Drugs for Chronic Ischemic Heart Disease Flashcards
adverse effects of CCBs
- cardiac depression, cardiac arrest, acute heart failure
- bradyarrhythmias
- AV block
- flushing, HA, anorexia, dizziness, peripheral edema, constipation
duration of amlodipine
long acting, half life is 30-50hr
if calcium channel blockers are contraindicated due to low BP, bradycardia, or AV block, what drugs should be used
long-acting nitrates
adverse effects of nitrates
- HA
- orthostatic HTN
- tachycardia
- increased contractility
- increased renal Na+ and H2O reabsorption
duration of nicardipine
short acting, half life is 2-4hr
in what type of angina is it useful to use vasodilators
prinzmtal (vasospastic)
why do nitrates cause headaches
due to meningeal vasodilation
why do you not prescribe nitrates to patients on ED drugs
causes severe increase in cGMP and dramatic drop in BP
- acute MIs have been reported
adverse effects of short acting dihydropyridine CCBs
vasodilation triggers reflex sympathetic activation
what nitrate has the highest bioavailability via oral root
isosorbide mononitrate
list the 4 types of tolerance to nitrates
- depletion of thiol compounds
- increased superoxide radicals
- reflex activation of sympathetics (HR)
- retention of Na and H2O
how do CCBs decrease myocardial O2 demand in atherosclerotic (classic) angina
- dilation of peripheral arterioles
- decreased cardiac contractility and heart rate
what are the biggest undesirable effects when using beta blockers or CCBs alone and not in combination therapy
- increase in end-diastolic volume
- increased ejection time
effect of superoxide radicals on NO
superoxide radicals depletes tissues of NO
what are the cardioactive and non-cardioactive (dihydropyidine) CCBs used in angina
cardioactive: diltiazem and verapamil
non-cardioactive: amlodipine, nifedipine, nicardipine
2 main effects of calcium channel blockers on angina
- decrease myocardial O2 demand (atherosclerotic angina)
2. increase blood supply (variant angina)
compare dihydropyridine and cardioactive calcium channel blockers
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
what are the biggest undesirable effects when using nitrates alone and not in combination therapy
- baroreceptor reflexive increase in HR
- baroreceptor reflexive increase in contractility
why do you not give nitrates via oral administration
significant first pass mechanism (high nitrate reductase activity in liver)
what are the routes and duration of short acting nitroglycerin
- sublingual and spray
- 10-30 min
what are the routes and duration of long acting isosorbide mononitrate
- oral (6-10hr)
List the three nitrates mentioned in this lecture
Nitroglycerin
Isosorbide dinitrate
Isosorbide mononitrate
significance of the dilation of veins by nitrates
- increased venous capacitance
- reduced ventricular preload
adverse effects of immediate release nifedipine
increases risk of MI in pts with HTN
MOA of nitrates in angina
nirates –ADH2–> release NO –> dilates veins > large arteries > small arteries
how do beta blockers decrease myocardial oxygen demand
- decrease HR –> improved perfusion and reduced O2 demand at rest and during exercise
- decrease contractility
- decrease BP –> decreased afterload
what are the routes and duration of short acting isosorbide dinitrate
- sublingual (30-60min)
- spray (90 min)
what is the effect of combining nitrates with beta blockers or calcium channel blockers
less/no undesirable effects
duration of nifedipine
short acting, half life is 4hr
main effect of beta blockers on angina
decrease myocardial oxygen demand
what is the first choice drug for variant angina
calcium channel blockers
what are the routes and duration of long acting isosorbide dinitrate
- oral (4-6hr)
how do CCBs increase blood supply in variant angina
dilation of coronary arteries relieves local spasm
what are the routes and duration of long acting nitroglycerin
- oral (4-8hr)
- ointment (3-6hr)
- patch (8-12hr)
significance of the dilation of arteries by nitrates
- may reduce afterload
- may dilate large epicardial coronary arteries
describe how nitrates cause smooth muscle relaxation
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
