Neuromuscular Relaxants (8-24-15)

Question 1

Succinylcholine

Answer 1

• Indication: Tracheal intubation or ECT
• Duration of action: Less than 8 mins
• MOA: DEPOLARIZING blockade of muscle nicotinic receptors (Depolarizing Nm blocker)
• Elimination: Metabolized by plasma cholinesterase
• Contraindications: family history of malignant hyperthermia
• Toxicity/side-effects: non-analgesic, apnea, muscle pain (from induction fasciculations), hyperkalemia (K+ release from motor end-plate), malignant hyperthermia, stimulation of N of autonomic ganglia and cardiac M in sinus node cause arrhythmia, HTN, bradycardia
• Note: causes flaccid paralysis, generally only use for Phase I and not Phase II
• PK: plasma cholinesterases (not at synapse) (not AChE); very short t 1/2 (

Question 2

Pancuronium

Answer 2

• Indication: Adjuvant in surgical anesthesia, especially abdominal wall relaxation and orthopedic procedures
• Duration of action: 30-60 min
• MOA: NON-DEPOLARIZING blockade of muscle nicotinic receptors
• Elimination: renal excretion, intermediate duration (30-60 min)
• Contraindications: renal failure
• Toxicity/side-effects: non-analgesic (pts must be given analgesic), apnea (pts must be ventilated)
• Drug-interactions: inhalation anesthestics (enhances effect) chemical antidotes: cholinesterase inhibitors (neostigmine), muscarinic blockers (glycopyrrolate– minimizes muscarinic effects of cholinesterase inhibitors)
• Overcome by excess Ach through 1) tetanic stimulation 2) cholinesterase inhibitors; at high concentrations blockade of channel pore develops so less sensitive to Ach
• Note: biological half life is longer than therapeutic effect because high receptor occupancy is required before reduced muscle twitch is observed (high receptor reserve); different in different tissues: respiratory > larger limb and trunk > fine muscles
• Drug action: muscle weakness followed by paralysis; affects small muscles first then large muscles: extraocular, hands + feet, head + neck, extremities, diaphragm + respiratory muscles; recovery in reverse order
• MOA: Competitive antagonist at nicotinic Ach receptors (competitive binding of curare-like drugs to Nm prevents opening of Nm ion channel thus preventing membrane depol and end-plate potentials (EPP))
• t 1/2 depends on route of elimination: kidney > liver >plasma cholinesterase

Question 3

D-tubocurarine

Answer 3

• Indication: Prototype only used in LETHAL INJECTION
• Duration of action: >60 min
• MOA: NON-DEPOLARIZING blockade of muscle nicotinic receptors
• Elimination: Liver clearance; renal elimination
• Contraindications: ???
• Toxicity/side-effects: non-analgesic (pts must be given analgesic), apnea (pts must be ventilated)
• Drug-interactions: inhalation anesthestics (enhances effect) chemical antidotes: cholinesterase inhibitors (neostigmine), muscarinic blockers (glycopyrrolate– minimizes muscarinic effects of cholinesterase inhibitors)
• Overcome by excess Ach through 1) tetanic stimulation 2) cholinesterase inhibitors; at high concentrations blockade of channel pore develops so less sensitive to Ach
• Note: biological half life is longer than therapeutic effect because high receptor occupancy is required before reduced muscle twitch is observed (high receptor reserve); different in different tissues: respiratory > larger limb and trunk > fine muscles
• Drug action: muscle weakness followed by paralysis; affects small muscles first then large muscles: extraocular, hands + feet, head + neck, extremities, diaphragm + respiratory muscles; recovery in reverse order
• MOA: Competitive antagonist at nicotinic Ach receptors (competitive binding of curare-like drugs to Nm prevents opening of Nm ion channel thus preventing membrane depol and end-plate potentials (EPP))
• t 1/2 depends on route of elimination: kidney > liver >plasma cholinesterase

Question 4

Rocuronium

Answer 4

• Indication: Intubation, muscle relaxation during surgery or ventilation
• Duration of action: ~25 min
• MOA: NON-DEPOLARIZING blockade of muscle nicotinic receptors
• Elimination: hepatic elimination; short duration (25 minutes)
• Contraindications: hepatic failure
• Toxicity/side-effects: ???

Question 5

Mivacurium

Answer 5

• Indication: Intubation, muscle relaxation during surgery or ventilation in pts with renal failure
• Duration of action: 15-20 min
• MOA: NON-DEPOLARIZING blockade of muscle nicotinic receptors
• Elimination: PChE (plasma cholinesterase, SHORTEST t 1/2 (15-20 minutes)
• Contraindications: ???
• Toxicity/side-effects: ???

Question 6

Vecuronium

Answer 6

• Indication: Adjuvant in surgical anesthesia, especially abdominal wall relaxation & orthopedic procedures
• Duration of action: 30-45 min
• MOA: NON-DEPOLARIZING blockade of muscle nicotinic receptors
• Elimination: liver metabolism and renal elimination, short duration (30-45 min)
• Contraindications: ???
• Toxicity/side-effects: non-analgesic (pts must be given analgesic), apnea (pts must be ventilated)
• Drug-interactions: inhalation anesthestics (enhances effect) chemical antidotes: cholinesterase inhibitors (neostigmine), muscarinic blockers (glycopyrrolate– minimizes muscarinic effects of cholinesterase inhibitors)
• Overcome by excess Ach through 1) tetanic stimulation 2) cholinesterase inhibitors; at high concentrations blockade of channel pore develops so less sensitive to Ach
• Note: biological half life is longer than therapeutic effect because high receptor occupancy is required before reduced muscle twitch is observed (high receptor reserve); different in different tissues: respiratory > larger limb and trunk > fine muscles
• Drug action: muscle weakness followed by paralysis; affects small muscles first then large muscles: extraocular, hands + feet, head + neck, extremities, diaphragm + respiratory muscles; recovery in reverse order
• MOA: Competitive antagonist at nicotinic Ach receptors (competitive binding of curare-like drugs to Nm prevents opening of Nm ion channel thus preventing membrane depol and end-plate potentials (EPP))
• t 1/2 depends on route of elimination: kidney > liver >plasma cholinesterase

Question 7

Baclofen

Answer 7

*Indication: Muscle spasticity associated with MS or spinal cord injury
Duration of action: 1.5 hrs
*MOA: Inhibits NT release from skeletal muscle sensory afferent
Elimination: Urine
*Contraindications:
*Toxicity/side-effects: drowsiness; can be given via intrathecal catheter at spinal level necessary to reduce side effects

• Drug action: Reduces Ca+ influx therefore reduces the release of excitatory transmitters from skeletal muscle sensory afferent
• MOA: Direct AGONIST of GABA-B receptors on 1a nerve terminals (muscle spindle)
• Note: starts with B = GABA-B

Question 8

Diazepam

Answer 8

(VALIUM)

*Indication: flexor & extensor spasm, spinal spasticity, multiple sclerosis
Duration of action: 43 hrs
*MOA: Benzodiazepine receptor agonist
Elimination: Liver
*Contraindications: ???
*Toxicity/side-effects: drowsiness, sedation

• Drug action: GABA-A agonist, increase Cl-influx to decrease excitability of neurons
• MOA: Facilitate GABA presynaptic inhibition
• Note: DiAzApAm gives you THREE clues that it is GABA-A

Question 9

Tizandine

Answer 9

*Indication: Muscle spasticity due to spinal cord injury or MS
Duration of action: 2.5 hrs
*MOA: Centrally acting alpha-2 agonist
Elimination: Liver
*Contraindications: ???
*Toxicity/side-effects: drowsiness, hypotension

• Drug action: promotes pre and post synaptic inhibition in the spinal cord
• MOA: A2 adrenergic agonist
• Note: remember alpha 2 on adrenergic/cholinergic nerve terminals!

Question 10

Dantrolene

Answer 10

*Indication: spasticity (stroke, spinal cord injury, MS or Cerebral Palsy), malignant hyperthermia (caused by sudden and prolonged Ca2+ release)
Duration of action: 8 hrs
*MOA: Uncouples excitation-contraction coupling of skeletal muscle (blocks Ca2+ release from SR in muscle via the ryanodine receptor)
Elimination: ???
*Contraindications: ???
*Toxicity/side-effects: muscle weakness, sedation