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Physiology and Pharmacology

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Answer
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  
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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  
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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  
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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  
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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  
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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  
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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  
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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  
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Selective alpha 2 agonists   Clonidine - anti hypertensive, central and peripheral actions Xylazine - sedative effects via CNS Presynaptic to decrease transmitter release, platelet aggregation, vasoconstriction  
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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  
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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  
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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  
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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  
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Main drawback of alpha antagonists   Postural Hypotension Blocking alpha receptors removes the reflex that prevents blood pooling in the legs  
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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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