autacoids for MBBS second year ppt

1. Autonomic Nervous System
ANTI-CHOLINERGIC
DRUGS
Dr BK Shoraisham
MBBS, MD
Senior Resident
GSVM Medical College,
kanpur

2. •Learning Objectives
•Define cholinergic and anticholinergic drugs and classify them
based on mechanism of action.
•Describe acetylcholine synthesis, release, receptors (muscarinic
& nicotinic), and termination of action.
•Explain the pharmacological actions, therapeutic uses, adverse
effects, and contraindications of cholinergic drugs.
•Explain the pharmacological actions, therapeutic uses, adverse
effects, and contraindications of anticholinergic drugs.
•Differentiate between cholinergic crisis and anticholinergic
toxicity based on clinical features and management.
•Apply knowledge to clinical scenarios, including organophosphate
poisoning and atropine use.

3. ANS

4. Autonomic Nervous System
Cholinergic Drugs
Dr BK Shoraisham
MBBS, MD
Senior Resident
GSVM Medical College
kanpur

5. Parasympathetic Nervous System
• Works to save energy, aids in digestion, and
supports restorative, resting body functions-
Rest & Digest.
–Decrease in heart rate
–Increased gastro intestinal tract tone and
peristalsis
–Urinary sphincter relaxation
–Vasodilation – decrease in blood pressure

6. Cholinergic Receptors
M1 Secretory glands salivation, stomach acid,
sweating, lacrimation
M2 Heart Decreases heart rate 
bradycardia
M3 Smooth muscle
(GI/GU/Resp)
Contraction of smooth
muscles (some)  diarrhea,
bronchospasm, urination
M3 Pupil and ciliary muscle Contracts  Miosis
Increased flow of aqueous
humor
Nm Skeletal muscle end
plate
Contraction of skeletal
muscle
Nn Autonomic ganglia,
Adrenal Medulla
Secretion of Epinephrine
Controls ANS

7. Cholinergic Receptors

8. Cholinergic Receptors

9. Cholinergic Drugs
• Often called parasympathomimetic drugs, because their
action mimics the action of the PSNS.
• Also called as cholinomimetic.
• Stimulate parasympathetic nervous system in same manner
as acetylcholine
• Cholinergic agonists are two types :
• 1.Direct acting
2.Indirect acting

11. Direct acting cholinergic agonist
• They act by binding directly to cholinoceptors.
• Direct acting cholinergics are lipid insoluble.
• Do not readily enter the CNS so effects are peripheral.
• Resistant to metabolism by acetylcholinesterase.
• Effects are longer acting than with acetylcholine.
• Acetylcholine
• Methacholine Muscarine
• Carbachol Pilocarpine
• Bethanechol Arecoline

12. Drug Effects of Cholinergic Agents
• Cardiovascular effects
– Decreased HR( Bradycardia)
– Vasodilation (NO mediated)
• Stimulate intestine and bladder
– Increased gastric secretions
– Increased gastrointestinal motility
– Increased urinary frequency

13. Drug Effects of Cholinergic Agents
• Stimulate pupil
– Constriction (miosis), Spasm of
accomodation
– Reduced intraocular pressure (increased
outflow)
• Respiratory effects
– Bronchial constriction, narrowed airways
• Increased salivation and sweating

14. Drug Effects of Cholinergic Agents
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• Miosis
• Salivation
• Lacrimation
• Urination
• Bronchoconstriction
• Defaecation
• Decreased heart rate

15. Acetylcholine
• One of the main neurotransmitters of the ANS is
acetylcholine
• Acetylcholine is released at preganglionic fibers of
both the sympathetic and parasympathetic nervous
system
• Also released from postganglionic sympathetic
neurons that innervate the sweat glands and from
motor neurons that innervate the skeletal muscles

17. Acetylcholine
• It is a quaternary ammonium compound so cannot
penetrate the membrane.
• Does not have any therapeutic importance, because
rapid inactivation by acetylcholinesterases.
• It has both Muscarinic & Nicotinic actions .

18. Bethanechol
• Not hydrolyzed by acetylcholinesterases.
• Actions:
• Directly stimulates M receptors causing increased
intestinal motility & tone.
• It stimulates detrusor muscle of the bladder while
trigone & sphincters are relaxed causing expulsion of
urine.

19. Bethanechol
• Therapeutic Uses:
• Paralytic ileus
• Urinary retentions
• Helpful for postsurgical atony of the bladder and
GI tract

20. Pilocarpine
An alkaloid, lipid soluble & is stable to hydrolysis by
cholinsterases.
Actions:
When applied locally to cornea produces rapid miosis
& contraction of ciliary muscle produces spasm of
accommodation.
Therapeutic Use :
In Glaucoma it opens trabecular meshwork around
schlemm’s canal
• causes drainage of aqueous humor
• IOP immediately decreases.

21. Indirect acting Cholinergic agonists
• They act through inhibition of Acetyl cholinesterase
enzyme, so increase Acetylcholine level in the synapse.
• Accumulation of acetylcholine then occurs which
enhances the activation of the nicotinic and
muscarinic receptors.
• Anticholinesterase drugs are either reversible or
irreversible inhibitors of acetylcholinesterase.

22. Reversible:
• Neostigmine
• Physostigmine
Echothiopate
• Pyridostigmine
Malathion
• Edrophonium
Soman
• Tacrine
• Donepezil
Irreversible:
Organophosphates
Dyflos,
Parathion,
Tabun, Sarin,
Carbamates
Carbaryl,
Propoxur(baygon)

23. • Physostigmine -
-only anticholinesterase capable of crossing the
blood brain barrier.
-Is more lipid soluble.
-Used as an antidote for overdosage of
anticholinergics such as: atropine,
antihistamines, TCA, phenothiazines.
-May also be used in treatment of glaucoma.

24. • Pyridostigmine -
• is the maintenance drug of choice for
patients with Myasthenia gravis.
• Neostigmine –
• prototype anticholinesterase agent.
• Used for long-term treatment of
myasthenia gravis and as an antidote for
tubocurarine and other non- depolarizing
agents in surgery.

25. • Donepezil -
• Used in the treatment of mild to
moderate Alzheimer’s disease.
• Helps to increase or maintain memory and
learning capabilities.

26. Uses of Indirect Cholinergic agonists
• Glaucoma – Pilocarpine, Physostigmine
• Edrophonium to test Myasthenia gravis,
Neostigmine and pyridostigmine in treatment of
M.gravis.
• Postoperative paralytic ileus - Neostigmine
• Postoperative decurarization –
Neostigmine(reverses muscle paralysis)

27. • Cobra bite – edrophonium (prevent respiratory
paralysis.
• atropine poisoning – Physostigmine
(antogonizes both central and peripheral
effects).
• Alzheimer’s Disease – Donepezil,
galantamine, tacrine, rivastigmine.
• TCA, Phenothiazines overdose -
Physostigmine.

28. Cholinergic Agents: Side Effects
Side effects are a result of overstimulation of the
PSNS.
• Cardiovascular:
– Bradycardia, hypotension, conduction
abnormalities (AV block and cardiac arrest)
• CNS:
– Headache, dizziness, convulsions
• Gastrointestinal:
– Abdominal cramps, increased secretions, nausea,
vomiting

29. Cholinergic Agents: Side Effects
• Respiratory:
–Increased bronchial secretions,
bronchospasms
• Other:
–Lacrimation, sweating, salivation, loss of
binocular accommodation, miosis

30. Acute toxic effects of irreversible
cholinesterase inhibitors (OP poisoning )
• These agents are lipid soluble
• Can enter the body by the eye,skin, respiratory
system and GI tract.
• organophosphate insecticides (malathion, parathion)
or nerve gases (sarin, tabun, soman)
• These agents cause excessive cholinergic
stimulation (muscarinic) and neuromuscular
blockade

33. Treatment of OP poisoning
Emergency treatment includes:
• Decontamination of clothing
• Flushing poison from skin and eyes
• Activated charcoal and lavage for GI ingestion
• Atropine to counteract the muscarinic effects
(2mg IV every 10 min till pupil dilates, max 50-
100mg)

34. • To relieve the neuromuscular blockade by
nicotinic effects, give pralidoxime, a
cholinesterase reactivator.
• Pralidoxime causes the anticholinesterase
poison to release the enzyme
acetylcholinesterase.
• Give Pralidoxime as soon as possible as if too
much time passes, the poison bond becomes too
strong (aging) for the pralidoxime to work.

36. Aging
The process by which the organophosphate–acetylcholinesterase
(AChE) complex becomes permanently inactivated due to loss of an
alkyl group, making the enzyme irreversible and non-reactivable by
oximes.
1.OP binds to AChE
1.OP phosphorylates the active site of AChE.
2.Initially reversible stage
1.At this stage, pralidoxime (2-PAM) can remove OP and reactivate
AChE.
3.Aging occurs
1.OP–AChE complex loses an alkyl group.
2.Bond becomes stronger and permanent.
4.After aging
1.Pralidoxime cannot reactivate AChE.

37. • Drugs that block or inhibit the actions of
acetylcholine (ACh) in the parasympathetic
nervous system (PSNS).
• Also called cholinergic blocking agents or
parasympatholytics.
• Often referred to as anticholinergics or
antimuscarinics
What are anticholinergics

38. Mechanism of Action
• Competitive antagonists
• Compete with acetylcholine
• Reversible blockade of acetylcholine at
muscarinic receptors by competitive binding
• Once these drugs bind to receptors, they inhibit
nerve transmission at these receptors.

39. ANTICHOLINERGIC DRUGS

40. Atropine
• Prototype antimuscarinic drug - derived from
Atropa belladonna (deadly nightshade), Datura
stramonium (thorn apple) and Hyoscyamus niger
(Black Henbane

41. Atropine
History:
• plant extracts were used as
cosmetic eye drops
• hence the name belladonna or
"beautiful lady" in Italian

42. Actions
Cardiovascular effects-
• Decreased cardiovascular response to vagal
stimulation resulting in tachycardia
• Tachycardia due to antagonism of the vagal affect.
• Vascular
– no (direct) effect
– except, dilate cutaneous vessels (red as a beet)
– block hypotensive effect of muscarinic agonists

43. Actions
CNS –
• At normal doses atropine stimulates
medullary centers, However, at higher
doses produce excitement, agitation,
hallucinations and coma.
• Depresses vestibular excitation and has
anti motion sickness properties
• Supresses tremor and rigidity of
parkinsonism by blocking cholinergic
overactivity in basal ganglia.

44. Actions
Eye:
• Dilated pupils (mydriasis)
• Blocks muscarinic innervations on the
circular muscles (Mydriasis) and relaxes
cilairy muscles (Cycloplegia)
• Worsens glaucoma

45. Actions
Gastrointestinal:
• Relax smooth muscles of GI tract
• Decrease intestinal and gastric secretions
• Decrease motility and peristalsis
• antispasmodic effect
• ­Sphincter contraction

46. Respiratory system -
• Decreases bronchial secretion (used as
preanesthetic Medication, COPD)
• Dilated bronchial airways (used for treatment of
Asthma)
Actions

47. Genitourinary -
• Relaxes detrusor muscle
• Increased constriction of internal sphincter
• Result: urinary retention
• Relaxation of smooth muscles of ureters.
• Therefore, they are contraindicated for prostate
hypertrophy patients.
Actions

48. Glandular –
• (-)Salivary secretion (Dry mouth)
• (-) gastric Acid (used for Peptic Ulcer )
• (-) Sweating ® Dry skin
• (-) Bronchial Secretion (used for COPD)
Actions

50. Therapeutic Uses
• Antidote Uses (Toxicology)
Atropine is a life-saving antidote for poisoning by
agents that excessively stimulate the cholinergic
system.
•Organophosphate Poisoning: This is a major
indication.
•Carbamate Insecticide Poisoning
•Certain Mushroom Poisoning: Effective against
mushrooms that contain muscarine (e.g., Amanita
muscaria).

51. Treatment of OP poisoning
Emergency treatment includes:
• Decontamination of clothing
• Flushing poison from skin and eyes
• Activated charcoal and lavage for GI ingestion
• Atropine to counteract the muscarinic effects (2mg IV
every 10 min till pupil dilates, max 50-100mg)

52. • To relieve the neuromuscular blockade by
nicotinic effects, give pralidoxime, a
cholinesterase reactivator.
• Pralidoxime causes the anticholinesterase
poison to release the enzyme
acetylcholinesterase.
• Give Pralidoxime as soon as possible as if too
much time passes, the poison bond becomes too
strong (aging) for the pralidoxime to work.

53. Therapeutic Uses
Central Nervous System Disorders-
• Parkinson’s disease –
Benztropine,Trihexyphenidyl
• Those who cannot take Levodopa
• Helpful in decreasing salivation, spasticity and
tremors
• Motion Sickness (Scopolamine)
• Drug-induced extrapyramidal reactions(due to
antipsychotics)

54. •CVS –
• Atropine is used to increase heart rate in
symptomatic bradycardias.
• Sinus node dysfunction
• Symptomatic second-degree heart block
• Sinus or nodal bradycardia (due to myocardial
infarction)
Therapeutic Uses

55. Respiratory system-
• Exercise-induced bronchospasms
• Chronic bronchitis
• Asthma
• Chronic obstructive pulmonary disease
• Ipratropium as inhalation (or Tiotropium)
Therapeutic Uses

56. Gastrointestinal agents
• Peptic Ulcer: Pirenzepine
• As antispasmodic : Butylscopolamine
• Irritable bowel disease: Propantheline
• GI hypersecretory states
Therapeutic Uses

57. Urologic disorders-
• Antispasmodic effects seen in overactive bladder and
in urinary incontinence- Oxybutynin
• Detrusor hyper-reflexia
• Enuresis
-Increase bladder capacity
-Decrease bladder pressure
Therapeutic Uses

58. Opthalmological Disorders-
• Homatropine, tropicamide
• Accurate measurement of refractive error in
uncooperative patients (e.g, children)
• Examination of retina (Mydriasis)
Therapeutic Uses

59. Side Effects of anticholinergics
Cardiovascular
CNS
Increased heart rate,
dysrhythmias
Excitation, restlessness,
irritability, disorientation,
hallucinations,delirium

60. Eye
Gastrointestin
al
Dilated pupils, decreased visual
accommodation, increased
intraocular pressure
Decreased salivation, decreased
gastric secretions, decreased
motility
Side Effects of anticholinergics

61. Genitourinary Urinary retention
Glandular Decreased
sweating
Respiratory Decreased bronchial
secretions
Side Effects of anticholinergics

65. Toxicity of Anticholinergics
• Anticholinergic overdose
syndrome (Belladona
poisoning- consumption of
seeds or berries of belladona
or dhatura plant) is
characterized by:
- Hyperthermia, delirium, dry
mouth, tacycardia, ileus, urinary
retention. Seizures, coma and
respiratory arrest may occur.

66. Toxicity of Anticholinergics
• Treatment –
- Gastric lavage with tannic acid, cold
sponging or ice bags, Physostigmine s.c.
or i.v., diazepam to control convulsions.

67. Contraindications
• Glaucoma
• Prostatic hypertrophy
• Urinary tract obstruction
• Gastrointestinal tract obstruction
• Infectious diarrhea
• Reflux esophagitis
• Tachyarrhythmias
• Angina
• Hyperthyroidism
• Pregnancy

68. Individual Drugs
• Atropine - prototype. Antidote in OP Poisoning.
• Ipratropium - Useful in rhinorrhea. Also excellent
bronchodilator.
• Scopolamine - depresses CNS and causes amnesia,
drowsiness, euphoria, relaxation and sleep. Also good for
motion sickness. Given parenterally, orally and
transdermally.
• Benztropine - temporary use in Parkinson’s disease.

69. Individual Drugs
• Trihexyphenidyl - also used for treating EPS by some
antipsychotics. Contraindicated in glaucoma.
• Flavoxate - relieves dysuria, urgency, frequency, and
pain with GU infections
• Oxybutynin - has direct antispasmodic effects on
smooth muscle and anticholinergic effects. Decreases
frequency of voiding.

70. Feature Myasthenic Crisis Cholinergic Crisis
Basic cause Under-treatment of Myasthenia Gravis Over-treatment with
anticholinesterase drugs
Pathophysiology ↓ Acetylcholine (ACh) at neuromuscular
junction due to insufficient AChE
inhibition
↑ Excess ACh causing continuous
stimulation depolarization
→
block
Drug status Inadequate dose or missed dose of
neostigmine / pyridostigmine
Excess dose of neostigmine /
pyridostigmine
Neuromuscular
weakness
Present and progressive Present and worsening
Muscle fasciculations Absent Present (due to excess ACh)
Muscarinic symptoms Absent Present (SLUDGE/DUMBELS)
Autonomic signs Normal or mild Bradycardia, miosis, sweating,
salivation, diarrhea
Pupils Normal or dilated Constricted (miosis)
Respiratory failure Due to worsening MG weakness Due to bronchoconstriction +
respiratory muscle paralysis
Response to Improves muscle strength Worsens weakness