4 - Muscarinic Antagonists Flashcards
Antimuscarinic agents act where
postganglionic neuroeffector junction
block Psy discharge
Nicotinic receptor blocker types (and site of action)
- NM blocker = act at NMJ to block Ach signaling
- Ganglionic blocker = act as antagonists at Psy and Sy ganglia
Muscaric receptors are all
GPCR
Two types of Ach regulated GPCR and their general mechanisms
M 1,3,5 = Signal via intracellular Ca++ increase and Protein Kinase C activity
M 2+4 = SIgnal via cAMP decrease and reducced cAMP-dependent protein kinase activity
Type and location of M1
(Gaq)
CNS
Sy Post ganglionic cells and presynaptic sites
Type and location of M3
(Gaq)
- Sm. muscle
- Lungs
- eyes
- effector cell membranes
Type and location of M2
(Gai)
Myocardium
Sm muscle
Presynaptic sites (K+ channel linked = slow HR)
Type and location of M4
(Gai)
CNS
Ocular exams: Conditions and causes
Mydyriasis (dil) = inhibit Ach action on M3 receptor in constrictor muscle
Cycloplegia (loss of focus/reg of lens thickness) = Inhibit Ach on M3 receptor on ciliary muscle
Primary clinical uses for antimuscarinics
Ocular exams (mydyriasis, Cycloplegia)
Incontinence (bladder relaxation)
IBS (induce GI paralysis)
Antimuscarinic effect on bladder
Relaxation = via M3 (bladder contraction mediator) and M2 (indirectly…inhibits relaxation)
GI effects of antimuscarinics (for IBS)
Induce GIT paralysis
Reduce secretion
Antimuscarinic agent for IBS
Mebeverine
Other uses for antimuscarinics
COPD (bronchodilate and reduce secretions)
Pre-op anti secretory
Motion sickeness
Parkinsons
MOA of antimuscarinic
competitive and reversible inhibition of muscarinic receptor activation
Two classes of antimuscarinics
Tertiary amines (atropine, used in ocullar and CNS)
Quaternary amines (Glyopyrrolate, used in GI and peripheral applications)
Long lasting tertiary amines
Atropine
Scopolamine
Atropine and Scopolamine are…
Non-selective (hit M1-M5)
Tertiary compounds that penetrate the CNS
Long lasting Tertiary amines (Atropine / Scopolamine) are used for
GI
Urinary
COPD (Ipratropium)
Motion sickness
Adjunct to LDOPA therapy
Naturally occuring tertiary amine
Scopolamine
(CNS penetration is better than atropine)
Scopolamine Sides
Drowsiness (low dose)
Hallucination (high dose)
Confusion
Dilated pupils
Tachycardia
Scopolamine used for
Motion sickness/nausea
Scopolamine may cause
amnesia (surgical use)
Scopolamine dose
1mg over 3 days transdermal
Scopolamine not recommended for…
kids or elderly (toxicity)
effect of Scopolamine discontinuation
Withdrawal because receptor sites are sensitized
Cholinergic NT’s accumulate
–> Overstimulation of vestibular nuclei and reticular formation of the emetic center
Tx for scopolamine withdrawal
- Meclizine (anti-histamine)
- Diphenhydramine + 8-chlorotheophylline (=dramamine)
Short acting tertiary amine
Tropicamide
Causes cycloplegia and mydriasis
(duration = .25 days)
Stress incontinence
Laxity of pelvic floor muscle
Treat with adrenergics
Urge incontinence
Increased detrusor activity (overactive bladder)
Nocturia
Treat with Anticholinergics
Outflow incontinence
Urinary retention secondary to obstruction or bladder atony
(nocturia, increased frequency)
Treat atony with cholinergics
Treat obstruction with alpha antagonists
Functional incontinence
Due to large volume intake
Mechanisms for incontinence from Diabetes
Overweight
Diabetic neuropathy (either overactive/urge incontinence or Cystopathy where sensatation is decreased)
Gestational diabetes = sphincter damage
CHF = water retention
Leftover urine can cause ___
UTI
Increase urge and frequency
Bladder receptors include _______, which are targets for _____
M3/M2
Tolteridine
Receptor on urethra
alpha1
Receptor on Ext. Urethral sphincter
Nicotinic
effect of muscarinic antagonists on urinary incontinence
Suppress involuntary bladder contraction
Increase threshold/maximal urine volume that causes involuntary bladder contraction
M3 selective agents
Darifenacin, Solifenacin
Longer acting than oxybutinin
M2/3 selective agents
Tolterodine
Fewer sides than oxybutinin
M1/3 selective
Oxybutinin
ER or patch, xerostomia common side effect
Probanthine used for __________
Pharmacodynamics?
GI spasms and peptic ulcers
Charged N makes crossing gut difficult
Peripherally restricted
Anti spasmotics =
Avoid in whom?
Atropine, Dicyclomine, Hyoscyamine
Avoid in glaucoma patients, avoid long term use
(causes constipation and difficulty urinating)
(COPD)
M3 receptors mediate ________
(effect of blocking?)
constriction of bronchial smooth muscle
(therefore M3 antagonist will block Ach-mediated constriction and open airways)
M3 antagonist is less effective _________
as a monotherapy
“-tropium”
Short and long acting examples
Ipra = short acting (rescue inhaler)
Tio = long acting (daily inhaler)
T1/2 of LAMA
5-6 days
Tertiary amines use for Parkinsons–
MOA
Use
Action through CNS M1 receptor
Adjunct with LDOPA
Treats extrapyramidal sides of antipsychotics
Drug catergories with anticholinergic activity
anti-psychotics
tricyclics
antiarrythmics
anti-histamines
Common Contraindications for antimuscarinics
- Worsen open/narrow angle glaucoma
- Tachycardia
- Ileus (intestinal obstruction) - further reduce GI fxn
- Urinary obstruction (BPH)
