Kruse Cholinergic Agonists and Antagonists Flashcards
muscarinic receptors activation of what kind of receptor?
G proteins, Gs and Gi,
M2 and M4= Gi
M1, 3, 5= Gs
in most end organs what is the muscarinic receptor? what do we normally see when activated
M3, contraction of smooth m.
what does M2 cause throughout body? specific found in high concentration in what organ?
also m. contraction; heart
how are cholinergic agonists classified? how do they work?
direct-acting (bind to receptors) or indirecting (increase Ach concentration)
MOA of direct-acting?
agonists at cholinergic receptors
choline esters have what kind of charge? consequence
permanently charged!, poor absorption
choinergic esters are broken down by what enzyme?
acetylcholinesterase
most choline esters have a greater activity on which AchR?
muscarinic
what are the other kinds of cholinergic agonists? charge? consequence?
alkaloids, uncharged tertiary amines, well absorbed
what are the 3 groups of AchE inhibitors?
alcohols, carbamic acid esters, organophosphates
which AchE inhibitor is irreversible?
organophosphate
what dictates the PK of an AchE inhibitor?
chemistry
charged: not lipid soluble, poorly absorbed
neutral: lipid soluble, well absorbed
cholinergic agonists have what kind of effect on the body?
parasympathetic effects (even slowing of the heart is not clinically useful from cholinergic agonist= beta blocker instead)
what is acetylcholine approved for?
intraocular surgery and causes misosis (reduces pupil size)
bethanechol is selective for what receptor? primarily effective where?
mAchR; urinary and GI tracts
what is varenicline (chantix)? MOA?
partial agonist for nAchRs, stimulation of moderate, sustained release of mesolimbic dopamine to reduce craving and withdrawal
what are the adverse effects of varenicline?
behavior, mood changes, agitation, suicidal ideation, etc.
what are the 2 major uses of direct-acting cholinergic agonists?
diseases of the eye
GI/GU disorders
what are some of the diseases of the eye direct-acting cholinergic agonists can be used for?
glaucoma
accomodative estropia: misalignment of eyes caused by hypermetropic accomodative error
What toxicities do muscarinic stimulation have?
N/V
SLUDGE= salivation, lacrimation, urinary urgency, vasoDilation, GI effects
which pt populations have contraindication for muscarinic stimulants?
asthma, hyperthyroidism, coronary insufficiency, acid-peptic disease
what are the nicotinic agonists toxicities?
effects on NMJ
Cholinergic antagonists have what kind of effect on the body?
sympathetic
pupil dilation, dry mouth, relaxation of bronchi, accelerate heart, GI secretion reduced, constipation, retention of urine
antinicotinic drugs work where?
NMJ: skeletal m. relaxants
ganglia: RARELY USED
what is the prototype antimuscarinic agent?
atropine
what do antimuscarinic agents do?
block effects of parasympathetic autonomic discharge
how are antagonists used to help with parkinson dz? drugs?
mAchR antagonists can reduce tremors, not as effective as dopaminergic therapy; tertiary amines benztropine, trihexyphenidol, and one more than i missed, he’s going too fast
what respiratory disorders can be treated with anticholinergics? drugs?
asthma and COPD; ipratropium and tiotropium (longer dilation effect, once daily)
What GI disorders can be treated with anticholinergics?
common traveler’s diarrhea and other mild or self-limited conditions of hypermotility
lomotil is a combo of what drugs and why?
atropine and diphenoxylate; opoid and anticholinergics- to discourage abuse of drug
GU disorders can be treated with drugs selective to what subtype?
M3- present in bladder wall and sphincter smooth m.
what is the prototype for GU disorders?
oxybutynin, effects not long enough though
what can cause cholinergic poisoning?
cholinesterase inhibitor insecticides, wild mushrooms, chemical warfare nerve gasses
what is the treatment for cholinergic poisoning?
atropine (antimuscarinic agents)- reduce mAchR stimulation
when is atropine useless?
mushroom posioning
what conditions are contraindicated for anticholinergics?
glaucoma, prostatic hyperplasia, acid-peptic disease
What flows thru an activating Nn receptor?
Na, K
