Cholinergic Agonist And Antagonists 1 Flashcards
Stimulation of adrenergic receptors in the pancrease will most likely cause an overall ________
↓ in insulin secretion
Where in the heart can you find high concentrations of muscarinic receptors?
Atria
_______ doses of acetylcholine will cause vasodilation, a fall in blood pressure (M3) and bradycardia (M2)
LARGE;
Small doses will not have bradycardia because the baroreceptor reflex will be more powerful than the drugs
Atropine is a _______________ and allows large doses of acetylcholine to produce only _______ effects such as _________ and ________
Muscarinic antagonist;
Nicotinic effects ;
↑ in BP and vasoconstriction
The effects of atropine as due to stimulation of ________ and release _________
SYMPATHETIC ganglia; epinephrine from adrenal medulla
What are the two families of direct acting cholinergic agonists
- esters of choline
- alkaloids
Drugs that are choline esters (4)
- acetylcholine
- methacholine
- carbachol
- bethanechol
choline esters differ in their susceptibility to hydrolysis by cholinesterase.
_____________ is very rapidly hydrolyzed
Acetylcholine;
Methacholine, carbachol, and bethanechol are more resistant to hydrolysis by cholinesterase
What is the clinical use of bethanechol?
- post operative and post partum urinary retention
- atonic bladders
It is a muscarinic agonist
What drugs would you give to someone to ↓ intraocular pressure after cataract surgery and for miosis during surgery?
Carbachol;
It is both a muscarinic and nicotinic agonist
What is the use of the methacholine challenge test?
Used to diagnose subclincal asthma;
Diagnosis of bronchial airway hyperactivity
What are the two natural alkaloids
- pilocarpine
- nicotine
What are the major uses for pilocarpine
- second line agent for open angle glaucoma
- management of acute angle closure glaucoma
- treatment of dry mouth
What is the effect of LOW doses of nicotine?
Ganglionic stimulation by depolarization → simultaneous discharge of both parasympathetic and sympathetic nervous systems
Low doses nicotinic actions on the CV system, GI and urinary tracts, and secretions
CV: mainly sympathomimetic effects such as ↑ HR and BP
GI and urinary: mainly parasympathetic such as nausea, vomiting, diarrhea, etc
Secretion: stimulation of salivary and bronchial secretions
What family of drugs that are indirect acting cholinergic agents (anti cholinesterases)
- edrophonium
- carbamates: physostigmine, neostigmine, pryridostigmine
- organophosphate: echothiophate, parathion and malathion, sarin
Mechanism of action of edrophonium
It is an acetylcholinesterase that binds reversible tot he activate site and DOES not involve a covalent bond and is short lived
Edrophonium‘s effect is short/long lived
Short
Which of the anti acetylcholinesterases forms a covalent bond?
Carbamates and organophosphate (organophosphate phosphorylates the enzyme and is stable and long lived)
Oraganophopshates undergoes a process called ageing which ________
Strengthens the phosphorous bond
What is the difference between LOW and HIGH concentrations of choilnesterase inhibitors on the CNS
Low: CNS activation
High: convulsions → coma and respiratory arrest
What are the systems that are well innervated by parasympathetic? And what is the effect of cholinesterase inhibitors on them?
eye, respiratory tract, GI, and urinary trac t
Similar to direct acting cholinomimetics
In the ________ cholinesterase inhibitors activate both sympathetic and parasympathetic but the ____________ predominates
Heart;
Parasympathetic → ↓ cardiac output
What is the effect of choliesterase inhibitors on the vascular smooth muscle?
MINIMAL EFFECTS because they dont have much cholinergic innervation
Moderate doses will cause ↑ in resistance and BP but due to the actuation of sympathies ganglia and central sympathetic centers
What are the net CV effects of cholinesterase inhibitors?
- modest bradycardia (M2 receptors in heart)
- ↓ CO
- ↑ vascular resistance
- ↑ BP
What is the effect of toxic doses of cholinesterase inhibitors on the CVS?
- marked bradycardia
- significant ↓ in CO
- HYPOtension
Cholinesterase inhibitors _______ the strength of contractions and it is useful for treating ________
Strength;
Myasthenia gravis;
Useful to reverse action of nondepolarizing neuromuscular blockers
___________ is used to treat myasthenia gravis
Edrophonium
________ is used tot real overdoses of anticholinergic drugs (atropine)
Physostigmine
What are two drugs used for postoperative urinary retention?
Bethanechol and neostigmine
What are some uses for neostigmine
- post op urinary retention
- reversing effect of non depolarizing NM blockers after surgery
- treating myasthenia gravis
Which of the cholinesterase inhibitors do NOT enter CNS?
Edrophonium, neostigmine, pyridostigmine
What are malathion and parathion used for?
Insecticides
What kind of people would be at risk for toxic symptoms of anti-cholinesterase and by which drugs?
Farmers exposed to heavy insecticides;
Malathion and parathion
What is the most potent acetylcholine esterase inhibitors?
Sarin
Another use of centrally acting acetylochilinesterase inhibitors in in slowing the progression of __________
Alzheimer’s Disease
What are the central acting acetylcholine esterase inhibitor drugs (3)
- donepezil
- rivastigmine
- galantamine
_________ is a reactivator of acetylcholinesterase and thus is used to treat anti acetylcholinesterase poisoning
Pralidoxime
A farmer using insecticides comes in with toxic symptoms, what would you give to reverse the effects?
Pralidoxime (give it before ageing has occurred) to regenerate the cholinesterase
Also give atropine to block the acetylcholine receptors so acetylcholine doesnt bind to them
