Cholinergic agonists and antagonists Flashcards
4 primary direct effects on the CV system
Vasodilation (M3)
Decrease cardiac rate (M2)
Decrease rate of conduction in the SA and AVnodes (M2)
Decrease force of contration (M2)
IV injection of small dose of ACh
fall in blood pressure- vasodilation, reflex tachycardia
IV injection Large dose ACh
brady cardia, decrease through Vnode, vasodilation and hypotension.- CV system
ACh effects on tissue
CV system- bradycardia, decrease in conduction velocity, AV block at high doses, decrease in contrctilty
Eye- contraction and miosis, accomodation of lens to near vision, watery lacrimal secretions
glands- secretions
bronchi- increase in secretions.
GI- increase in tone, peristaltic activity, increased in secretions and relaxation of sphincters.
Urinary- contraction of detrusor muscle, relaxation of sphincter.
sweat glands- diaphoresis
Male reproductive tract- erection
Uterus- varible.
large doses of ACh after atropine administration causes
nicotinic effects, increase in blood pressure due to sympathetic ganglia stimulation and vasoconstriction.
Choline esters-
ACh, carbachol, bethanechol, methacholine
poorly absorved and distributed into CNS
differ in susceptibility to be hydrolyzed by cholinesterase. ACh very rapid. others are more resistant.
quarternary ammonium compounds.
naturally occuring alkaloids
arecholine, muscarine, pilocarpine, nicotine, lobeline.
Acetylcholine uses.
no systemic use.
used to obtain rapid miosis after delivery of lens in cataract surgery, penetrating keratoplsty and iredectomy
Bethanechol
NOT hydrolyzed by AChE, inactivated by other esterases. little or no nicotinic action but
STRONG muscarinc activity
used to treat postop or post partum non obstructive urinary retention and for neruogenic atony of the urinary bladder with retention.
ADVERSE: can cause generalized cholinergic stimulation- sweating salivation, flushing, low BP, nausea, abdominal pain, diarrhea, bronchospasm.
Carbachol
both muscarinic and nicotinc agonist
poorly hydrolized by esterases
used for intraocular miosis during surgery, reduces intraocular pressure after cataract surgery.
Methacholine
hydrolyzed by ACh but slowly, resistant to non specific cholineesterase or butyrylcholinesterase.
predominantly MUSCARINIC, slight nicotinc
used in diagnosis of bronchial airway hyper-reactivity in subjects who do not have clinically apparent asthma
PIlocarpine
tertiary amine,
stable to hydrolysis by AChE
partial muscarinic agonist
used in Glaucoma- second line agent for open angle glaucoma. used to manage acute angle-closure,
you use several drugs to treat glaucoma- timolol, pilocarpine, apraclonidine, acetzolamide and an osmotic agent like glycerol and IV mannitol.
ADVERSE- can enter brain and cause CNS disturbances. stimulates seaeating and salivation.
Nicotine
Tertiary amine. affect NMJ slighlty more. causes ganglionic stimulation which means both para and sympathetic actions.
CVS- mainly sympathomimetic- increased heart rate and blood pressure due to release of adrenergic release.
GI- largely parasympathomimetic- nausea, diarrhea, vomiting, voiding of the urine. causes stimulation of salivary and bronchial secertions.
high doses cause NM blockade.
acute poisoning.- nausea, alsivation, ab pain, vomiting diarrhea, cold sweat, mental confusion, ewakness. low BP, weak pulse, collapse may be followed by convulsions, death may occur from paralysis of respiratory muscles and Central respiratory failure
highly liposoluble, so absorption is fast via oral mucosa, lungs, GI mucosa and skin. corsses placental membrane and is secreted in milk.
Indirect acting cholinergic agonists(anticholinesterases)
simple alcohols bearing a quaternary ammonium group- edropohonium
carbamates- neostigmine, physostigmine, pyridostigmine
Organophosphates- Ecothiophate, parathion, malathion
endrophonium
Quarternary ammonium
binds reversibly to active site of enzyme. short lived- 2-10 minutes.
used to diagnose myasthenia gravis, reverse neuromuscular block produced by non-depolarizing muscular blockers.
Carbamates-
form covalent bond with the enzyme. the carbamate-cholinesterase bond spontaneoulsy hydrolyzes in 30 min-6 hours. clinical recovery in several hours, rarely over 24