ADRENERGIC ANTAGONITS SAMUEL AGUAZIM ( MD)

Organization of Class The effect of the SNS can be blocked either by decreasing sympathetic outflow from the brain, suppressing release of NE from terminals or by blocking postsynaptic receptors. Adrenergic antagonists reduce the effectiveness of sympathetic nerve stimulation and effects of exogenously applied agonists, such as Isoproterenol.

What are adrenergic antagonists They are drugs that bind to adrenergic receptors but do not initiate the usual intracellular response They are divided into 2 main subdivisions 1. alpha blockers 2. beta blockers In this chapter we will discuss alpha 2 agonist because it reduce sympathetic nerve activity and are used to treat hypertension

ADRENERGIC BLOCKERS ALPHA BLOCKERS Alpha 1 Blockers Nonselective Alpha Doxazosin Phenoxybenzamine Prazosin Phentolamine Terazosin Most alpha antagonists allow vasodilatation and thus, decrease blood pressure( remember a-receptor activation results in vasoconstriction)

DRUGS AFFECTING NEUROTRANSMITTER UPTAKE OR RELEASE Cocaine Guanethidine Reserpine

Phenoxybenzamine Blocks alpha 1 and 2, irreversible blockade MOSTLY Noncompetitive inhibitor Actions - prevents Vaso-Constriction, induces a reflex tachycardia Epinephrine reversal Therapeutic uses : Opposing catecholamines --pheochromocytoma Causes vasodilation Benign prostatic hypertrophy Spinal cord injuries

SE: Postural hypotension Sexual dysfunction ( inhibit ejaculation) Tachycardia Contraindicated in ↓ coronary perfusion.

Phentolamine Alpha 1 and 2 blocker Competitive inhibitor Duration of action less Uses & SE – mostly same as Phenoxybenzamine.

Alpha 1 specific blockers Prazosin Terazosin Doxazosin – long acting Blockade of alpha 1 adrenergic receptors on vascular smooth muscle inhibits constriction of arterioles and veins. This results in decreased peripheral vascular resistance and lower blood pressure. Blockade in bladder ( relaxation and decreased resistance to urine flow)

Actions ----- Dose ---- Uses ----- Side effects ---- CVS Avoid high doses HTN and prevention of urinary retention in patients who have benign prostatic hypertrophy Orthostatic hypotension Nasal stuffiness Fatigue Sexual dysfunction (less)

Non Selective Beta 1 selective Blockers Blockers BETA BLOCKERS Non Selective Beta 1 selective Blockers Blockers Propranolol Metoprolol Timolol Atenolol Nadolol Esmolol Acebutolol Betaxolol Labetalol - Both Alpha and Beta Blocker Beta 1receptors found in the heart and their activation leads to an increase in HR and contractility . Beta 2 receptor are found in SM of the respiratory tract, the uterus and blood vessels. Their activation leads to relaxation of SM

Non selective beta antagonists Propranolol Timolol Nadolol

Propranolol CVS – HR ↓ , CO ↓ PERIPHERAL VESSELS – NO ALPHA ACTION BRONCHI - ↑ CONTRACTION SODIUM LEVELS - ↑ GLYCOGENOLYSIS -↓ GLUCAGON - ↓ BLOCKS DRUGS – Isoproterenol , & β actions of epinephrine

USES HTN ---- decreases CO ANGINA---decreases oxygen demand MI---- protects myocardium GLAUCOMA-- Timolol MIGRAINE HYPERTHYROIDISM– blunts sympathetic stimulation

SIDE EFFECTS BRONCHOCONSTRICTION CONTRAINDICATION –ASTHMA, COPD ARRHYTHMIAS – gradual reduction in dose SEXUAL IMPAIREMENT

NON SELECTIVE BETA ANTAGONISTS TIMOLOL NADOLOL → very long duration of action Considered more potent than propranolol. Same effects and SE as propranolol.

SELECTIVE BETA 1 ANTAGONISTS (Cardioselective) ATENOLOL METOPROLOL ESMOLOL USES – HTN,ANGINA CAN BE USED IN COPD, Diabetics CASES

ANTAGONISTS AND PARTIAL AGONISTS PINDOLOL ACEBUTOLOL They very mildly stimulate both beta 1 and beta 2 adrenergic receptors. USES : HTN with moderate bradycardia

ALPHA AND BETA BLOCKER LABETALOL( non-selective) Peripheral vasodilation -- ↓ B.P No vasoconstrictive effect USES : OLD AGE HTN, congestive heart failure SE: Orthostatic hypotension and dizziness.

NT AFFECTING DRUGS RESERPINE It blocks Norepinephrine transport from CYTOPLASM TO STORAGE VESICLE USES -- ↓B.P. ↓ H.R

NT AFFECTING DRUGS GUANETHIDINE –BLOCKS RELEASE OF stored NE IN VESICLE TO MEMBRANE USES—gradual lowering of B.P and H.R. in hypertensives SE: orthostatic hypotension and sexual dysfunction

NT AFFECTING DRUGS COCAINE Block Na-K ATPase REUPTAKE DECREASED (NE) USES ----local anesthetic???

General use of beta blockers Angina, hypertension, post MI ( ALL DRUGS) ANTIARRTHYMICS( CLASS 2 PROPRANOL,ACETABUTOLOL,ESMOLOL,) GLAUCOMA: TIMOLOL MIGRAINE, THYROTOXICOSIS, PERFORMANCE ANXIETY, ESSENTIAL TREMOL: PROPRANOLOL

COMBINED ALPHA 1 AND BETA BLOCKING ACTIVITY LABETALOL AND CARVEDILOR: USED IN CONGESTIVE HEART FAILURE POTASSIUM CHANNEL BLOACKADE AND BETA BLOCKING ACTIVITIY SOTALOL: USED IN ANTIARRTHYMIC (CLASS 3)