Selective alpha-2 antagonist?
Correct Answer: Yohimbine
Description: Ans. B. Yohimbine. (Ref. KDT 6th/p 132, 135).# It is a relatively selective a2, blocker with short action.KDT 6th/pg. 135........Yohimbine:# An alkaloid from West African plant Yohimbehe.# It is a relatively selective CL blocker with short duration of action.# Also blocks 5-HT receptors.# HR and BP are generally elevated due to increased central sympathetic outflow and peripheral NA release.# Other CNS effects include excitation, tremor, ADH release (antidiuresis), nausea and vomiting.# It may cause congestion of genitals and has been claimed to be an aphrodisiac.# This effect is only psychological, but can overcome psychogenic impotence in some patients. There is no valid indication for clinical use of yohimbine.Difference between a and b receptors; ab1.Rank order of potency of agonistsAdr NA > IsoIso > Adr > NA2.AntagonistPhenoxybenzaminePropranolol3.Effector pathwayIP3 / DAG| , cAMP|, K+ channel |cAMP| ,Ca2+ channel|Difference between a1 and a2 recptors: a1a2LocationPostjunctional on effector organsPrejunctional on nerve ending (a2A), also postjunctional in brain, pancreatic b cells, platelets and extrajunctional in certain blood vessels.Function subservedSmooth muscle - contractionVasoconstrictionGland - secretionGut - relaxationHeart - arrhythmiaInhibition of transmitter releaseVasoconstrictionDecreased central sympathetic flowDecreased insulin releasePlatelet aggregationSelective agonistPhenylephrine, MethoxamineClonidineSelective antagonistPrazosinYohimbine, RauwolscineEffector pathwayIP3/DAG|Phospholipase A2|cAMP |K+ channel |Ca2+ channel |-or |IP3/DAGta ADRENERGIC BLOCKING AGENTSThese drugs inhibit adrenergic responses mediated through the a adrenergic receptors without affecting those mediated through b receptors.CLASSIFICATIONI. Nonequilibrium type(i) b-Haloalkylamines-Phenoxybenzdnmne.II. Equilibrium type (competitive)A. Nonselectivei) Ergot alkaloids - Ergotamine, Ergotoxineii) Hydrogenated ergot alkaloids - Dihydroergotaminec (OHE), Dihydroergotoxineiii) Imidazolines - Tolazoline, Phentolamineiv) Miscellaneous - Chlorpromazine, KetanserinB. a1 selective - Prazosin, Terazosin, Ooxazosin, Tamsulosin0C. a2 selective - Yohimbine0A) Natural and hydrogenated ergot alkaloids :# Ergot alkaloids are the adrenergic antagonists with which Dale demonstrated the vasomotor reversal phenomenon.# The aminoacid alkaloids ergotamine and ergotoxine are partial agonists and antagonists at a adrenergic, serotonergic and dopaminergic receptors.# The amine alkaloid ergometrine has no a blocking activity.# The a blockade produced by clinical doses of ergot alkaloids is low grade and short lasting; they are hardly ever employed for this purpose.# The principal use is in migraine.# Diagnostic use of ergotamine has been made to precipitate ECG signs of ischaemia in coronary artery disease.0# Dihydroergotoxine has been used as a cognition enhancer.B) Tolazoline :# Its a blocking action is only modest and short lasting.# In addition, it is a direct vasodilator and stimulates the heart.0# It also blocks 5-HT receptors, has histamine like gastric secretagogue and ACh like motor action on intestines.# Side effects are frequent and include nausea, vomiting, cramps, diarrhoea, nervousness, chills, tachycardia, and exacerbation of myocardial ischaemia and peptic ulcer.# It has occasionally been used in peripheral vascular diseases and pulmonary hypertension of the newborn.C) Phentolamine :# It is a close congener of tolazoline, more potent in blocking a receptors, but other actions are less marked.# Generally, fall in BP occurs on i.v. injection. The duration of action is shorter (in minutes).# It equally blocks a, and oc, receptors - Na release is increased.# It has been used as a quick and short acting a blocker for diagnosis and intraoperative management of pheochro- mocytoma and for control of hypertension due to clonidine withdrawal, cheese reaction, etc.# It is the most suitable a blocker for local infiltration to counteract vasoconstriction due to extravasated NA/DA during their i.v. infusion.D) Prazosin:# It is first of the highly selective a, blockers having a,: a2 selectivity ratio 1000:1.# It blocks sympathetically mediated vasoconstriction and produces fall in BP which is attended by only mild tachycardia; NA release is not increased due to absence of a2 blockade.# Prazosin dilates arterioles more than veins. Postural hypotension occurs, especially in the beginning - dizziness and fainting as 'first dose effect'. This can be minimized by starting with a low dose and taking it at bedtime.# Subsequently tolerance develops to this side effect.# It also inhibits phosphodiesterase, which degrades cAMP. Rise in smooth muscle cAMP could contribute to its vasodilator action.# Prazosin is effective orally (bioavailability -60%), highly bound to plasma proteins (mainly to a, acid glycoprotein),metabolized in liver and excreted primarily in bile. Its plasma t1/2 is 2-3 hours; effect of a single dose tests 6-8 hours.# It's uses:- As an antihypertensive (primarily)- LVF not controlled by diuretics and digitalis,- Raynaud's disease and- Prostatic hypertrophy - blocks af receptors in bladder trigone and prostate and thus improves urine flow, reduces residual urine in bladder.E) Terazosin# It is chemically and pharmacologically similar to prazosin; differences are- higher bioavailability (90%) and- longer plasma t1/2 (-12 hr); a single daily dose lowers BP over 24 hrs.# Though terazosin equally blocks a1A, a1B and a1D subtypes (like prazosin), it is more popular for BHP due to single daily dose.F) Doxazosin# Another long acting (t1/2 18 hr) congener of prazosin with similar pharmacological profile, used in hypertension and BHP.G) Tamsulosin# Uroselective aIA blocker (a1A: a1B affinity 7-38 fold) has been found as effective as terazosin in improving BHP symptoms.# Because a1A subtype predominates in the bladder base and prostate, while a1B receptors are dominant in blood vessels, tamsulosin does not cause significant changes in BP or HR at doses, which relieve urinary symptoms.# No increase in adverse cardiovascular events, including postural hypotension has been noted.# Dizziness and retrograde ejaculation are the only significant side effects.# Its plasma t'/2 is 6-9 hrs, but the modified release (MR) cap needs only once daily dosing.H) Timazosin is a less potent congener of prazosin. Alfuzosin is a a1 blocker used primarily in BHP, but is subtype nonspecific.I) Indoramine and Urapidil are selective a, blockers chemically distinct from prazosin; are being used as antihypertensive in some countries.J) Chlorpromazine and some other neuroleptics have additional a adrenergic blocking activity - cause fall in BP, nasal stuffiness and inhibition of ejaculation as side effect. The antihypertensive activity of 5-HT2 blocker Ketanserin is partly due to its a adrenergic blocking action.
Category:
Pharmacology
Get More
Subject Mock Tests
Practice with over 200,000 questions from various medical subjects and improve your knowledge.
Attempt a mock test nowMock Exam
Take an exam with 100 random questions selected from all subjects to test your knowledge.
Coming SoonGet More
Subject Mock Tests
Try practicing mock tests with over 200,000 questions from various medical subjects.
Attempt a mock test now