Neuromuscular Junction Flashcards
Nerve Gases
Irreversible AChase
More toxic than organopesticides
Less than 10 mins to cause death
Ex. Sarin
-Nerve gas attack @ FB
- Use pesticides less sensitive/toxic to mammals/humans
- @ high doses = very dangerous
Somatic System
Under more conscious control
- EPP = 2 ACh bound, excitatory electrical event
- Opens nearby VG channels
- More direct diffusion of ACh onto receptor @ mem. (compared to varicosities of ANS neurons, stretch out + diffuse over broad A)
Cholinergic Antagonists (HATS)
Hexamethonium
- blocks N receptor
- many diff side effects (affects both SNS + PSNS systems)
- diff to control
Atropine
- competitive antagonist for M receptor
- Tx. for poisoning/toxicity
- rightward shift
- Ex. give to soldiers + Oxime, atropine = treatment to block M receptor activity (stop signalling overload), Oxime = regen AChase (prevent permanent AChase inhibition)
Tiotropium
- choline = bronchi constricts
- blocks M receptor, inhibition of constriction = dilation
- Tx. for COPD (mainly) + asthma
Scopolamine
- Tx. for motion sickness
- put transdermally (patch behind ear)
-also used in exams to dilate the pupil + overactive bladder + PD
NMJ Drugs
-3 broad types
- Prevent muscle weakness (MG)
- Muscle paralysis (in surgery + intubation)
- Reduce muscle convulsions/spams (botox)
Myasthenia Gravis (MG)
- Prevalence
- Cause
- 1st Sign of Disease
- Treatment
Prevalence
-rare = 1 in 10,000 ppl
Cause
- autoimmune + progressive
- body attacks Nm receptors via ABs
- continues until only a few Nm receptors left (in all muscles)
1st Sign of Disease
-droopy eyelid
Treatment
- AChase inhibitor
- keep ACh around longer to inc binding opportunity
- only works if sufficient number of Nm channels remain
- ST tx. (doesn’t prevent progression & only works if critical concentration of receptors remain)
**Only slows down the progression + manages the symptoms - no complete tx. **
Muscle Paralysis
- History
- Types
- Reversal
History
- Amazon natives used to crush up plants + dip/roll tips of darts in liquid
- shoot @ animals, causes muscle paralysis (into bloodstream - systemic circulation)
- paralysis of diaphragm (suffocate to death)
Types
- non-depolarizing = Rocuronium, Pancuronium
- depolarizing = Succinylcholine
Reversal
- Neostigmine
- Sugammadex
Non-Depolarizing Competitive Nicotinic Antagonist
- Prevents ACh from binding
- sim to atropine (attacks Nm instead of M)
- more commonly used in clinic
Rocuronium: intermediate acting
Pancuronium: long acting (for longer surgeries or ICU - ventilation)
Neostigmine
Anti-AChase
- inc ACh available
- outcompete antagonist if high ACh
- given after surgery
Sugammadex
Like a mop - surrounds Nm antagonist (encircles the toxin)
-Inhibition of Nm inhibition b/c too low amt of antagonist (ex. Rocuronium)
Pesticide Poisoning
Constricts airway + low HR
HR will then increase (reflex) but still can’t breath - bronchi constriction
Tx. Atropine
Depolarizing Competitive Nicotinic Antagonist
Succinylcholine
Phase 1: Depolarization
- Contraction
- violent - complaints of muscle pain after surgery (everything tenses up)
- side effect = muscle pain/cramping post-surgery
- possibility of vomiting + choking if food in stomach (in emerg. surgery)
Phase 2: Desensitization
- Mechanism? Channel repolarizes & loses ability to contract, antagonism
- Flaccid paralysis (like rocuronium or pancuronium)
- pseudo AChase = in blood + liver (breaks ACh down)
- succinylcholine = 2 Ach bound together
- easily targeted by pseudo breakdown (1 way of reversing- give pseudo AChase out of surgery)
- sometimes = abnormal enzymes - polymorphisms (stay paralyzed for long time, need to genotype b4 rx.)
Rocuronium + Neostigmine
Ach antagonist + AChase inhibitor
- cause paralysis but reverse
- less paralysis possibly
Succinylcholine + Neostigmine
Depends on phases
Phase 1:
- ACh agonist + AChase inhibitor
- greater depoly
- inc. F of contraction
Phase 2:
- ACh antagonist + AChase inhibitor
- possible inhibitor (depends on dosing + protein behaviour)
Rocuronium + Succinylcholine
Depends on phases
Phase 1:
- ACh antagonist + ACh agonist
- less depoly
- dec. F of contraction
Phase 2:
- ACh antagonist + AChase inhibitor
- greater paralysis
ACh + Neostigmine
ACh + AChase inhibitor
-lots of activation (high ACh without breakdown)
