Antianginal drugs- vasodilators Flashcards
Determinants of oxygen supply to myocardium
regional flow distribution, oxygen extraction. Coronary blood flow
determinants of oxygen demand from myocardium
HR, cardiac contractility, myocardial wall tension
What factors affect coronary blood flow
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.
What is variant angina
no plaques, but intense vasospasm
Primary prevention of angina
reduce risk factors (HTN, diabetes, smoking, dyslipidemia, post-menopausal), aspirin, statins
Goal of therapy in Angina (overall)
Improve coronary blood flow w/ bypass surgery, coronary angioplasty, or vasodilators. Reduce myocardial oxygen requirement with vasodilators or negative inotropic/chronotropic agents.
goal of therapy in stable angina
Chronic therapy aims at reducing oxygen demand with nitrates, Ca channel blockers and Beta blockers. Prevention with antithrombotics (aspirin) and statins
Goal of therapy in variant angina
reverse/prevent vasospasm and increase supply with vasodilators (nitrates and Ca channel blockers)
Goal of therapy in unstable angina
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
List examples of nitrates
Nitroglycerin, Isosorbide mononitrate, isosorbide dinitrate
Nitrates MOA
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)
Nitrates pharmacokinetics
Low oral bioavailability. Administered orally, sublingually, transdermally, parenterally. Best is sublingual which has very fast onset, but only lasts 30 minutes
Nitrate uses
Acute angina (sublingual), chronic angina prophylaxis (oral, topical), control of BP in perioperative HTN
Nitrates adverse rxns
Headache, orthostatic HTN, tachycardia, tolerance
Ca channel blockers MOA
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
Ca channel blockers with higher selectivity for vasculature
Dihydropyridines have greater vascular effects. Verapamil and diltiazem have prominent effects at cardiac nodal tissue
Ca channel blockers pharmacokinetics
Short acting Dihydropyridines may rapidly lower blood pressure and use should be avoided. Variable bioavailability.
Ca channel blockers uses
Angina (decreases peripheral vascular resistance which decreases heart O2 requirement and coronary arterial tone), arrhythmias, HTN, subarachnoid hemorrhage, inhibition of premature labor
Ca channel blockers adverse rxns
cardiac depression, gingival hyperplasia
Ranolazine MOA
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
Ranolazine uses
Added to standard anti-anginal therapy to reduce symptoms of chornic stable angina
Ranolazine adverse rxns
prolongs QT interval
Beta blockers MOA
Decreased HR, BP and contractility decreases O2 requireents. NOT a vasodilator
Beta blockers uses
Angina with HTN or arrhythmias
