Cholinergic Drugs - Pharmacology B. Pharma 5th Semester PDF Notes

Cholinergic Drugs

Content

ANS

•       Cholinergic drugs

•       Pharmacology of acetylcholine

•       Organophosphorous poisoning and its treatment

Intended Learning Outcomes

At the end of this lecture, student will be able to

•       List the cholinergic drugs

•       Explain the pharmacology of acetylcholine

•       Describe pharmacokinetic of Ach

•       Explain organophophorous poisoning

•       Describe treatment of poisoning

Cholinergic Drugs (Parasympathomimetics)

•       + effector cells innervated by cholinergic nerves

•       Ester of choline

–      Acetylcholine, methacholine, carbachol, bethanechol

•       Cholinomimetic alkaloids

–      Pilocarpine, muscarine, arecholine

•       Choline esterase inhibitors (Anticholine esterase)

–      Physostigmine, neostigmine, organophosphorous compounds

Pharmacological Actions of Acetylcholine

CVS

•       Heart

–      + vagus nerve

–      Depress SA Node: negative chronotropic

–      Decrease FOC:  negative Inotropic

–      May cause AV block

–      Increase CV

•       Blood vessels

–      Dilate skin, mucous membrane blood vessels

–      M3 – R: release NO

–      Dilates coronary arteries

–      Doubtful effect: cerebral, pulmonary vessels

–      IV: transient flushing, sense of warmth in skin, throbbing headache

–      Decrease PR – BP Falls

Smooth muscle

•       GIT: increase tone and peristalsis

•       Gall bladder: Contraction

•       Bladder: Detrusor muscle contraction, trigonal sphincter relaxation

•       Bronchial smooth muscle: constriction, bronchospasm

•       Ureter: usually contraction

•       Uterus: inconsistent response

Secretions

•       Increase gastric, intestinal, pancreatic, bronchial, salivary, lacrimal, nasopharyngeal

•       Increase bronchial secretion: accompanied by bronchospasm

•       May result in cough and dyspnea

•       Salivary: profuse and watery

•       Sweat glands: increase sweating

Eye

•       Instillation – no effect

•       Intracarotid injection: miosis

•       Contraction of circular muscle fibers

•       Decrease IOP

•       Increase the drainage of ocular fluid through canal of Schlemm

•       Contraction of ciliary muscle

•       Relaxation of suspensory ligaments

•       Lens bulge into anterior chamber

•       Increase thickness, decrease focal length

•       Vision fixed for short distance

•       Spasm of accomodation

Autonomic ganglia

•       Ach + ganglia

•       Post ganglionic site: Increase NA/ Ach

•       NA:   BP- Peripheral vasoconstriction

•       Large dose: Adrenal medulla +

•       Sustained increase in BP

Myoneural Junction

•       Contraction of skeletal muscle

•       High conc: paralysis by persistent depolarisation

Miscellaneous

•       Essential for normal behaviour and cognition

•       Does not cross BBB

Uses

•       Extreme transient action

•       Not used in clinical practice

•       Substitutes : Effective orally

•       More selective in actions

Cholinergic Drugs

Cholinomimetic alkaloids

•       Pilocarpine (P. microphyllus, P. jaborandi)

•       Muscarine (Amanita muscaria)

•       Arecholine (Areca catechu)

•       Cevimeline

–      M3 agonist

–      Incerase salivary and lacrimal secretion

–      Used in dry mouth  

Choline esterase inhibitors (Anticholine esterases)

•       Inhibits true and peudo choline esterase

•       Prevent inactivation of Ach

Reversible choline esterase inhibitors

•       Natural: Physostigmine

•       Synthetic: Neostigmine, pyridostigmine, ambenonium, demecaium, edrophonium, tacrine, rivastigmine

Irreversible choline esterase inhibitors

•       OPC

•       Useful: Di isopropyl fluorophosphate, metrifonate, echothiophate

•       Insecticides: Fenthion, malathion, sumithion, monocrotophos, octamethyl pyrophosphotetramide

Uses of reversible Anti ChE

•       Glaucoma

•       For decurarisation, Curare poisoning

•       MG

•       GIT: Post-operative paralytic ileus

•       Urinary retention (Rare)

•       AD

•       Snake venom poisoning

Irreversible Anti ChE

•       Absorbed by all the routes

•       Cross BBB

•       Glaucoma: echothiophate

•       Worm infestation: dichlorovos, dichlorofos (Not used)

•       Toxicological importance

OPC Poisoning

Muscarinic effects

•       Eyes: Miosis, spasm of accomodation, head ache, conjunctival hyperemia

•        inhalation: bronchospasm, cough, increases secretions, tightness in chest

•       Ingestion: anorexia, nausea, vomitting, abdominal cramps, tenesmus and diarrhoea

•       Severe bronchospasm, pulm. edema - fatal

Nicotinic effects

•       Fasciculations, twitching, generalised weakness, depolarisation type paralysis

Central effects

•       Giddiness, anxiety, confusion, ataxia, hypotension, respiratory depression, convulsion, coma

•       Death – due to respiratory paralysis

Neurotoxic effects

•       Demyelination of nerve tracts in CNS & PNS

•       Permanent functional derrangements

•       Not related to ChE inhibition

•       Weakness, fatiguability, twitching, loss of tendon reflexes

Treatment of acute OPC Poisoning

•       Remove soiled clothes

•       Wash soiled skin/ eyes

•       Nurse in prone position

•       Clear mouth, throat

•       Insert airway/ intubate

•       Gastric lavage

•       Atropine in sufficient qty.

•       ChE activator: Pralidoxime (1-2 g)

•       Supportive measures: Oxygen, shock treatment

•       Convulsion: Diazepam

•       Vigilance for delayed toxicity

•       Note: Mouth to mouth respiration to be avoided

Summary

•       Cholinergic drugs stimulate effector cells innervated by cholinergic nerves

•       Cholinergic drugs: Ester of choline, Cholinomimetic alkaloids, Choline esterase inhibitors (Anticholine esterase)

•       Acetylcholine actions - mostly inhibitory; stimulatory on digestion and exocrine glands

•       Pralidoxime is the antidote for OPC poisoning

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