Drugs for Chronic Ischemic Heart Disease

Question 1

adverse effects of CCBs

Answer 1

• cardiac depression, cardiac arrest, acute heart failure
• bradyarrhythmias
• AV block
• flushing, HA, anorexia, dizziness, peripheral edema, constipation

Question 2

duration of amlodipine

Answer 2

long acting, half life is 30-50hr

Question 3

if calcium channel blockers are contraindicated due to low BP, bradycardia, or AV block, what drugs should be used

Answer 3

long-acting nitrates

Question 4

adverse effects of nitrates

Answer 4

• HA
• orthostatic HTN
• tachycardia
• increased contractility
• increased renal Na+ and H2O reabsorption

Question 5

duration of nicardipine

Answer 5

short acting, half life is 2-4hr

Question 6

in what type of angina is it useful to use vasodilators

Answer 6

prinzmtal (vasospastic)

Question 7

why do nitrates cause headaches

Answer 7

due to meningeal vasodilation

Question 8

why do you not prescribe nitrates to patients on ED drugs

Answer 8

causes severe increase in cGMP and dramatic drop in BP

- acute MIs have been reported

Question 9

adverse effects of short acting dihydropyridine CCBs

Answer 9

vasodilation triggers reflex sympathetic activation

Question 10

what nitrate has the highest bioavailability via oral root

Answer 10

isosorbide mononitrate

Question 11

list the 4 types of tolerance to nitrates

Answer 11

1. depletion of thiol compounds
2. increased superoxide radicals
3. reflex activation of sympathetics (HR)
4. retention of Na and H2O

Question 12

how do CCBs decrease myocardial O2 demand in atherosclerotic (classic) angina

Answer 12

• dilation of peripheral arterioles

- decreased cardiac contractility and heart rate

Question 13

what are the biggest undesirable effects when using beta blockers or CCBs alone and not in combination therapy

Answer 13

• increase in end-diastolic volume

- increased ejection time

Question 14

effect of superoxide radicals on NO

Answer 14

superoxide radicals depletes tissues of NO

Question 15

what are the cardioactive and non-cardioactive (dihydropyidine) CCBs used in angina

Answer 15

cardioactive: diltiazem and verapamil

non-cardioactive: amlodipine, nifedipine, nicardipine

Question 16

2 main effects of calcium channel blockers on angina

Answer 16

1. decrease myocardial O2 demand (atherosclerotic angina)

2. increase blood supply (variant angina)

Question 17

compare dihydropyridine and cardioactive calcium channel blockers

Answer 17

dihydropyridines: greatest increase in vasodilation, lowest effect on contractility, automaticity, and conduction

cardioactive CCB: greatest effect on decreasing automaticity and conduction with big effects on decreasing cardiac contractility

Question 18

what are the biggest undesirable effects when using nitrates alone and not in combination therapy

Answer 18

• baroreceptor reflexive increase in HR

- baroreceptor reflexive increase in contractility

Question 19

why do you not give nitrates via oral administration

Answer 19

significant first pass mechanism (high nitrate reductase activity in liver)

Question 20

what are the routes and duration of short acting nitroglycerin

Answer 20

• sublingual and spray

- 10-30 min

Question 21

what are the routes and duration of long acting isosorbide mononitrate

Answer 21

• oral (6-10hr)

Question 22

List the three nitrates mentioned in this lecture

Answer 22

Nitroglycerin
Isosorbide dinitrate
Isosorbide mononitrate

Question 23

significance of the dilation of veins by nitrates

Answer 23

• increased venous capacitance

- reduced ventricular preload

Question 24

adverse effects of immediate release nifedipine

Answer 24

increases risk of MI in pts with HTN

Question 25

MOA of nitrates in angina

Answer 25

nirates –ADH2–> release NO –> dilates veins > large arteries > small arteries

Question 26

how do beta blockers decrease myocardial oxygen demand

Answer 26

• decrease HR –> improved perfusion and reduced O2 demand at rest and during exercise
• decrease contractility
• decrease BP –> decreased afterload

Question 27

what are the routes and duration of short acting isosorbide dinitrate

Answer 27

• sublingual (30-60min)

- spray (90 min)

Question 28

what is the effect of combining nitrates with beta blockers or calcium channel blockers

Answer 28

less/no undesirable effects

Question 29

duration of nifedipine

Answer 29

short acting, half life is 4hr

Question 30

main effect of beta blockers on angina

Answer 30

decrease myocardial oxygen demand

Question 31

what is the first choice drug for variant angina

Answer 31

calcium channel blockers

Question 32

what are the routes and duration of long acting isosorbide dinitrate

Answer 32

• oral (4-6hr)

Question 33

how do CCBs increase blood supply in variant angina

Answer 33

dilation of coronary arteries relieves local spasm

Question 34

what are the routes and duration of long acting nitroglycerin

Answer 34

• oral (4-8hr)
• ointment (3-6hr)
• patch (8-12hr)

Question 35

significance of the dilation of arteries by nitrates

Answer 35

• may reduce afterload

- may dilate large epicardial coronary arteries

Question 36

describe how nitrates cause smooth muscle relaxation

Answer 36

organic nitrates activate NO –> activates guanylyl cylase to convert GTP to cGMP –> activates protein kinase G to:

open potassium channels –> hyperpolarization and reduced calcium entry

and

activate myosin-LC dephosphorylation –> activates smooth muscle relaxation