SYMPATHOLYTICS slide preparation 12.pptx

presentation on sympatholytics

1. SYMPATHOLYTICS (ALPHA BLOCKERS AND BETA BLOCKERS)

2. CONTENTS INTRODUCTION ALPHA BLOCKERS CLASSIFICATION USES BETA BLOCKERS CLASSIFICATION USES

3. INTRODUCTION Alpha & Beta adrenergic receptor antagonists prevent the interaction of the endogenous neurotransmitter norepinephrine (N.E) or sympathomimetics (endogenous or synthetic catecholamines, synthetic noncatecholamines ) with the corresponding adrenergic receptor.

4. Alpha Blockers Bind selectively to alpha receptors Interfere with ability of catecholamines or other sympathomimetics to provoke alpha responses on the heart & peripheral vasculature Side effects: orthostatic hypotension, baroreceptor-mediated reflex tachycardia, impotence

5. CLASSIFICATION OF ALPHA BLOCKERS

6. ACTIONS: α 1-blockade inhibits vasoconstriction -vasodilation and reducesBP . α 2-blockade enhances the release of NA which stimulates β receptors Thus, the predominant effects of non selective α -blockade is hypotension with tachycardia. Selective α 1-blockade results in hypotension without significant tachycardia. This is because α 2 receptors are not blocked which means there is no increase in NA release. Selective α 2-blockade: Increases NA release resulting in hypertension.

7. PHENOXYBENAMINE Phenoxybenzamine binds covalently to α -receptors causing irreversible blockade or non-equilibrium type of blockade . It is used in the treatment of pheochromocytoma. ADVERSE EFFECTS : postural hypotension, palpitation, nasal stuffiness, inhibition of ejaculation and depression, hence started with a low dose and gradually increased

8. ERGOT ALKALOIDS: Ergotamine, ergotoxine and their derivatives are competitive antagonists and the blockade is of short duration. Ergotoxine is a more potent a blocker and less potent vasoconstrictor than ergotamine. USES: The principal use is in migraine . Used to control postpartum bleeding .

9. PHENTALOAMINE Mechanism of Action Non-selective alpha blockade(alpha-1 and alpha-2) Inhibits response to Serotonin(5HT) Peripheral vasodilation (alpha-1 block) & decreased BP within 2 min (lasts 10-15 min) elicit baroreceptor- mediated cardiac stimulation reflex↑. ADVERSE EFFECTS They include tachycardia,palpitation , arrhythmias; angina and MI may be precipitated.

10. SELECTIVE ALPHA 1-BLOCKERS PRAZOSIN: Prazosin is a potent, highly selective, α 1 blocker with 1000 times greater affinity for α 1 receptors. Arterioles and venules are dilated resulting in decreased peripheral vascular resistance and cardiac output. First dose phenomenon —one hour after the initial dose, marked postural hypotension occurs which may lead to fainting. To avoid this, prazosin should be started with a low dose (0.5 mg) and taken at bedtime. Other side effects include headache and dizziness.

11. Congeners of prazosin include terazosin, doxazosin, alfuzosin and tamsulosin. Others are indoramin and urapidil. Terazosin is highly selective for α -1 receptors, is more water soluble, has higher bioavailability (>90%) than prazosin. Longer acting and suitable for once-a-day administration. Another advantage-terazosin may induce apoptosis in the smooth muscle cells 1in the prostate. Hence, terazosin is indicated in BPH and in hypertension. Started with 1 mg once daily, the dose is gradually increased. Doxazosin is similar to terazosin but is longer acting. It also induces apoptosis of prostate cells like terazosin and is used in BPH and hypertension.

12. Tamsulosin is an α 1 blocker with higher activity on α 1A and α 1D receptors than α 1B subtype. α 1A is abundant in the bladder and prostate while α 1B in the blood vessels. Therefore, tamsulosin relieves the symptoms of BPH without a significant fall in BP (which is mediated by α 1B receptors). Hence, it is preferred in BPH. Tamsulosin has a high bioavailability and t½ of 9–15 hr but its duration of action is increased in the extended-release preparations Tamsulosin can cause abnormal ejaculation.

13. Selective alpha 2 blockers YOHIMBINE It is a relatively selective alpha-2 blocker with short duration of action.It blocks 5-HT receptors. Heart rate and BP are generally elevated due to increased central sympathetic outflow as well as peripheral NA release. Other CNS effects include excitation, tremor, ADH release (antidiuresis), nausea and vomiting. There are no valid indications for clinical use of yohimbine.

14. THERAPEUTIC USES OF ALPHA-BLOCKERS Pheochromocytoma Hypertensive emergencies Essential hypertension Benign prostatic hyperplasia Tissue necrosis Kidney stones Migraine

15. BETA RECEPTORS ACTIVATION OF BETA 1-RECEPTORS Heart: Cardiac stimulation. Kidney: Promote renin release. ACTIVATION OF BETA 2-RECEPTORS Liver: Stimulation of glycogenolysis. Skeletal muscle: Contraction. Lungs: Bronchodilation. Uterine relaxation (pregnant), bladder smooth muscles relaxation Uptake of K+ into cells. ACTIVATION OF BETA 3-RECEPTORS causes lipolysis

16. BETA BLOCKERS β-blockers are drugs that block the actions of catecholamines mediated through the β - receptors. Also called Beta adrenergic antagonists Beta blockers Beta receptor blockers Sympatholytic agents

17. CLASSIFICATION

18. Pharmacological actions CVS Heart : β blockers decrease heart rate, force of contraction and cardiac output. Blood pressure falls. β –blockers-improve exercise tolerance in angina patients. They prevent the exercise-induced increase in heart rate and force of contraction. Blood vessels — β -blockers reduce BP. On long-term use, β -blockers reduce peripheral vascular resistance in hypertensive patients. Respiratory tract : Blockade of β 2 receptors in the bronchial smooth muscle causes an increase in airway resistance may precipitate acute attack in asthmatics.

19. Eye : Many β -blockers reduce intraocular pressure by decreased secretion of aqueous humour . Metabolic: β -antagonists block lipolysis and glycogenolysis ( β 2 mediated) induced by sympathetic stimulation. Hence, nonselective β -blockers may interfere with recovery from hypoglycaemia in diabetics. Other effects: Many β -blockers in higher doses block sodium channels and have a local anesthetic effect—membrane- stabilizing effect. This is not used therapeutically because of the higher dose needed and the irritant property of propranolol

20. Adverse effects

21. First-generation β -blockers: Include non-selective β -blockers and propranolol is the prototype. Nadolol • Long acting β -blocker (t½ 20 hr OD dose. Used in hypertension, angina, oesophageal varices, migraine prophylaxis and in tremors. Timolol • Non-selective, short-acting. • Used in glaucoma as eye drops • Used orally in hypertension, angina and MI. Dose: Oral 10–40 mg 0.5% eye drops. TIMOPTAL, GLUCOMOL 0.25, 0.5% eye drops.

22. Pindolol, Oxprenolol and Penbutalol • Non-selective • Partial agonists at β 1 , β 2 receptors • Penbutolol in addition has weak intrinsic sympathomimetic activity. Advantages • Milder bradycardia • Milder myocardiac depression • Better tolerated in asthmatics • Milder effect on lipid profile • Less chances of rebound hypertension on withdrawal

23. Second-generation agents β -blockers ( cardioselective - β blockers) For example, atenolol, metoprolol, esmolol. Atenolol Selective β 1 –blocker • Longer acting—given once daily • Less lipid soluble—does not cross BBB, hence no CNS side effects • No side effects on lipid profile • Very commonly used in hypertension and angina where it is preferred to propranolol.

24. Third-generation β -blockers Include carteolol , carvedilol,labetalol,celiprolol and nebivolol. These are β -blockers with additional vasodilatory properties. Some of them, viz. celiprolol and nebivolol, selectively block β - 1 cardiac receptors Carteolol is a non-selective β -blocker with partial agonistic activity at the β 1 receptors and, therefore, may cause less bradycardia.Depression of AV conduction and membrane-stabilizing effects help. Carvedilol blocks β 1 , β 2 and α 1 receptors . It also has membrane-stabilizing and anti inflammatory properties.

25. Nebivolol • A highly selective β 1-blocker. • Also causes vasodilation through nitric oxide production. • No myocardial depression. • Reduce BP by reducing vascular resistance. Dose: 2.5–5 mg OD. NEBICARD, NEBISTAR 2.5, 5 mg tab. Labetalol blocks α 1, β 1 and β 2 receptors and is useful in pheochromocytoma and hypertension in the elderly. Butoxamine is a selective β 2-blocker but therapeutic applications are not known.

26. ALPHA AND BETA ADRENORECEPTOR ANTAGONIST Labetalol (beta 1 = beta 2 > alpha 1 > alpha 2) Carvidilol . Contraindications to β –blockers: • Bradycardia : β -blockers should be avoided in patients with bradycardia. • β -blockers are contraindicated in patients with heart block because they depress AV conduction. • They are to be avoided in patients with bronchial asthma and COPD . If needed, a cardioselective β -blocker may be used with caution

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