2. These are the agents which blocks the action of
cholinergic drugs by antagonizing their receptors.
3. • Based on the receptor blockage they are classified into:
Parasympatholytics
Nicotinic
blockers
Ganglion
blockers
Neuromuscu
lar blockers
Muscarinic
blockers
Anticholinergics
5. Anticholinergic drugs
Prototype drug of this category: Atropine
• Natural alkaloid obtained from Solanaceae family (Atropa belladonna).
• Present in racemic mixture (Levo-isomers are more active)
• Highly selective for muscarinic receptors.
• Synthetic substitute can be made which can act on Nicotinic receptor.
6. Pharmacological actions:
1. CNS:
• Overall CNS stimulant but at low doses produce peripheral effects because of
restricted entry into brain.
• Hyoscine produce central effect even at low doses.
• Stimulates medullary centers- vegal, respiratory, vasomotor
• Depresses vestibular excitation –antimotion sickness activity.
• Blocking cholinergic activity in basal ganglia- suppress tremors & rigidity-
antiparkinsonism activity.
• Hight doses causes cortical excitation, restlessness, disorientation of thoughts,
hallucination, delirium followed by respiratory depression and coma.
7. Pharmacological actions:
2. CVS:
a. Heart
• The most prominent effect is tachycardia due to blockade of M2 receptors on the SA
node through which vagal tone decreases HR.
• Atropine abbreviates (shorten) refractory period of A-V node and facilitates A-V
conduction, especially if it has been depressed by high vagal tone.
• P-R interval is shortened.
b. BP
• Does not have any consistent or marked effect on BP.
• Tachycardia and vasomotor center stimulation leads to raise BP, while histamine
release and direct vasodilator action (at high doses) tend to lower BP.
8. 3. Eye:
• Topical instillation of Atropine causes :
• Mydriasis
• Abolition of light reflex (Photophobia)
• Cycloplegia lasting 7–10 days- Ciliary muscle relaxation
• Loss of accomodation
• Blurring of near vision.
• i.o.t. tends to rise in narrow angle glaucoma.
Pharmacological actions:
9. 4. Body temperature:
Due to inhibition of sweating and stimulation of temperature regulating centre in the
hypothalamus.
Rise in body temperature at higher doses.
5. Local anaesthetic:
• Mild anaesthetic action on the cornea.
Pharmacological actions:
10. 6. Glands:
• Atropine block M3 receptor and markedly decreases secretions:
Sweat- skin become dry
Salivary-talking and swallowing may be difficult.
Tracheobronchial
Lacrimal-eyes become dry
• Intestinal and pancreatic secretions are not significantly reduced.
• Bile production is not under cholinergic control & thus not affected.
Pharmacological actions:
11. 7. Smooth muscle:
All visceral smooth muscles are relaxed by atropine (M3 blockade).
• Stomach and intestine- Tone and amplitude of contractions of
are reduced; the passage of chyme is slowed—constipation may occur.
• Bronchodilatation and reduces airway resistance, especially in COPD and asthma
patients.
• Ureter & urinary bladder- Atropine has relaxant action - urinary retention can
occur in older males with prostatic hypertrophy. However, it can be beneficial for
increasing bladder capacity and controlling detrusor hyperreflexia in neurogenic
bladder/enuresis.
• Effect on uterus is minimal.
Pharmacological actions:
12. Pharmacokinetics:
Hyoscine
• More completely metabolized
• Better blood-brain barrier
penetration.
ATROPIN
• Rapidly absorbed from g.i.t.
• Freely penetrate cornea.
• Passage across blood-brain
barrier is somewhat restricted.
• About 50% of atropine is
metabolized in liver.
• Rest is excreted unchanged in
urine.
• t½ - 3–4 hours.
13. SIDE EFFECTS AND TOXICITY
• Belladonna poisoning may occur due to drug overdose or consumption of seeds
and berries of belladonna/datura plant.
• Children are highly susceptible.
• Manifestations are due to exaggerated pharmacological actions:
• Dry mouth, difficulty in swallowing and talking.
• Dry, flushed and hot skin (especially over face and neck)
• Fever
• Difficulty in micturition
• Decreased bowel sounds.
• A scarlet rash may appear.
• Dilated pupil, photophobia, blurring of near vision, palpitation.
• Excitement, psychotic behaviour, ataxia, delirium, dreadful visual hallucinations.
• Hypotension, weak and rapid pulse, cardiovascular collapse with respiratory
depression.
• Convulsions and coma occur only in severe poisoning.
14. Diagnosis
• Methacholine 5 mg or neostigmine 1 mg s.c. fails to induce typical
muscarinic effects.
Treatment
• If poison has been ingested, gastric lavage should be done with tannic acid.
• The patient should be kept in a dark quiet room.
• Cold sponging or ice bags are applied to reduce body temperature.
• Physostigmine 1–3 mg s.c. or i.v. antagonises both central and peripheral
effects but has been found to produce hypotension and arrhythmias in some
cases.
• Other general measures (maintenance of blood volume, assisted
respiration, diazepam to control convulsions) should be taken as
appropriate.
SIDE EFFECTS AND TOXICITY
15. Contraindications
• A narrow iridocorneal angle—may precipitate acute
congestive glaucoma.
• Caution is advocated in elderly males with prostatic
hypertrophy—urinary retention can occur.
16. Interaction
• Absorption
• Absorption of most drugs is slowed because atropine delays gastric emptying.
• Levodopa- slower absorption and greater peripheral degradation of levodopa—less
of it reaches the brain.
• On the other hand, extent of digoxin and tetracycline absorption may be increased
due to longer transit time in the g.i.t.
• Antacids interfere with absorption of anticholinergics.
• Antihistaminics, tricyclic antidepressants, phenothiazines, disopyramide,
pethidine have anticholinergic property—additive side effects occur
with atropinic drugs.
• MAO inhibitors interfere with metabolism of anticholinergic
antiparkinsonian drugs — delirium may occur.
17. Therapeutic uses
1. Antisecretory
• Preanaesthetic medication
• When irritant general anaesthetics (ether) are used, to check increased
salivary and tracheobronchial secretions.
• Peptic ulcer
• Atropinic drugs decrease gastric secretion and afford symptomatic
relief in peptic ulcer, though effective doses always produce side
effects.
• Pulmonary embolism
• These drugs benefit by reducing pulmonary secretions evoked reflexly
by embolism.
18. 2. As antispasmodic
• Intestinal and renal colic, abdominal cramps: symptomatic relief is afforded.
• Nervous, functional and drug induced diarrhea may be controlled to some
extent, but anticholinergics are not useful in infective diarrhoea.
• Spastic constipation, irritable bowel syndrome: modest symptomatic relief
may be afforded.
• Pylorospasm, gastric hypermotility, gastritis, nervous dyspepsia may be
partially suppressed.
• To relieve urinary frequency and urgency, enuresis in children.
19. 3. Parkinsonism
• Central anticholinergics are less effective than levodopa.
• Used in mild cases, in drug induced extrapyramidal syndromes and as adjuvant to
levodopa.
4. Motion sickness
• Hyoscine is the most effective drug for motion sickness.
• The drug should be given prophylactically (0.2 mg oral); action lasts
4–6 hours.
• A transdermal preparation applied behind the pinna 4 hours before
journey has been shown to protect for 3 days.
• Side effects- dry mouth and sedation can occur: driving is risky.
• Dicyclomine is another anticholinergic used for motion sickness.
• Hyoscine is used in ‘lie detector’ test: its amnesic and depressant
action was believed to put the subject ‘off guard’ in the face of
sustained interrogation and sleep deprivation, so that he came out with
the truth.
20. 5. Mydriatic and cycloplegic
Diagnostic
• For testing error of refraction.
• Tropicamide having briefer action has now largely replaced homatropin and do
not cause sufficient cycloplegia in children.
• Atropine ointment (1%) applied 24 hours and 2 hours before is often preferred
for children below 5 years.
• Cyclopentolate drops are an alternative.
• To facilitate fundoscopy only mydriasis is needed.
• A combination of phenylephrine + tropicamide drops is frequently used.
Therapeutic
• Because of its long lasting mydriatic-cycloplegic and local anodyne (pain
relieving) action on cornea they are used in treatment of iritis, iridocyclitis,
choroiditis, keratitis and corneal ulcer.
21. 6. Cardiac vagolytic
• Useful in counteracting sinus bradycardia and partial heart block in
selected patients where increased vagal tone is responsible, e.g. in
some cases of myocardial infarction and in digitalis toxicity.
• However, cardiac arrhythmias or ischaemia may be precipitated.
7. 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.
22. 8. Bronchial asthma, asthmatic bronchitis, COPD
• Orally administered atropinic drugs are bronchodilators, but less
effective than adrenergic drugs; not clinically used.
• Inhaled ipratropium bromide is used in asthmatic bronchitis and
COPD, though less so in bronchial asthma.
• Given by aerosol, it neither decreases respiratory secretions nor impairs
mucociliary clearance, and there are few systemic side effects.
• Tiotropium bromide is an equally effective and longer acting
alternative to ipratropium bromide
23. Other drug s - Qua terna ry co mpo unds
• Incomplete oral absorption(10-30%)
• Poor penetration into eyes and brain
• Slower elimination- long acting
Atropine methonitrate
• 2.5-10mg oral,im
• Use for hyperacidity and
abdominal colics
Hyoscine butyl bromide
• 20-40mg oral,im,sc,iv
• Less potent & longer acting
than atropine
• Use for esophageal and git
spastic conditions
Ipratropium bromide
• 40-80 ug inhalation
• Act on bronchial muscles not
on secretions
• Gradual onset & late peak
(40-60min)- thus used as
prophylactic in bronchial
asthma not for rapid
symptomatic relief during
attack
• Action last for 4-6 hrs
• More effective in COPD than
asthma
• Side effects- dryness of
mouth, cough, scratching
sensations in trachea, bad
taste, nervousness.
Tiotropium bromide
• Newer congener of
ipratropium
• Binds to bronchial M1/M3
receptors
• Thus high selectivity for
bronchial action
• Do not absorb through git
like ipratropium
24. Propantheline
• 15-30mg oral
• Reduce gastric secretion at
low doses
• Thus used in peptic ulcers
and gastritis
• Delays gastric emptying and
thus increases action for 6-8
hrs.
• But not recommended now
for peptic ulcers.
Oxyphenonium
• 5-10mg oral
• Same as propantheline
• But still used for peptic ulcers
and gastrointestinal
hypermotility.
Clidinium
• 2.5-5 mg oral
• Used as antisecretory-antispasmodic,
Peptic ulcer, irritable bowl syndrome,
colic, gastritis, etc
Isopropamide
• 5 mg oral
• Used for hyperacidity, IBS, nervous
dyspepsia.
Other drug s - Qua terna ry co mpo unds
25. Dicycloamine
• 20 mg oral/im
• Direct muscle relaxant
• Antispasmodic with fewer side
effects
• Shows toxicity in infants thus not
recommended to below 6 months of
age
• Posses antiemetic action, thus used
in morning sickness and motion
sickness
Other drugs-tertiary amines
Pirenzepine
• Selective action on M1
receptor thus shows less
side effects
• Used to inhibits gastric
secretions
26. Other actions-Vasicoselective
Oxybutynin
• M1, M3 actions
• High affinity for receptors in urinary
bladder and salivary glands
• Used for detrusor instability
• Causes urinary retention thus used in
nocturnal enuresis, neurogenic bladder,
spina bifida
• Metabolized by CYP3A4, thus dose
should be reduce for the patients who
are on CYP3A4 inhibitors.
Darifenacin &
solifenacin
• M3 selective
• Preferential action on
bladder
• Used for urinary
incontinence
• T1/2-13-19hrs
27. Mydriatics
Atropine Homatropine
10 times less
potent than
atropine
Cyclopentolate Tropicamide
Onset of
action
45-60mins 30-60 mins 20-40mins
Duration of
action
• Pupil
dilation for
30-40 mins
• Cycloplegia
for 1-3 hrs
Mydriasis for
1-3 days
For few hours 3-6hrs
Recovery Weeks 1-2days 1day Within hours
Use Iritis & Uveitis Fund0scopic &
refraction
testing
