SYMPATHETIC NERVOUS SYSTEM Sympathetic nervous system The sympathetic

SYMPATHETIC NERVOUS SYSTEM

Sympathetic nervous system • The sympathetic division is the “fight-or-flight” system • Involves E activities – exercise, excitement, emergency, and embarrassment • Non-essential activities are dampened (GI/urinary) • Promotes adjustments during exercise – blood flow to organs is reduced, flow to muscles is increased

Sympathetic

ADRENERGIC TRANSMISSION • Adrenergic transmission is restricted to the sympathetic nervous system • Naturally occurring catecholamines Epinephrine, Norepinephrine, Dopamine.

ADRENERGIC TRANSMISSION • Nor epinephrine is the transmitter at post- ganglionic sympathetic nerves – except sweat glands • Epinephrine is secreted by the adrenal medulla • Dopamine is the transmitter in basal ganglia, limbic system, CTZ and anterior pituitary.

ADRENERGIC TRANSMISSION • SYNTHESIS : Catecholamines like Epinephrine, Norepinephrine, and Dopamine are synthesized from Tyrosine • Tyrosine hydroxylases is the rate limiting step in the synthesis of CA

Adrenergic receptors • Membrane bound G-protein coupled receptors vα receptor vβ receptor

Receptor Location G-Protein Second messenger α 1 Smooth muscles, salivary glands, liver cells Gq ↑ IP 3 /DAG α 2 Presynaptic on nerve endings; Postsynaptic in brain, beta pancreatic cells, vascular smooth muscles Gi ↓c. AMP β 1 Heart, juxta glomerular apparatus Gs ↑ c. AMP β 2 Bronchi, blood vessels, uterus, G. I. T and urinary tract Gs ↑ c. AMP β 3 Adipocytes Gs ↑ c. AMP

ADRENERGIC DRUGS / SYMPATHOMIMETICS

CLASSIFICATION q. BASED ON CHEMICAL STRUCTURE • Catecholamines endogenous - Adr, NA, DA synthetic - isoprenaline, dipivefrine, dobutamine • Non-catecholamines phenylephrine, methoxamine, naphazoline, amphetamine

q. Based on mode of action • Directly acting - Adr, NA, Isoprenaline, phenylephrine, salbutamol…. • Indirectly acting– tyramine • Mixed acting – ephedrine, amphetamine, mephentermine

THERAPEUTIC CLASSIFICATION Pressor agents Noradrenaline ephedrine dopamine phenylephrine methoxamine mephentermine Cardiac Stimulants Adrenaline dobutamine Isoprenaline Bronchodilators Adrenaline isoprenaline salbutamol terbutaline salmeterol formoterol Nasal decongestants Phenylephrine xylometazoline oxymetazoline pseudoephedrine Naphazoline CNS stimulants amphetamine methamphetamin dexamphetamine Anorectics fenfluramine sibutramine dexfenfluramine Uterine relaxants ritodrine isoxsuprine salbutamol terbutaline

Pharmacological Actions Cardiovascular Effects Heart - ↑ in heart rate & force of contraction ( 1) =↑ in cardiac output - ↑ Conduction velocity

Pharmacological Actions • Vascular effects vasoconstriction(α) , vasodilatation( 2 ) - constricts arterioles in skin, mucous membrane, viscera & renal beds ( α effect ) - Dilatation in skeletal muscle, liver & coronaries ( 2 )

Pharmacological Actions Blood pressure -Adrenaline : Biphasic response ↑ BP ( 1), subsequently when plasma conc. Of adrenaline declines , mean BP falls ( 2 ) - with blocker : vasomotor reversal of dale

Effect on Smooth Muscles Bronchial Smooth Muscle - Powerful bronchodilatation ( 2 ) - ↓ in bronchial secretions ( 1 ) GIT - Gut relaxation ( 2 & ( 2 ) Urinary tract - Relaxation of detrusor muscle ( 2 ) - Contraction of trigone & sphincter ( 1 ) Hinder micturition - Vas deferens ejaculation ( 1 ) -JG cells in kidney (increase renin release) ( 1 ).

Metabolic Effects ? Hyperglycaemia - glycogenolysis & gluconeogenesis in liver( 1) ? ↑ in free fatty acids due to lipolysis in adipose tissue ? Inhibition of insulin release ( 2) ? ↑ in BMR & CVS effects ↑ in body temperature ? Transient hyperkalemia followed by hypokalemia

Eye v Contraction of radial muscles - Mydriasis ( 1 ) v ↓aqueous humour formation ↓ IOP v Active Mydriasis with no Cycloplegia

CNS • Activation of receptors ( 2 )in brain – ↓sympathetic outflow - ↓ BP

Pharmacological Actions Skeletal muscles • Facilitates neuromuscular transmission • Enhanced firing of spindle

Pharmacological Actions • Platelets : aggregation ( 2 ) • Pancreas -- decrease insulin release ( 2 )

ADVERSE EFFECTS • Restlessness, palpitation, anxiety, tremor • Rise in BP – cerebral hemorrhage • Ventricular fibrillation contraindications • • • Hypertension Hyperthyroidism Angina

Adrenaline • Acts on α 1, α 2, 1 2 & 3 • Therapeutic uses Anaphylactic shock Cardiac arrest Bronchial asthma As a local haemostatic To prolong the duration of Local Anaesthetic action

Noradrenaline • α 1, α 2, 1 & 3 (no 2 action) • Rise in systolic & diastolic BP • Cardiogenic shock • Causes extravasation

Dopamine • D 1 , D 2 , α & 1 low doses – ↑ g. f. r , excretion of sodium Moderate doses - +ve inotropic effect High doses – vasoconstriction Ø Cardiogenic shock , severe CHF

Dobutamine • Derivative of DA • Acts on α & 1 • Force of contraction & output without change in HR & BP • Inotropic agent in pump failure accompanying MI, cardiac surgery, severe CHF

Isoprenaline • 1 , 2 , 3 (no α action) • ↑HR in patients with bradycardia

Ephedrine • • • Derived from ephedra vulgaris Effective orally Crosses BBB – stimulant action on CNS Tachyphylaxis Chronic bronchial asthma, hypotension during spinal anaesthesia

Phenylephrine • Stereoisomer of ephedrine • Selective α 1 agonist • Mydriatic & nasal decongestant

Amphetamine • Alertness, attention span, euphoria, sense of fatigue, wakefullness • Stimulate resp. centre, suppress hunger • Weak anticonvulsant, analgesic & antiemetics • Drugs of abuse –psychological dependence & tolerance • A/E – anxiety, restlessness, tremor, dysphoria, agitation, palpitation, arrhythmia, abdominal cramps & vascular collapse

Amphetamine • Treatment of toxicity – acidification of urine, diazepam or chlorpromazine • Uses Narcolepsy Attention deficit hyperactivity disorder Nocturnal enuresis & urinary incontinence

Tyramine • Found in cheese , beef, wine…. • With MAO inhibitors – hypertensive crisis • Not used clinically

Selective 2 stimulants • Relaxant effect on bronchi & uterus • Salbutamol, terbutaline, formeterol, metaproterenol, pirbuterol, clenbuterol • Bronchial asthma • A/E – palpitation, tremors, headache, hypokalemia

Nasal decongestants • α agonists – local vasoconstriction • Naphazoline, xylometazoline, oxymetazoline, pseudoephedrine, phenylpropanolamine • CNS depression & rise in BP • Long term use impairs mucosal ciliary function, causes atropic rhinitis & anosmia

Anorectic agents • Noradrenergic agents – phentermine, PPA, diethyl propion, mazindol • Serotonergic agents – Fenfluramine, dexfenfluramine, • Noradrenergic/ Serotonergic -Sibutramine

Adrenergic drugs