Pharm Exam 1 Flashcards
Choline esters
- Acetylcholine - very rapidly hydrolyzed.
- Methacholine - more resistant to hydrolysis.
- Carbachol and bethanechol - still more resistant to hydrolysis by cholinesterase.
Acetylcholine
- No systemic therapeutic applications dueto multiplicity of actions, and rapid hydrolysis by both acetylcholinesterase and plasma butyrylcholinesterase.
- Used to obtain rapid miosis after delivery of the lens in cataract surgery and other anterior procedures where rapid miosis is required.
Bethanecol
- Not hydrolyzed by acetylcholinesterase
- Inactivated by other esterases.
- Little or no nicotinic actions; strong muscarinic activity.
Uses
• Tx acute post op and postpartum urinary retention.
• Tx neurogenic atony of the urinary bladder with retention.
- Promote GI motility
Adverse effects
• Sweating
• Salivation
• Flushing
• Low blood pressure • Nausea
• Abdominal pain • Diarrhoea
• Bronchospasm
Carbachol
- Both muscarinic and nicotinic agonist.
- Poor substrate for acetylcholinesterase.
- Biotransformed by other esterases at much slower rate.
Uses
- Miosis during surgery
- Reduces intraocular pressure after cataract surgery
Methacholine
• Predominantly muscarinic agonist.
USES
• Dx bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.
Cholinergic agonists: natural alkaloids
- Muscarine: muscarinic agonist.
- Arecoline: muscarinic and nicotinic agonist.
- Pilocarpine: mainly muscarinic.
- The only natural alkaloid used clinically is pilocarpine: sialagogue and miotic.
Pilocarpine
Cholinergic agonist
• Tertiary amine - NOT ammonium! Can cross BBB
• Stable to hydrolysis by acetylcholinesterase.
• Partial muscarinic agonist.
Uses
• Second line agent for open angle glaucoma.
• Management of acute angle-closure glaucoma.
Nicotine actions
- Low doses: ganglionic stimulation by depolarization.
- The response resembles simultaneous discharge of both parasympathetic and sympathetic nervous systems.
- CV system: Mainly sympathomimetic effects. Increase in HR and BP due to catecholamine release from adrenergic nerve terminals and from adrenal medulla.
- GI & urinary tracts: Mainly parasympathomimetic effects: nausea, vomiting, diarrhea, voiding of urine.
- Secretions: Stimulation of salivary and bronchial secretions.
• High doses: ganglionic blockade and neuromuscular blockade.
- Symptoms of acute, severe nicotine poisoning: nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, mental confusion and weakness.
- The blood pressure falls, the pulse is weak.
- Death may occur from paralysis of respiratory muscles and/or central respiratory failure.
Edrophonium
Anticholinesterase. Quaternary ammonium. Bindsreversiblytotheactivesite of the enzyme. The enzyme-inhibitor complex doesn’t involve a covalent bond and is short- lived.
USES
• Dx myasthenia gravis. Edrophonium IV leads to rapid increase in muscle strength.
• Also used to reverse neuromuscular block produced by non-depolarizing muscular blockers.
Physostigmine
Anticholinesterase. Form a covalent bond with the enzyme. Tertiary amine. Can enter and stimulate CNS.
USES
• Treatment of overdoses of anticholinergic drugs.
NOTE:
• Physostigmine should not be given to a patient with suspected TCA overdose because it can aggravate depression of cardiac conduction.
Neostigmine
Anticholinesterase. Form a covalent bond with the enzyme. Quaternary ammonium. Doesn’tenterCNS.
USES
• To stimulate bladder and GI tract.
• Antidote for competitive blockers of the NMJ.
• Symptomatic treatment of myasthenia gravis
Pyridostigmine
Anticholinesterase. Form a covalent bond with the enzyme. Quaternary ammonium.
USES
• Treatment of myastheniagravis.
• Most commonly used anticholinesterase for this indication.
Echothiophate
Used for glaucoma.
Oral AChE inhibitors used to tx Alzheimer’s dz
- Tacrine
- Donepezil
- Rivastigmine
- Galantamine
Pralidoxime
Reactivator of AChE. If given before ageing has occurred, drugs like pralidoxime split the phosphorous-enzyme bond.
• Pralidoxime can be used as cholinesterase regenerator for organophosphate insecticide poisoning.
Atropine
Prototype for muscarinic rec antagonists
- Binds competitively to muscarinic receptors, preventing acetylcholine from binding.
- Tertiary amine: both central and peripheral muscarinic blocker.
- Eye: Mydriasis. Cycloplegia.
- GI: Reduces gastric motility.
- Urinary system: Decreases hypermotility of urinary bladder.
Cardiovascular system:
• Low doses: bradycardia. Due to blockade of presynaptic M2 receptors that normally inhibit ACh release.
• Moderate to high therapeutic doses: Blockade of atrial M2 receptors: tachycardia.
• High doses of antimuscarinic agents may cause cutaneous vasodilation. This is called ‘atropine flush’. The mechanism is unknown.
Secretions:
• Salivary, sweat and lacrymal gland sare blocked.
• Inhibition of sweat glands may cause high body temperature.
Atropine uses and adverse effects
Uses
• Mydriasis and cycloplegia.
• Antispasmodic: to relax GI tract andbladder.
• Antidote for cholinergic agonists.
• Antidote for mushroom poisoning due to muscarine, found in Amanita muscaria and other fungi.
• To block respiratory tract secretions prior to surgery.
Adverse
• Dry mouth, blurred vision, sandy eyes, tachycardia, constipation.
• Effectson CNS: restlessness,confusion, hallucinations, delirium, which may progress to depression, collapse of the circulatory and respiratory systems and death.
Scopolamine
Muscarinic antagonist
USES
• Preventionofmotionsickness.
• To block short-term memory: sometimes used in anaesthetic procedures.
Echothiophate
Organophosphate. Used to treat glaucoma
Ipratropium and tiotropium
Quaternary ammonium muscarinic antagonists.
- Used as inhalational drugs to tx (COPD).
- Also used as inhalational drugs inasthma.
Homatropine Cyclopentolate Tropicamide
Tertiary amine muscarinic antagonists
- For use in ophthalmology.
- Produce mydriasis with cycloplegia.
- Preferred to atropine bc of shorter duration of action.
Benztropine Trihexyphenidyl
Tertiary amine muscarinic antagonists.
• Used to tx parkinsonism and extrapyramidal effects of antipsychotic drugs.
Glycopyrrolate
Antimuscarinic agent.
- Used orally to inhibit GI motility.
- Used parenterally to prevent bradycardia during surgical procedures.
Tolterodine
Antimuscarinic.
• Used for overactive bladder.