CHOLINERGIC AGONISTS & ANTAGONISTS 1 Flashcards
What are the direct effects of ACh on the CARDIOVASCULAR SYSTEM?
DIRECT EFFECTS OF ACETYLCHOLINE
- Vasodilation (M3 effect).
- Decrease in cardiac rate (M2 effect).
- Decrease in rate of conduction in the SA and AV nodes (M2 effect).
- Decrease in force of contraction (M2 effect).
What effect does a low dose of ACh have on the CARDIOVASCULAR system?
• IV injection of a small dose of acetylcholineproduces a fall in blood pressure due to vasodilation (M3 effect) usually accompanied by
reflex tachycardia.
What effect does a large dose of ACh have on the cardiovascular system?
• Larger doses of acetylcholine cause vasodilation, a fall in blood pressure (M3 effect) and bradycardia (M2 effect).
What are someone of the effects of ACh on various organ systems?
What occurs If muscarinic effects are blocked
by a muscarinic antagonist such as
atropine?
large doses of acetylcholine produce nicotinic effects:
- Increase in blood pressure and vasoconstriction
- These effects are due to stimulation of sympathetic ganglia and release of epinephrine from the adrenal medulla.
what are the CHOLINE ESTERS?
• Acetylcholine • Methacholine • Carbachol • Bethanechol
What are CHOLINE ESTERS and what is their effects?
- Choline esters are quaternary ammoniums.
- Poorly absorbed and poorly distributed into the CNS.
• They differ in their susceptibility to hydrolysis by
cholinesterase.
- Acetylcholine is very rapidly hydrolyzed.
- Methacholine, carbachol and bethanechol are more resistant to hydrolysis by cholinesterase.
ACETYLCHOLINE uses?
• Used to obtain rapid miosis after delivery of the lens in cataract surgery and other procedures where rapid miosis is required.
What is BETHANECHOL function and uses?
• Muscarinic agonist.
USES :
- Postoperative and postpartum urinary retention.
- Atony of the urinary bladder.
What is CARBACHOL function and uses?
• Both muscarinic and nicotinic agonist.
USES:
- Miosis during surgery.
- Reduces intraocular pressure after cataract surgery.
What is METHACHOLINE function and uses?
• Muscarinic agonist.
USES:
• Diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.
What are the naatural alkaloids?
• PILOCARPINE • NICOTINE
What category does PILOCARPINE fall into and whats its effect/uses?
NATURAL ALKALOIDS
- Partial muscarinic agonist.
- Tertiary amine
- Stable to hydrolysis by acetylcholinesterase.
Uses: Second line agent for open angle glaucoma. • Management of acute angle-closure glaucoma. • Treatment of dry mouth due to radiotherapy for
cancer of head and neck. • Treatment of dry mouth caused by Sjogren’s
Syndrome.
What category does NICOTINE fall into and whats its effect/uses?
NATURAL ALKALOIDS
- Tertiary amine.
- Selective agonist of the nicotinic receptor.
- Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis.
- Low doses: ganglionic stimulation by depolarization.
CV system: Mainly sympathomimetic effects. ncrease in HR and BP due to catecholamine release from nerve terminals and 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.
NICOTINE: ACUTE POISONING
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.
What are the ANTICHOLINESTERASES
- Edrophonium
- Carbamates
• Physostigmine
• Neostigmine
• Pyridostigmine - Organophosphates
• Echothiophate
• Parathion & Malathion
• Sarin
How does Edrophonium work?https://www.brainscape.com/decks/7152716/cards/new
binds reversibly to the active site of the enzyme. The enzyme-inhibitor complex
doesn’t involve a covalent bond and is short-lived.
- Quaternary ammonium.
- Does not enter CNS.
USES • Used in diagnosis of myasthenia gravis. Edrophonium IV leads to rapid increase in muscle strength. • Used to reverse the neuromuscular block
produced by non-depolarizing muscular blockers.
How does Carbamates work as an ANTICHOLINESTERASES?
• Carbamates form a covalent bond with the
enzyme.
How does Organophosphates work as an ANTICHOLINESTERASES?
phosphorylate the enzyme. The covalent bond formed is extremely stable and hydrolyzes very slowly.
• The phosphorylated enzyme may undergo a process called ageing where it strengthens the phosphorous-
enzyme bond.
Types: ECHOTHIOPHATE, INSECTICIDES: MALATHION PARATHION, SARIN• Among the most potent synthetic toxic agents known
How does ANTICHOLINESTERASES cause its ORGAN SYSTEM EFFECTS
CNS
EYE, RESPIRATORY TRACT, GI TRACT & URINARY TRACT
CARDIOVASCULAR SYSTEM
THE NEUROMUSCULAR JUNCTION
CNS: • In low concentrations liposoluble cholinesterase inhibitors cause CNS activation. • In higher concentrations they cause convulsions,coma and respiratory
arrest.
EYE, RESPIRATORY TRACT, GI TRACT & URINARY TRACT: effects of cholinesterase inhibitors are similar to the effects of the direct-acting cholinomimetics
CARDIOVASCULAR SYSTEM: • Modest bradycardia • Fall in cardiac output • Increased vascular resistance • Increase in blood pressure. Toxic doses of cholinesterase inhibitors cause marked bradycardia, significant decrease of
cardiac output and hypotension.
THE NEUROMUSCULAR JUNCTION • Cholinesterase inhibitors increase strength of
contraction. • Useful to reverse action of nondepolarizing neuromuscular blockers. • Useful in myasthenia gravis.
How does PHYSOSTIGMINE work?
- Tertiary amine.
- Can enter and stimulate CNS.
USES • Treatment of overdoses of anticholinergic drugs.
What AChE INHIBITORS USED IN ALZHEIMER DISEASE?
use of centrally acting acetylcholinesterase inhibitors.
- Donepezil
- Rivastigmine
- Galantamine
How does NEOSTIGMINE work?
- Quaternary ammonium.
- Does not enter CNS.
USES • Postoperative urinary retention. • Reversal of effects of non-depolarizing
neuromuscular blockers after surgery. • Treatment of myasthenia gravis
How does PYRIDOSTIGMINE work?
- Quaternary ammonium.
- Does not enter CNS.
USES • Treatment of myasthenia gravis.
What is the REACTIVATOR OF AChE: PRALIDOXIME
• 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.
