ANTICHOLINERGIC DRUGS Profs Abdulqader Alhaider and Hanan Hagar

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 Naturally occurring alkaloids synthetic atropine substitutes Neuromuscular blockers

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 Quaternary amines Lipid soluble central actions Polar, water soluble No CNS effects Benztropine Homatropine Tropicamaide Pirenzepine Oxybutynin Ipratropium Glycopyrrolate N+

Muscarinic antagonists Quaternary amines

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

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.

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

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

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

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?

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

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

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

• 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.

• 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 ?