Muscarinic Antagonists Flashcards
Anticholinergic drugs do what?
Antagonists that prevent acetylcholine signaling
Antimuscarinic acts where?
Post ganglionic neuroeffector junction to block parasympathetic autonomic discharge
Neuromuscular blocker acts where?
Neuromuscular junction to block acetylcholine signaling
Ganglionic blockers act where?
They act as antagonists at both parasympathetic and sympathetic autonomic ganglia
How do Muscarinic Receptors M1, M3, and M5 signal?
Via increase in intracellular Ca2+and PKC activity
Where is M1 located? (3)
CNS
Sympathetic postganglionic cells
Presynaptic sites
M3 locations? (3)
Smooth muscle
Lungs
Eyes effector cell membranes
M2 and M4 are activated how?
Signal via cAMP decreased and reduced cAMP-dependent PK activity
Where is M2 located? (3)
Myocardium
Smooth muscle
Presynaptic sites
Where is M4? (1)
CNS
Atropa Belladonna (deadly nightshade) gave us what?
Atropine
Belladonna causes what effect in the eyes?
Increase in pupil size
Antimuscarinic drug use in ocular exams? (2)
Mydyriasis (pupil dilation)
Cycloplegia (Loss of focus/regulation of lens thickness)
Which M receptor is being targeted in antimuscarinic drugs?
M3
How does Muscarinic antagonists affect incontinence?
Triggers bladder relaxation via M3 receptor which mediates contraction of bladder and M2 which inhibits relaxation
Drug used in irritable bowel syndrome to induce GI paralysis and reduce secretions?
Mebeverine
What other uses are listed for antimuscarinic drugs? (4)
COPD
Pre-Op Anti-Secretory
Motion Sickness
Parkinson’s disease
For COPD use what is the effect of muscarinic antagonists? (2)
Reduce secretions
Cause Bronchial dilation
In COPD use what would I combine antimuscarinic drugs with?
B-adrenergic agonist
What is the purpose of anti-muscarinic in treating Parkinson’s?
Adjunct to L-DOPA
What is the mechanism of Antimuscarinic drugs?
Competitive and reversible inhibition of muscarinic receptor activation by preventing the binding of Ach.
Two classes of antimuscarinic?
Tertiary Amines (Atropine) Quaternary Amines/Ammonium (Glycopyrrolate)
Main use for Tertiary amines?
Ocular and CNS applications
Main use of Quaternary Amines/Ammonium?
GI tract and peripheral application
What specific tertiary amine do you use for COPD?
Ipratropium
Characteristics of tertiary amines? (2)
Can penetrate CNS
Non-selective antagonists
Which tertiary amine is better for CNS penetration?
Scopolamine is better than Atropine
What happens in low vs high doses of Scopolamine?
Low doses you get drowsiness
High doses you get hallucination
Why is Scopolamine not for children?
Toxicity
How do you give Scopolamine locally?
Patch form
Why is Scopolamine useful in surgery and childbirth?
Can cause amnesia
When Scopolamine treatment is stopped what effects can be seen?
Rebound effects which cause overstimulation of vestibular and reticular formation of the vomiting center
Short acting tertiary amine used in optical applications?
Tropicamide (0.25 days)
What does Tropicamide cause? (2)
Cycloplegia (loss of accommodation)
Mydriasis
Types of Urinary Incontinence? (4)
Stress (Leak)
Urge (Nocturia)
Outflow (Retention secondary to obstruction)
Functional (Large volume intake)
What do you treat stress incontinence with?
Adrenergic agonist
What do you treat urge incontinence with?
Anti-cholinergics
What do you treat outflow incontinence with?
Cholinergics for atony
alpha antagonists for obstruction
Diabetic neuropathy can cause what two dysfunctions?
1) Diabetic bladder dysfunction
2) Diabetic cystopathy
What is diabetic bladder dysfunction?
Overactive bladder leading to urge incontinence
What is diabetic cystopathy?
Decreased bladder sensation, increased capacity leading to outflow incontinence
How does pregnancy affect the bladder?
Increased weight from baby damages bladder sphincter
Effect of Congestive heart failure on bladder?
Retention of water causes more water in body causes too much urine causes nocturia
What do muscarinic antagonists do for urinary incontinence? (2)
Suppress involuntary bladder contraction
Increase maximal urine volume that causes involuntary bladder contraction
Which muscle in the bladder does M2 handle?
Detrusor
Benefit of M3 selective Darifenacin or Solifenacin in urinary incontinence?
Longer acting than oxybutinin
Benefit of M2/M3 selective Tolterodine?
Fewer side effects than oxybutinin
Downside of Tolterodine?
Too much/too long use can lead to acute urinary retention
Quaternary amine probanthine used for what?
Gastric disorders such as GI spasms/peptic ulcers
What restricts Probanthine from crossing the gut?
Charged Nitrogen
What type of restricted is Probanthine?
Peripherally
Main antispasmodics for irritable bowel syndrome? (3)
Atropine
Dicyclomine
Hyoscyamine
Who do you avoid giving antispasmodics to?
Glaucoma patients
Which muscarinic receptors mediate constriction of bronchial smooth muscle?
M3
So M3 antagonist will block Ach mediated constriction and open the airways
M3 antagonists enhance what?
B-adrenergic agonists in COPD
What is known as the “rescue inhaler”?
Ipratropium: short acting
What is known as the daily inhaler?
Tiotropium: long acting
What do tertiary amines for Parkinson’s act on?
CNS M1 receptors
What is the preferred Tri-cyclic Anti-depressant in elderly to moderate anticholinergic effects ?
Nortriptyline (Aventyl, Pamelor)
Important drug in treating Parkinson’s?
Trihexyphenldyl
When do you not give anti muscarinic drugs? (4)
Glaucoma
Tachycardia
Intestinal obstruction
Urinary obstruction
