Anesthesia Pharmacology: Depolarizing Agents and Neuromuscular Blockers

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Questions and Answers

What is the effect of depolarizing agents on the motor end plate?

They cause immediate destruction of the Ach receptor

They cause temporary depolarization followed by a competitive block (correct)

They cause persistent contraction of voluntary muscles

They have no effect on the motor end plate

What is a characteristic of neuromuscular blockers?

They are absorbed orally

They are quaternary compounds not absorbed orally (correct)

They are metabolized by the liver

They are lipid-soluble

What is a major advantage of succinylcholine?

It has a slow onset of action

It provides good intubation conditions (correct)

It has a long duration of action

It has minimal cardiovascular effects

What is a potential complication of succinylcholine?

Hyperkalemia Signup and view all the answers

What is a characteristic of pancuronium?

It has low histamine release Signup and view all the answers

What is a characteristic of vercuronium?

It has a slow onset but prolonged action Signup and view all the answers

What is a difference between pancuronium and vercuronium?

Pancuronium has a shorter duration of action Signup and view all the answers

What is a common use of succinylcholine?

Endotracheal intubation Signup and view all the answers

What is the mechanism of action of Non-depolarizing blockers?

By competition Signup and view all the answers

Which of the following is a Centrally Acting Muscle Relaxant?

Dantrolene Signup and view all the answers

Which of the following is a GABA Derivative?

Baclofen Signup and view all the answers

What is the result of Non-depolarizing blockers on muscle tone?

Flaccid paralysis Signup and view all the answers

Which of the following is an Alpha-2 Agonist?

Tizanidine Signup and view all the answers

How can the neuromuscular block caused by Non-depolarizing blockers be reversed?

With anticholinesterase drugs Signup and view all the answers

What is the mechanism of action of Depolarizing blockers?

By depolarization Signup and view all the answers

Which of the following is a Directly Acting Muscle Relaxant?

Dantrolene Signup and view all the answers

What is the primary mechanism of action of dantrolene?

Prevention of intracellular release of calcium ions through Ryanodine receptors Signup and view all the answers

Which of the following neuromuscular blockers is preferred in elderly and neonates?

Atracurium Signup and view all the answers

What is the primary effect of histamine release caused by neuromuscular blockers?

Hypotension and bronchospasm Signup and view all the answers

Which of the following is a common interaction between neuromuscular blockers and other medications?

Potentiation of blockers by aminoglycosides Signup and view all the answers

What is the primary advantage of rocuronium over succinylcholine for tracheal intubation?

Rapid intubation conditions without the need for reversal Signup and view all the answers

Which of the following is a common adverse effect of neuromuscular blockers on the cardiovascular system?

Hypotension and bradycardia Signup and view all the answers

What is the primary mechanism of action of directly acting relaxants like dantrolene?

Reduction of actin-myosin interaction and calcium release Signup and view all the answers

Which of the following is a common use of neuromuscular blockers?

All of the above Signup and view all the answers

Study Notes

MOA of Depolarizing Agents

Depolarizing agents activate the Ach receptor on the motor end plate, causing voluntary muscle contraction initially, but leading to depolarization block and eventually competitive block (dual block) with prolonged administration.
This results in desensitization of the receptor to Ach.

Pharmacokinetics of Neuromuscular Blockers

All neuromuscular blockers are quaternary compounds and are not absorbed orally.
They are practically always given IV.
Redistribution plays a significant role in the termination of action of a single dose.
These drugs do not cross the placenta or penetrate the brain.
Drugs excreted by the kidney have a longer half-life (e.g., d-tubocurarine, pancuronium), while those eliminated by the liver have a shorter duration of action (e.g., vecuronium).

Succinylcholine

Advantages:
- Most commonly used skeletal muscle relaxant for endotracheal intubation.
- Provides good intubation conditions, including relaxed jaw, separated vocal cords, and immobility.
- Quick onset of action (1-2 minutes).
- Can be used as a continuous infusion occasionally.
Disadvantages:
- Unpredictable BP, HR, and arrhythmias.
- Fasciculations.
- Muscle pain.
- Increased intraocular pressure.
- Increased intracranial pressure.
- Hyperkalemia.
- Not indicated for use below 8 years of age.
- May cause malignant hyperthermia.

Pancuronium

Steroid compound that is 5 times more potent.
No cardiac or respiratory toxicity (little ganglion block).
Low histamine release – no bronchospasm or flushing.
Long duration of action, requiring reversal.
Preferred only for long surgeries.

Vecuronium

Congener of pancuronium.
Slow onset but prolonged action.
CVS stability – no histamine release.
Spontaneous and quick recovery.
Most commonly used.

Rocuronium

Non-depolarizing agent.
Rapid and immediate action.
Alternative to succinylcholine for tracheal intubation.
Also used as a maintenance relaxant, with no reversal required.
Rapid intubation condition in 60-90 seconds.
Also used in ICU for mechanical ventilation.

Atracurium

Competitive blocker, less potent than pancuronium.
Reversal not required.
Non-enzymatic spontaneous degradation in addition to cholinesterase.
Preferred in elderly and neonates.

Other Actions of NM Blockers

Autonomic ganglia:
- Partial blockade of ganglia.
- Results in fall in BP and tachycardia.
Histamine release:
- Hypotension.
- Bronchospasm, excess bronchial and salivary secretion.
CVS:
- Fall in BP due to ganglion blockade, histamine release, and reduced venous return.
GIT:
- Paralytic ileus.

Interactions of NMB

Thiopentone sodium – same syringe.
General anesthetics – potentiate blockers.
Anticholinesterases – neostigmine.
Antibiotics – aminoglycosides.
Calcium channel blockers – potentiate blockers (verapamil) – both competitive and non-competitive.
Diuretics – hypokalemia: enhances competitive block.

Uses of Neuromuscular Blocking Drugs

Adjuvant to general anesthesia.
Assisted ventilation.
Convulsion and trauma from electroconvulsive therapy.
Status epilepticus.

Directly Acting Relaxants

Dantrolene:
- Different from neuromuscular blockers, with no action on NM transmission.
- MOA – Ryanodine receptors calcium channels – prevents depolarization – no intracellular release of Ca++.
- Reduces actin-myosin interaction; weakens skeletal muscle contraction.
- Absorbed orally, penetrates brain, and produces sedation, metabolized in liver, excreted in kidney.

Other CNS Depressants

Barbiturates.
Benzodiazepines.
Gama hydroxybutyric acid (GHB).

Skeletal Muscle Relaxants

Drugs that act:
- Peripherally at NMJ or muscle fiber itself.
- In the cerebrospinal axis to reduce muscle tone or cause muscle paralysis.

Classification of SMRs

A. Neuromuscular blockers:
- Non-depolarizing (competitive) blockers:
  - Long acting: d-Tubocurarine, pancuronium, Doxacurium, etc.
  - Intermediate acting: Vecuronium, Atracurium, Rapacuronium, Cisatracurium.
  - Short acting: Mivacurium.
- Depolarizing blockers: Succinylcholine (Suxamethonium), Decamethonium.
B. Directly acting: Dantrolene, quinine.
C. Centrally acting:
- 1. Mephesin congeners (e.g., mephensin, chlormezanone).
- 1. Benzodiazepines (e.g., Diazepam).
- 1. GABA derivatives (e.g., Baclofen).
- 1. Central alpha 2 agonist (e.g., tizanidine).

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Description

Understand the mechanism of action of depolarizing agents and pharmacokinetics of neuromuscular blockers, including their effects on Ach receptors and muscle contraction.