Antimuscarinic agents

1. CHOLINERGIC BLOCKING
DRUGS
Instructor: Dr.Anant Khot
Course: MBBS

2. Introduction
Cholinergic
receptor
Nicotinic
receptor
Ganglion
blockers
Neuromuscular
blockers
Muscarinic
receptors
Muscarinic
antagonists
Atropin
e
d-TC

3. Antimuscarinic agents
 Natural alkaloids: Atropine, Hyoscine
 Semisynthetic derivatives: Homatropine,
Atropine methonitrate, Hyoscine butyl
bromide, Ipratropium bromide, Tiotropium
bromide
 Synthetic compounds:
 Mydriatics: Cyclopentolate, Tropicamide

4.  Antisecretory-antispasmodics: Quaternary
compounds: Propantheline, Clidinium,
Pipenzolate methyl bromide, Glycopyrrolate
 Tertiary amines: Dicyclomine, Valethamate,
Pirenzepine
 Vasicoselective: Oxybutynin, Flavoxate,
Tolterodine
Antiparkinsonian: Trihexyphenidyl
(Benzhexol),
Procyclidine, Biperiden.

5. Atropine (d,l-hyoscyamine)
 Source: Atropa belladonna (Linnaeus-
Atropos, Belladonna means beautiful
woman in Italian)
 Datura stramonium-( Jimson-weed or
Thorn apple)
 Scopolamine (hyoscine)- Hyoscyamus
niger, or henbane

6. Datura stramonium

7. Hyoscyamus niger (Henbane)

8. Mechanism of action
 Competitive, reversible (surmountable)
blockade Inverse
agonists

9. Actions
 CNS- Atropine (RD)- minimal stimulant
effect
 Scopolamine- CNS depression manifest as
drowsiness, amnesia, fatigue & dreamless
sleep
 In toxic doses (S>A)- Can cause
excitement, agitation, hallucinations &
• Antimotion sickness property
• Blocking cholinergic activity in the basal
ganglia- ↓tremor, rigidity

10. Eye
 Mydriasis – Unopposed symp. Dilator
activity
 Cycloplegia- Paralysis of the ciliary muscle
 Loss of light reflex
 Lens fixed for far vision- Near objects
blurred
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IOT- No change in normal eye
C/I- Shallow anterior chamber or narrow
iridocorneal angle

12. Cardiovascular System
 Heart- Transient initial bradycardia → ↑ HR
with average clinical doses (Tachycardia-
h.dose)
 The resting HR is ↑ by ~35-40 bpm
 AV node- ↓ PR interval (facilitate AV
conduction)
 BV’s: Counteracts the peripheral

13. Smooth muscles
 GIT- ↓ in tone & amplitude of contraction of
stomach & intestine; passage of chyme is
slowed.
 RS: Bronchodilation – Vagal tone
 Genitourinary tract: relaxes smooth muscle of
the ureters & bladder wall & slows voiding. No
significant effect on uterus
 Biliary tract- Mild antispasmodic action
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14. Glands
 Sweat, salivary & tracheobronchial secretions
 ↓ Gastric secretion – volume & amount of acid,
pepsin & mucin
 Pancreatic & intestinal secretions are little
affected
 Miscellaneous:
 Atropine fever- Children are more susceptible
 Local anaesthetic action on cornea
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15. Pharmacokinetics
 Natural alkaloids –rapidly absorbed from
gut, conjunctival membrane, skin
 Distribution- In to CNS (S>A)
 50% metabolized in liver & remaining
excreted unchanged in urine (t1/2 ~4 hrs )
 Effect on the iris & ciliary muscle persist ≥
72 hrs
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16. Atropine -Uses
 Accurate measurement of refractive error in
uncooperative patients E.g.: Young children
 1% ointment – in children < 5 yrs is preferred
 In alternation with miotic - for prevention or
breaking of adhesions in uveitis & iritis-
Homatropine
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17.  Systemic uses:
 AntiChE poisoning
 As cardiac vagolytic to treat bradycardia in
MI
 Antispasmodic & Antisecretory- Lomotil
 Mushroom poisoning- Inocybe species

18. 2/22/2024
free template from www.brainybetty.com
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21. Management
 Gastric lavage with tannic acid
 Physical restraint, in dark room
 Intravenous benzodiazepines- Agitation,
convulsions
 Hydration, temperature reduction with ice water
or evaporative cooling with mist and fans
 Physostigmine- 0.5 mg IV over 5 minutes every 5
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22. Contraindications & DDI
 Individuals with a narrow iridocorneal angle
 Elderly males with prostatic hypertrophy
 DDI: Absorption of most drugs is slowed because
atropine delays gastric emptying- Levodopa,
 Antihistaminics, TCA’s, pethidine- Additive side
effects occur with atropinic drugs.
 MAO inhibitors interfere with metabolism of central

23. Atropine substitutes (Quaternary
compounds)
 Hyoscine butyl bromide: 10 mg tab & 20 mg/ml
 Used for esophageal & gastrointestinal spastic
conditions
 In COPD & Bronchial asthma:
 Ipratropium (SAMA), tiotropium (LAMA),
umeclidinium, aclidinium, glycopyrrolate
 Ipratropium bromide: 40-80 mcg by inhalation

24. A summary of the role of acetylcholine in asthma pathophysiology.
Reinoud Gosens, and Nicholas Gross Eur Respir J
2018;52:1701247
©2018 by European Respiratory Society

25.  It has a gradual onset & late peak (at 40-60 min)
of bronchodilator effect in comparison to inhaled
SABA
 The parasympathetic tone is the major reversible
factor in COPD- SAMA/LAMA is more effective in
COPD
 Tiotropium reduces the incidence of COPD

26.  Propantheline, oxyphenonium, clidinium,
isopropamide are mainly used as antisecretory-
antispasmodic.
 Cimetropium bromide is another quaternary
antispasmodic which is particularly promoted for
irritable bowel syndrome (IBS).
 Glycopyrrolate: 0.2-0.4 mg i.m (0.2 mg/ml)

27. Tertiary amines
 Dicyclomine- 20 mg oral/i.m., children 5- 10 mg
 It has additional direct smooth muscle relaxant
in addition to M1 blockade & antiemetic
properties
 It has been used in morning sickness, motion
sickness, IBS & in dysmenorrhea.
 Infants exhibited atropinic toxicity symptoms (C/I

28.  Valethamate: Anticholinergic-smooth muscle
relaxant
 Used to hasten dilatation of cervix when the
same is delayed during labour & as visceral
antispasmodic- for urinary, biliary, intestinal colic
 Drotaverine: It is a non-anticholinergic smooth
muscle antispasmodic. Acts by inhibiting PDE 4
enzyme & changes in membrane ionic fluxes.
Uses: Used in intestinal, biliary & renal colics, lBS,
uterine spasms etc.
Advantage: No anticholinergic side effects
A/E: Constipation, flushing, headache & ↓BP

29. Urinary Disorders
 TA: Darifenacin, Solifenacin, Oxybutynin,
Tolterodine, fesoterodine. QA: Trospium
 Uses: To relieve bladder spasm after urologic
surgery
 Reducing involuntary voiding in patients with
neurologic disease. E.g.: Children with
meningomyelocele

30. Other
 Parkinson disease: Trihexyphenidyl, procyclidine
and biperiden have more prominent central
antimuscarinic action. They are used in
parkinsonism.
 Motion sickness: Scopolamine by Injection, TDS,
PO

31. Drugs acting on Autonomic
ganglia
 Stimulants:
 Nicotine (Low dose)
 Lobeline
 DMPP
 Varenicline
 Blockers
 Hexamethonium
 Trimethaphan
 Mecamylamine
 Nicotine in large
dose