2. Cholinergic Drugs Flashcards
Location of M1 receptors
Gastric parietal cells
CNS neurons
Sympathetic postganglionic neurons
Location of M2 receptors
Myocardium
Smooth muscles
Location of M3 receptors
Glandular tissue
Vessels (smooth muscles and endothelium)
Location of nicotinic receptors
Skeletal NMJ
Adrenal medulla
Autonomic ganglia
Properties fo direct acting cholinergics
Binds and directly activates receptors
Have affinity and intrinsic activity
Independent of Ach release
Effects similar to endogenous Ach
Difference of metacholine from acetylcholine
Methyl substitution on the beta carbon side chain
The methyl group improved selectivity towards muscarinic receptors, and resistance to acetylcholinesterase
Difference of carbamic acid esters from acetic acid esterss
Presence of amino group causes resistant to acetylcholinesterase and increased duration of action
Properties of carbachol
Non-selective (binds to both muscarinic and nicotinic receptors)
Properties of bethanecol
More selective towards muscarinic receptors
Enumerate carbamic acid esters
Carbachol
Bethanechol
Pilocarpine: state selectivity, type of amine, and other important properties
Selective to muscarinic receptors, antagonized by atropine
Tertiary amine
Only cholinomimetic alkaloid with therapeutic use
Can penetrate the CNS at therapeutic doses
Used in the treatment of glaucoma
Carbachol (may also stimulate nicotinic receptors)
Pilocarpine
Muscarine: state selectivity, type of amine, and other important properties
Selective to muscarinic receptors, antagonized by atropine
Toxic when ingested and potentially fatal
No therapeutic use
Quaternary amine
Heart: state receptors involved and effects of cholinergic drugs
M2 receptors
Decreased HR, rate of conduction, force of contraction of the atrium
Decrease in cardiac output–> decrease in blood pressure
Blood vessels: state receptors involved and effects of cholinergic drugs
M3 receptors
Production of NO–> generalized vasodilation
GIT smooth muscles: state receptors involved and effects of cholinergic drugs
M3 receptors
increase tone and motility
increase in propulsive movement (ADR: cramps, colicky pain, spasm, nausea, vomiting, diarrhea)
increased intestinal gastric acid secretion
Urinary smooth muscles: state receptors involved and effects of cholinergic drugs
M3 receptors
Detrusor muscle contracts, sphincter muscles relax
increased urination
Used for GIT atony and urinary retention
Bethanechol
Respiratory smooth muscles: state receptors involved and effects of cholinergic drugs
M3 receptors
Bronchospasm
Increased bronchial secretions
Eye smooth muscles: state receptors involved and effects of cholinergic drugs
M3 receptors
Contraction of pupillary constrictor muscle and ciliary muscle –> miosis and cyclospasm
Lower IOP in glaucoma
Used in the treatment of glaucoma as a miotic agent over carbachol
Pilocarpine; can cross the conjunctival membrane
Glandular smooth muscles: state receptors involved and effects of cholinergic drugs
M3 receptors
Outpouring of secretions
CNS: state receptors involved and effects of cholinergic drugs
M1 receptor
increase in locomotor activity and improved cognition
Taclifenasine properties and indication
M1 selective agonist used in dementia
Used for glaucoma
Pilocarpine and carbachol
Used for GI disorders (postoperative abdominal distention, gastric atony, adynamic ileus)
Bethanechol
Neostigmine
Used for xerostomia
Pilocarpine
Used for dementia
Taclifenasine (muscarinic agonist)
Xanomeline
Contraindications to the use of direct acting cholinomimetics
Asthma Hyperthyroidism Coronary insufficiency Acid peptic disease GIT obstruction
ADRs of direct acting cholinomimetics
Flushing Sweating Salivation Belching Abdominal cramps Urinary bladder tightness Cyclospasm Bronchospasm Hypotension Bradycardia
Noncovalent acetylcholinesterase inhibitors
Edrophonium
Tacril and Donepezil
Edrophonium properties: type of amine, binding, solubility, affinity, indications
Quaternary amine - non-lipid soluble
Reversible binding
Moderate affinity for AchE, to the anionic site, no covalent bond
Only used for diagnosis of myasthenia gravis and Tensilon test
Tacrine and Donepezol properties
Inhibits AchE in the CNS, higher affinity
Lipid soluble, readily cross the BBB
Longer duration of action
Treatment of senile dementia of the Alzheimer type
Carbamate inhibitors
Site of action: both active sites of AchE, covalent bond
Physostigmine (tertiary amine, lipid soluble)
Pyridostigmine
Neostigmine
Rivastigmine
Prpoxur
Pyridostigmine indication
Chronic management of myasthenia gravis
Neostigmine indication and properties
Stimulation of the bladder and GIT
Antidote to tubocurarine
Symptomatic treatment of MG
Rivastigmine indication
Treatment of senile dementia of Alzheimer type
Used for senile dementia of Alzheimer type
Rivastigmine
Donepezil
Tacrine
Galantamine
used as a miotic agent in highly resistance case of glaucoma
Echothiophate
Two active sites for AchE
Anionic site (glutamate residue, basic moiety of Ach) Esteratic site (histidine and serine residue)
Site of action of organophosphates
Esteratic site
Given for organophosphate poisoning before aging
Pralidoxime (PAM)
Treatment for carbamate posoning
Atropine
Used in acute angle closure glaucoma
Physostigmine and Pilocarpine
Treatment of myasthenia gravis
Pyridostigmine
Abbenomium
Neostigmine
Difference of myasthenic and cholinergic crisis
Myathenic crisis: due to undermedication; little to no Ach on NMJ
Chlonergic crisis: due to overmedication; too much Ach causing neuromuscular block
After surgery, in reversing the neuromuscular block, what is administered?
Neostigmine or edrophonium PLUS atropine
To reverse the neuromuscular block without the muscarinic effect
Acetic acid esters are abundant in __
NMJ
RBC in placent
Vascular tissues
