Pharm - Lecture 9 - Cholinergic - muscarinic agonists/antagonists + acetylchoinsterase inhib. Flashcards
Which drugs are Muscarinic Receptor agonists?
Bethanechol
Pilocarpine
Acetylcholine (not bolded)
Muscarine (not bolded)
Which drugs are Choline esters? (2)
Acetylcholine (not bolded)
Bethanechol
What are the uses of Bethanechol?
Route of administration?
Used for urinary retention in the absence of obstruction
(post-op urinary retention, diabetic neuropthy, bladder disorders)
Route of administration: Oral or subcutanious
What drugs are naturally occuring alkaloids? (2)
Muscarine (not bolded)
Pilocarpine
How is Pilocarpine used?
1) orally to treat xerostamia (dry mouth)
2) Opthalmically: miotic agent - to treat wide angle glaucoma and emergency treatment of narrow angle glaucoma
How are Muscarinic receptor agonists adminstered?
Why?
Orally or subcutaniously: can’t administer by IV because it would cause hypotension
What does SLUDGE stand for?
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis
What are the side effects of muscarinic receptor agonists?
SLUDGE (salivation, lacrimatnio, urination, defecation, gastrointestinal upset, emesis (vomiting)
also: hypotension, bradycardia, difficulty with visual accomodation (blurred vision)
What drug blocks the toxicity of muscarinic receptor agonists?
atropine
What patients should muscarinic receptor agonists be used with caution? (3)
Asthma and COPD
Urinary or GI obstruction
Cardiovascular disease (bradycardia, hypotension, hyperthyroidism)
Why should you be careful about using muscarinic receptor agonists on patients with cardiovascular diseases?
may precipitate atrial fibrillation
Which drugs are acetylcholinesterase inhibitors? (5)
anticholinesterase agents:
Edrophonium
Physostigmine
Neostigmine
Sarin (nerve gas)
Malathion (insecticide)
How does Edrophonium bind? What is it’s onset and duration of action?
Can it penetrate CNS?
Truly reversible competitive enzyme inhibitor: non-covalent binding
Rapid onset and short duration of action (minutes)
Can’t penetrate CNS
What are the uses of Edrophonium? (3)
1) diagnosis of myasthenia gravis
2) distinguish cholinergic crisis from myasthenic crisis
3) reversal of paralysis by competitive neuromusclar blocking drugs
How is Physostigmine used?
1) wide angle glaucoma
2) toxicity by antimuscarinic drug poisoning
How does Physostigmine treat antimuscarinic drug poisoning?
Because Physostigmine is lipophilic, it can travel into the brain directly to treat this toxicity
How is Neostigmine used?
1) treatment of myasthenia gravis (oral)
2) prevention and treatment of post-operative atony of gut and bladder (oral)
3) reversal of paralysis by competitive neuromuscular blocking drugs (i.v.)
Has no CNS effects
Why is malathion a relativly safe insecticide?
Because it is rapidly detoxified in higher organisms
What is the cause of the side effects of acetylcholinesterase inhibitors?
results from activation of muscarinic and nicotinic receptors in both the periphery and CNS
What are the side effects of REVERSIBLE acetylcholinesterase inhibitors? (4)
SLUDGE
hypotension, bradycardia, difficulty with visual accommodation
What are the side effects of IRREVERSIBLE acetylcholinesterase inhibitors?
Same as reversible inhibitors and addisionally:
Medullary respiratory center depression
Muscle paralysis due to depolorazing neuromuscular junction blockade
Death due to respiratory failure
What are antidotes for acetylcholinesterase inhibitor toxicity? (2)
1) atropine (muscarinic receptor antagonist)
2) pralidoxime (reactivates acetylcholinesterase - must treat within 2-3 hours)
What are the effects of Muscarinic receptor antagonists? (5)
1) relax iris sphincter and cilary muscles (mydriasis and paralysis of accommodation)
2) relax non-vascular smooth muscle (airways, GI tract, urinary bladder)
3) inhibit exocrine gland secretion (sweat, salivary, lacrimal, intestinal, mucosal glands)
4) increase Heart Rate
5) CNS effects: low dose produces sedation
high dose produces: excitement, delirium, agitation, toxic psychosis
What drugs are muscarinic receptor antagonists? (7)
2 alkaloids
1 semi-synthetic alkaloid
4 synthetics
Atropine (alkaloid)
Scopolamine (alkaloid)
Ipratropium (semi-synthetic alkaloid)
Tropicamide (synthetic)
Oxybutynin (synthetic)
Darifenacin (synthetic)
Glycopyrrolate (synthetic)
What are the cardiac uses of Atropine? (2)
Used to treat bradycardia:
1) MI
2) syncope associated with hyperactive carotid sinus reflex
What are the opthalmic uses of Atropine?
mydriasis (dialation and cylcoplegia (paralysis of accoomadation)
What is the duration of action of Atropine? (opthalmically)
7-10 days opthalmically
How is Atropine used in anesthesia?
block responses to vagal reflexes induced by surgery of visceral organs
What types of toxicities is Atropine used for?
Anticholinesterase or muscarinic toxicity
How is Scopolamine used?
Used as a transdermal patch to teat motion sickness and vestibular disease
(greater CNS penetration and more prominent CNS effects)
How is Ipratropium used?
Via inhalation?
via nasal spray?
Does it penetrate CNS?
Inhaled: Treatement of COPD - reduces bronical secretions and constriction
Nasal spray: treatment of rhinorrhae associated with common cold
doesn’t penetrate CNS
How is Tropicamide used?
What is the onset and duration of action?
Opthalmic solution to produce mydriasis and cycloplegia
Onset of action: fast (20-40 minutes)
duration: short (4-6 hours)
How is Oxybutynin used?
Overactive bladder and incontinence
What types of side effects is Oxybutynin known for?
high incidence of anti-muscarinic side effects:
Mostly zerostomia but also blurred vision, constipation and drowsiness and confussion
What receptor is Darifenacin specific for?
M3
What is Glycopyrrolate used for?
used to block parasympathomimetic effects during reversal of neuromusclar blockade with anticholinesterase agents
What are the side effects of Muscaranic antagonists? (5)
1) hot as a hare (no sweating)
2) dry as a bone (dry mouth, dry hot skin, no sweating)
3) red as a beat (excessive heat and no sweating)
4) blind as a bat (mydriasis, cycloplegia, blurred vision)
5) drowsiness (CNS action)
When at a toxic dose, what side effect is added for muscuranic antagonists?
“mad as a hatter”
ataxia, restlessness, excitement, hallucinations, delirium, coma
What is physostigmine used for?
Muscaranic antagonist toxicity
What patients should you be careful with when giving muscuranic antagonists? (3)
1) Glaucomoa - could increase intraocular pressure
2) prostatic hypertrophy - increase difficulty voiding
3) tachycardia (ex. angina pectoris)
What is the mechanism of substrate inhibitors of acetylcholinesterase compared to non-substrate inhibitors?
Substrate inhibitors: bind as a substrate for acetylcholinesterase and is metabolized way slower than acetylcholine
Non-substrate inhibitor: blocks site of action for acetylcholinesterase
