Autonomic Drugs 1 Definition Adrenaline (epinephrine) (A) Noradrenaline (norepinephrine) (NA) Autonomic nervous system (ANS) Sympathetic nervous

system (SNS) Parasympathetic nervous system (PNS) Acetylcholine (Ach) Acetylcholinesterase (AchE) (enzyme that breaks down acetylcholine) Nervous System Action of Sympathetic, Parasympathetic on Effector Organs

Sympathetic (thoracolumbar) division Parasympathetic (craniosacral) division Functions Sympathetic Nervous System Adjust bodys responses to stress y Trauma y Fear y Hypoglycaemia y Exercise Sympathetic activation of effector organs & adrenal medulla occur y HR, BP y Mobilize body energy stores y Blood flow to skeletal muscles & heart y Diverting flow from skin & internal organs

Cholinergic & Adrenergic Receptors of ANS Parasympathetic Nervous System Maintain essential body functions y Digestive processes y Waste elimination Oppose/ balance actions of SNS Dominant over SNS in rest & digest situations

Autonomic Fibers Adrenergic Fibers Noradrenaline Adrenaline Autonomic Receptors Cholinoceptors Cholinergic receptors Activated by Ach Subtypes Muscarinic Nicotinic Receptors Receptors Neuro-effector Adrenal medulla junction of PNS Autonomic ganglia Nn (SNS, PSN) Neuromuscular junction (Nnmj)

Cholinergic Fibers Acetylcholine (Ach)

Anticholinesterases (Irreversible) Form very stable covalent bond with AchE Enzyme permanently inactivated (prolonged Ach ) At neuromuscular junction When AChE absent

Ach markedly accumulates

Adrenoceptors Respond to catecholamines (noradrenaline, adrenaline) Subtypes adrenoceptor (1, 2) adrenoceptor (1, 2, 3) Dopamine receptor

Cause muscles (throughout body) to cramp up in continual contraction

Cause depolarizing neuromuscular blockade

Paralysis of motor function (Eg. respiratory muscle, diaphragm muscle) (breathing difficulties)

CNS stimulation Cause convulsions Many are toxic Used in military as nerve agents (Soman, Sarin) Used as insecticides (organophosphates parathion, malathion)

Drugs acting on Cholinergic Receptors Cholinergic Agonists Direct Acting Acetylcholine Pilocarpine Indirect Acting Reversible Irreversible Pyridostigmine Organophosphates Physostigmine (toxic) Neostigmine (military use) Pralidoxime (reactivates acetylcholinesterase) Inhibit acetylcholinesterase (AchE) ACH in y Synaptic clefts y Neuro-effector junctions AchE breaks down Ach to y Acetate y Choline Produce response at y Muscarinic y Nicotinic y Neuromuscular junction y Brain HR (-ve chronotropy) Contractility (-ve inotropy) Conduction velocity Contractile strength Dilatation Dilatation

Cholinergic Antagonists (Antimuscarinic agents) Atropine Ipratropium Scopolamine (hyoxcine/ buscopan)

Directly bind Activate cholinergic receptors y Muscarinic y Nicotinic

Binds competitively to muscarinic receptors Prevent Ach binding & action Do not block nicotinic receptor (no action at neuro-muscular junction/ autonomic ganglia)

CVS Effects Heart

Blood vessels

Sinoatrial node Atria AV node Ventricles Arteries Veins

Primary effect y Peripheral vascular resistance y HR Respiratory Effects ung Bronchial smooth muscle M receptors Glands at tracheabronchial mucosa GIT Effects GIT Wall smooth ms (M3) Myenteric plexus (M1) Sphincters (M3) Secretion (M3)

Contraction of bronchial smooth ms (bronchoconstriction) Stimulation of secretion

Motility Peristaltic activity in gut Relaxation Stimulation of salivary & gastric glands (less on pancreas, small intestine)

Effects Eyes y Mydriasis (pupil dilatation) y Cyclopegia (inability to focus for near vision) GIT y Gastric motility y Used as antispasmodic Urinary system y Hyper motility states of urinary bladder CVS y Tachycardia ( dose) y Due to block heart muscarinic receptors Secretions y Block salivary glands y Drying effect on oral mucous membranes (xerostomia) y Sweat & lacrimal gland also affected y Inhibition of sweat gland (can body temperature)

Genitourinary Effects Genitourinary Detrusor muscle of Contraction bladder Trigone, sphincter Relaxation muscle of bladder Promotes voiding Human uterus not notably sensitive to muscarinic agonists Glands ThermoM receptors Secretion regulatory sweat glands Muscarinic agonists stimulate secretion by thermoregulatory sweat, lacrimal, salivary, gastric, intestinal, pancreatic, nasopharyngeal glands Therapeutic Applications Urology stimulate urine expulsion (post partum/ post operative urinary retention) Ophthalmology glaucoma ( IOP, intra-ocular pressure)(Pilocarpine) Myasthenia gravis GIT post-op GI ileus Adverse Effects Diarrhoea Diaphoresis Miosis Nausea Urinary urgency Muscarinic Toxicity CNS stimulation Miosis, spasm of accommodation Bronchoconstriction GIT, GU activity Secretory activity (sweat glands, airway, GIT) Vasodilatation Effects blocked completely by antimuscarinic (eg. Atropine)

Nicotinic Toxicity CNS stimulation Neuromuscular end plate depolarization

Therapeutic Applications Asthma & COPD (inhale Ipratropium) Anti-motion sickness (Scopolamine) Ophthalmic mydriasis for eye examination (Atropine (topical)) Antispasmodic control diarrhoea (hyoscine, buscopan) Antidote for cholinergic overdose (Atropine) Adverse Effects Dry mouth Hot, flushed skin Body temperature (children sensitive to hyperthermic effects) Blurred vision, sandy eyes, Mydriasis Constipation Urinary Retention CNS effects Restlessness, Confusion, Delirium Induce glaucoma attack