Adrenergic agonists. R. A. Nimmi Dilsha Department of pharmacy Faculty of Health Sciences The Open University of Sri Lanka
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1 Adrenergic agonists R. A. Nimmi Dilsha Department of pharmacy Faculty of Health Sciences The Open University of Sri Lanka
2 Outline Recall Introduction to adrenergic agonists Classification of adrenergic agonists Catecholamine Non catecholamine Direct acting adrenergic agonist Indirect acting adrenergic agonist
3 Recalling. Before the study of adrenergic agonist you should be able to recall the followings, Classification of Autonomic nervous system Adrenergic transmission Adrenergic receptors
4 Autonomic Nervous System
5 Adrenergic transmission
6
7 Adrenergic Receptors
8 Introduction to Adrenergic agonists/ Sympathomimetics An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors Two major classification of sympathomimetics 1. According to the chemical nature a)catecholamines b)non Catecholamines 2. basis of their sites of action a. direct acting adrenoceptor agonists- directly interact & activate adrenoceptors b. indirect acting by causing a release of noradrenaline from stores at nerve endings c.both direct & indirect acting Some drugs have both direct & indirect actions
9
10 Catecholamines Compounds containing a catechol moiety(3,4-dihydroxybenzene group) & an amine side-chain Noradrenaline (norepinephrine (NE) transmitter released by sympathetic nerve terminals Adrenaline (epinephrine) hormone secreted by adrenal medulla endogenous + Dopamine metabolic precursor of noradrenaline & adrenaline, also a transmitter/neuromodulator in CNS exogenous Isoproterenol (previously isoprenaline) - a synthetic derivative of noradrenaline, not present in body
11
12 Non catecholamines Compounds lacking the catechol hydroxyl group, but induces the sympathetic nerve actions Eg; Salbutmol Salmeterol Ephedrine Amphetamine Phenylepinephrine
13 Direct acting adrenergic agonists Adrenalin (epinephrine) Directly binding to the receptors It is a non selective adrenoceptor agonist Acts on both Alpha & beta receptors Administration SC, IM, IV, Inhalation Clinical Uses of adrenaline 1. Cardiac arrest Beta 1 effect given IV or into the endotracheal tube 2. Prolong the effect of local anaesthetic drugs 3. As a mydriatic (dilatation of the pupil) 4. Anaphylaxis
14 Noradrenalin (norepinephrine) Act directly binding to the receptor Mainly alpha effect with slight beta effect Clinical uses Acute hypotension(iv infusion) Metraminol, methoxamine hydrochloride have similar effects
15 Dopamine Action of the drug is base on dose D1 receptor CNS, renal & vascular beds (dialator) D2 receptor Presynaptic (suppress NAD release) small doses Β1 receptors heart α1 receptor vasoconstrictor high doses Uses Management of cardiogenic shock after MI
16 Dobutamine Primarily a beta 1 receptor agonist. Some alpha effects Greater inotropic than chronotropic effects Used in management of shock(cardiogenic & septic) Isoprenalin Nonselective beta agonist acting on both Beta 1 & 2 receptor Used in the treatment of heart block or severe bradycardia. Salbutamol Selective beta 2 agonist Uses Treatment of bronchial asthma Management of premature labour
17 Clonidine Treatment of hypertension, migraine & menopausal flushing Partial agonist Agonist at alpha 2 receptor in the brain (postsynaptic) and peripheral alpha 2 receptors (presynaptic autoreceptors) on the adrenergic nerve endings Overdose stimulate alpha 1 (postsynaptic) receptor
18 Adverse effect of direct acting adrenergic agonist 1. (α) tissue necrosis due to intense vasoconstriction as a result of leakage from IV infusion 2. Heart (β1) tachycardia, palpitations, cardiac dysarhythmias 3. (β2) muscle tremor 4. (β2) hypokalaemia
19 False transmission by methyldopa Methyldopa Mechanism Taken up by the noradrenergic neuron & converted into a false transmitter alpha methyl noradrenalin Alpha methyl noradrenalin is secreted in the same way as NAD Alpha methyl noradrenalin less active on alpha receptors causing less vasoconstriction Stimulate alpha 2 receptors more than NAD Above two actions reduce the BP Used in the treatment of hypertension in pregnancy
20 Indirect acting sympathomimetic drugs Ephedrine Mechanism Weak action on adrenoceptors Transported into the nerve terminal Taken up by the vesicles NAD escape into cytosol Action Bronchodilatation, BP, Vasoconstriction Develop tachyphylaxis/ anxiety,insomnia, tremor and nausea So this central effects limits its use a sympathomometic in asthma
21 Amfetamines Resistant MAO Their peripheral actions (eg; tachycardia, hypertension) and central stimulant actions are mainly caused by catecholamine release. Dexamfetamine and methylphenidate are sometimes used in hyperkinetic children. Dexamfetamine and modafinil may be beneficial in narcolepsy. Dependance is common
22 Cocaine A local anaesthetic, also a sympathomometic because it inhibits the reuptake of NAD by nerves terminals. It has an intense cental stimulant effect that has made it a popular drug of abuse. Tricyclic antidepressants Inhibits the reuptake of NAD by nerves terminals
23 Drug that effect the sympathomimetic drug action & NAD storage Reserpine Block the storage of amines within the vesicles present at the end of nerve terminals. It depletes the stores of the releasable transmitter
24 Thank you
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