Cardiovascular Drugs PDF

CARDIOVASCULAR DRUGS Presenter: Kimberley McKenzie ([email protected]) Cardiovascular Drugs Propranolol Nitroglycerin Digitalis Aspirin Heparin Warfarin Beta Blockers PROPRANOLOL Inhibits contraction of the HEART β1 PROPRANOLOL + ATP AC cAMP ↑Ca2+ influx in cell ↑heart rate & force...

CARDIOVASCULAR DRUGS Presenter: Kimberley McKenzie ([email protected]) Cardiovascular Drugs Propranolol Nitroglycerin Digitalis Aspirin Heparin Warfarin Beta Blockers PROPRANOLOL Inhibits contraction of the HEART β1 PROPRANOLOL + ATP AC cAMP ↑Ca2+ influx in cell ↑heart rate & force of contraction Propranolol Non selective β-antagonist Used for angina, hypertension, arrhythmias, glaucoma Adverse effects: bronchi-constriction, cardiac failure, fatigue and depression Route of administration: oral Half life= 4 hours, high first pass metabolism Vasodilator NITROGLYCERIN Dilates blood vessels (arteriolar & venous dilation) Nitroglycerin Smooth muscle relaxation Blood vessels dilation ↓ blood pressure ↓ work of the heart Nitric oxide Inhibition of smooth muscle contraction Increased blood flow ↓anginal symptoms ↑ blood supply to myocardium Nitroglycerin Prodrug: converted by mitochondrial aldehyde dehydrogenase (MtALDH) to give nitric oxide (NO) ROA: intravenous, sublingual Absorbed rapidly, often used in emergency situatations Peak conc. Time: approx. 4.4 mins. Plasma protein binding: appro. 60% Half-life: 2.8± 0.9 mins. (IV), 6 mins. (sublingual) Adverse effects: hypotension, vertigo, flushed skin, diaphoresis, fever, syncope, dyspnea, bradycardia Clinical uses: hypertensive emergency, angina (chest pain), acute heart failure with MI Cardiac Glycosides/ Digitalis DIGOXIN Increase force at which the heart muscles contract Digitalis Extracted from the foxglove plant (Digitalis spp.) Main drug in this class is digoxin (others: digitoxin, quabain) Digoxin acts mainly on the heart and is used in the treatment of congestive cardiac failure (CCF). CCF: failure of the heart to provide sufficient cardiac output to meet the physiological needs of the body Digitalis CCF: pumping action of ventricles is impaired resulting in back pressure of blood, with congestion of the lungs and liver, and swelling of legs In CCF- digoxin: ↑ force of contraction of the heart Digitalis MOA Binds to Na+/K+ ATPase pump and inhibits it ↑intracellular Na+ concentrations →increased intracellular Ca2+ concentrations Increased intracellular calcium concentration → increased release from the sarcoplasmic reticulum, which ↑ the FOC Digitalis Digoxin given orally or IV Half life=36- 40 hrs Interactions: quinidine, amiodarone, verapamil, NSAIDs, calcium channel blockers Adverse effects: arrhythmia (tachycardia, atrioventricular block) hypokalemia*, abdominal discomfort, nausea and vomiting Excreted via kidneys Antiplatelets ASPIRIN Prevents clotting of blood ASPIRIN MOA Irreversible inhibition of cyclooxygenase (COX) enzyme – specific interest – COX 1 ❖ in platelets prevents formation of thromboxane A2 (TX A2) – synthesized in platelets ❖platelet activation & aggregation prevented ❖Platelets do not synthesize new proteins ❖Therefore activity on platelet is permanent requiring new platelet formation – 7-10 days ASPIRIN Oral: 160- 320 mg /d Onset: 30-60 mins Chewable aspirin for quicker onset effect on PGI2 is spared at lower doses. Duration: 7-9 days ADR: GIT irritation Uses: prophylaxis intervention for ischemic stroke, MI ASPIRIN USED AT LOW DOSE WHY? Inhibition of PGI2 formation in endothelium at higher concentrations (prevent platelet aggregation) Anticoagulants HEPARIN & Low Molecular Weight HEPARIN (LMWH) Prevent clotting of blood HEPARINS MOA Inactivate clotting factors: II (thrombin), IXa, Xa, XIa and XIIa Inhibit coagulation cascade (end product fibrin) Prevent clotting of blood Heparins Given: IV, subcutaneous Monitored using the activated partial thromboplastin time (aPTT) Low therapeutic index (TI) Safe in pregnancy ADRs: osteoporosis >6 months, hyperkalemia, hypersentivity rxns, heparin induced thrombocytopenia Antidote: protamine sulphate (acid/base rxn) Metabolism: heparinase enzymes Uses: deep vein thrombosis, atrial fibrillation, valvular disease Heparin-induced Thrombocytopenia (HIT) Sequela Incidence Thrombosis 30-50% Amputations 20% Death 30% Anticoagulants WARFARIN Inhibits blood clot formation WARFARIN vitamin K antagonist Structurally related to vitamin K Prevent the synthesis of clotting factors II, VII, IX & X (2,7,9,10) Inhibit coagulation cascade Prevent fibrin formation Prevent blood clot formation WARFARIN Given orally Slow onset = 48 hrs Peak anticoagulant effect 72-96 hours duration 4-5 days PPB= 99% t½ 25 - 60hrs Crosses placenta- teratogenic Metabolised by CYP450 2C9 WARFARIN ADRs: diarrhoea, bleeding (reversed with vitamin K), warfarin induced skin necrosis Low TI Monitored using: prothrombin time (PT), international normalized ratio (INR) Drug/drug interactions: inhibition/ induction of CYP enzymes, decreased absorption of vitamin K, displacement of drug from plasma proteins Uses: atrial fibrillation, deep vein thrombosis, valvular disease WARFARIN INDUCED SKIN NECROSIS A rare , serious ADR Seen 3-6 days after initiation  Ratio in males: females = 1:4  Most likely in postmenopausal women obese women  Treated with heparin