angina relief

Question 24

Immediate release CCB

Answer 24

Nifedipine

Question 25

4 beta blockers used for angina

Answer 25

- Propranolol - Nadolol - Metoprolol - Atenolol

Question 26

MOA of beta blockers in angina

Answer 26

Decreased oxygen demand via decreased HR, contractility, and afterload

Question 27

Bad side effects of nitrates (2) Correction?

Answer 27

Reflex tachycardia, reflex contractility increase Combine w/ beta-blocker or CCB

Question 28

Ranolazine - MOA

Answer 28

Inhibits late Na+ influx in cardiomyocytes

Question 29

Describe how Ranolazine works against ischemic myocardium

Answer 29

- Ischemic myocardium = enhanced late Na+ current = Ca++ overload = repolarization abnormalities - Ranolazine = normalizes repolarization, reducing dysfunction

Question 30

Benefits of Ranolazine

Answer 30

Doesn't affect HR, contractility, coronary flow, or peripheral hemodynamics

Question 31

When is Ranolazine used?

Answer 31

- Stable angina not controlled w/ normal meds | - Together w/ nitrates, amlodipine, or atenolol

Question 32

Adverse effects of Ranolazine

Answer 32

- QT prolongation --> ventricular arrhythmias - Constipation - Nausea, dizziness, headache

Question 33

Drugs that alter Ranolazine metabolism

Answer 33

CYP3A4 inhibitors: Antifungal azoles, verapamil

Question 34

Drugs who's metabolism is altered by Ranolazine

Answer 34

CYP2D6 substrates: Amitriptyline, Fluoxetine, Metoprolol, opioids

Question 35

Other drugs that prolong QT interval

Answer 35

Quinidine (anti-arrhythmic), Thioridazine (anti-psychotic)