01 Ganglionic Flashcards
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)
succinylcholine
often used during surgery bc of fast onset
- depolarizing NMJ blocking agents
- metabolized by pseudocholinesterase (comes from plasma)
- some ppl has “atypical” pseudo-AchE which isn’t very good at metabolizing succinycholine so it takes 2-3 hrs instead of 5-10 minutes
- not reversed by AchE inhibitors (neostigmine would make it worse)
what are the adverse effects of succinylcholine and the treatment
- toxicity: similar to competitive blockers with less effects at ganglia or histamine release
- Treatment: artificial respiration
- Adverse reactions: ‘Atypical” psuedo-AchE=prolonged apnea (2-3) hours
- hyperkalemia (esp. burn trauma patients, response delayed 2-7 days)
- malignant hyperthermia (esp. with halothane)
when is succinylcholine contraindicated?
a burn or trauma victim two or three days after the incident bc of hyperkalemia
what is the treatment for malignant hyperthermia?
DOC: dantrolene (decreases Ca release)
the hyperthermia comes from increased Ca which causes increased muscle contractility, increased body temp
- inhibits calcium release from SR - significant liver toxicity
- muscle weakness
- DOC for malignant hyperthermia
dantrolene (dantrium)
what are the “problems/concerns” associated with succinylcholine?
1-‘atypical’ psuedo-AchE
2-hyperkalemia (esp burn, trauma patients 2-7 days later), this can lead to cardiac arrest
3-malignant hyperthermia (esp with halothane an anesthetic) treated with Dantrolene
