Adrenergic antagonist sympatholytic

1. Adrenergic antagonistsympatholytic By: DR.ISRAA OMAR

2. Adrenergic antagonist • These group of drug bind to adrenoceptors but do not trigger the usual receptor-mediated response • They can be selective or non-selective so they can be classified according to their affinity to the receptors • These drugs are either reversibly or irreversibly attached to the receptors, thus preventing the action of endogenous catecholamine

3. α blocking agents • Phenoxybenzamine: irreversibly block both α1 and2 because it make covalent bond with receptors • It causes hypotension by blocking α1 receptors in the blood vessels but blocking α2 may cause more release of NE from the presynaptic neuron which will act on unblocked β receptors in the heart leading to tachycardia so this drug is non suitable for treatment of hypertension

4. Continue • It is used as pre-surgical treatment of pheochromocytoma to reduce the effect of catecholamine released during manipulation of tissues ,it is also used of treatment of this condition if the tumor is inoperable and metastasized • It was used for treatment of peripheral vascular disease but this use is now largely obsolete • Adverse effect include nasal stuffiness , postural hypotension and reflex bradycardia mediated by baroreceptors . thus, it is contraindicated in patient with coronary vessels disease

5. α-blocking drugs • Phenatolamine :competitively reversibly block both α1 and 2 so their action last only 4 hours after single administration • It is used for treatment of pheochromocytoma • It was used in the past to treat impotence by injecting the drug intracavernosally to produce vasodilation of penile arteries

6. α-blocking drugs • Prazosin, terazosin, doxazosin and tamsulosin they selectively block α1 receptors . • They are useful in treatment of hypertension not like non selective blockers • Tamsulosin in particular is important in treatment of BPH because it reduces the tone of muscle at the bladder neck and facilitate bladder emptying, this drug has minimal effect on blood pressure compared to other drugs of this group because it selectively block Α1a in the bladder smooth muscle .

7. Continue…. • These drugs can cause first dose hypotension thus need adjustment of the first dose and should be given at bed time • If given as monotherapy for treatment of hypertension the risk of congestive heart failure is increased . • Side effect include hypotension and male sexual dysfunction +inhibition of ejaculation and retrograde ejaculation because it causes relaxation of the ejaculatory duct

8. α -blocking drugs • Yohimbine : is selective competitive α2 receptor antagonist. • It is naturally occurring alkaloids extracted from Yohimbine tree . • It is CNS and CVS stimulant drug . • It was used historically as sexual stimulant.

9. α-blocking drugs • Labetalol and carvedilol block both α andβ receptors :they causes vasodilation and reduction in the HR and contractility. • It is effective in treatment of hypertension in black and elderly patients. • Labetalol is effective in treatment of hypertension with pregnancy PIH. • Intravenous labetalol is used for treatment of hypertensive emergencies • S.E. include orthostatic hypotension and dizziness

10. β-blocking agents • They are divided in to two major groups non-selective beta antagonist which block both types of beta receptors and selective beta antagonist which block either b1 or b2.

11. Non -selective beta antagonist • Propranolol ,alprenolol, timolol and nadolol. • They are used to reduce blood pressure in hypertensive patients by reducing cardiac out-put , inhibition of renin release and reduce sympathetic flow from the CNS • They are also used in treatment of angina, arrhythmias, anxiety, glaucoma (particularly topically applied ones like timolol reduce the secretion of aqueous humor),migraine and hyperthyroidism .

12. Non -selective beta antagonist • Adverse effects include bronchoconstriction ,arrhythmias, sexual impairment ,disturbance of metabolism especially glucose (can cause sever hypoglycemia after administration of insulin because it inhibit glucagon release) and cold extremities because they block the peripheral vasodilation caused by beta 2 adrenoceptors .

13. selective beta antagonist • Acebutolol, atenolol, metoprolol and esmolol: • They particularly useful in treatment of hypertension in patient with pulmonary disease , patients with peripheral vascular disease and hypertension in diabetic patients

14. Antagonist with partial agonist action • Pindolol and acebutolol :they bound to beta 1 and 2 and cause partial stimulation of it but not the full effect and they inhibit the binding of more potent catecholamine . Thus these drugs are named blockers with ISA( intrinsic sympathomimetic action) . • It used for treatment of hypertension in patients with moderate bradycardia, because a further decrease in the heart rate is less pronounced with these drugs

15. β2-selective antagonist • Butoxamine :beta 2 antagonist with weak alpha agonist action . • No clinical use for this drug .

16. Drugs affecting NA release • Reserpine : depletes the stores of NE by inhibiting it is uptake to the vesicles ,it was used historically to treat hypertension ,it is action is very slow and once started it persists for many days after discontinuation of treatment . • Guanthethidine: inhibit the release of NE and also deplete it and can cause irreversible damage to NA neurons ,this drug cause transient hypertension at the beginning of treatment then hypotension, it is use for treatment of hypertension is obsolete.

17. references • Lippincottos pharmacology • Rang and Dales pharmacology

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