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62 Cards in this Set
- Front
- Back
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What drugs are the muscarinic receptor agonists?
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Bethanechol and Pilocarpine
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What do the muscarinic receptor agonists do? Ie what kind of effects?
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They are direct agonists of the muscarinic receptors. This means they are parasympathomimetics.
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What kind of structure does Bethanechol have?
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Quaternary amine
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What is the primary use of bethanechol
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Treating NONOBSTRUCTIVE urinary retention (post operation urinary retention dt anesthesia or diabetic neuropathy)
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What kind of structure does pilocarpine have?
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Tertiary amine
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What are the uses of pilocarpine?
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Treat xerostomia (dry mouth) orally.
Treat wide angle glaucoma topically (narrow angle glaucoma in emergency situations) |
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What are the routes of administration for the muscarinic receptor agonists (Bethanechol and Pilocarpine)
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They are never given via IV because they can cause hypotension - muscarinic receptors are on the endothelium.
They are both given orally. Bethanechol can be given subcutaneously. Pilocarpine can be applied opthalmically. |
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What are the contraindications to systemic use of the muscarinic receptor agonists?
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Bethanechol and pilocarpine should not be given in asthma or COPD - can cause bronchoconstriction.
Should not be given if there is urinary/GI obstruction and peptic ulcer since these drugs increase acid secretion. People with hypotension, bradycardia, hyperthyroidism should not use these drugs. |
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What is the side effects of the muscarinic receptor agonists?
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diaphoresis (Excess sweating), diarrhea, abdominal cramps, nausea/vomitting, hypotension, visual accomodation problems
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What is the treatment for toxicity from muscarinic receptor agonists?
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Give atropine.
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What are the classes of acetylcholinesterase inhibitors?
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Reversible
Irreversible Organophosphorus inhibitors |
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What are the reversible inhibitors of acetylcholinesterase
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Edrophonium, Physostigmine, Neostigmine
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What are the irreversible inhibitors of acetylcholinesterase?
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Sarin (nerve gas)
Malathion (insecticide) Echothiophate |
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How does the acetylcholinesterase mechanism work?
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The glutamate on acetylcholinesterase serves as an anionic site that interacts with the ammonium group on acetylcholine. The ser, his, glu triad interacts with the ester group of acetylcholine. When acetylcholine binds, serine performs a nucleophilic attack. This leads to hydrolysis of ACh. Choline is freed and serine is acetylated. The acetylated serine is then hydrolyzed giving free enzyme again. This is a very fast rxn 10^4/sec
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What kind of duration of action does edrophonium have?
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Edrophonium has a short duration of action.
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What are the uses of edrophonium?
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1) distinguish between Myasthenia gravis and cholinergic crisis.
In myasthenia gravis, giving edrophonium should improve symptoms as Ach is low in the disease and this increases Ach. In cholinergic crisis, muscles stop responding to an excess Ach. If you give this ACh esterase inhibitor, you will have even more Ach, and the problem will get worse. It can reverse paralysis by competitive neuromuscular blocking drugs. |
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How are physostigmine and neostigmine different from edrophonium?
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Edrophonium competes with acetylcholine for acetylcholinesterase. It binds reversibly.
Physostigmine and Neostigmine are actually cleaved by AChesterase, but in this process yield a carbamylated enzyme that is inactive for a longer period of time. |
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What is the structure of physostigmine?
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Physostigmine is a tertiary amine (which is lipophilic and can have cns effects)
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What is the use of physostigmine?
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Physostigmine is used to treat chronic wide angle glaucoma
and CNS effects of antimuscarinic poisons. |
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What is the structure of neostigmine?
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Neostigmine is a quaternary amine (+ charge, no cns effect)
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What is the use of neostigmine therapeutically
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Reversal of paralysis by competitive neuromuscular blocking drugs
treating postoperative atony of gut and bladder |
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How do irreversible organophosphorus inhibitors work?
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They irreversibly phosphorylate the serine in the substrate binding domain of AChesterase. Return of enzyme activity depends on synthesis of new enzymes.
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Why does malathion work as a pesticide?
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Rapidly detoxified in us but not in insects- they get Ach excess levels.
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What is echothiophate used to treat?
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Glaucoma since it has a long duration of action applied topically.
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What is a concern with using echothiophate?
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Long term use may be associated with cataracts
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What is the toxicity associated with irreversible organophosphorus inhibitors?
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They can activate muscarinic and nicotinic receptors in both periphery and CNS.
This can cause 1) medullary respiratory center depression 2) nmj paralysis 3) bronchoconstriction/bronchial gland secretion 4) bradycardia and decreased CO 5)death due to resp failure. |
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How to treat toxicity from irreversible organophosphorus inhbitors of AChesterase
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Remove the poison source
Maintain a patent airway Give atropine (muscarinic antagonist - blocks peripheral and central muscarinic effects) or pralidoxime - reactivates the enzyme peripherally (need to give very quickly) before enzyme ages |
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What are the classes of muscarinic receptor antagonists?
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Naturally occurring alkaloids, semisynthetic derivatives of alkaloids, and synthetic antagonists.
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What are the naturally occuring alkaloids
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These muscarinic receptor antagonists include atropine and scopolamine
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What are the semisynthetic derivatives of alkaloids?
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These include ipratropium
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What are the synthetic antagonists (muscarinic)
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tropicamide
oxybutynin darifenacin glycopyrrolate |
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What are the uses of atropine?
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Atropine is used to
1) treat peptic ulcer disease, irritable bowel disease but has been replaced by better therapies 1) bradyarrhythmia treatment 2) opthalmic uses (mydriasis production or cycloplegia - paralysis of accomodation. these last a long time (days) and allow for treatment of iritis/chorditis and allow for thorough examination of retina/optic disk. 3) in anesthesia to block vagal reflexes induced by surgical manipulations of visceral organs 4) ACh or muscarinic toxicity. |
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What are the uses of scopolamine
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Greater CNS penetration and used as a patch to treat motion sickness and vestibular disease.
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What is ipratropium used to treat?
How is it administered? What is is its chemical structure? |
COPD. It is administered by inhalation. It is a quaternary amine - no CNS penetration
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What are the effects of ipratropium
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Reduces bronchial secretion and reduces bronchial constriction and can treat rhinorrhea associated with the common cold.
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What are the effects of tropicamide?
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Used as an opthalmic solution to produce mydriasis and cyclopegia. It has a fast onset and short duration of action
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What is oxybutynin used to treat?
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Oxybutynin is used to treat overactive bladder and incontinence.
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What is the issue with oxybutynin?
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Oxybutynin has a lot of antimuscarinic side effects: xerostomia, blurred vision, GI, CNS (confusion)
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Why is darifenacin a better option than oxybutynin?
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Darifenacin is specific for M3 receptors- this means less cns side effects.
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What is glycopyrrolate used for?
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Glycopyrrolate is used to block parasympathomimetic effects when neostigmine is used to reverse skeletal muscle relaxation. IT has no CNS penetration.
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What are the contraindications of muscarinic antagonists?
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Glaucoma (these can increase intraocular pressure)
Prostatic hypertrophy Diseases where tachycardia is a problem (angina, arrythmia) |
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What are the symptoms of toxivity of muscarinic antagonists?
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Hot as a hare (no sweating)
red as a beet (excessive heat) dry as a bone (xerostomia) mad as a hatter (CNS delirium etc) blind as a bat ( mydriasis, cycloplegia) |
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What kind of things can lead to muscarinic receptor antagonist poisoning.
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Consuming belladona alkaloids,
histamine blockers, antipsychotics, tricyclics can lead to posioning. |
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How to treat muscarinic receptor antagonist poisoning?
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Physostigmine
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What is the purpose of neuromuscular blocking agents?
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They produce paralysis of skeletal muscle - useful during anesthesia to allow operative manipulations (allows for much less anesthesia)
As well to control muscle spasms, facillitate intubation with a tracheal tube |
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What are the two classes of nm blocking agents?
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Depolarizing and competitive/nondepolarizing
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What are some important features of competitive nm blocking agents
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They compete with Ach for end plate receptors without activating the ion channel. They are poorly absorbed from GI tract and have no CNS effects. They can stimulate mast cells and can have vacolytic actions.
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What are the 4 competitive NM blocking agents?
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Rocuronium, atracurium, vecuronium, pancuronium
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All of the competitive nm blocking agents are aminosteroids except
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Atracurium which is a benzylisoquinoline
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Comment on duration of action, onset of action, and metabolism of rocuronium
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Duration is intermediate 30-60
Onset is rapid 1-2 mins Metabolized by liver |
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Comment on duration of action, onset of action, and metabolism of atracurium
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Duration is intermediate 30-60 mins
Onset is 2-4 mins Metabolism: spontaneously degrades in plasma to inactive metabolites and also metabolized by plasma esterases; renal elimination Has minimal CV effect but some histamine release |
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Comment on duration of action, onset of action, and metabolism of vecuronium
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Intermediate duration of action
Onset is 2-4 mins Liver metabolism No CV or histamine effect |
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Comment on duration of action, onset of action, and metabolism of pancuronium
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Long duration of action 120-180 mins onset
Metabolized by kidney Increases HR and BP |
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What is the depolarizing nm blocker?
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Succinylcholine
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What is the general MOA of depolarizing neuromuscular blockers?
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activates nicotinic receptors at nmj maintaining depolarization and prevents another action potential.
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What is the effect seen in muscle tissue under succinylcholine
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Fasciculations followed by flaccid paralysis
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What metabolizes succinylcholine
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Pseudocholinesterase
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What is the structure of succinylcholine
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2 acetylcholine molecules joined together- no CNS entering
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What is the duration of action and onset of action of succinylcholine?
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Very rapid onset of duration 1 min (allows tracheal intubation)
Duration of action 5-8 mins |
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Why is succinylcholine administration a problem in some people?
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Some people have liver dysfunction or genetic variations in pseduocholinesterase activity- can lead to longer lasting succinylcholine.
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What are the adverse affects associated with nm blocking agents
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Malignant hyperthermia and prologned apnea/cv collapse
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Elaborate on malignant hyperthermia
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Can be caused by nm blocking agents- contracture, rigidity, hyperthermia, acidosis. Cause is uncontrolled ca release form sr of skeletal muscle. Usually caused by coadministration of hydrocarbon anesthetic and succinylcholine. Treat with dantrolene (blocks calcium)
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