This document discusses anticholinergic drugs, with a focus on atropine. It provides details on: - Atropine's mechanism of action as a competitive muscarinic receptor blocker. - Its pharmacological effects including mydriasis, tachycardia, dry mouth, constipation, and increased body temperature. - Therapeutic uses such as a pre-anesthetic, to treat peptic ulcers, bronchospasm, Parkinson's disease, and motion sickness. - Atropine poisoning symptoms and treatment involving gastric lavage and physostigmine administration. - Atropine substitutes like hyoscine butylbromide and ipratrop

1. ANTICHOLINERGIC DRUGS
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong

2. Introduction
• Drugs that block Cholinoreceptors have
important clinical effects, some of which are
of great clinical value
• What are the Cholinoreceptors learned so far?
RECALL !

3. Cholinergic Receptors
• Muscarinic and Nicotinic
– M1, M2, M3, M4 ad M5
– NN and NM
• Muscarinic blockers
– Atropine is the prototype – many synthetic and semi synthetics are
available now
– All are competitive blockers
– Conventionally – Anticholinergics (Blocking of ACh action on
autonomic effectors)
• Antinicotinic – are ganglion blockers and myomeural junction
blockers

4. Classification - Anticholinergics
• Natural: Atropine and Hyoscine (scopolamine)
• Semisynthetic derivatives: Homatropine, Atropine methonitrate,
Hyoscine butylbromide, Ipratropium bromide, Tiotropium bromide
• Synthetic Compounds:
 Mydriatics: Cyclopentolate and Tropicamide
 Antisecretory:
 Quartenary ammonium compounds: Propantheline, Oxyphenonium, Clidinium,
Glycopyrrolate, Isopropamide
 Tertiary amines: Dicyclomine, Valethamate, Pirenzepine
 Vasicoselective: Oxybutynin, Flvoxate, Tolterodine
 Antiprkinsonian: Trihexyphenidyl (Benzhexol),
Procyclidine, Biperiden

5. Atropine as Prototype
• Atropine (hyoscyamine) is found in the plant Atropa belladonna, or
deadly nightshade
• Also in Datura stramonium, also known as jimsonweed (Jamestown weed)
or thorn apple
• Scopolamine (hyoscine) occurs in Hyoscyamus niger
• Many antihistaminics: Histamine, Serotonin, & Ergots alkaloids,
Antipsychotic Agents & Lithium and antidepressant drugs have similar
structures and, predictably, significant antimuscarinic effects
Datura stramonium
Atropa belladona

6. Atropine - Chemically
• Atropine: Ester of tropic acid (aromatic acid) + tropine
• Scopolamine: Ester of tropic acid (aromatic acid) + scopine
• Chemically tropine and scopine are closely similar
• Most of the actions of both are similar

7. Atropine - Mechanism
• Atropine causes reversible (surmountable) blockade of
cholinomimetic actions at muscarinic receptors
– blockade by a small dose of atropine can be overcome by a larger
concentration of acetylcholine or equivalent muscarinic agonist
• Atropine is highly selective for muscarinic receptors
• Does not distinguish between the M1, M2, and M3
• Some quaternary amine antimuscarinic agents have
significant ganglion-blocking actions

8. Atropine - Pharmacokinetics
• Absorption:
– The natural alkaloids and most tertiary antimuscarinic drugs are well absorbed from the
gut and conjunctival membranes – some even over the skin (scopolamine)
– Penetrates cornea freely
– Quaternary ones – only upto 30%
• Distribution:
– Atropine and the other tertiary agents are widely distributed in the body
– Scopolamine is rapidly and fully distributed into the central nervous system where it has
greater effects than most other antimuscarinic drugs
– Quaternary derivatives are poorly taken up by the brain
• Metabolism:
– Atropine is metabolized in liver by conjugation and 60% excretes unchanged in urine
– Effects disappear quickly within 2 Hrs except eye

9. Pharmacological Effects - Atropine
• Central Nervous System: Overall CNS stimulant
– Atropine has only peripheral effects and minimal minimal stimulant
effect on CNS – low entry
– Scopolamine has more marked central effects – amnesia and
drowsiness
– Atropine stimulates many medullary centres – vagal, respiratory and
vasomotor
– Depresses vestibular excitation – antimotion sickness property
– Block basal ganglia cholinergic over activity – blocks tremor, rigidity

10. Pharmacological Effects of Atropine –
contd.
• CVS:
– Moderate and high doses: TACHYCARDIA
– Blockade of M2 receptor on SA node (vagal tone decreases HR)
– Higher the vagal tone – more Bradycardia - in young adults
– AVN – Atropine produces PS blockade – higher AV conduction rate (reduced
PR interval in ECG)
– IM/SC injection initially – transient BRADYCARDIA – may be due to inhibition
of prejunctional postsynaptic M1 autoreceptor inhibition (not due to
stimulation of vagal centre)
• Evidenced by Pirenzepine injection does not cross BBB
– BP: Parasympathetic impulses are not involved in maintenance of vascular
tone – little increase due to tachycardia and VMC
• But, histamine release cause direct vasodilatation
– However, No marked effect on BP

11. Pharmacological Effects
of Atropine – contd.
• Eye: Mydriasis
– Topical atropine and other
tertiary antimuscarinic drug -
results in unopposed
sympathetic dilator activity and
mydriasis
– Cycloplegia: desirable in
Ophthalmology
– Photophobia and blurring of near
vision
– IOP rises: hazardous in narrow
angle glaucoma
– Dry Eye: Not desirable

12. Effect of Scopolamine

13. Atropine on Smooth Muscle
• GIT: Relaxation – mediated by M3 blockade
• Contraction of Stomach and Intestine reduced – constpation
• But, less peristalsis suppression – ENS (with other
neurotransmitters involved)
• More effective to exogenous Ach administration
• Respiratory: Bronchodilatation (COPD)
– Also antagonizes Histamine, PG, leucotrienes etc. mediated vagal
overactivity
• Urinary: Relaxation of ureter and bladder – BHP
– Sometemes useful in neurogenic bladder/enuresis

14. Atropine on Glands
• Decreases salivary, sweat, tracheobronchial
tree and lacrimal secretions
– dryness of mouth, dry skin and conjunctiva and
difficulty in swallowing
• Decreases acid pepsin and mucus secretion – and overall
volume (pH changes little) – H2 blockers are more effective
• No effect on intestinal and pancreatic secretion
• No effect on bile production

15. Pharmacological Effects of Atropine –
contd.
• Temperature: Increases – decrease sweating
+ stimulation of temperature regulating
centre in hypothalumus
• Local anaesthetic action: on cornea

16. Various Effects of Atropine

17. Therapeutic Uses Anticholinergics
• Antisecretory:
1. Preanaesthetic medication: atropine, hyoscine
and glycopyrrolate etc.
• To reduce secretions and also halothane induced ventricular
arrhythmia
• To prevent laryngospasm – due to increased secretions
1. Peptic ulcer
2. Pulmonary embolism: reduce pulmonary
secretions induced by embolism
3. Hyperhidrosis

18. • Antispasmodic:
1. Intestinal and renal colic – not in biliary colic
2. Diarrhoea (nervous and drug induced) – Lomotil
3. Pylorospasm, gastric hypermotility, gastritis,
nervous dyspepsia etc.
4. Urinary frequency and urgency and enuresis
(children)
5. Dysmenorrhoea

19. Anticholinergics -Mydriatic and
Cycloplegic - Ophthalmic uses
• Used as eye drop or ointment:
– Diagnostic: Atropine 1% ointment is used
– Measurement of refractive error
– Preferred ones: Homatropine, Tropicamide and
cyclopentolate – shorter action
– However – no cycloplegia in children by newer ones
– Ophthalmic examination of retina – fundoscopy
(shorter acting preferred)
– Therapeutic Uses:
• For resting eye: Iritis, iridocyclitis, keratitis, corneal ulcer etc.
• Alternating with miotics (prevention of synechia)

20. Anticholinergic uses – contd.Anticholinergic uses – contd.
• CVS:CVS:
– Vagolytic - Marked reflex vagal discharge in myocardial infarction and
digitalis toxicity – sinus bradycardia and paretial heart block -
Parenteral atropine or a similar antimuscarinic drugs
• Respiratory:
– Ipratropium Bromide – in COPD and chronic bronchitis
• Improves mucociliary clearance and bronchodilatation

21. Uses Anticholinergics – contd.
– Parkinsonism: Mild cases of parkinsonism (early
cases), Drug induced Parkinsonism and adjunct to
Levodopa
– Motion sickness:
• Hyoscine (scopolamine) is the drug used – Oral, injection
and transdermal patch
• 0.2 mg orally given as prophylaxis before journey
• Not effective in other type of vomiting
– Twilight sleep: sedation and amnesia
• To antagonize Muscarinic effects of Drugs and Poisons: Anti-ChE, Mushroom
poisoning, and to block Muscarinic effects of Neostigmine, Cobra
envenometion

22. Anticholinergic - ADRs
• Commonly occurring but of non serious type
• Mydriasis and cycloplegia – using as antisecretory or
Preanaesthetic medication
• Poisoning:
– Causes:
• Drug overdose
• Consumption of Belladona and Datura seeds
– Symptoms:
• Dry mouth, difficulty in swallowing and talking
• Dry, flushed and hot skin, fever, decreased bowel sound, photophobia
• Excitement, psychotic behavior, delirium and hallucinations
• Hypotension and cardiovascular collapse

23. Atropine Poisoning – contd.
• Diagnosis: Methacholine 5 mg or Neostigmine
1 mg SC – no muscarinic effects
• Treatment:
– Gastric lavage in case of ingestion – tannic acid
– Dark Room
– Cold sponging and ice bags
– Physostigmine 1–3 mg SC or IV
– Maintenance of blood volume, assisted
respiration and Diazepam to control convulsions
– Other supportive measures

24. Anticholinergic - Contraindications
• Glaucoma – Narrow angle (Precipitation of
angle closure)
• BHP – urinary retention
• Acid peptic ulcer diseases (Non-selective
ones) – precipitation of symptoms

25. THANK YOU
• NEXT CLASS ????
• Atropine Substitutes, ganglion stimulants and
blockers

26. Atropine Substitutes - Quarternary compounds
• Incomplete Oral absorption, Poor penetration in Eye and CNS, Longer
acting than Atropine, Higher Nicotinic Blocking Property, NM Blockade
• Drugs:
– Hyoscine Butylbromide: Oesophageal and GIT spastic conditions – Buscopan
– Atropine methonitrate: Abdominal colics and hypercidity
– Ipratropium Bromide: Selective action on Bronchial SM
• Enhanced mucocilliary clearance (contrast to Atropine)
• Slowly acting Bronchodilator - 1-2 Hrs (prophylactic use)
• Acts mainly on larger Central airways (contrast to sympoathomimetics)
• More effective in COPD than Asthma
• Other Drugs – Tiotropium bromide, Propantheline, Oxyphenonium, Clidinium and
Glycopyrrolate

27. Tertiary Amines
• Dicyclomine and valethamate
• Dicyclomine: Direct SM relaxant and weak antispasmodic
– Lesser side effects than Atropine
– Atropine toxicity in infants (not recommended below 6 months)
• Valethmate: Dilatation of Cervix in delayed labour

28. Individual Drugs –
Vasicoselective
• Oxybutynin:
– Specific selectivity for receptors in Urinary bladder and salivary gland (M1/M3)
– Additional smooth muscle relaxation property
– Uses:
• Bladder surgery after urologic surgery
• Spina bifida and nocturnal enuresis
• Involuntary voiding in patients with neurologic disease - children with
meningomyelocele
• Dose: 5 mg BD/tds or local instillation
• Tolterodine – M3 selective
• Flavoxate – similar to Oxybutynin
• Drotaverine: Newer Drug - Non anticholinergic smooth muscle relaxant –
elevation of cAMP/cGMP
– Renal colic, biliary colic, IBS, uterine spasms etc.
– Dose: 40 – 80 mg tds

29. Mydriatics
Homatropine,
Cyclopentolate and
Tropicamide – various
ophthalmological
procedures as substitutes
of Atropine

30. Drugs acting in Autonomic ganglia
• Ganglion stimulants:
– Selective agonists: Nicotine, Lobeline, DMPP and TMA
– Non-selective: Acetylcholine, carbachol, Pilocarpine,
Anticholinesterases
• Ganglion Blockers:
– Competitive blockers:
• Quaternary compounds: Hexamethonium, Pentolinium
• Secondary/tertiary: Mecamylamine, Pempidine
– Persistent depolarizers: Nicotine (large dose) and Anticholinesterases

31. Remember !!!
• Atropine and its Pharmacological Effects
– Therapeutic uses of Atropine
– Mechanism of Mydriasis and Cycloplegia
• Names of Atropine Substitutes with their Uses
– Details of Atropine Substitutes – Ipratropium
bromide
• Treatment of Atropine Poisoning
• Ganglion Stimulants and Blockers Drugs

32. THANK YOU