4 - Muscarinic Antagonists Flashcards by Chris Rodarte

Antimuscarinic agents act where

postganglionic neuroeffector junction

block Psy discharge

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Muscaric receptors are all

GPCR

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Type and location of M1

(Gaq)

CNS

Sy Post ganglionic cells and presynaptic sites

How well did you know this?

Not at all

Perfectly

Type and location of M3

(Gaq)

Sm. muscle
Lungs
eyes
effector cell membranes

How well did you know this?

Not at all

Perfectly

Type and location of M2

(Gai)

Myocardium

Sm muscle

Presynaptic sites (K+ channel linked = slow HR)

How well did you know this?

Not at all

Perfectly

Type and location of M4

(Gai)

CNS

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Primary clinical uses for antimuscarinics

Ocular exams (mydyriasis, Cycloplegia)

Incontinence (bladder relaxation)

IBS (induce GI paralysis)

How well did you know this?

Not at all

Perfectly

Antimuscarinic effect on bladder

Relaxation = via M3 (bladder contraction mediator) and M2 (indirectly…inhibits relaxation)

How well did you know this?

Not at all

Perfectly

GI effects of antimuscarinics (for IBS)

Induce GIT paralysis

Reduce secretion

How well did you know this?

Not at all

Perfectly

Antimuscarinic agent for IBS

Mebeverine

How well did you know this?

Not at all

Perfectly

Other uses for antimuscarinics

COPD (bronchodilate and reduce secretions)

Pre-op anti secretory

Motion sickeness

Parkinsons

How well did you know this?

Not at all

Perfectly

MOA of antimuscarinic

competitive and reversible inhibition of muscarinic receptor activation

How well did you know this?

Not at all

Perfectly

Two classes of antimuscarinics

Tertiary amines (atropine, used in ocullar and CNS)

Quaternary amines (Glyopyrrolate, used in GI and peripheral applications)

How well did you know this?

Not at all

Perfectly

Long lasting tertiary amines

Atropine

Scopolamine

How well did you know this?

Not at all

Perfectly

Atropine and Scopolamine are…

Non-selective (hit M1-M5)

Tertiary compounds that penetrate the CNS

How well did you know this?

Not at all

Perfectly

Long lasting Tertiary amines (Atropine / Scopolamine) are used for

Urinary

COPD (Ipratropium)

Motion sickness

Adjunct to LDOPA therapy

How well did you know this?

Not at all

Perfectly

Naturally occuring tertiary amine

Scopolamine

(CNS penetration is better than atropine)

How well did you know this?

Not at all

Perfectly

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)