Angina Tx Flashcards
nitrate
release NO -> GC ->increase cGMP -> relax vascular sm. muscle -> venodilation and coronary vasodilation
CO and pulmonary vascular resistance reduced
HR and BP same
AE: hypotension, tachycardia (may worsen angina), dizzy, syncope, headache (tolerance develops), loss of efficacy with continuous exposure (nitrate free interval at night)
CI: sildenifil (PDE5 inhibitors)
How does venodilation reduce angina?
decrease preload: reduce wall stress and MvO2
subendocardial blood flow increased
How does coronary vasodilation reduce angina?
prevents/reverses coronary vasospasm
redistribution of blood flow to area of ischemia; selective dilation of epicardial and collateral coronary vessels
sublingual tablet nitrate
fast onset, short duration
small dose
buccal nitrate
aerosol: fast onset, short duration
small dose
tablet: med. duration
isosorbide dinitrate
oral nitrate
med. onset and duration
Nitro-SR capsule
oral nitrate
med. onset, 8-12 hours
isosorbide mononitrate
oral nitrate
med. onset, 8-12 hours
use eccentric dosing
transderm nitro
patch: MUST remove at night
med. onset, duration: 24 hrs
small dose
AE: rash
nitrol 2% ointment
med. onset and duration
IV nitrate
immediate onset
titrate dose up to maintain effect
do NOT suddenly interrupt in unstable angina: can get coronary vasospasm (overlap with other forms)
How does nitrate tolerance occur?
volume expansion, neurohumoral activation, depletion of cysteine stores needed to release NO
Dihydropyridine
voltage-dependent binding: selective vasodilators: reduce after load
AE: GI, edema, coronary steal (decreased with slow release), increase HR, contractility and O2 demand
CI: hypotension, advanced CHF
ONLY use with B-blocker
Use in angina when patients (with B-block) with valvular insufficiency, bradycardia, SA/AV block
Non-dihydropyridine
Use-dependent binding: equipotent for cardiac tissue and vasculature
use: a. fib, PSVT, prevent/reverse VASOSPASM
AE: bradycardia, systole, AV block
CI: B-blocker, CHF
cross placenta/breast milk
Use in angina when patients have asthma, COPD, severe PVD, DM
verapamil
non-dihydropyridine
metabolized by and inhibits CYP3A4
diltiazem
non-dihydropyridine
metabolized by and inhibits CYP3A4
nifedipine
dihydropyridine
amlodipine
dihydropyridine
felodipine
dihydropyridine
long T1/2
nicardipine
dihydropyridine
isradipine
dihydropyridine
long T1/2
Ca effects on
- cardiac muscle
- sm. muscle (arterial)
- intracellular Ca binds troponin C removing tropomyosin: actin-myosin can contract
- bind calmodulin to activate MLCK which phosphorylates myosin triggering contraction
Ca channel blockers
inhibit L-type Ca channel
other Ca channels (neural N and P-type) insensitive
extensive first pass metabolism
short T1/2: now have slow release formulas
USE: exertional and vasospastic angina
add on to B-blockers or for patients unable to tolerate B-blockers
concerns: HTN: higher rates of MI and CHF, inhibit apoptosis (cancer)
ranazoline
metabolic modulator: MOA unknown
partial FA oxidase inhibitor (increase glucose oxidation and efficiency of O2 utilization)
use: chronic stable angina in combo with amlodapine, B-block, nitrate
NOT for acute angina
expensive
AE: dizzy, headache, constipation, nausea, increased BUN/creatine, syncope, asthenia
CI: CYP3A4 inhibitors, prolonged QT, class IA or III, tricyclic antidepressants, increase digoxin concentrations (inhibit p-gp), hepatic or renal impairment
no improvement for mortality
