Cholinergic Agonists and Antagonists- Kruse Flashcards
what is the parasympathetic neurotransmitter
Ach
what are the parasympathetic receptors
nAchR, mAChR
what are the sympathetic neurotransmitters
NE>Epi (DA) and Ach
what are the sympathetic receptors
alpha, beta, (D), nAchR, and mAChR
what are the 4 steps that occur at the cholinergic nerve terminal
1) ACh synthesis
2) ACh storage
3) ACh release
4) ACh destruction
what are the 4 steps that occur at the adrenergic nerve terminal
1) Synthesis
2) Storage
3) Release
4) Reuptake
two molecules that come together to synthesize Ach
AcCoA and Choline
Enzyme that synthesizes Ach
ChAT
Ach is stored in…
a vesicle
what stimulates the Ach vesicle to fuse and release the Ach
Ca2+
Ach is destroyed by
Acetylcholinesterase
enzyme that synthesizes dopa from tyrosine
is this outside/inside the vesicle
tyrosine hydroxylase
outside the vesicle
enzyme that synthesizes dopamine from dopa
is this outside/inside the vesicle
aromatic amino acid decarboxylase
outside the vesicle
dopamine is then stored in…
a vesicle
dopamine is converted to NE by…
dopamine Beta hydroxylase
what stimulates fusion of dopamine/NE vesicle
Ca2+
Once the catecholamines bind to receptor they are..
taken up again into the pre-synaptic cleft
M1, M3, and M5 are what type of GPCRs
Gq/11 that use the IP3, DAG cascade
M2 and M4 are what type of GPCRs
Gi/o that inhibit cAMP production
M2 also activates K+ channels
M1 main location?
nerves
M2 main locations?
heart, nerves, smooth muscle
M3 main locations?
glands, smooth muscle, endothelium
M4 and M5 main locations?
CNS
In most organs, except heart, which Muscarinic receptor is predominant
M3
which M receptor is dominant in the heart
M2
two types of cholinergic agonists are?
direct-acting drugs
and
indirect-acting drugs (by inhibiting the action of acetylcholinesterase)
what are the 4 direct-acting cholinergic agonists that are uncharged and highly absorbed
Muscarine and Pilocarpine (action mainly at muscarinic)
AND
Nicotine and Lobeline (action mainly nicotinic)
what are the 4 direct-acting cholinergic agonists that are charged and poorly absorbed
Acetylcholine, Methacholine, Carbachol, and Bethanechol
What are the 3 groups of AChE inhibitors
Alcohols (reversible)
Carbamic acid esters (reversible, but longer lasting than alcohols)
Organophosphates (irreversible)
what are the 4 charged and poorly absorbed AChE inhibitors
Neostigmine, Carbaryl, Physostigmine, Edrophonium
what are the 6 uncharged and highly absorbed AChE inhibitors
Echothiophate, Soman, Parathion, Paraoxon, Malathion, Malaoxon
what is the treatment if there is toxicity due to the action of direct-acting cholinergic agonists
atropine and parenteral anticonvulsants
Use of Acetylcholine as a direct-acting agent
approved for intraocular use during surgery and causes miosis (reduction in pupil size)
Use of Bethanechol as a direct-acting agent
primarily affects urinary and GU tracts
Use of Carbachol as a direct-acting agent
treatment for glaucoma or produce miosis during surgery
Use of Cevimeline as a direct-acting agent
treats dry mouth (xerostomia) in patients with Sjogren
Use of Pilocarpine as a direct-acting agent
approved for xerostomia in pts with Sjogren, miosis during surgery, and glaucoma
What is the FDA approved drug for smoking cessation
Varenicline (Chantix)
Varenicline (Chantix) is…
a partial agonist that binds with high affinity and selectivity to nAChRs
MOA of Varenicline
sustained release of dopamine to help with withdrawl symptoms of smoking cessation
Adverse effects of Varenicline
nausea, neuropsychiatric symptoms
clinical uses of indirect-acting cholinergic agonists
Glaucoma, Dementia, Antidote to anticholinergic poisoning, Reversal of neuromuscular paralysis, Myasthenia gravis, AChE inhibitor toxicity(SLUDGE symptoms, effects on NMJ)
prototype antimuscarinic agent is…
atropine
drug used for motion sickness
scopolamine
drugs used for GI disorders
atropine, dicyclomine, glycopyrrolate, hyoscyamine
drugs used in opthalmology
atropine, cyclopentolate, homatropine, scopolamine, tropicamide
drugs for respiratory disorders
ipratropium, tiotropium
drugs for urinary disorders
Darifenacin, Oxybutynin, Solifenacin, Toterodine, Trspium
Drugs used for cholinergic poisoning
atropine and pralidoxime
drugs for movement disorders
benztropine, biperiden, orphenadrine, procyclidine, trihexyphenidyl
Anticholinergics for Parkinson
mAChR antagonists can reduce tremors
not as effective as standard dopaminergic therapy
tertiary amines benztropine, trihexyphenidyl, and procyclidine
Anticholinergics for motion sickness
Scopolamine
Anticholinergics for Anesthesia
Atropine given to block vagal reflexes induced by manipulation of visceral organs
Atropine or glycopyrrolate paired with cholinesterase inhibitor to block parasympatheitc effects
anticholinergics for opthalmologic disorders
mAChR used for cycloplegia or prolonged mydriasis is required
alpha adrenergic receptor agonists are shorter acting and have less adverse effects
Homatropine and atropine used to prevent synechia formation in uveitis and iritis (long-acting agents)
Anticholinergics for respiratory disorders
asthma and COPD will use Ipratrpium and tiotropium; these are inhalation mAChR antagonists
Anticholinergics for GI disorders
mAChR antagonists treats Traveler’s diarrhea
often combined with opioid antidiarrheal drug to discourage abuse of opioid agent (ex. Lomotil - combo of atropine and diphenoxylate)
Anticholinergics for GU disorders
mAChR antagonists provide relief in urinary urgency
agents are usually selective of the M3 subtype
Oxybutynin is prototype selective M3 antagonist- has side effects of dry mouth, dizziness, constipation
Darifenacin, Solifenacin, and Tolterodine are also selective for M3- have longer half-lives and reduced incidence of xerostomia and onstipation
anticholinergics for cholinergic poisoning
atropine given, no effective treatment at nAChR (pralidoxime)
atropine useless in delayed onset mushroom poisoning
anticholinergics adverse effects and contraindications
glaucoma
prostatic hyperplasia
acid-peptic disease
