Dr. Manoj Kumar presented on anticholinergic drugs. He discussed how they block the action of acetylcholine through muscarinic receptor antagonism. Atropine was highlighted as the prototypical anticholinergic, being a tertiary amine that competitively blocks muscarinic receptors. Its widespread effects include drying secretions, pupil dilation, tachycardia, urinary retention, and relief of Parkinson's symptoms. Adverse effects include dry mouth, blurred vision, fever, and delirium at high doses.

1. presented
By
Dr. Manoj Kumar
Assistant Professor
Dept. of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

2. Introduction
Anticholinergic Drugs – Block the Action of ACh
 Divided into Muscarinic & nicotinic Subgroup
 Anti Nicotinic Drugs – Ganglion blockers & NMJ
blockers
 Muscarinic Antagonist – Parasympatholytic drugs also
Anti Muscarinic Drugs – Atropine prototype – block the
action ACh induced contractions in Guinea pig Ileum
 Competitive antagonist
3/21/2023 Dept of Pharmacology

3. Classification
 Natural Alkaloids – Atropine, Hyoscine
 Semisynthetic Derivative – Homatropine, Atropine
Methonitrate, Ipatropium Bromide
 Synthetic derivatives –
Mydriatics – Cyclopentolate, Tropicamide
Antisecretory-antispasmodic –
1. Quarternary compounds – Propantheline, Clidinium,
Glycopyrrolate
2. Tertiary Compounds – Dicyclomine, Pirenzepine
Antiparkinsonian Drugs – Trihexyphenidyl,
Benztropine, Biperiden
3/21/2023 Dept of Pharmacology

4. Atropine
 Atropine sulphate is a tertiary amine & the
naturally occurring 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.
3/21/2023 Dept of Pharmacology

5. Mechanism of Action
 Atr – Reversible blockade of Cholinomimetic action
- prevents release of IP3/ inhibition of ACh
 Effectiveness varies with tissue & source of agonist –
Salivary, bronchial & sweat gland most sensitive &
gastric cells.
 More effective on Exogenous Muscarinic agonist
3/21/2023 Dept of Pharmacology

6. 3/21/2023 Dept of Pharmacology

7. Pharmacological Actions CNS : -
 Atropine has CNS stimulant action.
 These effects are not appreciable at low doses.
 Atropine stimulates many medullary centers –
vagal, respiratory, vasomotor.
 It depresses vestibular excitation and has anti-
motion sickness property.
 It suppresses tremor & rigidity of parkinsonism.
3/21/2023 Dept of Pharmacology

8. Organ System effects - CNS
 High doses cause cortical excitation, restlessness,
disorientation, hallucination & delirium followed
by respiratory depression & coma.
 Scopolamine – marked effect – Drowsiness to
amnesia, in toxic doses – excitement,
disorientation, delirium, agitation, hallucination,
coma.
3/21/2023 Dept of Pharmacology

9. CVS : -
 Most prominent effect is to cause tachycardia due
to blockade of M2 receptors at SA node.
 In large doses vasodilatation and hypotension in
coetaneous blood vessels (Atropine flush)
 In therapeutic doses has no significant effect on
the BP.
3/21/2023 Dept of Pharmacology

10. Organ system effect Eye –
 Topical instillation of atropine causes mydriasis by
blocking muscarinic receptors in sphincter pupillae.
 Abolition of light reflex
 Photophobia & blurring of near vision.
 Weakening of contraction of ciliary muscle – Cycloplegia.
 Reduction of Lachrymal secretion,
 Increase in IOP
3/21/2023 Dept of Pharmacology

11. Respiratory system –
 Even in normal individual – Bronchodilation &
reduction in secretion significant in Airway disease
– effectiveness limited as block of auto inhibitory
M2 opposes Bronchodilation by block of M3.
 Used prior to GA
3/21/2023 Dept of Pharmacology

12. Smooth muscles : -
 All visceral smooth muscles that receive parasympathetic
motor innervations are relaxed by atropine due to M3
blockade.
 Genitourinary Tract –
 Atropine Relaxes Sm of Ureters, bladder, which cause
urinary retention in elderly men
3/21/2023 Dept of Pharmacology

13. Organ system effect GIT –
 Dry mouth
 Gastric secretion blocked – vol & amt of acid, pepsin
& mucin reduced.
 Basal secretion more effectively blocked, Pirenzepine
& Telenzepine, tone & propulsive movement
decreased, prolongs gastric emptying & intestinal
transit time.
3/21/2023 Dept of Pharmacology

14. Glands : -
 Atropine markedly decreases sweat, salivary,
tracheobronchial & lacrimal secretions by M3
blockade.
 Skin & eyes become dry.
 Talking & swallowing may be difficult.
3/21/2023 Dept of Pharmacology

15. 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 susceptible to Atropine fever.
3/21/2023 Dept of Pharmacology

16. 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.
3/21/2023 Dept of Pharmacology

17. Drugs
 Atropine Methonitrate – abdominal colics,
hyperacidity, bronchial asthma, asthmaticus bronchitis
 Ipatropium - bronchial muscle
 Propantheline – peptic ulcer, gastritis
 Clidinium – with benzodiazepines for nervous
dyspepsia, gastritis, irritable colon, peptic ulcer
 Glycopyrrolate – rapidly acting for pre anesthetic
medication
 Dicyclomine –direct smooth muscle relaxant effect
 Drotaverine – non anti-cholinergic smooth muscle
antispasmodic inhibits Phosphodiesterase-4,
 AE – headache, dizziness, constipation, flushing
3/21/2023 Dept of Pharmacology

18. Uses
 As anti-secretory :
 Pre-anesthetic medication : reduces excessive
salivation & respiratory secretions.
 Peptic ulcer : decreases gastric secretions & provide
symptomatic relief in peptic ulcer now
 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.
3/21/2023 Dept of Pharmacology

19. .
 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 antagonize muscarinic effects of anti-
Cholinesterase i.e. OP Poisoning with dose 2mg IV
with repeated doses and early mushroom poisoning.
3/21/2023 Dept of Pharmacology

20. Therapeutic Applications
 CNS disorders – Parkinson's Disease – practice of
poly pharmacy.
 Motion Sickness – sea sickness – scopolamine – inj,
po, TTS, lie detector
 Ophthalmologic disorders – Accurate measurement
of refractory error in uncooperative patients,
 Examination of retina, not used unless mydriasis
required for prolonged duration
 prevents synechia formation in uveitis & iritis
3/21/2023 Dept of Pharmacology

21. Therapeutic Applications
 Respiratory Disorders – Pre anesthetic medication
(Ether) – Decrease Secretion, amnesia,
 Asthma – hyperactive Neural bronchoconstrictor
reflex
 Ipatropium used – Through aerosol. Also COPD
3/21/2023 Dept of Pharmacology

22. Therapeutic Applications
 CVS – Parenteral Atr for depressed SAN/ AVN
following AMI, in Hyperactive carotid sinus
reflexes,
 In Idiopathic dilated cardiomyopathy –
Circulating AB – Parasympathomimetic action
3/21/2023 Dept of Pharmacology

23.  GIT – Traveler’s diarrhea, hypermotility disorder,
in peptic ulcer,
 Nervous & drug induced diarrhea, spastic
constipation, irritable colon,
 Urinary Disorder – symptomatic relief in urinary
urgency,
 Oxybutynin – after urologic surgery
3/21/2023 Dept of Pharmacology
Therapeutic Applications

24. Therapeutic Applications
 Cholinergic Poisoning – Antimuscarinic therapy (to
reverse muscarinic effect – tertiary amine – 1-2 mg every
5-15 min till reversal of miosis),
 Cholinesterase regenerator Compounds (Oxime agents
–Pralidoxime (PAM) – 1-2 g every 15-30 min,
Diacetylmonoxime (DAM) not for Carbamates reversal)
 Other application – Hyperhidrosis
3/21/2023 Dept of Pharmacology

25. Side effects
 Belladona poisoning due to drug
overdose.
 Dry mouth, difficulty 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.
3/21/2023 Dept of Pharmacology

26. Diagnosis -
 – Methacholine/neostigmine inj fail to induce
muscarinic effects
 Treatment Symptomatic
 Contraindication – Glaucoma, history of
Prostatic hyperplasia, acid peptic disease (non
selective)
3/21/2023 Dept of Pharmacology

27. 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 :
 Glycopyrolate can’t cross.
 Potent inhibition of salivary gland & respiratory tract
secretions
 Glycopyrolate as pre-medication.
 Heart rate increases after IV administration.
 It has longer duration of action than atropine sulphate
i.e 2- 4 hrs.
3/21/2023 Dept of Pharmacology

28. Scopolamine
 Scopolamine is a naturally occurring 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
 Avoided in patients with closed angle glaucoma.
3/21/2023 Dept of Pharmacology

29. 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 CAS.
3/21/2023 Dept of Pharmacology

30. 3/21/2023 Dept of Pharmacology