Antimuscarinic
Drugs
·
Classification of antimuscarinics.
·
Physiological effects of antimuscarinics.
·
Therapeutic uses.
·
Contraindications.
·
Antimuscarinic drugs
Classification of antimuscarinics
1.
Consists of:
a.
Naturally-occurring compounds: atropine, hyoscine (scopolamine) and
homatropine (semi-synthetic).
b.
Tertiary amines: dicyclomine, tropicamide, benztropine.
c.
Quarternary amines: propantheline, glycopyrrolate, ipratropium.
2. Main
effects due to competitive blockade of post-synaptic muscarinic receptors in the
autonomic and central nervous systems.
3. The
specificity and selectivity of action of such compounds decrease with increasing
concentrations as other receptor types (histamine and 5-HT) may also be blocked.
4. They
are less effective in blocking acetylcholine than exogenously administered
muscarinic agonists.
5. The
naturally occurring compounds and tertiary amines are well absorbed orally and
cross the conjunctiva whereas the quarternary compounds are poorly absorbed.
6. The
quarternary compounds generally lack central effects due to poor penetration but
they have more potent actions at nicotinic sites.
Physiological effects of antimuscarinics
|
Organ |
Effects |
|
Glandular secretions |
·
Dryness of eye, mouth, upper respiratory tract and
skin. ·
Gastric secretion is partially inhibited, more so
with selective agents. |
|
Eye |
·
Dilation of pupil (mydrasis) causing photophobia
and paralysis of accommodation (cycloplegia). ·
Blurring of near vision. ·
Rise in intraocular pressure (no effect on normal
eyes). ·
Normal reflexes may not be regained for 2 weeks
– cause of unequal sized & unresponsive pupils. |
|
Heart |
·
Increase heart rate. ·
Enhance conduction in the bundle of His. ·
Blood pressure and cardiac output are not
affected. |
|
Smooth muscle |
·
Decrease in tone and motility of the gut and
peristalsis. ·
Relaxation of smooth muscle of ureters and muscle
wall – micturition is slowed and urinary retention may occur. |
|
CNS |
·
Atropine generally causes stimulation – high
doses lead to restlessness, disorientation, hallucinations, delirium, coma
and death. ·
Hyoscine is a CNS depressant. |
Therapeutic uses
|
Use |
Description |
|
Ophthalmology |
·
Atropine, homatropine and cyclopentolate are used
to produce mydriasis and cycloplegia for examination and treatment of
various eye conditions. ·
Transient unpleasant stinging sensation &
inability to read or drive for at least 3 – 4h. ·
Effects on ciliary muscles can persist for up to
72h. |
|
Antispasmodic |
·
Relieve smooth muscle spasm in gastrointestinal,
biliary & urinary tracts. ·
Atropine + diphenoxylate as lomotil used as an
antidiarrhea agent. ·
Flavoxate, propantheline and oxybutynin are used
to relieve muscle spasm accompanying infection in cystitis & for
detrusor instability. |
|
Peptic ulcer |
·
Relieve pain & reduce acid secretion. ·
Pirenzepine and telenzepine block M1-receptors
selectively. |
|
Anaesthesia |
·
Atropine, glycopyrronum & hyoscine block the
vagus & reduce secretion. |
|
Motion sickness |
·
Hyoscine is used as a prophylactic. ·
A transdermal preparation is placed behind the
eye. ·
Used at least 4h before and effect last for 72h. |
|
Parkinsonism |
·
Benzhexol and benztropine are used against the
rigidity & tremor of parkinsonism. |
|
Antidote |
·
Useful antidote to poisoning by anticholinesterase
agents & choline esters. ·
Atropine is used in anaesthetic practice to
counter the muscarinic effects produced by neostigmine in enhancing
recovery from competitive neuromuscular blockade. |
|
Respiratory tract |
·
Reduce secretion. ·
Relieve symptoms of acute rhinitis. ·
Ipratropium bromide is used as an aerosol in the
treatment of asthma. |
|
Cardiovascular |
·
Acute myocardial infarction to reduce excess vagal
tone. ·
Risk of ventricular tachycardia &
fibrillation. |
Contraindications
1.
Patients with glaucoma: precipitate high intraocular pressure.
2.
Elderly patients with prostatic hypertrophy: severe urinary retention.
3.
Asthmatics: viscid formation of respiratory tract secretions may worsen
obstruction.
4.
Combined used with:
a.
Antihistamines.
b.
TCAs.
c. Anti-parkinsonian
drugs.
d.
Phenothiazine tranquilizers.
e.
Opioid analgesics.
5.
Mutual potentiation of the antimuscarinic effects can lead to serious
parasympathetic blockade.
6.
Atropine poisoning:
a.
Presents with dry mouth, mydriasis, blurred vision, hot, flushed, dry
skin and hyperthermia, restlessness, anxiety, hallucinations and mania.
b.
Infants and young children are especially susceptible to atropine
poisoning which can occur even after conjunctival instillation of eye drops
containing such drugs.
c.
Poisoning caused by more polar compounds may produce significant
ganglion-blockade with marked orthostatic hypotension.
d.
Treatment involves giving activated charcoal to adsorb the drug,
anticholinesterases and diazepam for excitement.
Antimuscarinic drugs
1.
Atropine:
a. Half-life:
2h.
b. An
alkaloid from the plant Atropa belladomma
c. In
general, the effects of atropine is inhibitory but in large doses it stimulates
the CNS.
d.
Readily absorbed from the alimentary tract.
e.
Destroyed in part in the liver and in part excreted unchanged by the
kidney.
2.
Hyoscine:
a.
Differs from atropine in being a CNS depressant.
b. The
old are often confused by hyoscine and so it is avoided in their anaesthetic
premedication.
3.
Hyoscine butylbromide (Buscopan):
a. Also
blocks autonomic ganglia.
b. An
effective relaxant of smooth muscle, including the cardia in achalasia, the
pyloric antral region and the colon.
4.
Homatropine:
a. Used
for its ocular effects (1% and 2% solutions as eye drops).
b.
Action is shorter than atropine.
5.
Flavoxate: used for urinary frequency, tenesmus and urgency incontinence.
6.
Oxybutynin: used for detrusor instability.
7.
Glycopyrronium: used in anaesthetic premedication to reduce salivary
secretion; given i.v.
8.
Propantheline:
a. Has
ganglion-blocking properties.
b. Used
as a smooth muscle relaxant, e.g. for irritable bowel syndrome and diagnostic
procedures.
9.
Tropicamide and cyclopentolate: useful for mydriasis and cycloplegia;
duration of action is 4 – 12h.