Alpha blockers class

classification of alpha blockers, general effects of blockers ,and its pharmacological actions, drugs with therapeutic uses and its side effects

1. ALPHA-ADRENERGIC BLOCKERS

2. Classification Non Selective α 1 & α 2 (a) Reversible: Eg . Phentolamine , Tolazoline (b) Irreversible: Eg . Phenoxybenzamine II. Selective blocker (a) α 1 Blocker : Eg . Prazosin , Terazosin , Doxazosin , Alfuzosin , Bunazosin,Tamsulosin & Silodosin (b) α 2 Blocker : Eg . Yohimbine , Idazoxan III. Others : Ergot Alkaloids

3. General effects of α blockers Blood vessels α 1 -blockade→reduces peripheral resistance Fall in BP Postural hypotension α 2 -blockade in brain ↑ se vasomotor tone. Block pressor action of adrenaline, fall in BP due to β 2 . action- “ vasomotor reversal of Dale” Actions of selective α-agonists supressed .

4. Heart Reflex tachycardia due to:- fall in mean arterial pressure Blockade of presynaptic α 2 receptors- ↑ NA release. Nose: nasal stuffiness Eye: miosis GIT: intestinal motility ↑ se Kidney: Hypotension ↓ se GFR NA + & H 2 O reabsorption

5. Urinary bladder α 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 α receptors. Blockade results in impotence.

6. Irreversible non-selective α - blockers Phenoxybenzamine Cyclizes spontaneously to highly reactive ethyleniminium intermediate. Binds covalently to α -receptors- irreversible or non-equilibrium 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 compartment-relaxation 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 2 o shock, PVD.

8. Reversible non-selective α -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 α -blocker than tolazoline . Other actions are less marked. Duration of action is shorter (min). Equally blocks α 1 & α 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 α 1 - blockers Prazosin Highly selective α 1 -blocker , α 1 : α 2 selectivity 1000:1 Fall in BP with only mild tachycardia. Dilates arterioles more than veins Postural hypotension occurs as 1 st 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 ( α 1 acid glycoprotein).

11. Metabolized in liver, 1 o excreted in bile. t 1/2 – 2-3hrs, effect lasts for 6-8hrs. Uses Primarily as antihypertensive. LVF not controlled by diuretics & digitalis. Raynaud’s disease BPH Scorpion sting

12. Terazosin & Doxazosin Long acting( t 1/2 12 & 18hr) congener of prazosin . Used in HTN & BPH as single daily dose. Tamsulosin & Silodosin Uroselective α 1 A blocker α 1 A –bladder base, prostrate. α 1 B - blood vessels. Don't cause significant changes in BP & HR. t 1/2 - 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 α 1 blockers similar to prazosin . Alfuzosin t 1/2 4hrs (2.5mgTDS or 10mg SR OD). CI in hepatic impairment, metabolized in liver. Bunazosin slightly longer t 1/2 . Primarily used in BPH.

14. α 2 -receptor blockers Yohimbine Natural alkaloid from Pausinystalia yohimbe . No established clinical role . Idazoxan Has membrane stabilizing action. Ergot alkaloids Ergotamine & Dihydroergotamine Competitive α -receptor blockers. Principal use is migraine.

15. Uses of α -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. R x Phenoxybenzamine Definitive therapy for inoperable or malig.tumors . Preoperative- orally x 2wks, i.v during surgery as-

16. Normalizes blood volume & body H 2 O distribution. During surgery excess release of CAs in to blood. Phentolamine drip can also be used. Hypertension Selective α 1 blocker prazosin is preferred. 2 o shock Fluid loss leads to vasoconstriction. Should not be given without fluid replacement.

17. Peripheral vascular disease Little benefit in Buerger’s 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 + & H 2 O retension . Migraine Ergotamine more effective

18. Benign prostrate hypertrophy Two classes of drugs are available. α 1 -blockers- ↓ tone of prostrate and bladder neck. 5-α reductase inhibitors: finasteride & dutasteride . arrest growth/reduce size of prostrate. α 1 -blockers gives faster and greater symptomatic releif than finasteride . Effect of α 1 -blockers decline after several years of use, must be combined with fiasteride . Terazosin , doxazosin , tamsulosin are preferred.

19. Side effects of α-blockers Palpitation Postural hypotension Nasal blockade Diarrhea Fluid retention Inhibition of ejaculation & impotence.

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