and adrenoceptor blockers and Diuretics

Learning objectives: 1. Regulation of blood pressure by autonomic nervous system and renin-angoitensin mechanism 2. Different classes of drugs for hypertension 3. Classification of and adrenoceptor blockers 4. Diuretics used for the treatment of hypertension

Autonomic and hormonal control of cardiovascular function The prime determinents of arterial blood pressure are cardiac output ( heart rate and stroke volume) and systemic vascular resistance

Hypertension
Definition Aetiology - primary secondary causes Risk factors -age, gender, dietary habit, obesity, stress, physical inactivity, tobacco and alcohol, genetics Complications- MI,stroke,CRF Management - avoid the risk factors antihypertensives

Different classes of antihypertensives

1. Diuretics thiazides 2. adrenoceptor blockers phentolamine, phenoxybenzamine, prazosin 3. adrenoceptor blockers propranalol, atenolol 4. Calcium channel blockers nifedipine, diltiazem 5. Angiotensin converting enzyme inhibitors captopril 6 . Angiotensin receptor blockers losartan, 7. Direct vasodilators hydralazine

Alpha adrenoceptor blockers Mechanism of action Reversible or irreversible binding of the drug molecules with 1 ( vascular smooth muscle) and 2 ( presynaptic adrenergic nerve terminal) receptors lower peripheral resistance &

BP

Phenoxybenzamine irreversible binding with receptor both 1 and 2 receptor blocker

Phentolamine reversible binding with receptor both 1 and 2 receptor blocker

Prazosin selective 1 receptorblocker relaxation of both arterial and venous smooth muscle General side effects of receptorblockers postural hypotension ( orthostatic hypotension ) reflex tachycardia

Therapeutic uses

Phentolamine is used in Pheochromocytoma Hypertensive emergency

Prazocin is used in Mild to moderate hypertension

Beta adrenoeceptor blockers

1 receptors - at postsynaptic cardiac muscle cells

2 receptors - at postsynaptic bronchial smooth muscle cells

Mechanism of action of blockers blockade of both 1 and 2 receptors (non cardioselective) ( or ) 1 receptor only (cardioselective) results in; decreased heart rate decreased force of myocardial contraction bronchospasm

Propranolol
The first blocker used to treat hypertension and IHD Nonselective blocker with no ISA Therapeutic uses- hypertension angina (IHD) Adversed effects- AV block masked hypoglycemia in diabetics bronchospasm rebound hypertension Contraindicated in bronchial asthma ,COPD heart block peripheral vascular disease

Atenolol 1 selective blocker or cardioselective Therapeutic uses hypertension ischemic heart disease safer to use in diabetics , asthmatics and peripheral vascular disease risk of rebound hypertension

Diuretics Thiazide diuretics Hydrochlorothiazide

MOA inhibits NaCl transport in distal convoluted tubule(DCT) of the kidney Therapeutic uses mild to moderate hypertension Adverse effects compete with the secretion of uric acid elevation of serum uric acid (hyperuricemia) hypeglycemia hyperlipidaemia allergic reaction because thiazides are sulfonamides