AUTONOMIC DRUGS Cholinergic and Anticholinergic Drugs Presented by

AUTONOMIC DRUGS (Cholinergic and Anticholinergic Drugs) Presented by Sasan Zaeri (Pharm. D, Ph. D)

Neurotransmitters SOMATIC NERVOUS SYSTEM AUTONOMIC NERVOUS SYSTEM Sympathetic ACh ACh Parasympathetic ACh NE ACh Ad. M. ACh Striated muscle Heart Sm. mus. Glands Sweat glands E, NE ACh Heart Sm. mus. Glands

Cholinergic Drugs that have the same effects on the human body as stimulation of the parasympathetic nervous system by acetylcholine. Muscarinic agonists Nicotinic agonists Synthetic derivatives of endogenous compounds Bethanechol, pilocarpine Can act indirectly by blocking acetylcholinesterase which inactivates ACh (anticholinesterases) Neostigmine (reversible) Malathion and parathion (irreversible)

Location Receptor type Effect Heart M ↓ heart rate Vascular Smooth Muscle M dilation Bronchiole M ↑ contraction Urinary bladder M ↑ contraction GI tract M ↑ contraction Circular pupillary muscle M ↑ contraction (miosis) ciliary muscle M ↑ contraction M Increase secretion M Glycogen synthesis Other smooth muscle: Eye: Exocrine glands: Salivary glands Metabolic effects: Liver

Indications for use of cholinergic drugs Urinary retention Contracts bladder Paralytic ileus Increases GI motility Glaucoma Reduces intraocular pressure Diagnosis and treatment of myasthenia gravis Reverse skeletal muscle paralysis produced by neuromuscular blocking agents Treatment of Alzheimer’s disease Improves cholinergic neurotransmission in the brain Antidote to anticholinergic poisoning from atropine

Contraindications for use of cholinergic drugs Urinary or GI obstruction Asthma Peptic ulcer disease Pregnancy

ﻣﻬﺎﺭ کﻨﻨﺪﻩ ﻫﺎی کﻮﻟیﻨﺮژیک Antimuscarinic agents Antinicotinic agents Ganglion blockers Neuro-muscular junction blockers

Antimuscarinic drugs Source Alkaloids of a plant Examples: Atropine Scopolamine Hyoscine Dicyclomine

Effects on Organs Reversible blocked of muscarinic receptors The effectiveness of antagonist varies from tissue to other tissue Most sensitive Salivary Bronchial Sweat glands Intermediate sensitive Heart and vessels smooth muscles Least sensitive Acid secretion

Effects on Organs CNS In usual dose : sedation, drowsiness and amnesia Scopolamine has more CNS effects Toxic dose Excitement , agitation , hallucination and coma

Effects on Organs CNS Decrease Parkinson tremor and rigidity Vestibular disturbances ; motion sickness Scopolamine and dimenhydrinate Eye Relaxation of pupillary constrictor muscle Cause mydriasis relaxation of ciliary muscle Cause cycloplegia (loss of accommodation for near vision ) Decrease lacraminal secretion Cause sandy eyes (large doses )

Effects on Organs Cardiovascular system SA node is very sensitive Tachycardia AV node same as SA node Increase conduction Less effects on atrial and ventricular cells

Effects on Organs Respiratory system Bronchodilation Decrease secretion GI tract Decrease salivary secretion Induce dry mouth Less effects on gastric secretion Decrease smooth muscle motility in all GI tract Increase intestinal transient time

Effects on Organs Genitourinary tract Relax smooth muscle of ureters and bladder wall Urinary retention in elderly men Sweat glands Suppress thermoregulatory sweating Increase body temperature Atropine Fever

Clinical Uses CNS Parkinson disease As adjunctive therapy Motion sickness Scopolamine, Dimenhydrinate Ophthalmologic disorder Measurement of refractory errors require cilliary paralysis Examination of retina facilitated by midriasis

Clinical Uses Asthma and COPD Ipratropium bromide

Clinical Uses Urinary disorder Urinary Bladder urgency spasm after urinary surgery Examples: Oxybutynin Tolterodine

Clinical Uses Cholinergic poisoning Nerve gases Cholinomimetics

Adverse effects Atropine is safe in adults But lethal in infants (Atropine Fever ) Symptoms Dry mouth Mydraisis Dry eyes Tackycardia Hot and flushed skin Agitation Delirium Elevated body temperature