Dobutamine acts on which of the following receptors?
Ans. B. Alpha/Beta. (Ref. KDT 6th/pg. 126, 129; 507)# Dobutamine is not a D1 or D2 receptor agonist. It acts on both a and b adrenergic receptors, but as such considered to be a relatively selective b1 agonist.Difference between b1: ,b2 andb3 recptors; b1b2b31.LocationHeart, JG cells in kidneyBronchi, blood vessels, uterus, g.i.t., urinary tract, eyeAdipose tissue2.Selective agonistDobutamineSalbutamol, terbutalinBRL 373443.Selective antagonistMetoprolol, AtenololICI 118551a-methyl propranololCGP 20712A (also b1)ICI 118551 (also b2)4.Potency of NA as agonistStrongWeakStrongDobutamine:# A derivative of DA, but not a D1 or D2 receptor agonist.# Though it acts on both a and b adrenergic receptors, the only prominent action of clinically employed doses (2.5-10 mg/kg/ min i.v. infusion) is increase in force of cardiac contraction and output, without significant change in heart rate, peripheral resistance and BR# As such it has been considered to be a relatively selective b, agonist.# It is used as an inotropic agent in pump failure accompanying myocardial infarction, cardiac surgery, and for short- term management of severe congestive heart failure.# It is less arrhythmogenic than Adr.Dopamine (DA):# It is a dopamine (D1 and D2) as well as adrenergic a and bl (but not b2) agonist.Q# The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of low dose of DA dilates these vessels (by raising intracellular cAMP) increasing GFR and Na+ excretion.# Moderately high doses produce a positive inotropic (direct bl action + that due to NA release), but little chronotropic effect on heart.# Vasoconstriction (al action) occurs only when large doses are infused.# At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP.# It has practically no effect on nonvascular a and b receptors; does not penetrate blood brain barrier - no CNS effects.- Dopamine is used in patients of cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.- It is administered by i.v. infusion (0.2-1 mg/min) which is regulated by monitoring BP and rate of urine formation.DrugReceptor SelectivityClinical UseCommentsEpinephrineb = b2>al* = a2*Anaphylactic shock; cardiogenic shock; cardiac arrestLow doses produce cardiac stimulation and vasodilation, which turns to vasoconstriction at high doses.*At high plasma concentrations, a = b selectivity.Norepinephrineb1 = a1>b2 = a2Severe hypotension; septic shockReflex bradycardia masks direct stimulatory effects on sinoatrial node.Dopamineb1 = b2>a1Acute heart failure, cardiogenic shock and acute renal failureBiosynthetic precursor of norepinephrine; stimulates norepinephrine release.*At low doses, it stimulates the heart and decreases systemic vascular resistance; at high doses, vasodilation becomes vasoconstriction as lower affinity ?- receptors bind to the dopamine; also binds to D1 receptors in kidney, producing vasodilation.Dobutamineb1 > b2 > a1Acute heart failure; cardiogenic shock; refractory heart failureNet effect is cardiac stimulation with modest vasodilation.Isoproterenolb1 = b2Bradycardia and atrioventricular blockNet effect is cardiac stimulation and vasodilation with little change in pressure.Additional Educational points:ADRENERGIC DRUGS(Sympathomimetics)Direct sympathomimetics -They act directly as agonists on a and / or b adrenoceptors - Adr, NA, isoprenaline (Iso), phenylephrine, methoxamine, xylometazoline, salbutamol and many others.Indirect sympathomimetics -They act on adrenergic neurone to release NA which then acts on adrenoceptors - tyramine. Mixed action sympathomimetics - act directly as well as indirectly - ephedrine, amphetamine, and mephentermine.ACTIONSAdr: a1+a2 + b1 + b2 and weak b3NA: a1 + a2 + b1+ b3 but no b2 actionIso: b1 + b2 + b3 but no a action Step/siteActionDrugResponse1.Synthesis of NAInhibitionUtilization of same synthetic pathwaya-methyl-p-tyrosine a-methyl dopaDepletion of NAReplacement of NA by a methyl NA (false transmitter)2.Axonal uptakeBlockadeCocaine, desipramine, guanethidine, antihistaminics, ephedrinePotentiation of NA (endo-and exogenous), inhibition of tyramine3.Granular uptakeBlockadeReserpineDepletion of NA (degraded by MAO)4.Nerve impulse coupled release of NAInhibitionGuanethidine, bretyliumLoss of transmission5.Granular NADisplacementGuanethidineInitially sympathomimetic, depletion later.6.Membrane NA poolExchange diffusionTyramine,ephedrineIndirect sympathomimetic7.MetabolismMAO inhibitionCOMT inhibitionNialamid tranylcypromineTolcapone, entacaponePotentiation of NA (slight),-of tyramine (marked)Potentiation of NA (slight)8.ReceptorsMimickingPhenylephrineClonidinea1 sympathomimetic a2-inhibition of NA release, | sympathetic outflow Isoprenalineb1 + b2 - sympathomimetic Salbutamolb2-sympathomimetic BlockadePhenoxybenzaminePrazosinYohimbinePropranololMetoprolola1+ a2 - blockadea1- blockadea2 - blockadeb1 + b2 - blockadeb1 - blockade
D1
Alpha/Beta
D2
All of the above
A.N.S.