Anti-cholinergic drug

ANTICHOLINERGIC DRUG

·         Anticholinergics are those antagonize the effect of 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 the class of drugs that blocks the neurotransmitter (Ach) in CNS and PNS.

·         It combine 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)

·         Cardiac vagal nerve is completely blocked with larger dose (severe bradycardia).

PHARMACOLOGICAL ACTION

1.      CNS

·         It shows CNS stimulant action, but not appropriate at low dose.

·         Stimulate many medullary centres, vagal respiratory, vasomotor (controlling the internal diameter of blood volume).

·         In high dose causes: 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 sphincter pupillae).

·         Paralysis of Accommodation (Cycloplegia)

·         Increase in IOP.

4.      Smooth muscle

·         GIT relaxation: Mediated by M₃ blockade.

·         Contraction of stomach and intestine is reduced leads to constipation.

·         Bronchodilation: Especially COPD and Asthma patient.

·         Also antagonizes histamine, prostaglandin, leukotrienes, mediated vagal over activity.

·         Relaxation of ureter and bladder.

5.      Glands

·         Atropine markedly decrease sweat, salivary tracheobronchial and lacrimal secretion by M₃ blockade.

·         Skin and eyes becomes dry, 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 tissue: saliva, sweat, bronchial smooth muscle, heart smooth muscle, intestine, GIT.

PHARMACOKINETICS

·         Rapidly absorbed from g.i.t.

·         Freely penetrate cornea.

·         Crosses BBB is somewhat restricted.

·         About 50% metabolized in 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: reduce excessive salivation and respiratory secretions.

·         Peptic Ulcer: decrease gastric secretion and provide symptomatic relief in peptic ulcer.

Anti-spasmodic:

·         Gastritis, gastric hyper motility 

·         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 over dose.

·         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 comma.