Neuromuscular Blocking Drugs Flashcards
What is the purpose of neuromuscular blocking drugs
Temporary paralysis of skeletal m. and m. relaxation
Prevent interaction between ACh and Nicotinic receptors
Act as nicotinic acetylcholine receptor Nm
MOA of competitive (non-polarizing) neuromuscular blocking drugs
Competitive ACh antagonism –> ACh can’t act –> Repolarized plate –> relaxation
NO DEPOLARIZATION (contraction)
How is the block relieved?
By increasing ACh levels at the synaptic cleft (Ach competing with the drugs)
Ex: use cholinesterase inhibitors
MOA of depolarizing neuromuscular blocking drugs
Sustained repolarization and later block –> ACh cannot act –> depolarization plate
CONSTANT DEPOLIZATION in 2 phases
Phases of depolarizing neuromuscular blocking
- Agents activate Nicotinic ACh receptor –> channels open –> endplate membrane potential to -55 mv —> flaccid paralysis due to continued activation
- Membrane repolarizes but receptor desensitized to ACh
Centrally acting neuromuscular blockers
Dantrolene sodium and Quinine
Peripherally acting neuromuscular blockers
Depolarizing blockers (non competitive)
Non-depolarizing blockers (competitive)
Depolarizing blockers
Succinylcholine and Decamethonium
Long acting non depolarizing blockers
D-tubocurarine, Gallamine, pancuronium, doxacurarium, pipercuronium
Intermediate acting non depolarizing blockers
Vecuronium, atracirum, roccuronium
Short acting non depolarizing blocker
Mivacirum
Non-depolarizing neuromuscular blockers pharmokinetics
Poor oral absorption (IV)
Poor membrane permeability (doesn’t cross BBB)
Generally excreted unchanged (not metabolized)
Low metabolism
Pancuronium
Not metabolized (long acting, depolarizing blocker)
Excreted through the kidney
Duration of action is 2-3 hours
Onset of action: 2-6 minutes
Vecuronium and roccuronium pharmokinetics
Liver metabolism
DOA increases in the liver
Duration of action is 30-40 minutes
Onset of action: 2-6 minutes
Non depolarizing blockers therapeutic uses
In general anesthesia: facilitate tracheal intubation
Induce muscle relaxation
Make orthopedic surgery east
Reduce dose of anesthetics
(descending paralysis)
Non depolarizing blockers adverse affects
Hypotension, increased respiratory secretion, bronchospasms
Hyperkalemia
Increased intraocular pressure
Which NDMB drugs prolong the action of NDMB?
Aminoglycosides antibiotics (streptomycin)
Calcium channel blockers (Verpamil)
Halogenated anesthetics (Isoflurane)
Cholinesterase inhibitors (NDMB)
Neostigme- decreases the effectiveness of NDMB
Calcium channel blockers
Verpamil- prolongs the action of NDMB
Halogenated anesthetics
Isoflurane will prolong
Depolarizing muscle blockers uses
Adjuvant drugs in surgical anesthesia
Effects similar in action to ACh, but longer acting
Succinylcholine uses
Only depolarizing drug in clinical use
Use muscle relaxant for passing endotracheal tube
DMB interactions
Halothane with DMB produces malignant hyperthermia in some
Tx: rapid cooling of the body and dantrolene
____________ augment DMB effects
AChE inhibitors
How does age prolong the neuromuscular blockade?
Neonates or old age
How does disease prolong the neuromuscular blockade?
Obesity, hepatic disease, renal disease, neuromuscular disease
How does drugs prolong the neuromuscular blockade?
Inhalational agents will prolong the blockade of depolarizes and NDMB
Antibiotics(dantrolene, tetracyclines)
How does electrolytes prolong the neuromuscular blockade?
Hypokalemia, hypermagnesia, hypocalcemia, hypothermia and metabolic acidosis
Drug that antagonize NMB
Cholinesterase inhibitors
Calcium
Phenytoin
Carbamazepine
Azathioprine
Steroids
Paralysis in humans
Competitive: Flaccid
Depolarizing: Fasciculation resulting in flaccidity
Paralysis in chicks
Competitive: Flaccid
Depolarizing: Splastic
Species sensitivity
Competitive: Rat> rabbit > cat
Depolarizing: cat<rabbit < rat
Neostigmine
Competitive: Antagonism block
Depolarizing: no effect
Inhalation anesthetic (ether)
Competitive: Synergist
Depolarizing: no effect
Order of paralysis
Competitive: fingers –> eyes –> limbs –> neck –> face –> trunk –> intercostal muscles
Depolarizing: neck –> limbs –> jaw –> eyes –> pharynx –> trunk –> intercostal muscles
Central and direct muscle relaxants
- Doesn’t affect neuromuscular transmission of EPP
- Depolarization triggered release of calcium ion from sarcoplasmic reticulum reduced
- Fast contracting twitch muscles
- Reduce muscle tone by a selective action in cerebrospinal axis without altering consciousness
- No effect on neuromuscular transmission
- Reduces rigidity, spasticity and hyperreflexia
Centrally acting muscle reactants
Muscle tone decreased
No reduction in voluntary movements
Postsynap. relfexes in CNS inhibited
CNS depression
Administered orally/ parentally
Value in the treatment of spastic muscle spasms, tetanus
Peripherally acting muscle relaxants
Muscle paralysis
Voluntary movements are lost
Neuromuscular transmission is blocked
CNS effect no significant
Administed IV
Used for short procedures
Dantrolene (central muscle relaxant)
Absorbed orally
Penetrated BBB and produces sedation
Metabolized by liver, excreted by kidney
Malignant Hyperthermia
Adverse effects of dantroene
Muscle weakness, sedation, malaise, light headedness
Other central muscle relaxants
Mephenesin group: mephenesin, carisoprodol, chlorzoxazone
Benzodiazepines (diazepam)
GABA derivatives: baclofen
Clinical uses to centrally acting muscle relaxants
Acute muscle spasms, tension, torticollis, lumbago, neuralgia, anxiety, tetanus
