Pharmacology Kruse Flashcards
what is the enzyme that catalyzes choline transport? also what reaction does it catalyze?
what kind of patients have reduced production of this enzyme?
Choline acetyltransferase (ChAT) AcCoA + choline --> ACh
Alzheimer’s patients
what is the molecule involved in ACh storage?
ACh vesicular transporter
What kind of channels open during ACh release?
what facilitates vesicle-plasma membrane fusion?
Voltage-gated Ca2+
VAMP(synaptobrevin) and SNAP
what enzyme destroys ACh—> choline and acetate?
AChE
what are the 4 steps in junctional transmission?
ACh synthesis
storage
release
destruction
where are nAChR receptors located?
what are the agonists?
what kind of receptor?
skeletal m.
ACh and nicotine
ligand-gated
where are mAChR receptors located?
what type?
Agonists?
function?
smooth and cardiac m.
GPCR
ACh and Muscarine
for cardiac m. - DEC HR, conduction velocity, contraction
what do the fastest synaptic events in the nervous system use?
nAChRs (miliseconds)
what amino acids line the nAChR pores?
what charge do they have?
glutamic and aspartic acid
negative
what are the nAChR antagonists?
VAPiD
Vecuronium
Atracurium
Pancuronium
d-turbocurarine
what are the Nm subunits?
where are they found?
a,b,d,e,g
skeletal m. motor end plates
what are the Nn subunits?
where are they found?
a and b OR all a
CNS, autonomic ganglia, adrenal medulla
what is tetrodotoxin?
MOA?
symptoms?
puffer fish poison
inhibits VG-Na+ channels and blocks axonal conductance
weakness, dizziness, paralysis
what is the MOA for local anesthetics?
examples of some?
inhibition of VG-Na+ channels, inhibits axonal conductance
lidocaine, bupivacaine, procaine
what is Batrachotoxin?
what does it cause?
poison dart frog
INC in permeability of Na+ channels, persistent depolarization
what causes Botulism?
where is it found?
MOA?
Clostridium botulinum
veggies, fruit, seafood, soil
cleaves SNARE complex involved in exocytosis, prevents ACh release
what toxin targets synaptobrevin (VAMP)?
Tetanus
Botulinum B, D, F, G
what toxin targets Syntaxin?
Botulinum C1
what toxin targets SNAP-25
Botulinum A/E
how is botulism classically described?
what are the symptoms of foodborne botulism?
acute onset of bilateral cranial neuropathies, symmetric weakness, blurred vision
nausea, ab pain, diarrhea
what are the clinical uses for botulinum?
face wrinkles, prevention of migraine headaches
what causes tetanus?
MOA?
symptoms?
Clostridium tetani found in soil
blocks SNARE by targeting synaptobrevin
spastic paralysis, lock jaw, stiff neck, tachycardia, sweating, restlessness
what is the protypical curare alkaloid?
MOA?
clinical use?
destruction of drug?
d-tubocurarine (antagonist)
competes with ACh for nAChR on motor end plate, dec. EPP size (it is a NONdepolarizing nAChR comp)
anesthesia to relax skeletal m.
increase ACh in the NMJ
what is succinylcholine?
MOA?
how is it reversed?
agonist that causes muscle fasciculations
depol neurom. blocker that binds to nAChRs and initially causes depol and continued depol which leads to receptor blockade and paralysis
TIME
what is succinylcholine used for?
induction agent for anesthesia
what do cholinesterase inhibitors do?
clinical uses?
bind AChE and block its enzymatic activity thus INC [ACh] at NMJ
dementia, Alzheimer’s, MYASTHENIA GRAVIS, reverse neurom. blockade during anesthesia
what does tetrodotoxin do?
blocks outer mouth of Na+ channels and inhibits APs
what does Dantrolene do?
clinical uses?
inhibits ryanodine receptors in SR, blocks Ca2+ release
malignant hyperthermia and spasticity
what is synaptotagmin?
Ca2+ sensor that detects a rise in intracellular Ca2+ and triggers membrane fusion and exocytosis
