Antianginal drugs- vasodilators

Question 1

Determinants of oxygen supply to myocardium

Answer 1

regional flow distribution, oxygen extraction. Coronary blood flow

Question 2

determinants of oxygen demand from myocardium

Answer 2

HR, cardiac contractility, myocardial wall tension

Question 3

What factors affect coronary blood flow

Answer 3

Perfusion pressure/aortic pressure: blood flows only during diastole and it is decreased by an increased end diastolic pressure. Coronary vascular resistance: coronary blood flow decreases with increased vascular resistance.

Question 4

What is variant angina

Answer 4

no plaques, but intense vasospasm

Question 5

Primary prevention of angina

Answer 5

reduce risk factors (HTN, diabetes, smoking, dyslipidemia, post-menopausal), aspirin, statins

Question 6

Goal of therapy in Angina (overall)

Answer 6

Improve coronary blood flow w/ bypass surgery, coronary angioplasty, or vasodilators. Reduce myocardial oxygen requirement with vasodilators or negative inotropic/chronotropic agents.

Question 7

goal of therapy in stable angina

Answer 7

Chronic therapy aims at reducing oxygen demand with nitrates, Ca channel blockers and Beta blockers. Prevention with antithrombotics (aspirin) and statins

Question 8

Goal of therapy in variant angina

Answer 8

reverse/prevent vasospasm and increase supply with vasodilators (nitrates and Ca channel blockers)

Question 9

Goal of therapy in unstable angina

Answer 9

acutely: Aspirin, heparin, GPIIb/IIIa inhibitors, nitrates, PTCA/CABG, fibrinolytics, anti-arrhythmic (beta blockers) and pain treatment (morphine). Post MI: ACEI, statins, BB, aspirin, clopidogrel

Question 10

List examples of nitrates

Answer 10

Nitroglycerin, Isosorbide mononitrate, isosorbide dinitrate

Question 11

Nitrates MOA

Answer 11

Nitrates are converted to nitric oxide (NO) at or near the plasma membrane of vascular smooth muscle cells. NO then activates guanylate cyclase, increasing the conversion of GTP to cGMP → increased levels of cGMP then lead to relaxation of smooth muscle. Decreases myocardial oxygen requirement (primary) and improves perfusion of ischemic myocardium (secondary)

Question 12

Nitrates pharmacokinetics

Answer 12

Low oral bioavailability. Administered orally, sublingually, transdermally, parenterally. Best is sublingual which has very fast onset, but only lasts 30 minutes

Question 13

Nitrate uses

Answer 13

Acute angina (sublingual), chronic angina prophylaxis (oral, topical), control of BP in perioperative HTN

Question 14

Nitrates adverse rxns

Answer 14

Headache, orthostatic HTN, tachycardia, tolerance

Question 15

Ca channel blockers MOA

Answer 15

Block of L-type Ca++ channels in cardiac and smooth muscle (vascular smooth muscle is most sensitive, arterioles > veins).Leads to smooth muscle relaxation and vasodilation

Question 16

Ca channel blockers with higher selectivity for vasculature

Answer 16

Dihydropyridines have greater vascular effects. Verapamil and diltiazem have prominent effects at cardiac nodal tissue

Question 17

Ca channel blockers pharmacokinetics

Answer 17

Short acting Dihydropyridines may rapidly lower blood pressure and use should be avoided. Variable bioavailability.

Question 18

Ca channel blockers uses

Answer 18

Angina (decreases peripheral vascular resistance which decreases heart O2 requirement and coronary arterial tone), arrhythmias, HTN, subarachnoid hemorrhage, inhibition of premature labor

Question 19

Ca channel blockers adverse rxns

Answer 19

cardiac depression, gingival hyperplasia

Question 20

Ranolazine MOA

Answer 20

Inhibits late Na current, preventing intracellular Na overload which is seen in ischemia and hypertrophy. Intracellular Na overload can lead to reversal of Na/Ca exchanger, and intracellular Ca overload causing mechanical dysfunction and imbalance btw O2 demand and sypply

Question 21

Ranolazine uses

Answer 21

Added to standard anti-anginal therapy to reduce symptoms of chornic stable angina

Question 22

Ranolazine adverse rxns

Answer 22

prolongs QT interval

Question 23

Beta blockers MOA

Answer 23

Decreased HR, BP and contractility decreases O2 requireents. NOT a vasodilator

Question 24

Beta blockers uses

Answer 24

Angina with HTN or arrhythmias