cholinergic receptors Flashcards
muscarinic receptors
mAChR located on parasympathetic neuroeffector sites
mAChR’s mediate parasympathetic responses
M1
nerve cells
M2
heart and SM
M3
heart and SM
M4
SM and glands
M5
?
probably central NS
Blocks mAchR?
Atropine
Nicotinic receptors
nAchR located on autonomic ganglia
nAchR’s are also involved in neuromuscular transmission
Nm
Nn
Nm
nicotinic receptor
Neuromuscular
Blocks Nm receptors?
Tubocurarine
Nn
nicotinic receptor
autonomic ganglia, adrenal medulla and CNS
Blocks Nn receptors?
Trimethaphan
Cholinomimetic Direct acting drugs
interact with receptor
ACh, bethanechol, pilocarpine, carbachol, cevimeline, methacholine
Cholinomimetic Indirect acting drugs
Potentiate effect of ACh, inhibit AChase, nonspecific
Physostigmine
Neostigmine
edrophonium
Ach
non-specific = Muscarinic and Nicotinic
Poor side effect profile
IV small dose - transient fall in BP (generalized vasodilation) accompanied by reflex Tachycardia
Large dose = bradycardia or block of AV nodal conduction (direct action on heart)
Cholinergic agonists: Eye
Miosis
improved near vision
Cholinergic agonists: Heart and vasculature
Decreased HR, CF, conduction
Vasodilation
Cholinergic agonists: Lung
Bronchoconstriction
increased secretion
Cholinergic agonists: GI and glands
increased motility
relaxation of sphincters
increased secretion
Cholinergic agoinsts: Urinary bladder
contraction
relaxation of sphincters
Bethanechol
selective for GI and urinary tracts
Urinary retention*
reflux esophagitis
Carbachol
muscarinic and nicotinic
Mainly Glaucoma
cataract surgery
Reduces intraocular pressure and produces miosis
Pilocarpine
specific for muscarinic receptors
reverses mydriatic and cycloplegic agents
Most common drug given for Glaucoma*
promotes salivation
Side effects of direct acting Cholinergic agonists (parasympathetic overstimulation)
sweating salivation bronchoconstriction miosis cutaneous vasodilation with flushing nausea, vomiting and diarrhea changes in HR hypotension
Contraindications of Cholinergic agonists
Asthma
Peptic ulcer
Parkinsonism
obstruction of GI or urinary tract
Reversible Anticholinesterases
Prolong the action of Ach and nonspecific Physostigmine Pyridostigmine Demecarium Neostigmine Ambenonium Edrophonium
Irreversible Anticholinesterases
Malathion - lice Parathion sarin/tabun/soman paraoxon echothiophate/ isoflurophate = glaucoma but obsolete now
Physostigmine
tx gluacoma but Pilocarpine is still preferred
tx anticholinergic intoxication*
side effect of too much = seizure and bradycardia
Neostigmine
Muscarinic action - tx distention and urinary retention
Nicotinic actions - reverse paralysis induced by NMJ blocking agents
elevate skin temp, sweating, salivation, brady w/ hypotension, skeletal muscle fasciculations
Neostigmine substitutes
Pyridostigmine - for chronic Myasthenia gravis
Ambenonium - to manage Myasthenia
Demecarium - glaucoma
Edrophonium
short duration of action
*diagnostic tool and for therapy adjustment in Myasthenia Gravis
Antidote to curare
How would you check the severity of organophosphorus anticholinesterase intoxication?
measure RBC AChase
Therapeutic uses of Organophosphates
Glaucoma - must minimize drainage through lacrimal ducts and ciliary spasm can cause discomfort, risk of cataracts with prolonged use
insecticides, chem warfare
Organophosphate Toxicity
plasma cholinesterase regen. in 2 wks
Neural cholinesterase may require 1 to 3 months
Death second to respiratory complications
N/V/D, abdominal pain, weakness, blurred vision, dizzy, HA
Muscarinic manifestations of Organophosphate tox
bronchoconstriction, increased bronchial secretions, sweating, salivation, lacrimation, bradycardia, miosis, blurred vision, urinary incontinence
Nicotinic manifestations of organophosphate tox
depolarizing neuromuscular blockade
CNS - restlessness, insomnia, tremors, confusion, ataxia, convulsions, respiratory depression, CVS collapse
Pralidoxime
used to regenerate AChase after inhibited by irreversible anticholinesterase, given before aging of the phosphate bond
has its own anticholinesterase activity
Tx of organophosphorus toxicity
tx symptoms - support respiration and CVS
Pralidoxime reverses neuromuscular effects
Atropine for muscarinic and CNS effects
scopolamine may be more effective for CNS effects
Cholinergic antagonists
competitive antagonists
prototype agents - atropine and scopolamine
scopolamine is more effective in the eye and has more prominent CNS actions
sensitivity of tissues to atropine
salivary glands>sweat glands>eye and heart>GI and urinary tract
Cholinergic antagonists: CVS
moderate to high therapeutic dosages produce tachycardia (blocks muscarinic receptors which mediate bradycardia)
large doses of atropine may cause flushing
Cholinergic anatagonists: GI and urinary
require large doses
reduces motility and tone more than secretion
*Favors urinary retention by promoting sphincter contraction
Cholinergic antagonists: Eye
prolonged (up to 2 wks) mydriasis and cycloplegia
contraindiated for narrow angle glaucoma
Cholinergic antagonists: CNS
high doses - excitation, hallucinations, delirium
Scopolamine - motion sickness, sedation
can produce amnesia
Uses for Cholinergic Antagonists
tx Mydriasis, break adhesions (alternate agonists and antagonists)
perioperative uses: dry secretion, prevent vagal bradycardia, reduce dose of anesthetic, scopolamine -sedative and amnesic
tx - peptic ulcer by decreasing vagal mediated secretion, relieve spasm and slow gastric emptying
antimuscarinic therapy
asthma
Homatropine, cyclpentolate, tropicamide
atropine substitues
Mydriatics - short acting
Anticholinergic SM relaxants
selective action on GI
less lipid soluble
does NOT cross BBB
Irritable bowel syndrome
Dicyclomine
more bowel selective anticholinergic
Anticholinergic for Overactive bladder
uroselective drugs
darifenacin, solifenacin, tolterodine, trospium
Neuromuscular blocking agents act on
Nicotinic recetors
nondepolarizing compete with ACh for receptors
depolarizing agents initially stimulate NMJ and block
Nondepolaring NM agents
competitive blockade
includes: tubocurare, metocurine, pancuronium, gallamine, atracurium, vecuronium
Effective antagonists for nondepolarizing agents
Reversible Anticholinesterases
b/c blocks break down of Ach prolonging it and increasing Ach concentration to better compete with the nondepolarizing (these block nicotinic receptors) agent for receptors
depolarizing neuromuscular blocking agent
Succinylcholine (depolarizing muscle relaxant)- produces 2 phase response
1. stim receptors, associated with muscle contraction
2. follows rapidly desensitizes receptors, making them refractory to stimulation.
half life is 8 minutes
GOOD FOR INTUBATION
Botulinum toxin
enters cholinergic nerve endings and inhibits exocytosis
used for tx of strabismus and blepharospasm of eye
side effects: excessive tearing and unilateral ptosis
Ganglionic blocking drugs
used as antihypertensives
Hexmethonium
Trimethaphan
rarely used due to toxicity
