PHL 313 Lab 3 Effect of adrenergic drugs

PHL 313 Lab. 3 Effect of adrenergic drugs on intestine and identification of unknown. 1

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Adrenergic Receptors α 1 receptor α 2 receptor • vasoconstriction • inhibit release of (nor-epinephrine) blood pressure • negative feedback 3

Adrenergic Receptors β 1 receptor β 2 receptor • heart rate • vasodilatation • bronchodilatation • Force of contraction • glycogenolysis • release of glucagons 4

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Catecholamines • They are sympathetic hormones • They are released by the adrenal glands in response to stress • They are part of sympathetic nervous system • They contain a catechol group and amino acid tyrosin 6

Production and degradation • Catecholamines are produced mainly by the chromaffin cells of the adrenal medulla and postsganglionic fibers of sympathetic nervus system. • Dopmaine is the first catecholamine to be synethesied. Ep. And NE are createdand modified from dopamine. • Tyrosin is created from phenylalanine by hydroxylation by enzyme phenylalanine hydroxylase. 7

• Catecholamine synthesis is inhibited by alphamethyl-p- tyrosine (AMPT) which inhibits tyrosine hydroxylase. 8

Catecholamines degradation • Catecholamines have a half- life of a few minutes when circulating in blood. • They are degraded by COMT or MAO. • Amphetamines and MAOIs bind to MAO in order to inhibit its action of breaking down catecholamines. • This is the primary reason why the effects of amphetamines have a longer lifspan than cocaine and other substances 9

• Amphetamines not only cause a rlease of dopamine, ep, and NE into blood stream but also supress re- absorption. • Two catcholamines, NE and dopamine act as neuromodulators in CNS and as hormones in blood circulation. • High catecholamine level in blood are associated with stress. 10

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Receptor type Agonist potency order : α 1 norepinephrin e≥ epinephrine >> isoprenaline : α 2 13 Selected action of agonist smooth muscle contraction norepinephrin smooth muscle e ≥ contraction and epinephrine neurotransmitte r inhibition >> isoprenaline Mechanism Agonists G q: α 1 agonists phospholipas norepinephrine • e C (PLC) Phenylephrin • activated, IP 3 e and calcium Methoxamine • up Cirazoline • Gi: adenylate cyclase inactivated, c. AMP down α 2 agonists Clonidine • Lofexidine • Xylazine • Tizanidine • Antagonists α 1 blockers Alfuzosin • Doxazosin • Phentolamin • e Prazosin • Tamsulosin • Terazosin • α 2 blockers Yohimbine • Idazoxan •

Receptor type Agonist potency order β 1 isoprenaline > epinephrine = norepinephrin e heart muscle Gs: adenylate contraction cyclase activated, c. AMP up norepinephrine • β 2 isoprenaline > epinephrine >> norepinephrin e smooth Gs: adenylate muscle cyclase relaxation activated, c. AMP up Short/long) Salbutamol • Formoterol • Isoprenaline • Salmeterol • Terbutaline • 14 Selected action of agonist Mechanism Agonists Isoprenaline • Dobutamine • Antagonists (Beta blockers) Metoprolol • Atenolol • Propranolol • (Beta blockers) Propranolol •

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Identification of unknown 1 - 0. 2 ml of Unknown , record & wash 2 - 0. 2 ml of C 6 - blocker, leave 2 min. without wash add 0. 2 ml of Unknown, if (1) block so unknown is nicotine-like drug but if unknown gives a response so the unknown may be muscarinic or direct acting- like drug. 3 - If unknown gives a response wash and continue 4 - 0. 2 ml of atropine , leave 2 min. without wash add 0. 2 ml of of unknown , if block, so the unknown is muscarin-like drug but if unknown gives a response so it is direct acting- like drug. 16