Anticholinergic Drugs: Classification, Sources and Uses | Pharmacology

These drugs block muscarinic receptors only. That’s why, it is more appropriate to term them as anti-muscarinic agents. They are also called as atropine-like drugs.

Classification of Anticholinergic Drugs:

(A) On the Basis of Source:

(B) On the Basis of Mode of Action:

Sources and Chemistry of Anticholinergic Drugs:

Atropine is obtained from Atropa belladonna, and Datura stramonium. Scopolamine is found in the shrub Hyoscyamus niger and Scopolia carniolica. Atropine consists of equal parts of d-and 1-hyoscyamine, but the anitimuscarinic activity is almost wholly due to the 1-isomer. The active ingredient in scopolamine is 1-hyoscine. Atropine (hyoscyamine) is composed of tropic acid (active) and tropine (tropanol-inactive).

Scopolamine (hyoscine) is the structural combination of tropic acid (active) and scopine (inactive). Homatropine is the combination of mandelic acid and tropine. The intact ester of tropine/scopine and tropic/mandelic acid is essential for the significant anti-muscarinic action of these drugs. The free OH group in the acid portion is also important.

Mechanism of Action:

Atropine and related drugs are competitive antagonists of Ach and other muscarinic agonists . They compete with such agonists for a common binding sites on the muscarinic receptor. The receptors affected are those of exocrine glands and smooth and cardiac muscles.

Muscarinic receptors in ganglia and on intramural neu­rons are also affected. In extremely high non-therapeutic doses, atropine can also block the nicotinic receptors of autonomic ganglia and the motor end-plate of skeletal muscles; however, these sites are not affected with ordinary doses.

Pharmacological Properties:

(i) CVS:

(a) Atropine initially produces bradycardia, a central action (increase in vagal activity).

(b) Slightly larger doses of it produce tachycardia due to M₂ receptor blockade. Cardiac output is also increased.

(c) Low doses of scopolamine produce more marked slowing of heart rate than that of atropine. High doses accelerate the heart beat which is short lived.

(d) Atropine-like drugs antagonize the fall in B.P. caused by choline esters.

(e) Atropine alone can not affect B.P.

(ii) CNS:

(a) Atropine at therapeutic dose produces minimal effects on CNS (only mild vagal excitation → mild restlessness), but higher doses cause stimu­lation followed by depression of the CNS.

(b) Scopolamine in low dose produces depression and in high dose causes excitement and delirium.

(iii) GIT:

(a) Atropine reduces the gastrointestinal motility by preventing the effect of endogenous Ach.

(b) Atropine and more important pirenzepine inhibits gastric acid secretion, hence used in the treatment of peptic ulcer.

(iv) Glands:

(a) Atropine markedly decreases sweat, salivary, tracheobronchial and lacrymal secretions.

(v) Smooth Muscles:

(a) Atropine relaxes GIT, bronchial, biliary and urinary tract smooth mus­cles.

(vi) Eye:

(a) Mydriasis and cycloplegia due to blockade of muscarinic receptors on circular muscle of iris and ciliary muscle respectively.

(vii) Other effects:

(a) Increase in body temperature (atropine fever).

(b) Atropine has a mild anaesthetic action on the cornea.

Clinical Uses of Anti-Muscarinic Agents:

(i) As spasmolytic to decrease hyper-motility of GIT and hyper-tonicity of the uterus, urinary bladder, ureter, bile ducts and bronchioles.

(ii) As preanesthetic – to inhibit excessive salivation and respiratory secre­tions. e.g. atropine (Dogs-0.045 mg/kg b.wt., s.c. inj.)

(iii) In peptic ulcer – Pirenzepine.

(iv) To dilate the pupil- Homatropine 2-5% sol.

Tropic amide eye drops (short acting) and Cyclopentolate eye drops (long acting) are more commonly used.

(v) In renal colic – Atropine + an opioid.

(vi) In bronchial asthma-Ipratropium by inhalation.

(vii) In organophosphates, carbamate and mushroom poisoning- Atropine sulphate (all animals- 0.2-0.5 mg/kg b.wt., 1/4 th i.v. inj. and 3/4 th i.m. inj., at 3-6 hours intervals).

(viii) To antagonize the toxic effects of neostigmine (administered in myasthenia gravis).