Shared Flashcard Set

Details

Pharm Exam 1
Set 8: Muscarinic Pharmacology
116
Pharmacology
Graduate
10/08/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
What stimulates mAchR's?
Definition
Ach
Term
What competitively blocks mAchR's?
Definition
Atropine
Term
What are muscarinic receptors couple with to produce downstream effects?
Definition
G proteins
Term
Which mAchR's couple with Gq?
Definition
Odd #, M1, M3, M5
Term
Which mAchR's couple with Gi?
Definition
Even #, M2, M4
Term
Effect mAchR activation of Gq?
Definition
increase cytosolic calcium => stimulatory
Term
Effect mAchR activation of Gi?
Definition
increase potassium conductance & decrease AC => inhibitory
Term
Do muscarinic agents (agonist & antagonist) show selectivity for mAchR's?
Definition
no
Term
What is muscarinic activity of the CNS associated with?
Definition
cognition
Term
What account for the majority of CNS agonists?
Definition
quaternary amines that don't cross the BBB
Term
What is the prototype anti-muscarinic drug?
Definition
atropine
Term
Structure

atropine
Definition
natural alkaloid
Term
Toxic CNS Sx

Atropine
Definition
delirium, hallucinations,coma, death
Term
What are the 3 ways aropine is administered?
Definition
PO, parenterally, topically
Term
Structure

scopolamine
Definition
natural alkaloid (from Atropa belladonna- same as atropine)
Term
Why is scopolamine given thru an adhesive patch for motion sickness?
Definition
topical absorption is very effective
Term
What metabolizes both atropine & scopolamine?
Definition
liver
Term
How are atropine & scopolamine both excreted?
Definition
renally
Term
MOA

atropine & scopolamine
Definition
competitive antagonists of mAchR
Term
How is scopolamine different from atropine in effects?
Definition
produces 100x greater CNS depression => anxiolytic, hypnotic, anti-motion sickness, & amnestic effects
Term
What mediates atropine & scopolamine effects on CNS?
Definition
their muscarinic blocking action at cholinoceptive sites in brainstem & cortex
Term
How were the amnestic effects of scopolamine used as an advantage?
Definition
In preoperative medication or childbirth
Term
Is delirium & hallucinations also seen with scopolamine?
Definition
yes, but unlike atropine where it's only seen in toxic levels, they can be seen at therapeutic dose levels with scopolamine
Term
What is atropine used for clinically?
Definition
alleviate motor Sx of Parkinson's
Term
What synthetic muscarinic antagonist is used to alleviate Parkinson's Sx?
Definition
Benztropine (you Park your Benz)
Term
Structure

Benztropine
Definition
teritary amine
Term
What are the atropine SE? (think mnemonic)
Definition
Red as a beet
Dry as a bone
Blind as a bat
Mad as a hatter
Hot as a hare
Term
What autonomic innervation does the eye recieve?
Definition
both PS & SS
Term
What is controlled by the PS in the eye?
Definition
1) sphincter pupillae of iris
2) ciliary muscle controling lens shape
Term
What of the PS in the eye are mAchR agonist therapeutic targets?

mAchR antagonist therapeutic targets?
Definition
agonist: sphincter pupillae of iris
antagonist: ciliary muscle of lens
Term
What synthetic mAchR agonist is used to cause miosis?
Definition
Carbamylcholine
Term
Structure

Carbamylcholine
Definition
quaternary amine
Term
Can Carbamylcholine bind only to mAchR?
Definition
no, it can also bind nAchR
Term
Why is Carbamylcholine only employed as a topical mitoic agent?
Definition
too much of a widespread activity
Term
What is special about Carbamylcholine?
Definition
Not broken down by cholinesterases

(note: is this done by something else, or does this lead to a long lasting effect?)
Term
What in the eye is controlled by SS?
Definition
radially oriented fibers of the iris
Term
When PS & SS of the iris are stimulated, what occurs?
Definition
both cause contraction => opposition to eachother
Term
Effect

mAchR agonist in the eye
Definition
miosis
Term
How can mAchR agonists in glaucoma cause reduced intraocular pressure?
Definition
enhance drainage of intraocular fluid via canal of Schlemm
Term
What natural teritary amine is used for topical glaucoma miotic effect?
Definition
Pilocarpine
Term
Which AchR do pilocarpine work on?
Definition
mAchR
Term
Why might pilocarpine be used to treat salivary disfunction or dry mouth?
Definition
increase saliva
Term
Effect

mAchR antagonist in the eye
Definition
mydriasis
Term
Why isn't atropine used for mydriasis?
Definition
lasts too long
Term
What topical mAchR antagonist is shorter-acting and therefore more suitable for mydriasis effect?
Definition
Tropicamide
Term
Structure

Tropicamide
Definition
teritary amine
Term
Effect

Contraction of lens ciliary muscle
Definition
increase lens convexity => focus of near objects
Term
What do cholinergic agonists do to vision focusing?
Definition
blur distant objects
Term
What do cholinergic antagonists do to vision focusing?
Definition
distance focusing
Term
Why is atropine not given in glaucoma?
Definition
can lead to dangerous increase of pressure in the eye
Term
def

cycloplegia
Definition
paralysis of ciliary muscle by mAchR antagonist => blurred near vision (focus in distance only)
Term
What is the typical SE of tropicamide?
Definition
photophobia
Term
What mAchR receptors does the heart possess that decreased cellular activity when stimulated?
Definition
M2
Term
Where is muscarinic action on the heart directed?
Definition
SA node
atria
AV node
Term
What does M2 activation in the heart do?
Definition
1) slows HR
2) decreased force of contraction
3) suppresses AV conduction
Term
What major effects does Ach have on atrial pacemaker cells?
Definition
1) AP => shortened due to increased K+ permeability, or threshold may not even be met. 2) diastolic depolarization phases of cycle => steeper slope caused by hyperpolarization
Term
What causes the negative ionotropic action of Ach on atrial tissue?
Definition
shortened AP duration since it shortens the release & influx of Ca2+ => weaker contraction
Term
When are vascular Ach responses the most prominent pharmacological effect?
Definition
when administered IV
Term
What mAchR receptors are avilable in vasculature?
Definition
M3
Term
Effect

mAchR binding in vasculature
Definition
vessel dilation
Term
When the M3 is bound in the blood vessel, what does the increase in incracellular calcium cause?
Definition
EDRF (endothelial-derived relaxing factor) to be realeased & diffuse to smooth muscle
Term
def

EDRF
Definition
NO
Term
How is EDRF (NO) derived?
Definition
calcium stimulated NO synthase
Term
What happens to BP & HR when mAchR is activated in vasculature?
Definition
decreased BP w/ reflex tachycardia
Term
When are Ach effects ONLY seen in the vasculature?
Definition
low doese IV administration (since Ach is metabolized so quickly in the plasma)
Term
Is reflex tachycardia seen in low dose Ach IV administration?
Definition
yes, due to dilation of the blood vessels
Term
What happens when high does of Ach is administered IV?
Definition
cardiac depression through Ach action on M2 receptors
Term
What happens if you give extra high IV dose of Ach?
Definition
Complex results due to cadiac stimulation via SS nAchR => NE release
Term
Why would cardiac stimulation be prominant if atropine is given prior to Ach administration?
Definition
mAchR are blocked, but nAchR are not. The only nAchR's not coupled with mAchR's are SS => cardiac stimulation
Term
Why does atropine, if administered alone, typically produce prominent tachycardia, but have no effect on BP?
Definition
BP is regulated by factors outside of AchR and atropine would have no effect on them.
Term
Why does atropine cause skin to become red, warm, & dry?
Definition
Redness is due to vasodilation via reflex mechanism
Warm & dry is due to the blocking of sweat
Term
Why is atropine toxicity more likely to cause death in young children?
Definition
They are less capable to handle hyperthermic effects
Term
Why is atropine given after a MI?
Definition
to treat sinus bradycardia
Term
What effect does mAchR agonists have on GI smooth muscle from lower esophagus to rectum?
Definition
increased tone & motility
Term
What are the only muscles in the GI that relax due to mAchR agonists?
Definition
sphincter muscles (except lower esophageal sphicter which contracts)
Term
Which mAchR's mediate GI Ach effect?
Definition
M3
Term
Structure

Bethanechol
Definition
synthetic quaternary amine
Term
Function

Bethanechol
Definition
Tx of GI or urinary stasis, esp. post-partum or post-op.
Term
How is bethanechol similar to Carbamylcholine?
Definition
not metabolized by cholinesterases (or pseudocholinesterases)
Term
Why can't you give bethanechol when there's a mechanical GI or urinary obstruction?
Definition
will caused increased pressure of the lumen and may cause perforation
Term
What AchR do bethanechol work on?
Definition
mAchR
Term
Why may atropine be used to treat mild diarrhea?
Definition
slows down GI movement
Term
Why was atropine previously used to treat peptic ulcer/gastric reflux?
Definition
contriction on esophogeal sphincter & decrease in HCl secretion of stomach
Term
Why shouldn't atropine be used to treat peptic ulcer?
Definition
decreased GI motility will keep acids in the stomach, even tho will slow some HCl secretion
Term
Structure

Propantheline
Definition
quaternary amine
Term
Function

Propantheline
Definition
spasmolytic of GI (decrease spasms) => hypermotility Tx
Term
Would atropine or propantheline be DOC for GI hypermotility?
Definition
propantheline b/c its a quaternary amine (they're better in GI, biliary, & urinary spasm Tx)
Term
What muscle of the bladder is stimulated by mAchR to faciliate urination?
Definition
detrusor
Term
Effect

mAchR antagonist on bladder
Definition
inhibit emptying
Term
What direct mAchR agonist is used to promote micturation (urination)?
Definition
Bethanechol
Term
What indicrect mAchR agonist (i.e. AchE inhibitor) is also selective for promoting micturation (& GI motility)?
Definition
neostigimine
Term
What atropine SE are men with prostatic hyperplasia particularly sensitive to?
Definition
urinary retention
Term
What 2 mAchR antagonist variants are specifically for urge incontinence & post-op bladder spasms?
Definition
Tolterodine
Oxybutynin
Term
What metabolizes oxybutynin?
Definition
CYP3A4
Term
What metabolizes Tolterodine?
Definition
CYP2D6
Term
Structure

Oxybutynin & Toterodine
Definition
tertiary amine
Term
Effect

mAchR agonists on uterus
Definition
very sm. increase in tone/contractions
Term
Effect

mAchR agonist in lung
Definition
bronchiolar smooth muscle contraction
Term
What mAchR receptors are in the lungs?
Definition
M3
Term
What patients are especially sensitive to bronchiolar constriction of mAchR agonists?
Definition
asthmatics
Term
Structure

Methacholine
Definition
synthetic quaternary amine
Term
What mAchR's do methacholine show preference for?
Definition
heart
Term
What is methacholine used for?
Definition
Perviously: tachycardia
Currently: Aerosol form for Dx of bronchial airway hyper-reactivity in subclinical asthma
Term
Why does methacholine have a longer duration of action than Ach?
Definition
not metabolized by pseudocholinesterase & slowly degraded by AchE
Term
Why was atropine formerly smoked as afolk remedy?
Definition
mAchR antagonist => bronchial dilation
Term
What mAchR antagonist structure is preferred to cause bronchial dilation?
Definition
quaternary amine
Term
What 2 quarternary amines are administered via aerosol to Tx emphysema & chronic bronchitis?
Definition
1) ipratropium
2) tiotropium
Term
How is tiotropium different from ipratropium?
Definition
longer half-life & less antagonistic activity on M2 receptors
Term
Effect

mAchR agonists on glands
Definition
stimulate secretion
Term
Why are mAchR agonists used to treat dry mouth?
Definition
increase salivary secretion
Term
What mAchR agonist (previously discussed) is used for salivary & sweat gland stimulation?
Definition
Pilocarpine
Term
What recently approved synthetic mAchR agonist is also used for Tx of dry mouth?
Definition
cevimeline
Term
What mAchR receptors does cevimeline show selectivity for?
Definition
M1 & M3
Term
What metabolizes cevimeline?
Definition
CYP2D6 & CYP3A3/4
Term
Why was atropine formerly used in preanesthetic medication?
Definition
eliminate the increased secretions associated with their irritant actions
Term
Patient was brought to ER after hallucinations & then collapsing while drinking a gin & tonic prepared by husband. Exam reveals non-responsive 45 yo woman with flushed appearance, dilated pupils, & absence of bowel sounds. What is the source of her intoxication?
Definition
atropine poisoning
Supporting users have an ad free experience!