Cholinomimetics Flashcards
Which receptors do cholinomimetics bind to?
Muscarinic or nicotinic receptors
Name the direct acting cholinomimetics
Ach
Bethanecol
Carbachol
Methacholine
Cevimeline
Varenicline
Pilocarpine Lobeline Arecoline Nicotine Muscarin
Name the quaternary cholinomimetics
Ach Bethanechol Carbachol Methacholine Muscarin
Name the tertiary direct acting cholinomimetics
Pilocarpine
Lobeline
Arecoline
Nicotine
What are the clinical uses of Bethanechol?
Non-obstructive GIT dysmotility e.g., Ileus, gastric atony, post op abdominal distension
Urinary retention
What are the clinical uses of Carbachol?
Glaucoma (during surgery)
What are the clinical uses of Acetylcholine?
No clinical use due to the half life.
Exception: when short myosin is needed e.g., cataract surgery
What is the action of Methacholine?
Bronchoconstriction
What is the clinical use of Methacholine?
Methacholine challenge for the diagnosis of pulmonary function
What are the side effects of Bethanechol?
Sweating Salivation Flushing Decreased BP Nausea Abdominal pain Diarrhoea Bronchospasm
What is the antidote for bethanecol toxicity?
Atropine sulfate
What is the clinical use of Cevimeline?
Sjogren syndrome
What is the clinical use of Varenicline?
Cessation of smoking as it is a partial nicotinic agonist
Which cholinomimetic is a partial nicotinic agonist?
Varenicline
What are the clinical uses of Pilocarpine?
Glaucoma
Xerostomia
Sjogren syndrome
Salivary gland hypofunction due to radiotherapy of head and neck
How is pilocarpine administered in the treatment of glaucoma?
Topically
What is the mechanism of action of Pilocarpine in the treatment of glaucoma?
Pilocarpine causes myosin and ciliary contraction which decreases aqueous humour production which decreases IOP.
What are the side effects of pilocarpine?
Cyclopegia
Night blindness
Brow ache
What is the antidote for pilocarpine toxicity?
Parenteral atropine
What are the alkaloids?
Pilocarpine Lobeline Arecoline Arecoline Nicotine Muscarine
What is the mechanism of action of Pilocarpine?
increased salivation
What is the mechanism of action of Arecoline and Nicotine?
inhibits reward effect of nicotine in the limbic system
Is muscarine a quaternary or tertiary amine?
Quaternary
Can muscarine enter the CNS?
Why?
No
Quaternary amine
What are the indirect acting cholinomimetics?
Ach esterase inhibitors
What are the reversible AChEIs?
Edrophonium
Carbamates
Is Edrophonium competitive or non-competitive?
Competitive
Are carbamates competitive or non-competitive?
Non-competitive
What are the characteristics of Edrophonium?
Short acting
Alcohol
Quaternary amine
What is the duration of action of Edrophonium?
5-15 mins (injection)
What is the clinical indication of Edrophonium?
Tensilon test
What are the characteristics of Physostigmine?
Tertiary amine
Carbamate
Can physostigmine enter the CNS?
Why
Yes
Tertiary amine
What is the duration of action of Physostigmine?
0.5-2 hours
What are the clinical uses of Physostigmine?
Glaucoma
Antidote in atropine overdose
What are the characteristics of Rivastigmine?
Tertiary amine
Carbamate
Can rivastigmine enter the CNS?
Why?
Yes
tertiary amine
What is the clinical indication of Rivastigmine?
Alzheimer
What is the duration of action of Neostigmine and Distigmine?
0.5h-2h
What are the clinical indications of Neostigmine, Distigmine?
Ileus
Urinary retention
MG
Reversal of non-depolarising Nm blockers
What are the characteristics of Neostigmine and Distigmine?
Quaternary amins
Carbonate
Can Neostigmine, Distigmine, Pyridostigmine, Ambenonium and Demecarium enter the CNS?
Why?
No
Quatenary amine
What is the duration of action of Pyridostigmine?
3-6h
What is the duration of action of Ambenonium?
4-8h
What is the duration of action of Demecarium?
4-6h
What is the clinical indication of Pyridostigmine?
- MG (chronic management)
- Prevention of nerve gas
What is the clinical indication of Ambenonium?
MG (chronic management)
What is the clinical indication of Demecarium?
Glaucoma
What are the characteristics of Doneperzile and Tacrine?
Lipid soluble (CNS entry)
What are the clinical indications of Doneperzile and Tacrine?
Alzheimers disease
What are the clinical indications of Organophosphates?
Glaucoma
What is the duration of action of organophosphates?
100 hours
What are the characteristics of organophosphates?
Lipid soluble
Irreversible inhibitors
What is the antidote given in reversible AChE inhibitors?
Atropine
What are the symptoms of acute toxicity with cholinomimetics? (Muscarinic effects)
Diarrhea Urination Miosis Bradycardia Bronchoconstriction Lacrimation Salivation Sweating CNS stimulation
What are the symptoms of acute toxicity with cholinomimetics? (Nicotinic effects)
Skeletal muscle excitation followed by paralysis (cholinergic crisis) - this is irreversible
CNS stimulation
What are the symptoms of chronic toxicity with cholimomimetics?
Peripheral neuropathy causing muscle weakness and sensory loss (Like MS)
Demyelination not due to AChE inhibition
Why does demyelination due to chronic toxicity of cholinomimetics occur?
AChE are very lipid soluble so they can go into the myeline sheath, bind to happen and then lead town immune response