Anticholinergic drugs

2. ANTICHOLINERGIC DRUGS

4. CLASSIFICATION

6. Quaternary compounds
 poorly lipid soluble .
 Poorly absorbed from GIT.
Cannot cross BBB.
 PERIPHERAL effects.
 NMJ
 NEOSTIGMINE ,
PYRIDOSTIGMINE .
Tertiary amines
HIGHLY lipid soluble .
Good oral absorption
CROSS BBB
CENTRAL effects
CNS, Autonomic organs and
ganglion
Physostigmine .

7. Selective antagonist for muscarinic receptors
 M1. Pirenzepine, telenzepine
 M2. AF-DX116, methoctramine, himbacine,tripitramine.
 M3. Hexahydrosiladifenidiol and darifenacin.

8. BELLADONAALKALOIDS

10. Mechanism of action
Atropine and related compounds compete with ACh and other
muscarinic agonists for the orthosteric ACh site on the
muscarinic receptor.
Antimuscarinic drugs prevents: the release of IP3- the
inhibition of adenylcyclase (That are caused by muscarinic
agonist).

11. Pharmacokinetics
Tertiary amines will absorbed from GIT
Quaternary amines 10-30% absorbed from GIT
Tertiary amines are widely distributed in the body
Quaternary amines limited in their distribution
Atropine is excreted largely as unchanged drug in urine
Only about 1% of the oral dose of scopolamine is excreted in
urine as unchanged
Atropine effects in body remain only for a few hours but in the
eye its effects persist for about 72 hours

12. EFFECTS ON CNS
 Atropine stimulates many medullary centres—vagal, respiratory,
vasomotor.
 By blocking the relative cholinergic overactivity in basal ganglia,
it suppresses tremor and rigidity of parkinsonism.
 High doses cause cortical excitation, restlessness, disorientation,
hallucinations and delirium followed by respiratory depression
and coma.

13. EFFECTS ON CVS
Heart
 Small dose – bradycardia due to blockade of M1 receptors.Larger
dose – tachycardia due to blockade of M2 receptors
 abbreviates refractory period of A-V node and facilitates A-V
conduction.
 P-R interval is shortened
Blood Vessels
 Tachycardia and vasomotor centre stimulation tend to raise BP
 histamine release and direct vasodilator action (at high doses) tend to
lower BP.

14. EFFECTS ON EYE
Mydriasis
Photophobia
Cycloplegia
Dry eye
Increase IOP
M3 Receptors
Alpha 1 receptors

15. EFFECTS ON SMOOTH MUSCLES
M3 blockade.
Tone and amplitude of contractions of stomach and intestine are
reduced; the passage of chyme is slowed—constipation may occur,
spasm may be relieved.
Atropine causes bronchodilatation and reduces airway resistance,
especially in COPD and asthma patients. Atropine attenuates
Inflammatory mediators action by antagonizing the reflex vagal
component.
Atropine has relaxant action on ureter and urinary bladder.

16. Relaxation of biliary tract is less marked and effect on uterus is
minimal.
Effects on glands
decreases sweat, salivary, tracheobronchial and lacrimal
secretion (M3 blockade).
Skin and eyes become dry, talking and swallowing may be
difficult.
Atropine decreases secretion of acid, pepsin and mucus in the
stomach, but the primary action is on volume of secretion so that
pH of gastric contents may not be elevated unless diluted by
food
Since bicarbonate secretion is also reduced, rise in pH of
fasting gastric juice is only modest.

17. Relatively higher doses are needed and atropine is less
efficacious than H2 blockers in reducing acid secretion.
 Intestinal and pancreatic secretions are not significantly
reduced.
 Bile production is not under cholinergic control, so not
affected.
Rise in body temperature occurs at higher doses. Children are
highly susceptible to atropine fever.
 Mild anaesthetic action on the cornea.

18. CLINICAL USES OFANTICHOLINERGICS

19. I. As antisecretory
 Preanaesthetic medication
 Peptic ulcer
 Pulmonary embolism
 To check excessive sweating or salivation, e.g. in parkinsonism.

20. II. As antispasmodic
 Intestinal and renal colic, abdominal cramps: symptomatic relief is afforded if there is
no mechanical obstruction.
 Nervous, functional and drug induced diarrhea.
 Spastic constipation, irritable bowel syndrome: modest symptomatic relief may be
afforded.
 Pylorospasm, gastric hypermotility, gastritis, nervous dyspepsia.
 To relieve urinary frequency and urgency, enuresis in children. Oxybutynin,
tolterodine and flavoxate have demonstrated good efficacy,

21. III. Bronchial asthma, asthmatic
bronchitis, COPD
Orally administered atropinic drugs are bronchodilators, but less effective than
adrenergic drugs; not clinically used.
They dry up secretion in the respiratory tract, may lead to its inspissation and
plugging of bronchioles resulting in alveolar collapse and predisposition to infection.
The mucociliar clearance is also impaired.
Inhaled ipratropium bromide has been found to be specially effective in asthmatic
bronchitis and COPD, though less so in bronchial asthma

22. IV. As mydriatic and cycloplegic
Diagnostic
For testing error of refraction, both mydriasis and cycloplegia are needed.Tropicamide.
Cyclopentolate drops are an alternative.
To facilitate fundoscopy only mydriasis is needed; phenylephrine is preferred, especially
in the elderly. A combination of phenylephrine +tropicamide drops is frequently used.
Therapeutic
Atropine is very valuable in the treatment of iritis, iridocyclitis, choroiditis, keratitis and
corneal ulcer.
It gives rest to the intraocular muscles and cuts down their painful spasm.
Atropinic drugs alternated with a miotic prevent adhesions between iris and lens or iris
and cornea and may even break them if already formed.

23. V. As cardiac vagolytic
 Atropine is useful in counteracting sinus bradycardia
 partial heart block in selected patients where increased
vagal tone is responsible, e.g. in some cases of myocardial
infarction and in digitalis toxicity.

24. VI. For central action
1. Parkinsonism
2. Motion sickness
3. lie detector

25. VII. To antagonise muscarinic effects of
drugs and poisons
 Atropine is the specific antidote for anti ChE and early
mushroom poisoning.
 Atropine or glycopyrrolate is also given to block muscarinic
actions of neostigmine used for myasthenia
gravis,decurarization or cobra envenomation.

26. Dhatura / belladonna Poisoning
Diagnosis Methacholine 5 mg or neostigmine 1 mg s.c.
Treatment
lavage with tannic acid.
dark quiet room.
Cold sponging/ice bags.
Physostigmine 1–3 mg s.c. or i.v. antagonises both central and
peripheral effects.
blood volume, respiration, diazepam.

27. CONTRAINDICATIONS OFATROPINE
 Narrow angle glaucoma
 BPH
 Delayed type of mushroom poisoning
 Pyloric stenosis
 Congestive heart failure with tachycardia
 Patients over the age of 40 years.
 Chronic lung disease.