Angina Tx

Question 1

nitrate

Answer 1

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)

Question 2

How does venodilation reduce angina?

Answer 2

decrease preload: reduce wall stress and MvO2

subendocardial blood flow increased

Question 3

How does coronary vasodilation reduce angina?

Answer 3

prevents/reverses coronary vasospasm

redistribution of blood flow to area of ischemia; selective dilation of epicardial and collateral coronary vessels

Question 4

sublingual tablet nitrate

Answer 4

fast onset, short duration

small dose

Question 5

buccal nitrate

Answer 5

aerosol: fast onset, short duration
small dose
tablet: med. duration

Question 6

isosorbide dinitrate

Answer 6

oral nitrate

med. onset and duration

Question 7

Nitro-SR capsule

Answer 7

oral nitrate

med. onset, 8-12 hours

Question 8

isosorbide mononitrate

Answer 8

oral nitrate
med. onset, 8-12 hours
use eccentric dosing

Question 9

transderm nitro

Answer 9

patch: MUST remove at night
med. onset, duration: 24 hrs
small dose
AE: rash

Question 10

nitrol 2% ointment

Answer 10

med. onset and duration

Question 11

IV nitrate

Answer 11

immediate onset
titrate dose up to maintain effect
do NOT suddenly interrupt in unstable angina: can get coronary vasospasm (overlap with other forms)

Question 12

How does nitrate tolerance occur?

Answer 12

volume expansion, neurohumoral activation, depletion of cysteine stores needed to release NO

Question 13

Dihydropyridine

Answer 13

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

Question 14

Non-dihydropyridine

Answer 14

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

Question 15

verapamil

Answer 15

non-dihydropyridine

metabolized by and inhibits CYP3A4

Question 16

diltiazem

Answer 16

non-dihydropyridine

metabolized by and inhibits CYP3A4

Question 17

nifedipine

Answer 17

dihydropyridine

Question 18

amlodipine

Answer 18

dihydropyridine

Question 19

felodipine

Answer 19

dihydropyridine

long T1/2

Question 20

nicardipine

Answer 20

dihydropyridine

Question 21

isradipine

Answer 21

dihydropyridine

long T1/2

Question 22

Ca effects on

1. cardiac muscle
2. sm. muscle (arterial)

Answer 22

1. intracellular Ca binds troponin C removing tropomyosin: actin-myosin can contract
2. bind calmodulin to activate MLCK which phosphorylates myosin triggering contraction

Question 23

Ca channel blockers

Answer 23

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)

Question 24

ranazoline

Answer 24

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

Question 25

B-blockers

Answer 25

first choice in angina
reduce mortality (MI and CHD)
reduce after load, HR, inotropy
does NOT: prevent vasospasm or reduce preload
combine with nitrates: reduce LVEDP, LV volume, dilate coronary artery
CCB (dihydropyridine): prevent vasospasm, reduce vascular resistance
*block reflex tachycardia and inotropy of nitrates and CCB
Unstable: with nitrates, ASA, heparin
Exertional: reduce HR, contractility
MI

Question 26

prinzmetal’s angina

Answer 26

variant
vasospasm blocks flow
normal coronary angiograms, excellent prognosis

Question 27

unstable angina

Answer 27

atherosclerosis or thrombosis blocks flow
recurrent with minimal exertion, prolonged and frequent
HIGH correlation with myocardial infarction

Question 28

exertional angina

Answer 28

coronary circulation can meet oxygen demands on myocardium at rest, but now when heart work is increased by exercise due to atherosclerosis
usually due to fixed coronary vascular obstruction
Tx: surgical revascularization or angioplasty

Question 29

Ways to Tx angina

Answer 29

1. increase coronary flow
2. reduce MvO2 (decrease HR, contractility, work load (preload/afterload)
3. prevent platelet deposition and atherosclerosis (aspirin and statins)

Question 30

When does perfusion of the heart occur?

Answer 30

diastole

slow HR increases time spent in diastole for heart perfusion

Question 31

Preventing MI and CHD in patients with angina

Answer 31

1. B-blockers
2. aspirin
3. ACE I
4. revascularization (angioplasty, CABG, atherectomy)
5. thrombolytics
6. LDL reduction/HDL increase