Anti-muscarinic drugs

and OP poisoning
Dr A K Dubey MD
 Learning Objectives
Describe the mechanism of action of atropine.
Explain the rationale for the therapeutic use in diseases such as
COPD, Pre-anesthetic medication, salivation, and motion sickness.
Explain the rationale for the therapeutic use to produce Mydriasis
and cycloplegia.
Explain why muscarinic antagonists cause xerostomia, blurred
vision, photophobia, tachycardia, anhidrosis, difficulty in micturition,
hyperthermia, glaucoma and mental confusion in the elderly.
Explain why muscarinic antagonists are contraindicated in
glaucoma, obstructive disease of the gastrointestinal tract or urinary
tract, intestinal atony.
.

 Learning Objectives
To list atropine congeners useful in refractive
error examination and mydriasis, Chronic
Obstructive Pulmonary Disease, Pre-anesthetic
medication, motion sickness, anti-spasmodic
and basis for their preference.
To predict the signs and symptoms of
Organophosphate poisoning and describe
about its management.
Important or prototypic drugs: atropine,
scopolamine, Trihexiphenidyl, Glycopyrrolate
and Ipratropium
 ANTIMUSCARINIC DRUGS

Prototype atropine; Atropa belladona-

source of atropine
Mechanism: competitive antagonist
and prevent binding of Ach to muscarinic
receptors.
Natural alkaloid : atropine,
scpolamine(hyoscine)- tertiary
ammonium compounds
Semisynthetic/Synthetic :
Ipratropium, Glycopyrrolate- quaternary
compounds
 Pharmacological actions of atropine

CNS: Atropine mild stimulation in therapeutic dose,

toxic dose results in stimulation followed by
depression.
Hyoscine CNS depression, useful in motion
sickness.
Eye- mydriasis, cycloplegia, abolished light reflex &
dryness of eyes.
Mydriasis : due to paralysis of constrictor pupillae and
unopposed action of dilator pupillae (Indirect or
passive mydriasis).
Abolished light reflex: due to paralysis of constrictor
pupillae.
Cycloplegia: due to paralysis of ciliary muscle
contraction of suspensory ligament of lens lens shape
becomes flat vision focused for far objects
(Cholinomimmetic drugs cause spasm of
accommodation)
Heart increase in HR & AV conduction.
 Mechanisms of Mydriasis

alpha1

M3

#Anti-Muscarinic drugs like atropine cause paralysis of circular muscle by

blocking M3 receptors; unopposed action of radial muscle causes Mydriasis
Sympathetic stimulation causes radial muscle to contract : Mydriasis
 Therapeutic uses
1. Eye- fundoscopy, refractive error
examination, retinoscopy, prevention
of adhesions.
Differences between atropine,
homatropine,cyclopentolate &
tropicamide.??
2. COPD, bronchial asthma- acute
exacebations-Ipratropium given by
MDI or nebulizer.
3.CVS: bradycardia, AV block- atropine .
4. Motion sickness- hyoscine oral, T T S
 Drugs for Mydriasis
Drug Duration of Cycloplegia
Mydriasis
ATROPINE 7 -10 DAYS ++++

HOMATROPINE 3 DAYS +++

CYCLOPENTOLATE 1 DAY ++

TROPICAMIDE 1/4TH OF A DAY +

** Drug of choice for Mydriasis with Cycloplegia: Tropicamide

# Drug of Choice for Mydriasis without cycloplegia: Phenylephrine
( Alpha-1 adrenergic agonist)
6. Pre-anesthetic medication:
glycopyrrolate
7. Mushroom poisoning.- atropine
8.To reduce urine frequency in spastic
paraplegia- oxybutynin.
9. Peptic ulcer- pirenzepine. Not used.
Why??
Physostigmine is a reversible
Atropine poisoning
indirect cholinomimmergic
drug that will inc Ach and will
Signs and symptoms displace atropine from M-rec.

Treatment physostigmine. Why?

Contraindications of atropine
glaucoma
 O.P. Poisoning/War Gases
Ex: Malathion, parathion, War gases
(Tabun, Sarin)
Accidental, homicidal or suicidal
poisoning
account for 80% of pesticide related
hospital admissions.
Acute intoxication results in both
muscarinic and nicotinic signs & CNS
signs.
Hypotension, increased secretions,
 CNS- confusion, loss of reflexes,
convulsions, coma & central respiratory
paralysis.
Respiratory failure- primary cause of death.
Treatment
1. General supportive measures eg.
Termination of exposure, A.B.C., oxygen,
correction of shock.
2. Atropine 2-4mg IV rpt every 5-10min till
signs of atropinization i.e. increase in HR,
dilation of pupils & dryness of secretions.
3. Oximes / Cholinesterase reactivators :
pralidoxime (2-PAM), Obidoxime, diacetyl
mono-oxime (DAM)
 Pralidoxime 1-2gm Iv & rpt after 20-
60min.

Oximes/ Cholinesterase Reactivators

Pralidoxime (PAM), obidoxime, diacetyl
monoxime(DAM).

Form a oxime phosphorus complex at

phosphorylated esteratic site of ChE
enzyme.

Complex undergoes hydrolysis

regenerating ChE enzyme.
Aging of ChE resistant to oximes
 A/E: Nm blockade, headache, diplopia,
tachycardia.

Uses- treatment of OP poisoning

Not useful in carbamate poisoning and

if aging occurs

Dose- 1-2gm IV, can be repeated after

30 mins if required.
Comparison of effects of
Ach & atropine
 Anticholinergics : Must
Know
Atropine: Non selective competitive anti-muscarinic.
--Causes: mydriasis with abolished light reflex and
cycloplegia, dryness of mouth, sedation,
tachycardia, increased body temp, urinary
retention.
--Contraindicated in glaucoma, BPH
Atropine overdose: Treat with physostigmine??
Other drugs: Tropicamide for mydriasis and
cycloplegia, glycopyrrolate for pre-anesthetic
medication, ipratropium for COPD, Scopolamine in
motion sickness, Trihexiphenidyl and beztropine for
drug induced parkinsonism