Cholinergics - Muscarinic Receptor Antagonists Flashcards
What is the general mechanism of a muscarinic receptor antagonist?
competitively block muscarinic receptors
What are 2 other names for muscarinic receptor antagonists?
Parasympatholytics
Antimuscarinics
What are the effects of muscarinic antagonists? (5)
Eye - Relax iris sphincter and cillary muscles -> mydriasis and paralysis of accommodation
Smooth muscle -> relax non vascular (airway, GI, urinary bladder)
Inhibit exocrine gland secretion
Heart - Increase heart rate
CNS - low dose -> sedation, high dose -> excitement, delerium, psychosis (toxic)
What is an alkaloid?
Naturally occurring plant derivative,
What are the uses of atropine?
Peptic ulcer disease
irritable bowel disease
spastic bladder
bradyarrhythmias (b/c of high vagal tone)
What are the current uses of atropine? (4)
Bradycardia during acute MI, and due to hyperactive carotid sinus reflex (high vagal tone)
Mydriasis and cycloplegia (paralysis of accommodation) -> treatment of acute inflammation in the eye ( iritis, choroiditis)
Anesthesia -> block vagal responses
AChE or muscarinic toxicity
What was the ancient Italian use of atropine?
Produce mydriasis (dilation) for beauty
What is the duration of action of atropine?
LONG (7-10 days)
Why is atropine no longer used to treat other ailments?
Too many side effects
What is the major therapeutic use of Scopolamine?
motion sickness -> decrease nausea
What is the route of administration of Scopolamine and what makes this possible?
Transdermal patch -> lipophillic, can penetrate CNS and skin
What are the 2 naturally occurring alkaloids?
Atropine and Scopolamine
What drug is a semi-symthetic derivative of an alkaloid?
Ipratropium
What are the major therapeutic uses of Ipratropium?
COPD
What is the route of administration of Ipratropium?
inhalation
What is significant about the structure of ipratropium?
Quaternary ammonium -> (+) -> no CNS penetration and poor systemic absorption when inhaled
What are the effects of ipratropium?
reduce bronchial secretions and reduce bronchial constrictions
What is a second approved use for Ipratropium?
nasal inhalers for treatment of rhinorrhea -> due to common cold or rhinitis
What are the 4 synthetic antagonists?
Tropicamide
Oxybutynin
Darifenacin
Glycopyrrolate
Tropicamide
1) Duration of action/onset
2) Therapeutic use/effects
Fast onset (20-40 minutes), Short duration (4-6h) Used to produce mydriasis, cycloplegia (eye exams) ->dilation
Oxybutynin
1) Therapeutic uses
2) Side Effects
1) Overactive bladder and incontinence -> decreases parasympathetic action causing constriction of urinary muscles
2) High incidence of side effects -> untolerable
drowsiness, confusion, blurred vision, constipation, xerostomia
Darifenacin
1) Why unique
2) Therapeutic uses
3) Why preferred
1) M3 selective muscarinic antagonist
2) overactive bladder, incontinence
3) M3 receptors on bladder/muscles involved in urination -> fewer CNS side effects
Glycopyrrolate
1) Therapeutic uses
2) Structure significance
1) block parasympathomimetic effects during reversal of neuromuscular blockade with AChE agents
2) + amine so no CNS penetration
What are the side effects of muscarinic antagonists (5) Low dose
- hot as a hare (no sweating)
- dry as a bone (dry mouth, dry hot skin, no sweating)
- red as a beet (b/c heat and no sweat)
- blind as a bat (b/c no accommodation)
- drowsiness (CNS)
What are the side effects of muscarinic antagonists at high doses (toxic)?
All of low dose + mad as a matter (ataxia, restlessness, excitement, hallucinations, delirium, coma)
What condisitons should be taken into consideration with muscarinic antagonists?
glaucoma - b/c could increase intraocular pressure
prostatic hypertrophy - could increase difficulty voiding
any disease with tachycardia
How do you treat muscarinic antagonist poisoning?
physostigmine
limit absorption if taken orally
