ANTICHOLINERGIC DRUGS

Presented by:
Dr. Vishal
kr. Kandhway
 ANTICHOLINERGIC DRUGS
Anti cholinergic drugs
Are those which antagonise the effect of neurotransmitter
Acetylcholine (ACh) on autonomic effectors & in the CNS
exerted through “Muscarinic receptors”. Though nicotinic
antagonists also block certain actions of Ach, they are
referred to as “Ganglion blockers” & “Neuromuscular
blockers”
• Muscarinic receptor site-
• Heart
• Salivary glands
• Smooth muscles of GIT
• Genitourinary tract
• Urinary bladder
• Nicotinic acetyl choline receptor site-
– Nerve endings of neuromuscular junction.
• Acetylcholine is also the neurotransmitter at
postganglionic nicotinic receptors located at
the NMJ (Neuromuscular junction) &
autonomic ganglia.
• Effects of anticholinergic drugs at nicotinic
cholinergic receptors is little / nil as compared
at muscarinic receptors.
• Anticholinergic drugs are considered –
selectively antimuscarinic.
Naturally Occurring (Tertiary Amine)
Atropine Scopolamine
(Alkaloids of belladonna plants

Synthetic compound
(Glycopyrrolate)
(Quaternery Ammoniums
Derivatives)

• More potent than parent

compounds
• Lack CNS activity because of
poor penetration in brain
 Classification
• Natural alkaloid – Atropine,
Scopolamine(hyoscine)

• Semi-synthetic derivative – Homatropine,

Atropine mithonitrate, Ipratropium bromide.

• Synthetic compound –
a) Mydriatics : Cyclopentolate, tropicamide

b)Anti-seceretory -
Quarternary : Glycopyrolate, Propantheline,
Isopropamide.

Tertiary amines : Pirenzepine, Dicyclomine

c)Vasicoselective : Oxybutynin, flavoxate.

d)Anti-parkinsonian : Benzhexol, biperiden.

 Mechanism of action
• Anticholinergic are the class of drugs that
block the neurotransmitter acetylcholine in
CNS and PNS.

• Anticholinergic drugs combine reversibly with

muscarinic cholinergic receptors thus
preventing access of neurotransmitter
acetylcholine in these sites.
 Muscarinic Receptor Subtypes
M1 M2 M3 M4 M5
Location • CNS • Heart • CNS • CNS • CNS
• Stomach • CNS • Salivary • Heart
• Airway glands
Smooth • Airway
Muscle smooth
muscle
• Vascular
endothelial
cells
Clinical Effects • Hydrogen • Bradycardia • Salivation ? ?
Ion Secretion • Bronchodilati
on
• Vasodilation
Clinically Yes No No No No
selective drugs
available
 Atropine
• Atropine sulphate is a tertiary amine & the
naturally occuring levorotatory form is active.
• Administered IV/IM in a range of 0.01-0.02
mg/kg upto adult dose of 0.4-0.6 mg.
• Larger IV doses upto 2 mg may be required to
completely block the cardiac vagal nerves in
treating severe bradycardia.
 Pharmacological Actions
• CNS :
-Atropine has CNS stimulant action. However
these effects are not appriciable at low doses.
-Atropine stimulates many medullary centres –
vagal, respiratory, vasomotor.
- It depresses vestibular exitation and has anti-
motion sickness property.
- It supresses tremor & rigidity of parkinsonism.
- High doses cause cortical exitation, restlessness,
disorientation, hallucination & delirium followed
by respiratory depression & coma.
• CVS :
- Most prominent effect is to cause tachycardia
due to blockade of M2 receptors at SA node.

• Eye :
- Topical instillation of atropine causes
mydriasis, abolition of light reflex and
cycloplegia resulting in photophobia &
blurring of near vision.
• Smooth muscles :

- All visceral smooth muscles that receive

parasympathetic motor innervation are relaxed
by atropine due to M3 blockade.
- Tone & amplitude of contractions of stomach &
intestine are reduced, the passage of chyme is
slowed – constipation may occur & spasm may be
relieved.
- Atropine causes bronchodilatation & reduces
airway resistance especially in COPD & Asthma
patients.
- Atropine has relaxant action on ureter & urinary
bladder.
• Glands :
- Atropine markedly decreases sweat, salivary,
tracheobronchial & lacrimal secretions by M3
blockade.
- Skin & eyes become dry, talking & swallowing
may be difficult.
• Body temperature :
- Rise in body temperature occur at high doses due
to both inhibition of sweating as well as
stimulation of temperature regulating centre in
the hypothalamus.
- Children are highly succeptible to Atropine fever.
• Local anaesthetic : Atropine has mild anesthetic
action on the cornea.
• Sensitivity of different organs & tissues to
atropine varies & can be graded as –

• Saliva, sweat, bronchial secretion > eye,

bronchial muscle, heart > smooth muscle of
intestine, bladder > gastric glands & smooth
muscles.
 Uses
• As anti-secretory :
- Pre-anesthetic medication : reduces excessive
salivation & respiratory secretions.
- Peptic ulcer : decreses gastric secretions &
provide symptomatic relief in peptic ulcer now
been superseded by H2 blockers.
• As anti-spasmodic :
- If there is no mechanical obstruction intestinal &
renal colic, abdominal cramps symptomatic relief
is affordable.
- Gastritis, gastric hypermortility.
- To relive urinary frequency & urgency.
• Can be given in patients of Bronchial Asthma
• As mydiatric & cycloplegic.
• As cardiac vagolytic
• For central actions in Parkinsonism as an
adjuvant to levodopa.
• To antagonise muscarinic effects of anti-
Cholinesterase i.e OP Poisoning with dose 2mg
IV with repeated doses and early mushroom
poisoning.
 Side effects
• Belladona poisoning due to drug overdose.
• Dry mouth, difficutly in swallowing and talking.
• Dry ,flushed and hot skin.
• Fever difficulty in micturition , decreased bowel
sounds.
• Dilated pupil, photophobia, blurring of near
vision.
• Excitement, ataxia, delirium, hallucination.
• Convulsion and coma may occur in severe
poisoning.
• Treatment :
Physostigmine 15- 60 micro gram / kg IV every
1- 2 hourly.
• Contraindications :
- Narrow angle glaucoma
- BPH
- Hyperthyroidism
- CAD
 Glycopyrolate
• Glycopyrolate is a synthetic product that differs from
atropine in being a quaternary amine.
• The pre-medication dose is 0.005 – 0.01 mg/kg upto 0.2-0.3
mg in adults.
• Clinical consideration :
• Because of its quaternary structure, glycopyrolate can’t
cross BBB & is almost devoid of CNS & Opthalmic activity.
• Potent inhibition of salivary gland & respiratory tract
secretions is the primary rationale for using glycopyrolate
as pre-medication.
• Heart rate increases after IV administration.
• It has longer duration of action than atropine sulphate i.e 2-
4 hrs.
 Scopolamine
• Scopolamine is a naturally occuring tertiary amine.
• It’s dose is 0.3-0.5 micro gram I/M.
• Clinical Consideration :
• Lipid soluble.
• Easy penetrate BBB.
• More potent antisialagogue than Atropine & causes
greater CNS effects
• Clinical doses results in restlessness, drowsiness,
amnesia, dizziness & delirium.
• It has the added virtue of preventing motion sickness.
• The lipid solubility allows trans-dermal absorption &
has been used to prevent post-operative nausea &
vomiting
• Best avoided in patients with closed angle glaucoma.
 Differences
Atropine Glycopyrrolate
1. Lipid solubility - Lipid soluble - Poorly soluble (Quaternary
ammonium compound)
2. Blood brain - Good - Minimum ability of crossing
barrier crossing BBB
3. Metabolization - 50% from liver -
4. Excretion - 18% unchanged - 80% unchanged
5. Treatment - bradycardia at low dose Intra operative bradycardia
- 0.2 – 0.4 mg IV

-Dose for intra operative

bradycardia
1.2 mg

-Max dose for bradycardia

3 mg
Hiccups (Occurring after
laryngeal mask placement)
 Differences
Atropine Glycopyrrolate
7. Effect on smooth Decreases tone of smooth
muscles muscles of biliary tract & ureter
8. Antisialagauge - Less then scopolamine More
effect
9. T½ - 2.3 hrs Prolonged in uremic patients
1.25 hrs
 Comparative effects of anticholinergic drugs
Sedation Antisialagogue Increase Heart Relax smooth
Rate Muscles
Atropine + + +++ ++
Scopolamine +++ +++ + +
Glycopyrrolate 0 ++ ++ ++

Mydriasis Prevent Decrease Alter Fetal

cycloplegia Motion Gastric Heart Rates
induced Hydrogen Ion
Nausea secretion
Atropine + + + 0
Scopolamine +++ +++ + ?
Glycopyrrolate 0 0 + 0
 Central Anticholinergic Syndrome
• Anticholinergic drugs like scopolamine, atropine can
enter central nervous system (CNS) and produce some
unusual symptoms which are characterized in a
syndrome which is known as central anticholinergic
syndrome.
Symptoms are -
– Restlessness
– Hallucination to somnolence
– Unconsciousness

Glycopyrrolate does not easily cross BBB & not likely

cause CACS.
• References :-
Stoelting’s Pharmacology & Physiology.
Morgan & Mikhail’s Clinical Anesthesiology.
KD Tripathi Essentials of Medical Pharmacology.
THANK YOU