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Adrenoreceptors

Physiology and Pharmacology

QuestionAnswer
Agonist An agent binding to a receptor to stimulate a response White sympathetic a and b receptors, an agonist can be called A sympathetic agonist A sympathomimetic agent An adrenergic agonist An adrenoreceptor agonist
Direct vs indirect effects Direct - noradrenaline, adrenaline, isoprenaline - act directly on receptor Indirect - tyramine, ephedrine and amphetamine - increase release of transmitter Sympathetic denervation blocks their effects
How do we know there are different receptors Same conc, same compound, same animal - can give different effects Adrenaline increases BP in contracting vascular smooth muscle Adrenaline and ergot decreases BP by relaxing smooth muscle
Potency order - Ahlquist Divided receptors into alpha and beta Decided potency order using isolated and in vivo smooth muscle preparations Alpha - Noradrenaline> adrenaline > Isoprenaline Beta - Isoprenaline > Adrenaline > Noradrenaline
Types of receptors in key locations Heart - alpha 1 Blood vessels - Alpha 1 and 2 and Beta 2 Bronchi - Alpha 1 and Beta 2 GIT - Alpha 1 and Beta 1 Liver - Alpha 1 and Beta 2 Eye - Alpha 1 Skeletal muscle - Beta 2 and 3 Adipose tissue - Beta 3
Modulation of effects by baroreceptors Isoprenaline binds solely to beta receptors Causes a decrease in resistance due to vasodilation Increase in heart rate due to baroreceptor reflex Overall decrease in BP
Non-selective adrenoreceptor agonists Adrenaline and noradrenaline Non-selectivity limits use, as well as being unstable Risk of ventricular fibrillation Used in anaphylactic shock to reverse bronchospasm and vasoconstriction Used in acute cardiac failure to stimulate the heart
Selective alpha 1 agonists Phenylephrine - counter acute hypotension, treat nasal decongestion and cause mydriasis Xylometazoline - nasal decongestion Metaraminol - acute hypotension, partially IAS Vascular and uterine smooth muscle contraction, salivary secretion
Selective alpha 2 agonists Clonidine - anti hypertensive, central and peripheral actions Xylazine - sedative effects via CNS Presynaptic to decrease transmitter release, platelet aggregation, vasoconstriction
Selective beta 1 agonists Isoprenaline - cardiac stimulant Dobutamine - cardiogenic shock, ionotropic support in infarction Increase rate and force of heart contraction, relax GI smooth muscle
Selective beta 2 agonists Isoprenaline - cardiac stimulant Salbutamol, terbutaline - short acting bronchodilators Salmeterol - long acting, preventative Bronchodilation, vasodilation, especially coronary and skeletal muscle beds, uterine relaxation, glycogenolysis
Adrenoreceptor antagonists - Ergot First discovered were ergot alkaloids by Dale - ergot poisoning Includes histamine, ACh, tyramine Derivatives of lysergic acid - ergotamine and ergometrine Partial alpha agonist as well as antagonist - stimulate then block
Alpha antagonists Phentolamine - non-selective, associated with raised heart rate as it blocks alpha 2 feedback Prazosin - selective alpha 1 used as an antihypertensive Phenoxybenzamine - irreversible non-selective used to prevent swings in BP and heart rate in surgery
Main drawback of alpha antagonists Postural Hypotension Blocking alpha receptors removes the reflex that prevents blood pooling in the legs
Beta antagonists Propranolol - non-selective so risk of bronchodilation, fatigue and claudication Atenolol - beta 1 selective so less likely to give bronchodilation Both give cold hands and feet Used in hypertension, cardiac dysrhythmia and angina
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