Anti-cholinergic Drugs

ANTICHOLINERGIC DRUG

• Anticholinergics are those that antagonize the effect of the neurotransmitter (Ach) on autonomic effectors and in the CNS.

CLASSIFICATION

1. Natural alkaloid

e.g. Atropine, Hyoscine (Scopolamine)

2. Semisynthetic derivatives

e.g. Homatropine, Atropine Methonitrate, Hyoscine butyl bromide, Ipratropium bromide, Tiotropium bromide

3. Synthetic derivatives

A) Mydriatics:

e.g. Cyclopentolate, Tropicamide

B) Quaternary Compound

e.g. Propantheline, Oxyphenonium, Clidinum, Pipenzolate, Methylbromide, Isopropamide, Glycopyrolate.

C) Tertiary amine

e.g. Dicyclomine, Valethamate, Pirenzepine.

D) Vasicoselective

e.g. Oxybutynin, Flavoxate, Tolterodine.

E) Anti-parkinsonian

e.g. Bipiridine, Procyclidine, Trihexyphenidyl (Benzhexol)

MECHANISM OF ACTION

• Anticholinergics are a class of drugs that block the neurotransmitter (Ach) in the CNS and PNS.
• It combines reversibly with muscarinic cholinergic receptor thus preventing access of neurotransmitter (Ach) in these sites.

ATROPINE

• Atropine sulphate is a tertiary amine.
• Administered i.v./i.m. in a range of 0.01-0.02mg/kg up to 0.4-0.6mg (Adult dose)
• The cardiac vagal nerve is completely blocked with a larger dose (severe bradycardia).

PHARMACOLOGICAL ACTION

1. CNS

• It shows CNS stimulant action, but is not appropriate at low doses.
• Stimulate many medullary centres, vagal respiratory, and vasomotor (controlling the internal diameter of blood volume).
• In high dose causes: include cortical excitation, Restlessness, Disorientation (A state of mental confusion), Hallucination, and delirium (mental confusion).

2. CVS

• Tachycardia (Most prominent), due to blockade of M₂ receptor at SA node.

3. Eye

• Topical ingestion of Atropine causes Mydriasis (Paralysis of the sphincter pupillae).
• Paralysis of Accommodation (Cycloplegia)
• Increase in IOP.

4. Smooth muscle

• GIT relaxation: Mediated by M₃
• Contraction of the stomach and intestine is reduced leads to constipation.
• Bronchodilation: Especially for COPD and Asthma patient.
• Also antagonizes histamine, prostaglandin, and leukotrienes, mediated vagal overactivity.
• Relaxation of the ureter and bladder.

5. Glands

• Atropine markedly decreases sweat, salivary tracheobronchial and lacrimal secretion by M₃
• Skin and eyes become dry, and talking and swallowing may be difficult.

6. Body temperature

• Increase temperature, due to inhibition of sweating as well as stimulation of temperature regulating centre in the hypothalamus.

7. Local anaesthetic

• Mild anaesthetic action on the cornea.
• Sensitive to different organs and tissues: saliva, sweat, bronchial smooth muscle, heart smooth muscle, intestine, GIT.

PHARMACOKINETICS

• Rapidly absorbed from g.i.t.
• Freely penetrate cornea.
• Crosses BBB are somewhat restricted.
• About 50% metabolized in the liver.
• Excreted unchanged in urine.
• t ½ 3-4 hours.
• Hyoscine is more completely metabolized and has better blood-brain barrier penetration.

USES

Anti-secretory

• Pre-anesthetic medication: reduces excessive salivation and respiratory secretions.
• Peptic Ulcer: decrease gastric secretion and provide symptomatic relief in peptic ulcer.

Anti-spasmodic:

• Gastritis, gastric hypermotility
• Bronchial asthma
• As Mydriatics and Cycloplegia
• Parkinsonism as an adjuvant to Levodopa.
• Antagonize muscarinic effects of anticholinesterase (Mushroom poisoning)

SIDE EFFECT

• Belladonna poisoning due to drug overdose.
• Dry mouth
• Difficulty in swallowing and talking.
• Dry flushed and hot skin.
• Difficulty in micturition
• Decrease bowel sounds.
• Dilated pupil, photophobia, blurring of near vision.
• Excitement, ataxia, delirium, hallucination.
• Convulsion and coma.