Neuromuscular Blockers

Front 1

Qualities of Anesthesia (4)?

Back 1

Qualities of Anesthesia
1. Amnesia
2. Loss of consciousness
3. Analgesia
4. Muscle relaxation

Front 2

Non-Depolarizing Neuromuscular Blockers
Mechanism of action?
Benzylisoquinolines?
Ammoniosteroids?

Back 2

Non-Depolarizing Neuromuscular Blockers

Mechanism of Action:
1. Competitive antagonists at the nicotinic receptors of the neuromuscular junction
2. All contain at least one quaternary nitrogen - not orally active

Two main classes
1. Benzylisoquinolines - complex ring structures similar to d-tubocurarine
2. Ammoniosteroids - structures containing steroid nucleus

Front 3

Benzylisoquinolines - Drugs in group?

Ammoniosteroids - Drugs in group?

Back 3

Benzylisoquinolines
1. Tubocurarine
2. Atracurium
3. Mivacurium

Ammoniosteroids
1. Pancuronium
2. Vecuronium
3. Rocuronium

Front 4

Sequence of Paralysis?

Back 4

Sequence of Paralysis

1. Muscles of fine movement - eyes, jaw, larynx, fingers
2. Limbs
3. Trunk
4. Intercostals
5. Diaphragm

Not that recovery is in reverse order and breathing will recover first

- Block in fingers is easy to monitor, when fine movement is blocked --> time to intubate

Front 5

Problems Associated with Neuromuscular Blockade?
1. Ganglionic Blockade
2. Histamine release
3. Muscarinic receptor blockade

Back 5

Problems associated with Neuromuscular Blockade

1. Ganglionic Blockade --> Decreased BP
- d-TC > Pancuronium > Atracurium, Vecuronium

2. Histamine release --> Decreased BP, Bronchospasm, increased secretions
- d-TC > Atracurium, mivacurium >> Ammoniosteroids

3. Muscarinic Receptor Blockade ("Vagolytic") --> Tachycardia
- Pancuronium, Vecuronium

Front 6

Pharmacokinetics - The elimination of Non-depolarizing Neuromuscular Blockers

1. Quaternary Amines?
2. Rocuronium, Vecuronium
3. Atracurium?
4. Mivacurium?

Speeding up RECOVERY?

Back 6

Pharmacokinetics - The elimination of Non-depolarizing Neuromuscular Blockers

1. Quaternary Amines - Primarily renal except for the following:
2. Rocuronium, Vecuronium - hepatic metabolism --> Intermediate duration of action
3. Atracurium - Spontaneous breakdown (Hoffman elimination) and plasma esterases --> Intermediate duration of action
4. Mivacurium - Plasma esterases --> Shortest duration of action

Recovery from paralysis of any non-depolarizing neuromuscular blocker can be accelerated by administration of a cholinesterase inhibitor

Front 7

Drugs that enhance the neuromuscular blockade of curare type neuromuscular blockers?

Back 7

Drugs that enhance the neuromuscular blockade of curare type neuromuscular blockers?

1. Calcium channel blockers - pre and post-synaptic effects
2. Aminoglycosides - Inhibit ACh release

Front 8

Depolarizing Neuromuscular Blocker
Drug in Class?
Mechanism of action?
Time to onset?
Initial response to administration?

Back 8

Depolarizing Neuromuscular Blockers

Drug: Succinycholine

- Shortest time to onset and duration of action --> Great for intubating

-Mechanism = Depolarizing Blockade

Hydrolyzed by plasma cholinesterase

Really an agonist that is acting like an antagonist

Initial response to administration of succinylcholine is a wave of fasciculations

Front 9

Phase 1 Block?

Phase 2 Block?

Back 9

Phase 1 Block = Endplate depolarized (depolarization block) Cholinesterase inhibitors intensify block

Phase 2 block = Endplate potential partially repolarized (receptor desensitization) cholinesterase inhibitors may partially reverse block

Front 10

Problems Associated with Depolarizing Neuromuscular blockade (Succinylcholine)

Back 10

Problems Associated with Depolarizing Neuromuscular blockade (Succinylcholine)
1. Myalgia (muscle soreness) - changing ionic concentrations
2. Potassium release from skeletal muscle --> Hyperkalemia --> cardiac arrhythmias
--> NEED TO BE CAREFUL IN PATIENTS WIHT SOFT TISSUE DAMAGE AND IN PARAPLEGICS
3. Atypical pseudocholinesterase --> Prolonged Paralysis
4. Malignant Hyperthermia - uncontrolled release of calcium from sarcoplasmic reticulum (seen most often in combination of succinylcholine and halothane)
5. Fasiculations

Front 11

Baclofen
Mechanism of Action?
Clinical Use?
Adverse Effects?

Back 11

Baclofen
Class: GABA-B receptor agonist

Mechanism of action: Thought to act in spinal cord to inhibit excitation to motor neurons presynaptically; may also act in supraspinal CNS

Clinical use:
1. Treatment of spasticity associated with MS
2. Spinal cord injury or disease
3. Treatment of Trigeminal Neuralgia

Adverse Effects:
1. Drowsiness, Dizziness, Lightheadedness, confusion, muscle weakness

Front 12

Dantrolene
Mechanism of Action?
Clinical Use?
Adverse Effects?

Back 12

Dantrolene

Mechanism of Action: Inhibits calcium release from the sarcoplasmic reticulum in skeletal muscle

Indications: Treatment of malignant hyperthermia (reduces mortality 80% to < 10%)
Adverse Effects: Muscle weakness

Given orally or IV

Metabolized hepatically