Muscarinic (M) receptor blockers (Antagonists) Anti muscarinic drugs Anti cholinergic drugs

Dr P Sabitha

Although, all drugs that interfere with NT Ach action in body ought to be referred to as Anti cholinergic drugs, By convention, only M receptor antagonists are called as Anti cholinergic drugs

Anti cholinergic Drugs

Synthetic / semi synthetic
Bladder selective Oxybutinin Flavoxate Antiparkinsonian Benzhexol

Natural Alkaloids
Atropine Hyoscine Bronchodilators ( inhalation) Ipratropium bromide Mydriatics (eye drops) Homatropine Cyclopentolate

Anti spasmodic/ Anti secretory Dicyclomine Glycopyrrolate

Explain the basis for uses of Atropine ( Injection) Only Atropine (no oral tablets) is available as injection only. Injection Atropine uses are restricted and few doses only. 1. Management of OP poisoning: ( Basis explained before) 2. Management of bradycardia/ AV block: Whether it is drug induced, or cardiac disease induced; ultimately it is as a result of excess of vagal (parasympathetic) stimulation to myocardial where Ach is NT at M receptors. So block of M receptors by Atropine. 3. Biliary colic: Excess contraction smooth muscle of biliary tract gives rise to colicky pain. Opioid analgesic used to relieve pain here but by itself can contract the biliary smooth muscle. Since NTAch action at M receptors are involved in contraction of biliary smooth muscle block M receptors by Atropine. 4. Pre anesthetic medication: During anesthesia, respiratory tract secretions need to be decreased to facilitate endotracheal intubation. Secretions mediated through NT Ach action (M receptor), block M receptor using Atropine. 5. With Neostigmine: After surgery is over, Neostigmine is used for receovering skeletal muscle paralysis( basis explained earlier). We want N action only at skeletal muscle and not at M receptors. So block M receptor using Atrpoine

Explain the uses of Hyoscine Hyoscine is used to prevent vomiting of motion sickness. In some individuals, shaking or rotation movements ( bus, train flight journey) can stimulate the labyrinthine system (inner ear) which in turn stimulates the vomiting center resulting in vomiting. The pathway involves NT Ach action M receptors. Blockade of M receptors by Hyoscine prevents voming of motion sickness. Hyscine appears to have more selective action for this condition. Hyoscine also produces sedation which helps to suppress the reflex vomiting. Hyoscine given orally hr before onset of journey (action lasts for 4-6 hrs) or as transdermal patch behind ear 4 hrs before onset of journey ( action lasts for 3 days). Dry mouth is the AE of Hyoscine Shaking Rotation + Labyrinthine system + Vomiting center (Ach) M X Hyoscine

Explain uses of bladder (vescico) selective anticholinergic drugs [Oxybutinin, Flavoxate, Valethemate]? Genitourinary smooth muscle contraction is mediated by NTAch at M receptor. Ureteric colic : painful contraction of ureteric smooth muscle After bladder surgery: Contraction of bladder muscle interferes with wound healing Neurogenic bladder: Urinary incontinency ie; urination is not under control. So need to decrease contraction of urinary bladder muscle. Dysmenorrhoea: Painful contractions of uterine muscle during menstruation Oxybutinin, Flavoxate, Valethemate more selectively block M receptors at GU tract. Hence used in above said conditions. AE due to blockade of M receptors elsewhere can be minimal. Name the antispasmodic drugs used for intestinal / biliary colic Dicyclomine, Propantheline Intestinal / biliary colic are because of excess contraction of smooth muscle ( NTAch at M ). Above drugs more selectively block M receptors at GIT so preferred to relieve pain of colic

What are the toxic effects of Atropine or Atropine like drugs? How to treat? Eye: Mydriasis, photophobia; difficulty in near vision CVS: Hypotension GIT: bowel movement Urinary tract: Difficulty in urination

Skin: Dry; hot, fever Salivary glands: dryness of mouth CNS: Excitement; delirium, psychotic behavior, ataxia These toxic effects could be seen with any drugs that block M receptors when used over prolonged period How to treat above toxic effects? General measures Specific measures: Neostigmine is used to increase concentrations of NTAch which will overcome (reversible) antagonism of M receptor by Atropine. However, Neostigmine cannot penetrate BBB, so, CNS toxicity of Atropine is not countered by Neostigmine. General CNS depressants like Benzodiazepines are used to depress CNS toxicity of Atropine

Explain use of Ipratropium bromide Ipratropium is used by inhalation route in chronic obstructive pulmonary disease & bronchial asthma. Cholinergic stimulation (NTAch at M receptor) can worsen broncho constriction produced by various chemical mediators. So block M receptor by Ipratropium which when inhaled has selective action on tracheo bronchial tree so AE due to blockade of M receptor elsewhere, can be least.

Ipratropium M

2 agonist
11

Explain the basis for using anti cholinergic drugs in Parkinsons disease or drug induced Parkinsonism.
Benzhexol is used to treat Parkinsons disease ( Benzhexol with L-dopa) Drug induced parkinsonism ( only Benzhexol) Parkinsons disease is due to degeneration of dopaminergic fibres. So unopposed action of cholinergic nerves (NT Ach- M receptor) on extra pyramidal system results in rigidity of skeletal muscles. So block M receptors by using Benzhexol which can penetrate BBB better as we want action on CNS only. Drugs that block D receptors used to treat psychosis can also give rise to extrapyramidal manifestations that can be treated with Benzhexol Benzhexol Extra Pyram D idal M system

Dopaminergic

Cholinergic

Benzhexol is used to treat Parkinsons disease ( Benzhexol with L-dopa) Drug induced parkinsonism ( only Benzhexol) Parkinsons disease is due to degeneration of dopaminergic fibres. So unopposed action of cholinergic nerves (NT Ach- M receptor) on extra pyramidal system results in rigidity of skeletal muscles. So block M receptors by using Benzhexol which can penetrate BBB better as we want action on CNS only. Drugs that block D receptors used to treat psychosis can also give rise to extrapyramidal manifestations that can be treated with Benzhexol Benzhexol Extra Pyram D idal M system

Dopaminergic

Cholinergic

Explain the basis of using anti cholinergic drugs in ophthalmological conditions

M M Homatropine

Physiology- Cholinergic stimulation (NTAch at M) contracts circular muscle brings about pupil constriction. Adrenergic stimulation ( NTNE at ) contracts radial muscles brings bout pupil dilatation. Cholinergic stimulation (NTAch at M) contracts ciliary muscle aslo Homatropine; Cyclopentolate (eye drops) block M receptors, relax ciliary muscle and sphincter pupillae Refractive errors testing (needs ciliary muscle paralysis) Fundoscopic examination ( better vision of fundus) Inflammatory conditions of eye ( iritis; iridocyclitis; uveitis ) to give rest to muscle thereby relieve painful spasm