Introduction to CRNA School Pharmacology: Paralytics

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Introduction to CRNA School Pharmacology: Paralytics

Neuromuscular Blocking Agents (Paralytics)

Depolarizing

  • Succinylcholine (Anectine)

Non-depolarizing

  • Rocuronium (Zemuron)
  • Vecuronium (Norcuron)
  • Pancuronium (Pavulon)
  • Atracurium (Tracrium)
  • Cisatracurium (Nimbex)

CRNA School Prep Course

 

History

  • Neuromuscular blocking agents have been very important in the history of anesthesia. Curare (Chondodendron tomentosum) came from Peruvian “wild grape”, which was commonly placed on arrows by South American tribes to hunt animals. The curare poison would competitively block nicotinic acetylcholine receptors in the neuromuscular junction of skeletal muscle. An anesthetist named Harold Randall Griffith was given credit for introducing curare to anesthesia. In 1942 he administered curare to a patient undergoing an appendectomy.

 

 

Why Do We Use Them

  • Facilitates intubation
  • Improves conditions for tracheal intubation by relaxing skeletal muscle we are able to prevent trauma to the cords.
  • Facilitates surgeon
  • Provides immobility during surgery.
  • Reduces tone during retraction of tissues. (Less tissue damage if they’re relaxed.)
  • Facilitates mechanical ventilation.
  • Better ventilatory mechanics (Relaxing skeletal muscle allows the chest to expand freely, and prevents the patient from trying to breath over or “fight” the ventilator.)

CRNA School: Inhaled Anesthetics

 

 

How They Work

Depolarizing neuromuscular blockers

  • Nicotinic acetylcholine (ACh) receptor agonist.
  • Directly stimulate nicotinic acetylcholine receptors in the motor end-plate of skeletal muscle. This causes persistent depolarization of the motor end plate. The cells are unable to re-polarize preventing the skeletal muscle from eliciting a contraction.

 

Non-depolarizing neuromuscular blockers

  • Competitively antagonize acetylcholine (ACh) receptors.
  • Specifically, they target post-synaptic nicotinic acetylcholine receptors in the motor end-plate of skeletal muscle. This prevents ACh molecules from being able to attach themselves to their target receptors. These channels are kept from opening resulting in the inability of the skeletal muscles cells to depolarize and elicit a muscle contraction.

 

 

How They Are Measured

Peripheral Nerve Stimulator

  • Also known as a train-of-four monitor.
  • CRNAs use to this assess neuromuscular transmission after paralytics are given to block musculoskeletal activity. The nerve stimulator is placed on certain areas of the body to asses for muscle contraction.
  • The muscles tested with the nerve stimulator include the adductor pollicis which is located on the wrist (used most often), and the corrugator supercilii, which is found by the eyebrow. (Best indicator of intubating conditions.)

 Introduction to CRNA School Pharmacology: Paralytics

 

Train of Four (TOF)

  • Gold standard
  • Produces 4 equal single twitch stimuli (2Hz) delivered at intervals of 0.5 seconds.
  • The CRNA will apply the TOF stimulus and count how may muscle twitches are observed. The number of twitches indicates how many acetylcholine (ACh) receptors are still blocked. (Simply put, how paralyzed the patient is.)

– 4/4: 0-75% block

– 3/4: 75% receptor blockade

– 2/4: 80% receptors blocked

– 1/4: 90% receptors blocked

– 0/4: 100% receptors blocked

 CRNA School: Induction Agents

 

Factors That Potentate Neuromuscular Blockers

  • Pseudocholinesterase deficiency (Only effects succinylcholine.)
  • Acidosis
  • Increased magnesium levels
  • Hypocalcemia
  • Hypothermia
  • Certain antibiotics (strepomycin, neomycin, gentamicin)

 

 

 

Succinylcholine (Anectine)

 Introduction to CRNA School Pharmacology: Paralytics

Class

  • Depolarizing neuromuscular blocker

 

Mechanism of Action

  • Nicotinic acetylcholine (ACh) receptor agonist

 

Preparation

  • 20 mg/cc, (10 mL vial)

 

Indications

  • Gold standard for rapid sequence induction.

 

Doses

  • 1.5 mg/kg IV (Adult dose)
  • 2mg/kg IV (Children) 4mg/kg IM (Onset 4 min)

 

Pharmacokinetics

  • Onset: 30-60 seconds
  • Duration: Short (7-10 minutes)

 

Metabolism

  • Metabolized in the blood stream  by pseudocholinesterase.

 

Side Effects

  • Hyperkalemia
  • Bradycardia (children)
  • Skeletal muscle myalgia (pain)
  • Increased intraoptic pressure (IOP)
  • Increased intracranial pressure (ICP)
  • Allergic reaction

 

Contraindications

  • Hyperkalemia
  • Neurovascular injury
  • Spinal cord injury
  • History of malignant hyperthermia (Can trigger MH event.)
  • Burn patient: can not give if > 48 hours after injury. (Can cause a potentially fatal rise in serum potassium levels.)
  • Eye trauma (Increases intraoptic pressure.)
  • Muscular Dystrophy
  • Myasthenia Gravis

 

 

 

Atracurium (Tracrium)

Introduction to CRNA School Pharmacology: Paralytics

Class

  • Non-depolarizing neuromuscular blocker

 

Mechanism of Action

  • Competitively antagonizes acetylcholine (ACh) receptors.

 

Pharmacokinetics

  • Onset: 2-3 min
  • Duration: “Intermediate” (30-90 min)

 

Preparation

  • Supplied: 10 mg/cc
  • Must keep it refrigerated.

 

Doses

  • 0.5 mg/kg
  • IV Infusion: 5-10 mcg/kg/min

 

Metabolism

  • Ester hydrolysis
  • Hofmann elimination
  • Laudanosine Metabolite

 

Side Effects

  • Skin flushing
  • Occasional bronchoconstriction

 

Contraindications

  • None

 

 

 

Cisatracurium (Nimbex)

Introduction to CRNA School Pharmacology: Paralytics

Class

  • Non-depolarizing neuromuscular blocker

 

Mechanism of Action

  • Competitively antagonizes acetylcholine (ACh) receptors.

 

Pharmacokinetics

  • Onset: 3-5 minutes
  • Duration: ‘Intermediate” (30-90 min)

 

Preparation

  • Supplied: 2mg/ml
  • ICU: 10/mL for infusions
  • Must be kept refrigerated

 

Doses

  • 0.2mg/kg IV
  • Infusion: 1-2 mcg/kg/min

 

Metabolism

  • Ester hydrolysis Hofmann elimination
  • Laudanosine metabolite

 

Side Effects

  • Might see seizures with infusions in the ICU. This does not occur with clinical anesthesia doses in the operating room.

 

Contraindications

  • None

 

 

 

Vecuronium (Norcuron)

Introduction to CRNA School Pharmacology: Paralytics

Class

  • Non-depolarizing neuromuscular blocker

 

Mechanism of Action

  • Competitively antagonizes acetylcholine (ACh) receptors.

 

Pharmacokinetics

  • Onset: (3-5 minutes)
  • Duration: “Intermediate” (30-90 min)

 

Preparation

  • Supply: 1mg/ml

 

Doses

  • 0.1mg/Kg
  • Infusion: 1-2 mcg/kg/min

 

Metabolism

  • Hepatic metabolism (30-40%)
  • Biliary excretion of metabolites (25%)
  • Renal excretion 40-50%

 

Side Effects

  • Slightly prolonged in renal failure
  • Prolonged duration in obesity.
  • Tolerance develops with prolonged use. (ICU patient)
  • Prolonged infusion can cause lasting receptor dysfunction and paralysis.

 

Contraindications

  • Avoid prolonged use.

 

 

 

Rocuronium (Zemuron)

Introduction to CRNA School Pharmacology: Paralytics

Class

  • Non-depolarizing neuromuscular blocker

 

Mechanism of Action

  • Competitively antagonizes acetylcholine (ACh) receptors.

 

Pharmacokinetics

  • Onset: (2-3 min)
  • Duration: “Intermediate” (30-90 min)

 

Preparation

  • Supplied: (10 mg/cc)

 

Doses

  • 0.6 mg/kg IV
  • Rapid sequence induction (RSI) 1.2 mg/kg
  • Infusion: 5-12 mcg/kg/min

 

Metabolism

  • Minimal to none.
  • No active metabolites.
  • Excreted unchanged by kidneys

 

Side Effects

  • Slightly prolonged in elderly & pregnancy.

 

Contraindications

  • None

 

 

 

Pancuronium (Pavulon)

Introduction to CRNA School Pharmacology: Paralytics

Class

  • Non-depolarizing neuromuscular blocker

 

Mechanism of Action

  • Competitively antagonizes acetylcholine (ACh) receptors.

 

Pharmacokinetics

  • Onset: (2-3 min)
  • Duration: “Long” (60-120 min)

 

Preparation

  • Supply: (1 or 2 mg/ml)

 

Doses

  • 0.1 mg/kg

 

Metabolism

  • 85% renal excretion
  • 10-20% hepatic metabolism
  • 15% biliary excretion
  • Decreased drug clearance in chronic renal failure patients.

 

Side Effects

  • Cardiac vagal blockade – atropine-like effect in the sinoatrial (SA) node resulting in tachycardia.
  • Activation of sympathetic nervous system (SNS) resulting in elevated heart rate, blood pressure, and cardiac output. (10-15% increase)

 

Contraindications

  • Coronary artery disease (CAD) – The tachycardia produced by pancuronium will increase the myocardial oxygen demand putting the patient at risk for a myocardial infarction.

 

 

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