DRUGS USED IN ANGIANA Beta blockers mechanism of

DRUGS USED IN ANGIANA

Beta blockers mechanism of action Selectively block the effects of adrenaline and noradrenaline on receptor Cardiovascular effects of blockade reduced automaticity ( heart rate/ chronotropy) reduced myocardial contractility ( inotropy)

Beta blockers Reduced HR causes reduction of cardiac output and cardiac O 2 consumption falls Effects are more on exertion than at rest

Classification of b blockers Selective Non selective

Non cardioselective Drugs Propanolol Sotolol Labetolol

Cardioselective Atenalol Esmolol Metaprolol

Pharmacokinetics of blockers First order kinetics apply to elimination from plasma (Eg: propranolol - plasma t 1/2 about 4 h but receptor block and action persists longer thus effective t 1/2 is much prolonged

Lipid soluble drugs are subject to extensive hepatic metabolism ( eg. propranolol - 80%) Water soluble drugs have more predictable plasma concentrations (eg. atenolol) lipid soluble drugs also enter the CNS and cause side effects

Clinical uses of b blockers: Angina pectoris hypertension Tachyarrhythmias - class II antiarrhythmic After MI - for secondary prevention of MI when started before discharge and given for at least 2 years reduces mortality and re-infarction

Clinical uses of b blockers: Cardiac failure: carvedilol, bisoprolol improve survival Portal hypertension anxiety, tremor Thyrotoxicosis glaucoma - as eye drops Phaechromocytoma Prophylaxis of migraine

Adverse effects of b blockers Bronchoconstriction - due to b 2 blocking precipitation of cardiac failure bradycardia and worsening of heart block hypotension - when given after acute MI aggravation of peripheral vascular disease

hypoglycaemia sympathetic mediated mechanisms of normalising blood sugar affected and masks symptoms of hypoglycaemia precipitation of angina - on abrupt withdrawal of therapy alteration of plasma lipids - HDL/LDL ratio reduced

Contra indications for beta blockers Bronchial asthma worsening heart failure Heart block peripheral vascular disease

Calcium channel blockers(CCB) Mechanism of action at cellular level Ca+ involved in initiation of smooth muscle and cardiac cell contraction When Ca+ enters cells through slow Ca+ channels, contractile proteins actin and myosin are activated and contracts vascular smooth muscle cells

Mechanism of action at cellular level Cardiac action also leads to negative inotropic action with some drugs depressing conducting system leads to negative chronotropic effect

Calcium channel blockers - mechanism of action at physiological level relaxation of vascular smooth muscle leads to vasodilatation reduced work load on heart and also dilates coronaries in vasospasm

Calcium channel blockers Cardiac action also leads to negative inotropic action with some drugs depressing conducting system leads to negative chronotropic effect

Different classes of CCB and individual CCB 1. Dihydropyridines eg. Nifedipine 2. Phenylakylamine eg. verapamil 3. Benzothiazepines eg. Diltazem

Indications for the use of CCB hypertension - verapamil, amlodipine, sustained release nifedipine (avoid short acting nifedipine) angina- diltiazem, amlodipine, verapamil cardiac arrhythmias - Class IV drug After SAH - to prevent rebleed nimodipine

Pharmacokinetics Well absorbed from GIT Most drugs undergo first pass metabolism in the liver and action terminated by hepatic metabolism the t 1/2 varies with individual drug and preparation eg long acting preparations

Adverse effects of CCB Headache, dizziness, hypotension in the first few hours after dosing ankle oedema - due to vasodilatation and does not signify fluid retention; thus no response to diuretics constipation - may be troublesome palpitations and lethargy

Other methods of treatment used in angina 1. Antiplatelet drugs by decreasing platelet aggregation these drugs inhibit thrombus formation in coronary arteries Low dose aspirin (75 -150 mg/day) proven to reduce mortality in secondary prevention after MI (by 25% in ISIS 2 trial) thus given to patients with IHD and angina clopidogrel - a new antiplatelet drus given in unstable angina

Other methods of treatment used in angina -ctd 2. anticoagulants - prevent clot formation Heparin - reduces mortality in unstable angina 3. Statins – prevent MI by reducing plaques

4. revascularisation -improves survival in some patients Surgery - CABG insertion of stents Angioplasty

Questions ?

THANK YOU