1. 1. By Dr.Elza Emmannual ALPHA ADRENERGIC BLOCKERS
2. 2. CLASSIFICATION
3. 3. REVERSIBLE NONSELECTIVE ALPHA BLOCKERS PHENTOLAMINE AND TOLAZOLINE Competitive Antagonist CARDIOVASCULAR EFFECTS Alpha 1 receptor blockade at the periphery VASODILATATION DECREASED PERIPHERAL RESISTANCE HYPOTENSION
4. 4. HYPOTENSION BARORECEPTOR REFLEX SYMPATHETIC DISCHARGE STIMULATION OF BETA 1 RECEPTORS OF HEART TACHYCARDIA ,PALPITATION
5. 5. EPISODES OF POSTURAL HYPOTENSION Due to absence of efficient peripheral vasoconstriction in erect posture due to alpha 1 blockade peripheral pooling of blood cerebral hypoxia,vertigo,fainting DALES VASOMOTOR REVERSAL PHENOMENON - Prior treatment with alpha1 blocker prevents pressor response of epinephrine ,hence the unopposed vasodilating beta 2 effect is observed.
6. 6. OTHER EFFECTS Nasal stuffiness vasodilatation & congestion of nasal mucosa Miosis Due to loss of tone of radial muscles of iris Improved urine flow rates-due to smooth muscle relaxation of bladder neck & prostate Failure of ejaculation & impotence-due to inhibition of contraction of vas deferens & ejaculatory ducts. Nausea,vomiting,diarrhoea
7. 7. THERAPEUTIC USES Administered as IV For diagnosis & management of PHEOCHROMOCYTOMA - If after giving 5mg of phentolamine,BP falls by 25-35mm of Hg,it is a potential case of pheochromocytoma & if it is less it is a case of essential hypertension. PVD- Raynauds syndrome & frostbite To prevent dermal necrosis can be used locally(S.C.)to prevent dermal necrosis after incidental extravasation of NE from IV infusion. To treat HYPERTENSIVE CRISIS that follows abrupt withdrawal of clonidine or those resulting from interaction of ingested tyramine containing food with MAO inhibitors.
8. 8. IRREVERSIBLE NONSELECTIVE ALPHA BLOCKERS PHENOXYBENZAMINE Binds covalently to alpha 1 & alpha 2 receptors causing irreversible blockade for longer duration Also inhibit reuptake of release noradrenaline by adrenergic nerve terminals Preferred drug for pheochromocytoma Marked postural hypotension with initial first few doses first dose phenomenon,tolerance develops later. Other toxic effects- reversible inhibition of ejaculation,salt & water retention,cardiac arrhythmias,sedation,fatigue & nausea.
9. 9. USES Treatment of pheochromocytoma- controls episodes of severe hypertension during surgical manipulation.- 1mg/kg as i.v infusion. PVD-Raynauds phenomenon & frostbite.
10. 10. REVERSIBLE SELECTIVE ALPHA 1 BLOCKERS PRAZOSIN Less tachycardia as it lacks alpha 2 receptor blocking actions,decreases cardiac preload,it suppresses sympathetic outflow from CNS. Potent inhibitor of cyclic phosphodiesterase enzyme causing rise in cAMP Causes rise in HDL & adecrease in LDL & TGL Relaxes smooth muscle in bladder neck,prostatic capsule &prostatic urethra & improves urine flow in BPH.
11. 11. THERAPEUTIC USES Well absorbed orally. Treatment of hypertension- initial dose -1mg at bedtime Treatment of BPH- 1-5mg orally BD Treatment of Raynauds disease.
12. 12. TERAZOSIN & DOXAZOSIN Long duration of action Terazosin 2-5mg orally OD Doxazoin 1 4 mg OD More effective than fenasteride due to faster action to decerease urine flow. Combination is better as it decreases prostate volume.
13. 13. BUNAZOSIN & ALFUZOSIN Both are orally effective Alfuzosin 2.5mg TID,has to be avoided in patients with hepatic impairment. Bunazosin- longer t1/2 TAMSULOSIN & SILODOSIN UROSELECTIVE Selective alpha 1A receptor antagonist which are primarily located on bladder neck & urethra. More effective for treatment of BPH. Better bioavailability than prazosin Side effect abnormal ejaculation & intra operative floppy iris syndrome.
14. 14. INDORAMINE & URAPADIL No clinical use
15. 15. ALPHA 2 BLOCKERS YOHIMBINE & IDAZOXAN Yohimbine natural alkaloid from Pausinystalia yohimbe. No established clinical role. Although efficacy not clearly established ,can be used to treat male sexual dysfunction , diabetic neuropathy & postural hypotension. Drug can abruptly reverse antihypertensive effect of alpha 2 agonist like clonidine which is an important drug interaction.
16. 16. MISCELLANEOUS ERGOT ALKALOID Ergotamine & dihydroergotamine Competitive alpha receptor blocking activity Also act as partial agonist at alpha receptors and at 5HT2 receptors. Some of these are oxytocics or dopamine receptor agonists
17. 17. THANKYOU