ANTICHOLINERGIC DRUGS Profs. Abdulqader Alhaider and Hanan Hagar Pharmacology Department

Anticholinergic drugs What students should know: Student should be able to : Describe Kinetics of muscarinic antagonists The effects of atropine on the major organ systems. To list the clinical uses of muscarinic antagonists. To know adverse effects & contraindications of anticholinergic drugs. To identify at least one antimuscarinic agent for each of the following special uses:mydriasis, cyclopedia, peptic ulcer & parkinsonism.

Anticholinergic drugs are drugs that block cholinergic receptors. Two types are available 1. Nicotinic blockers (antinicotinics). Ganglionic blockers (not used Clinically Why?) Neuromuscular blockers (Skeletal Muscle Relaxants) 2. Muscarinic blockers (antimuscarinics) Naturally occurring alkaloids (e.g: Atropine) Synthetic atropine substitutes.

Anticholinergic drugs Antimuscarinics (Parasympatholytics) Antinicotinics Ganglionic blockers Neuromuscular blockers Naturally occurring alkaloids synthetic atropine substitutes

Muscarinic antagonists Natural alkaloids History (Thousants of years) Atropine (Hyoscyamine) Hyoscine (scopolamine) Esters of tropic acid and tertiary amines Lipid soluble Good oral absorption Good distribution Cross blood brain barrier (have CNS actions)

Muscarinic antagonists Synthetic atropine substitutes Tertiary amines Lipid soluble central actions Benztropine Homatropine Tropicamaide Pirenzepine Oxybutynin Quaternary amines Polar, water soluble No CNS effects Ipratropium Glycopyrrolate N+

Muscarinic antagonists Quaternary amines

Antimuscarinic drugs Pharmacokinetics DRUG Natural alkaloids Tertiary amines, lipid soluble, well absorbed, well distributed, good penetration to CNS Natural alkaloids Atropine (Hyosyamine) Hyoscine (scopolamine) Synthetic atropine substitutes Tertiary amine Benztropine Tertiary amines Tropicamide Homatropine Quaternary amines, not absorbed well, poor distribution, no CNS effects Ipratropium Pirenzepine Quaternary amines Glycopyrrolate Oxyphenonium Oxybutinin

Antimuscarinic drugs Mechanism of action Reversible competitive blockade of muscarinic receptors. Can antimuscarinic drugs reverse the action of Ach on skeletal muscles?

Pharmacological Effects of Antimuscarinic Drugs CNS CNS depression Antiemetic effect (block vomiting center) antiparkinsonian effect (block ACH at basal ganglia). Toxic dose: Hyperthermia - excitement-hallucination.

Tachycardia (increase heart rate) Cardiovascular system (CVS) Tachycardia (increase heart rate) AV conduction ( + ve dromotropic effect) Therapeutic dose:  Vasodilatation induced by cholinomimetics. Toxic dose: Cutaneous vasodilatation  (atropine flush). Respiratory system Bronchial Relaxation (bronchodilator)  Bronchial secretion   viscosity

Eye Passive mydriasis due to paralysis of circular muscle Cycloplegia (loss of near accommodation) due to paralysis of ciliary muscle. Loss of light reflex. Increase I.O.P (worsens glaucoma).  Lacrimal secretion  sandy eye

Salivary secretion  ( Dry mouth ). Secretions Salivary secretion  ( Dry mouth ).  Sweating  Dry skin  Fever in infants and children.  Bronchial secretion   Viscosity Lacrimal secretion  Sandy eye 13

GIT Relaxation of smooth muscles.  GIT motility  Antispasmodic effect.  Sphincter contractions Constipation Urinary Tract Relaxation of smooth muscles of ureters. Sphincter contraction. Urinary retention (worsens prostate hypertrophy).

Hyoscine (SCOPOLAMINE) What is difference between atropine and hyoscine? Hyoscine has Shorter duration of action More CNS depressant action Antiemetics action in motion sickness Amnesic action. Less CVS effect Can you put a question for exam? 15

Anticholinergic actions Mydriasis Cycloplegia relaxation of ciliary muscles Eye 1. Contraction of circular muscle of iris (miosis) 2. Contraction of ciliary muscles for near vision Tachycardia ( heart rate) Heart bradycardia ( heart rate ) Relaxation of muscles contraction of sphincter Urinary bladder Contraction of muscles Relaxation of sphincter

Anticholinergic drugs Decrease all secretion Exocrine glands Increase of sweat, saliva, lacrimal, bronchial, intestinal secretions peristalsis secretion Contraction of sphincter GIT relaxation of sphincter 1. Bronchodilatation 2. Decrease secretion Lung Bronchoconstriction 2. bronchial secretion

Uses of antimuscarinic drugs organ Drugs Cardiac Arrest How? Rx of pesticide Toxicity CNS Atropine Preanesthetic medication, Motion sickness, antispasmodic Hyoscine Parkinson's disease Benztropine Fundus examination of eye Eye Tropicamide Homatropine asthma, COPD, inhalation Respiratory system Ipratropium Peptic ulcer Stomach Pirenzepine Antispasmodics in hypermotility GIT Glycopyyrolate Propantheline Urinary urgency, Urinary incontinence GUT Oxybutynin

Antidote: Physostigmine ( IV slowly). Adverse effects (usually can be observed with antidepressant s and antipsychotics) Eye: Blurred vision – Mydriasis CVS: Tachycardia - Atropine flush GUT: Urinary retention GIT: Constipation, paralytic ileus Secretions: Dryness of mouth , Sandy eye Increased body temperature. CNS: sedation, hallucination, excitation (Toxic dose). Treatment Gastric lavage. Anticonvulsant. Cooling blanket. Antidote: Physostigmine ( IV slowly).

Treatment of anticholinergic Toxicities Gastric lavage. Anticonvulsant. Cooling blanket. Antidote: Physostigmine ( IV slowly).

Contraindications Glaucoma (angle closure glaucoma) Tachycardia Prostate hypertrophy in old patients. Constipation, paralytic ileus, intestinal obstruction. Children in case of atropine

Thank you Questions ?