Antianginal Drugs Flashcards
Organic nitrites and nitrates
Amyl nitrite
Nitroglycerin
Isosorbide dinitrate
Isosorbide mononitrate
Organic nitrites and nitrates - MoA
Act by releasing nitric oxide in vascular smooth muscle cells. Nitric oxide activates guanylyl cyclase forming cGMP, cGMP activates cGMP dependent kinases that appear to cause relaxation of vascular smooth muscle by phosphorylating proteins that decrease intracellular calcium mobilization and decrease myosin light chain-phosphatase. They relax venous smooth muscle, with small effect on arteriolar. This leads to venous pooling of blood, a decrease in venous blood return to the heart and a decrease in ventricular volume, pressure, and wall tension. The nitrites reduce cardiac preload and output, which leads to reduction in BP
Organic nitrites and nitrates - Adverse effects
Hypotension Reflex tachycardia (to prevent this, can give B-blocker) Headache Dizziness Euphoria Increased libido
Methemoglobinemia (Only nitrites, not nitrates)
Pharmacodynamics tolerance to their vasodilate effects (transdermal patches should be removed for at least 10h every day, while drugs should be adm no more than two times per day)
Organic nitrites and nitrates - Interactions
Phosphodiesterase-V inhibitors (sildenafil)- potentiate the hypotensive effect
Amyl nitrite - Clincal use
Treatment of acute angina attacks
Initial management of cyanide poisoning (given iv, thiosulfate is also given to convert cyanide to inactive thiocyanate)
Nitroglycerin - Clinical use
Prevent and treat angina attacks
Reduce preload and afterload in pat who have acute heart failure associated with MI or other(iv)
Isosorbide dinitrate and Isosorbide mononitrate - Clinical use
Prevent and treat angina attacks
Calcium Channel Blockers
Amlodipine Felodipine Isradipine Nicardipine Nifedipine Nimodipine Diltiazem Verapamil
Calcium Channel Blockers - MoA
By blocking calcium ion channels in the plasma membranes of smooth muscle, the CCBs relax vascular smooth muscle and causes vasodilation. They have greater effect on arteriolar smooth muscle then venous, effect on BP is mainly because a reduction in PVR.
Calcium Channel Blockers - Adverse effects
Fatigue Headache Dizziness Flushing Peripheral edema Gingival hyperplasia (not diltiazem and verapamil) Constipation
Amlodipine, Felodipine and Nicardipine - Clinical use
Hypertension
Treatment of angina pectoris
Isradipine - Clinical use
Hypertension
Nimodipine - MoA
Dilates small cerebral vessels and increases collateral circulation to the affected areas of the brain.
It also reduces neuronal damage caused by the excessive release of calcium that is evoked by cerebral ischemia
Nimodipine - Clinical use
Reducing neurologic complications of Subarachnoid hemorrhage
Nimodipine - Contraindications
IV administration causes severe hypotension, cardiac arrest and fatalities
Diltiazem and Verapamil - MoA
Decrease SA node automaticity, cardiac contractility and AV node conduction velocity to a greater degree then other CCBs
Diltiazem and Verapamil - Clinical use
Cardiac arrhythmias
Management of angina pectoris
Typical and variant angina
Diltiazem and Verapamil - Contraindications
Patients with heart failure because it suppress cardiac contractility
Diltiazem and Verapamil - Adverse effects
Reduce peristalsis
Diltiazem and Verapamil - Interactions
Reduce the clearance of digoxin and can thereby increase serum digoxin levels and precipitate digoxin toxicity.
Beta blockers
Atenolol
Metoprolol
Nadolol
Propanolol
Beta blockers - MoA
Prevent ischemic episodes due to their ability to prevent exercise induced tachycardia and increased myocardial oxygen demand. They also can prevent reflex tachycardia induced by either organ nitirates or dihydropyridine CCBs
Beta blockers - Clinical use
Typical angina pectoris
Acute MI
Beta blockers - Interactions
Avoid verapamil, due to reduction in cardiac output.
Heart rate-lowering drug
Ivabradine
Ivabradine - MoA
Reduces heart rate by blocking the If current (funny current) in the SA node, which is mixed Na+-K+ inward current activated by hyperpolarization, modulated by the autonomic nervous system, and responsible for diastolic depolarization and cardiac impulse initiation
Ivabradine - Clinical use
Chronic angina
Heart failure
Ivabradine - Adverse effects
Headache Visual disturbances Bradycardia Atrial fibrillation AV block
Drugs that modify myocardial metabolism
Ranolazine
Trimetazidine
Ranolazine - MoA
Block the pathologic activation or prolongation of the late inward sodium current (INa-L) in myocardial cells. This abnormal current leads to increased sodium-calcium exchange, intracellular calcium accumulation, and increased left ventricular wall tension. By blocking INa-L, ranolazine decreases diastolic wall tension, improves diastolic subendocardial perfusion, and reduces oxygen consumption. It has no effect on heart rate or blood pressure
Ranolazine - Clinical use
First line - Chronic stable angina
Ranolazine - Adverse effects
Dizziness
Headache
Nausea
constipation
Ranolazine - Contraindications
Contraindication: Persons with QT prolongation and in those taking QT-prolonging drugs or this with hepatic impairment (because the drug is metabolized in the liver)
Trimetazidine - MoA
Inhibits ketoacyl coenzyme A thiolase, a key enzyme in B-oxidation pathway of fatty acid metabolism. The resulting decrease in fatty acid oxidation evokes a compensatory increase in glucose metabolism and reduces oxygen consumption by about 20%.
Trimetazidine - Clinical use
Angina, decreases number of episodes
Increase ejection fraction in persons with left ventricular dysfunction
Nifedipine - Contraindication
Coronary heart disease because of increased risk of mortality
