01 Ganglionic Flashcards
(30 cards)
what is the structure of the autonomic ganglia and nicotine receptors? (sympathetic and parasympathetic
they are ion channels,
- pentamers, two alpha subunits
- when open, Na flows in, K flows out
- Ach binds
Nicotine,
what is the fatal dose?
fatal dose is 40 mg it is metabolized and excreted rapidly -it is a ganglionic stimulant -slight increase in heart rate -some rise in blood pressure -modest increase in respiratory rate -not in the body naturally
what are the toxicity effects on ganglionic stimulants?
- CNS stimulation: convulsions, headache
- NMJ paralysis: depolarizing blcokade
- hypertension, hypotension, cardiac arrhythmias
- vomiting, diarrhea, salivation
if insecticides are ingested, what treatment would be rendered?
-induce vomiting
treatment of poisoning from ganglionic stimulants (symptom-directed)
- muscarinic excess: anticholinergic (atropine)
- NMJ blockade: mechanical respiration
- CNS stimulation: anticonvulsant (diazepam)
ach is what kind of agonist?
nicotinic and muscarinic agonist
what are the ganglionic blocking agents?
- Mecamylamine
- Timethapan
- both will cause a drop in blood pressure
Mecamylamine
ganglionic blocking agent
- effective orally, CNS effects
- causes a drop in blood pressure
- inactive orally
- used in hypertensive emergency (CNS origin)
- controlled hypotension during surgery (causes a drop in bp)
- short duration of action, 5-10 min, no CNS action
Trimethapan
what is the enzyme that breaks down ach?
cholinesterase
-ach is NOT taken back up into the nerve terminal
myasthenia gravis
normal nerve, but a deficient post-junctional site
- the body produces antibodies to the nicotinic receptors and they get destroyed
- muscle weakness and fatigue
diagnosis for myasthenia gravis
Edrophonium (Tensilon, short acting) is used for diagnosis and determination of maintenance dose
treatment for myasthenia gravis
Treatment: Neostigmine has direct (stimulates receptor) and indirect actions (inhibition of AchE). No cns activity.
-it’s a cholinesterase inhibitor so the ach that is released stays longer
Neuromuscular Junction blocking agents
- competitive (non-depolarizing) agents (curare
- noncompetitive (depolarizing) agents (succinylcholine)
what is the only non-competitive NMJ blocking agent that is clinically used?
succinylcholine
-curare is a competitive NMJ blocking agent
non-competitive NMJ blocking agents?
- succinylcholine, , it’s long lasting, especially compared to Ach (minutes compared to milli seconds
- cannot be reversed, just have to wait for drug to wear off
- it binds to the site like Ach, causes a depolarization (Na in, K out) muscle contracts, but bc the stimulation is persistent, it causes muscle paralysis
competitive (non-depolarizing) agents
- compete with Ach for binding to receptor
- flaccid, relaxed paralysis
- non-NMJ effects: ganglia, muscarinic blocking, histamine release
how can a NMJ block be reversed?
for a competitive agent: can be reversed by AchE inhibitors
-for non-competitive: NMJ block not reversed by AchE inhibitors
competitive NMJ blocking agents…
(nondepolarizing)
- Curare is the prototype
- pancuronium, rocuronium, atracurium
- tubocurarine, dimethyltubocarine (metocarine)
- no effect on nerve transmission
- muscle can still be stimulated
- can cause histamine release (mast cells)
- can block ganglionic receptros (higher concentrations)
source(s) of curare
frog (poison-arrow frog)
some plants, the brighter the animal, the more dangerous it is
Pancuronium
- More potent than tubocurarine (X5)
- reduce histamine release than curare
- lack of ganglionic blockage
Rocuronium
-fast onset (1-2 min), 30-40 min duration, hypersensitivity
atracurium
(about 10 isomers
- hydrolysis by AchE
- replaced by cisatracurium, Hoffmann degradation, ORGAN INDEPENDENT, so I guess it’s often used during surgery bc it is more predictable
what drug could be used to reverse the affects of competitive NMJ blocking agents?
Neostigmine (AchE inhibitors)
