Alpha adrenergic blockers

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  • 1. Dr. K. R. Prabhakar, Resident.

2. CLASSIFICATION -Adrenoceptor Antagonists Non-selective block 1 & 2SelectiveMiscellaneous Ergot alkaloidsReversible Irreversible 1-blockers 2-blockers Phentolamine Phenoxyben- Prazosin Yohimbine zamine Terazosin Tolazoline Idazoxan Doxazosin (priscoline) Alfuzosin & Bunazosin Tamsulosin &Silodosin 3. General effects of blockers Blood vessels 1-blockadereduces peripheral resistance Fall in BP Postural hypotension 2-blockade in brain se vasomotor tone. Block pressor action of adrenaline, fall in BP due to2. action- vasomotor reversal of Dale Actions of selective -agonists supressed. 4. Heart Reflex tachycardia due to: fall in mean arterial pressure Blockade of presynaptic 2 receptors- NA release. Nose: nasal stuffiness Eye: miosis GIT: intestinal motility se Kidney: Hypotension se GFR NA+ & H2O reabsorption 5. Urinary bladder 1A blockade- se tone of smooth muscle in trigone, sphincter & prostrate. Improved urine flow, used in BPH.Reproductive system Contraction of vas deferens result in ejaculation through receptors. Blockade results in impotence. 6. Irreversible non-selective - blockers Phenoxybenzamine Cyclizes spontaneously to highly reactive ethyleniminium intermediate. Binds covalently to -receptors- irreversible or nonequilibrium competitive block. Blockade is slow onset & longer duration (3-4 days). Also inhibits reuptake of NE. Shifts blood from pulmonary to systemic circuit. Shift fluid from extravascular to vascular compartmentrelaxation of postcapillary vessels. 7. PK Preferred ROA- i.v. Lipid soluble penetrates brain. Mainly excreted through urine in 24 hrs. Accumulates in adipose tissue on ch. Administration.Dose 20-60 mg/d oral 1mg/kg/1hr slow i.v infusion. Uses Pheochromocytoma, occasionally 2oshock, PVD. 8. Reversible non-selective -blockers Tolazoline Block is modest & short lasting. Direct vasodilator & stimulates the heart. Also blocks 5-HT receptors, histamine like gastric secretagouge & Ach like motor action on intestine. SE N, V, cramps, diarrhoea, nervousness, chills Tachycardia, Exacerbation of MI, peptic ulcer. Use PVD Pulmonary HT of newborn. 9. Phentolamine More potent -blocker than tolazoline. Other actions are less marked. Duration of action is shorter (min). Equally blocks 1 & 2 receptors- NA release sed.Uses sis & intraop.management of pheochromocytoma. 5mg i.v- B.P falls by 25(D)or35(S)mmHg. HTN due to clonidine withdrawl, cheese reaction. Dermal necrosis due to extravasated i.v NA/DA. Given S.C as local infiltration. 10. Reversible, selective 1- blockers Prazosin Highly selective 1-blocker , 1: 2 selectivity 1000:1 Fall in BP with only mild tachycardia. Dilates arterioles more than veins Postural hypotension occurs as 1st dose effect, minimized by starting with low doses at bed time. Also inhibits PDE- se cAMP in smooth muscle. PK Effective orally, BA- 60%. Highly bound to plasma proteins (1 acid glycoprotein). 11. Metabolized in liver, 1o excreted in bile. t1/2 2-3hrs, effect lasts for 6-8hrs.Uses Primarily as antihypertensive. LVF not controlled by diuretics & digitalis. Raynauds disease BPH Scorpion sting 12. Terazosin &Doxazosin Long acting( t1/212 & 18hr) congener of prazosin. Used in HTN & BPH as single daily dose. Tamsulosin & Silodosin Uroselective 1A blocker 1A bladder base, prostrate. 1B- blood vessels. Don't cause significant changes in BP & HR. t1/2- 6-9hr, MR cap(0.2-0.4 mg) can be taken OD. Efficacious in Rx of BPH. SE: retrograde ejaculation, dizziness,, floppy iris syd. Silodosin weaker(4-8mg/d) but longer acting. 13. Bunazosin & Alfuzosin Orally effective 1 blockers similar to prazosin. Alfuzosin t1/2 4hrs (2.5mgTDS or 10mg SR OD). CI in hepatic impairment, metabolized in liver. Bunazosin slightly longer t1/2. Primarily used in BPH. 14. 2-receptor blockers Yohimbine Natural alkaloid from Pausinystalia yohimbe. No established clinical role. Idazoxan Has membrane stabilizing action. Ergot alkaloids Ergotamine & Dihydroergotamine Competitive -receptor blockers. Principal use is migraine. 15. Uses of -Blockers Pheochromocytoma Tumor of adrenal medullary cells-excess Cas. Cause intermittent or persistent hypertension. Diagnosed by- se urinary VMA, normetanephrine. phentolamine test can also be performed. Rx Phenoxybenzamine Definitive therapy for inoperable or malig.tumors. Preoperative- orally x 2wks, i.v during surgery as- 16. 1. Normalizes blood volume & body H2O distribution. 2. During surgery excess release of CAs in to blood. Phentolamine drip can also be used.Hypertension Selective 1 blocker prazosin is preferred. 2o shock Fluid loss leads to vasoconstriction. Should not be given without fluid replacement. 17. Peripheral vascular disease Little benefit in Buergers disease & int.claudication. More useful in Reynaud's disease & acrocyanosis where vasoconstriction is prominent. Prazosin or phenoxybenzamine are useful.CHF Short term benefit, leads to Na+ & H2O retension. Migraine Ergotamine more effective 18. Benign prostrate hypertrophy Two classes of drugs are available. 1. 1-blockers- tone of prostrate and bladder neck. 2. 5- reductase inhibitors: finasteride & dutasteride. arrest growth/reduce size of prostrate. 1-blockers gives faster and greater symptomatic releif than finasteride. Effect of 1-blockers decline after several years ofuse, must be combined with fiasteride. Terazosin, doxazosin, tamsulosin are preferred. 19. Side effects of -blockers Palpitation Postural hypotension Nasal blockade Diarrhea Fluid retention Inhibition of ejaculation & impotence. 20. Thank you