Pharmacology of Sympathetic Nervous System PDF

DR. Marwa G. Gamea SYMPATHETIC NERVOUS SYSTEM 1- SYMPATHOMIMETICS  Sympathomimetics are drugs that produce actions similar to sympathetic nerve stimulation.  Types of adrenergic receptors: (1) α1-adrenergic receptors: - Blocked by prazosin and found in: a) Most of vascular smooth muscl...

DR. Marwa G. Gamea SYMPATHETIC NERVOUS SYSTEM 1- SYMPATHOMIMETICS  Sympathomimetics are drugs that produce actions similar to sympathetic nerve stimulation.  Types of adrenergic receptors: (1) α1-adrenergic receptors: - Blocked by prazosin and found in: a) Most of vascular smooth muscles causing contraction. b) Genitourinary smooth muscles causing contraction of trigone and sphincter c) Pupillary dilator muscle of eye causing contraction (active mydriasis) d) Pilomotor smooth muscles causing erection of hair e) Liver causing glycogenolysis, and gluconeogenesis increasing blood glucose level. f) Intestine causing relaxation of the wall. (2) α2-adrenergic receptors: - Blocked by yohimbine and found in: a) Vascular smooth muscles causing contraction b) B-cell of pancreas causing decrease in insulin secretion c) Platelets causing aggregation. d) Presynaptic nerve terminals causing decrease in transmitter release (NE). (3) β1-adrenergic receptors: - Blocked by atenolol and found in: a) Heart causing increase in force of contraction, heart rate and A-V nodal conduction. b) Juxtaglomerular cells causing increase in renin secretion. (4) β2-adrenergic receptors: Found in: a) Vascular, genitourinary, intestinal, and bronchial smooth muscles causing relaxation. 1  DR. Marwa G. Gamea b) Liver causing glycogenolysis, and gluconeogenesis increasing blood glucose level. c) B-cell of pancreas causing increase in insulin secretion d) Skeletal muscles causing increase in contraction, K+ uptake, and an increase in glycogenolysis causing increase in blood lactic acid. (5) β3-adrenergic receptors: Adipose tissues causing lipolysis.  Classifications of sympathomimetics (adrenergic agonists): (I) Catecholamines: a) Endogenous: epinephrine, norepinephrine, and dopamine. b) Non-endogenous: isoproterenol and dobutamine. (II) Non-catecholamines: (1) Selective β2-agonists: - Terbutaline - Salbutamol - Formoterol – Salmeterol. (2) Selective α1-agonists: - Phenylephrine. (3) Selective α2- agonists: - Clonidine - α-methyldopa. (5) Indirect acting sympathomimetics: - Amphetamine 1- SYMPATHOMIMETICS I) CATECHOLAMINES All are ineffective orally due to metabolism in GIT, so used parenteral. (1) Epinephrine (EP)  Mechanism of action: Acts by direct stimulation of all types of adrenergic receptors (α1, α2, β1 andβ2).  Pharmacological action: (l) C.V.S: (a) Heart - EP is a powerful cardiac stimulant, acting on β1 receptors of the heart - EP causes: 2  DR. Marwa G. Gamea Increase force of contraction (+ve inotropic effect). Increase heart rate (+ve chronotropic effect). (b) Systemic blood vessels and blood pressure: Blood vessels contain 2 types of receptors: α1 and α2: they are vasoconstrictor receptors, their stimulation causes vasoconstriction and increase in blood pressure. β2: vasodilator receptors, their stimulation causes vasodilation and decrease in blood pressure. (2) Smooth muscles: a) GIT: Relaxation of the smooth muscles which causes reduction in motility and contraction of the sphincter (action on α and β2). b) Bronchial muscles: Bronchodilation (β2) especially if there is constriction due to disease (asthma) or drug (histamine). c) Urinary muscles: Relaxation of the muscle (β2) and contraction of the sphincter (α1) so may cause retention of urine. d) Pupillary dilator muscle of the eye:  Contraction (α1) causing active mydriasis.  Decrease I.O.P due to vasoconstriction of blood vessels (α1) so it decreases aqueous humor formation.  No effect on accommodation. (4) Metabolic effects: Increase blood glucose (hyperglycemia)  Therapeutic uses of EP: 1- Local haemostatic to control bleeding as in epistaxis (nasal bleeding), bleeding after tooth extraction. 2- With local anesthetic as it causes vasoconstriction so it decreases systemic absorption of anesthetic agent, increases duration of action of anesthetic and decreases bleeding. 3- Sudden cardiac arrest during anesthesia. 4- Acute anaphylactic shock: S.C. EP is the drug of choice as it can treat hypotension, bronchospasm (physiological antagonist of histamine). 5- Acute bronchial asthma: EP can be used SC or by inhalation as it causes bronchodilation.  Side effects of EP: (1) CVS: tachycardia, palpitation, and hypertension. 3  DR. Marwa G. Gamea  In severe cases: arrhythmia, angina pectoris, and cerebral hemorrhage. Contraindications and precautions: 1- Hypertension. 2- Angina pectoris. 3- Hyperthyroidism (as may cause cardiac arrhythmia). 4- Diabetes mellitus (as it causes hyperglycemia). (2) Norepinephrine  It differs from EP in: - It acts mainly on α, and β1 receptors (but doesn't act on β2- receptors)  Therapeutic uses: -It is used in treatment of hypotension as in shock, used by IV infusion. (3) Isoproterenol (non-selective β-agonist). - It acts on all types of beta receptors (non-selective β agonist). - It acts similar to EP on the above mentioned beta actions. II) NON-CATECHOLAMINES 1- Selective β2-adrenergic agonists  Drugs used in asthma: a) Short acting: Salbutamol and terbutaline. b) Long acting: Salmeterol and Formoterol 2- Selective α2-adrenergic agonists (i) Clonidine: Used in hypertension. (ii) α-methyl dopa Used in hypertension during pregnancy. INDIRECT ACTING AGONISTS Amphetamine  Mechanism of action: They act by releasing of norepinephrine from sympathetic nerve endings. 2- SYMPATHOLYTICS ADRENERGIC RECEPTORS BLOCKERS (1) α-adrenergic blockers: a) Non- selective α –blockers: competitive blockers as Phentolamine & non-competitive blockers as phenoxybenzamine b) Selective α1- blockers: Prazosin used in uncontrolled hypertension (2) β-adrenergic blockers: 4  DR. Marwa G. Gamea a) Non-selective β -blockers: e.g., Propranolol. b) Selective β1-blockers: e.g., Atenolol. β-adrenergic receptors blockers  Therapeutic uses: 1) Mild to moderate hypertension. 2) Chronic stable angina 3) Cardiac arrhythmia 4) Hyperthyroidism 5) Timolol can be used in treatment of glaucoma  Advantages of the selective β1 -blockers: - Better to use in cases of bronchial asthma, diabetes mellitus. 5