Skeletal Muscles Flashcards
Drugs causing contraction
- Tetanus toxin - strong spastic contraction
- Halothan, succinylcholine, antipsychotics - activators of the mutated ryanodine receptors
- Sympathomimetics - increase muscle strength
- Centrally acting - any convulsive agent
Muscle relaxants
- Centrally acting
- spasmolytics - Peripherally acting
- block the nmj - paralysis
- botulinum toxin
- tetracycline, aminoglycosides
Centrally acting muscle relaxants
Baclofen Mephenesine Guaiphenesine Chlorzoxasone Diazepam/benzodiazepines Tiazanidine Tolperisone Carisoprodol
Drugs for spasticity
Baclofen
- GABAb agonist (inhibitory neurotransmitter)
- highly sedative
- only for chronic events, e.g., ms
- rapidly absorbed after oral administration
- excreted by kidneys
- half-life: 2-4 h
Drugs for acute muscle spasm
Due to overdose, trauma, disc herniation, ostheoarthritis
- Mephenesine - parenteral
- Guaiphenesine - parenteral
- Chlorzoxasone - enteral
Drugs for acute spasticity
- Diazepam and benzodiazepines potentiate GABAa
- used for locked mouth - Tizanidine - a2 agonist - sedative
- Tolperisone - not sedative, unknown mechanism
- Carisoprodol - abuse potential, hepatotoxic
Possibilities to relax skeletal muscles
- Spasmolytics - centrally acting
- decrease tone of the skeletal muscle - Peripheral muscle relaxant
- paralyze the muscle (total relaxation)
- presynaptic drug:
— botulinum toxin, omega-conotoxin (full relaxation)
— aminoglycosides, tetracycline (weakness)
- postsynaptic drug:
—curare derivatives - complete block
— depolarize got muscle relaxants - agonist of Nm
— ryanodine antagonists - special indication
Indication of peripheral muscle relaxants
- muscular relaxation during surgery
- relax muscles of artificially respired patients
- electroshock
- intubation
- tetanus
- epileptic seizure not relieved by antieleptic
- intoxication with certain medicine, eg; theophylline, amphetamine
Classification of curare
- Izoquinolones - curium
- d-tubicurarine (not used)
- doxacurium
- atracurium
- cisatracurium
- mivacurium - Steroids - curonium
- pancuronium
- pipecuronium
- vercuronium
- rocuronium
Time order of curare paralysis
Full paralysis 2-6 min
- outer eye muscles
- facial muscles
- pharyngeal muscles
- extremities
- truncal muscles
- respiratory muscles
Curare type muscle relaxants
Competitive antagonist to Nm ACh receptor in NMJ
4amine, no CNS effect
Iv administration
Selective
Long lasting curare
60-180 min
- doxacurium
- pancuronium
- pipecuronium
Intermediate acting curare
20-40 min
Vercuronium
Rocuronium
Atracurium
Cisatracurium
Short acting curare
10-15 min
Mivacurium
Adverse effect of curare
Recurarization - after suspending the effects reappearing muscle weakness
Ganglion blockade - pancuronium: HT, tachycardia
Histamine release - mivacurium, atracurium: itching, brinchospasm, hypotension
M2 block - pancuronium: tachycardia
Ne release and reuptake inhibition - pancuronium: tachycardia
Metabolite of atracurium - laudanosin: muscle spasm, convulsions
Suspending/terminating the curare effects
AChE INHIBITORS: neostigmine, distigmine - coadministered with atropine in order to antagonize their parasympathomimetic effects
SUGAMMADEX: neutralize the steroid structure in the plasma
Factors influencing the curare effects
- Enhancing
- general anesthesia
- aminoglycosides and tetracycline
- local anesthesia
- myasthenia gravis - Decreasing
- AChE inhibitors - peripheral motor neuron
- motor neuron lesion
Depolarizing muscle relaxants
Succinylcholine
Succinylcholine/suxamethonium
- depolarizing muscle relaxants
- divides depolarizing blockade that cannot be antagonized by AChE inhibitors
- no antidote- need to restore the membrane potential in the muscle (done by muscle)
- duration after iv: 5-10 min
- order of paralysis; arms-neck-legs-respiratory muscles-facial muscles-pharyngeal muscles
- metabolism: pseudo cholinesterase In the blood to the liver
Indication: short surgeries, intubation, electroshock, short diagnostic procedures (bronchoscope)
Development of depolarizing blockade
Succinylcholine is a selective agonist of the Nm receptor and AChE does not metabolize it.
Due to the longer stimulus of the receptor, Sodium influx is higher resulting in depolarization of the surrounding membrane.
In this are, the VGSC cannot return to their resting closed state. Instead they remain the the inactive state causing AP generation to stop and the muscle is paralyzed.
This can not be antagonized by AChE in the beginning.
Adverse effects of succinylcholine
Muscle pain Arrhythmia Bradycardia Hyperkalemia Vomiting Higher intraocular pressure MALIGNANT HYPERTHERMIA
REASONS FOR Malignant hyperthermia
- genetic disorder affecting ryanodine receptors
- idosynchrasia
- shivering - heat production
- lactacidosis
- myoglobinemia/Uria
- acute renal failure
Treatment of malignant hyperthermia
- danteolone - hepatotoxic
- bicarbonate infusion to acidosis
- physical cooling of patient
