Cholinergic & Anti-Cholinergic Mechanisms& Drugs Flashcards
Two types of cholinergic receptors
Nicotinic
Muscarinic
Synthesis of ACH
choline acetyl transferase
Choline + Acetyl CoA ——————> Acetyl Choline
Degradation of Ach
- Ach is broken down by Acetyl choline esterase
- to form choline + acetic acid
Which drugs are direct acting cholinergic agonist
Acetylcholine
Methacholine
Bethanecol
Pilocarpine
ACETYLCHOLINE MOA & Therapeutic Use
MOA :
binds to muscarinic/nicotinic AChR → direct AChR agonism
Therapeutic use:
to produce MIOSIS during ophthalmic surgery
BETHANECOL MOA & Therapeutic Use
MOA :
Bind to muscarinic AChR → direct AChR agonism
-Shows mild nicotinic agonism
Therapeutic Use:
↑ intestinal motility postoperatively
-Treat urinary retention ( inability to empty the bladder) by causing the detrusor muscle to contract during micturition.
METHACHOLINE MOA & Therapeutic Use
MOA:
binds to muscarinic AChR → direct AChR agonism
Therapeutic Use: Diagnosis of asthma and bronchial hypersensitivity
PILOCARPINE MOA & Therapeutic Use
MOA:
Binds to muscarinic AchR -> direct receptor agonism
Therapeutic uses:
Good stimulator of miosis
Good at stimulating opening of trabecular meshwork around canal of Sclemn ► used treatment of glaucoma.
Adverse Effects:
Crosses the BBB -> hallucinations, convulsions & generalized cholinergic stimulation
PILOCARPINE MOA & Therapeutic Use
MOA:
binds to muscarinic AChR → direct AChR agonism
Therapeutic Use:
- Good stimulator of miosis
- Good at stimulating the the opening of the trabecular network around the canal of sclemn in the treatment of glaucoma.
Adverse Effects:
- can cross the BBB
- causing hallucinations, convulsions & generalized cholinergic stimulation
Which drugs are indirect acting cholinergic agonist ( aka ACHE inhibitors)
Physostigmine
Neostigmine
Pyridostigmine
Edrophonium
Physostigmine MOA , Therapeutic Use &
Adverse Effects
MOA:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels in synapse
Therapeutic Use:
Use to treat Atropine, phenothiazine & tricyclic antidepressants overdose.
Adverse Effects:
Convulsions
Muscle paralysis secondary to overstimulation
Generalized cholinergic stimulation
Neostigmine MOA , Therapeutic Use &
Adverse Effects
MOA:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels in synapse
Therapeutic Use:
Treatment of:
-Myasthenia gravis
-Postoperative and paralytic ileus and urinary retention
-Postoperative reversal of neuromuscular blockade
Adverse Effects:
- Excessive cholinergic stimulation
Endophonium MOA , Therapeutic Use &
Adverse Effects
MOA:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels in synapse
Therapeutic Use:
Used to diagnose myasthenia gravis
Used to differentiate MG from cholinergic crisis (excessive Ach)
Adverse Effects:
Excessive cholinergic stimulation
Pyridostigmine MOA , Therapeutic Use &
Adverse Effects
MOA:
Inhibit AchE → ↓ breakdown of ACh → ↑ ACh levels in synapse
Therapeutic Use:
- Used for long term treatment of myasthenia gravis
- Longer action compared to neostigmine
Adverse Effects
Excessive cholinergic stimulation
What are organophosphates
IRREVERSIBLE anticholinesterases
- irreversibly inhibits AchE
Cholinoesterase inhibitor
PRAILDOXIME
Drug used to sea skickness
SCOPOLAMINE
Therapeutic uses of atropine
Treatment of bradycardia
Mydriasis
Cycloplegia -A loss of lens accommodation due to paralysis of the ciliary muscle
Gastrointestinal spasms
Organophosphate poisoning
TOXIC EFFECTS OF ATROPINE
Mydriasis Delirium Flushing Hyperthermia Decreased secretions and dry skin Paralytic ileus and urinary retention Tachycardia
Pharmacologic actions of atropine
CNS- restlessness, hallucinations, delusions
CVS- Low doses – reduces heart rate through central stimulation of vagus nerve
High doses- blocks M2 receptors of heart→ tachycardia
GIT- Reduces salivary gland secretion & GI motility
Pulmonary - Reduces bronchial secretions & stimulates bronchodilation
Sweat glands- Suppresses sweating
Eye- Causes paralysis of sphincter m of iris & ciliary m of lens → mydriasis and cycloplegia
Urinary system- Blocks M receptors in bladder wall → bladder wall relaxation
Adverse effects of ACHResult from excessive generalized cholinergic stimulation
Diarrhoea & decreased blood pressure
Urination
Miosis
Bronchoconstriction & bradycardia
Excitation of skeletal muscle
Lacrimation
Salivation & sweating
