Neuromuscular Relaxants Flashcards
Neuromuscular relaxants
selectively block nicitinic receptors at the NMJ. Some muscle relaxation can also be achieved by blocking interneurons at the level of the spinal cord.
Types of neuromuscular blockers
non depolarizing agents (curare type) competative anatagonists of the NM receptor. can be outcompeted by endogenous antagonist.
Depolarizing agents (succinylcholine)- prolonged activation of membrane depolarization. They bind to the nicotinic receptor and stay there or for a long time, resistdegradation. Don’t allow repolarization of the membrane and the fast Na channels cannot return to the relaxed state.
Non-depolarizing agent (Curare)
Competative antagonism of NM. Prevents opening of nicotinic receptor ion channel, preventing membrane depolarization and end plate potentials.
inhalations anestetics and antibiotics enhance their effect
biological half life tends to be longer than their effect, high receptor occupanc required for effect.
can be over come by excess Ach, tetanic stimulation, or AchE inhibitors.
Channel pore bloackade at higher concentrations, less sensitive to AchE inhibitors
have rapid distribution and do not cros the BBB
Elimination: renal > hepatic > plasma CE
According to longest half life: Tubocurarine > Pancuronium > Vecuronium < Rocuronium < Mivacurium
Clinical uses: muscle relaxation for surgery; intubation (rocuronium, mivacurium); Reduced resistance during ventilation.
Side effect: non anelgesic, apnea, histamine release (hypotension, bronchospasm, mivacurium); muscarinic blockade (increased HR and CO, pancuronium, rocuronium)
antidotes: CE inhibitors - neostigmine
muscarinic blockers- glycopyrrolate (minimizes muscarinic effects of cholinesterase inhibitor)
Pancuronium
non-depolarizing blockade of muscle nicotinic receptors.
30-60 min
Renal Excretion
Adjuvant in surgical anesthesia. abdominal wall relaxation and & orthopedic procedures.
Rocuronium
Duration 25 min
non-depolarizing blockde of muscle nictonic receptors
metabolized in liver
used during intibation and muscle relaxation during surgery or ventilation
Mivacurium
15-20 min
non-depolarizing blockade of muscle nicotinic receptors.
metabolized by plasma CE
intubation during surgery, muscle relaxation dueing surgery or ventilation. used in patients who have renal failure
Vecuronium
30-45 min
non-depolarizing blockade of muscle nicotinic receptors
liver metabolism and clearance, renal elimination
adjuvant in surgical anesthesia. Abdominal wall relaxation and surgical procedures. Abdominal wall relaxation and surgical procedures.
Mode of elimination of non-depolarizing drugs
Renal: Pancuronium, vecuronium
Liver: rocuronium
Renal and hepatic: tubocurarine
CE: Mivacurium
Phases of Succinylcholine
metabolized by plasma cholinesterase not acetylcholinesterase.
Phase 1 block: occupancy of the receptor causes opening of the ion channel, and depolarization of the motor end plate, insensitive to Ach. it enters the chanel causing prolonged flickering of ion conductance. Flacid paralysis. Cholinesterase inhibitors augment bloackade.
Phase II block: when expose exceed 30 min the membrane becomes repolarized. Receptor remains desensisitzed. (can be by CE’s and tetanic stim but must wait until succinylcholine is gone)
Succinylcholine
Depolarizing agent
8 min
Uses: intubation and control of convulsions during ECT.
Side effets: non anelgesic, apnea, muscle pain from fasiculations, increased intraocular/intragastric pressure. stimulation of ganglionic nicotinic receptors. stimulation of muscarinic receptors in the SA node (arrythmia, HTN due to nicotnic)( bradycardia due to muescarinic SA node activation), hyperkalemia due to K+ release from motor end plate. can initiate malignant hyperthermia.
local anesthetics enhance effect, CE inhibtord enhance paralysis of phase I.
Antidotes: phas I has none, rapidly hydrolyzed by CE. Atropine for bradycardia du to muscarinic effects.
Phase II- CE inhibitors
contraindication: familial hyperthermia. recent acute trauma, myopathies
Idication for spasmolytic drugs
heigthened skeletal muscel tone due to:
1) release from inhibitory supraspinal control
2) increased activity of facilatory pathways
3) heightened excitability of alpha and gama motor systems.
treatment of spacticity
reduce activite of 1a fibers that excite the primary motor neuron. Enhance activity of inhibitory internuncial neurons
Gaba prevents the 1a afferent from activating motor neuron.
Baclofen
GABAB rceptor agonist
physiological effect: Inhibits N-type Ca channels. reduced Ca influx at afferent 1a nerve temrinal. Thsi causes reduced NT release. reduced substance P release in spinal cord.
inhibits NT release from SKM sensory afferent
Indication: Spinal cord spacticity/ injury, muscle spacticity due to MS.
Toxicity: drowsiness, mental disturbances.
Can be given orally or through intrathecal catheter.
Benzodiazapines
positive allosteric modulators of GABAA. Increase GABA mediated Cl influx.
GABAnergic neurons provide presynaptic inhibition of 1A afferents, bezodiazapines enhance this effect.
Do not give to glaucoma pts
Diazapam
Prototype
Benzodiazapine receptor agonist
Physiological effect: Positive allosteric modulation of GABAA. Opens Cl channel
Indications: Flexor/extensor spasms. Spinal spasticity, MS. Muscle spasm due to local injury (inflammation), muscle spasm due to loss of descending inhibitory input, i.e. CP
Toxicity: Drowsiness, Sedation
Contraindications: Glaucoma
