Neuromuscular Blocking Drugs Mechanism

Mechanism of Action

• Neuromuscular blocking drugs (NMBDs) work by blocking the action of acetylcholine (ACh) at the neuromuscular junction
• They compete with ACh for binding sites on the nicotinic receptor, preventing muscle contraction
• Can be classified as depolarizing or non-depolarizing blockers

Depolarizing NMBDs

• Examples: Succinylcholine (SCh)
• Mechanism: Causes persistent depolarization of the muscle membrane, leading to muscle paralysis
• Characteristics:
  • Fast onset and short duration of action
  • Can cause muscle fasciculations, hyperkalemia, and cardiac arrhythmias
  • Not reversed by anticholinesterases

Non-Depolarizing NMBDs

• Examples: Atracurium, Vecuronium, Rocuronium, Cisatracurium
• Mechanism: Competitive inhibition of ACh at the nicotinic receptor
• Characteristics:
  • Slower onset and longer duration of action compared to depolarizing blockers
  • Can be reversed by anticholinesterases (e.g., neostigmine)
  • May cause histamine release, leading to hypotension and bronchospasm

Pharmacokinetics and Pharmacodynamics

• NMBDs are highly protein-bound and have a large volume of distribution
• Elimination half-lives vary among agents, ranging from minutes (SCh) to hours (Atracurium)
• Dose-response curves are steep, with significant interindividual variability
• NMBDs can be affected by factors such as age, renal and hepatic function, and underlying medical conditions

Clinical Uses and Adverse Effects

• Used in anesthesia to facilitate tracheal intubation and provide muscle relaxation during surgery
• Adverse effects:
  • Respiratory: respiratory depression, bronchospasm
  • Cardiovascular: hypotension, tachycardia
  • Neuromuscular: postoperative residual curarization, muscle weakness
  • Other: anaphylaxis, malignant hyperthermia

Mechanism of Action

• Neuromuscular blocking drugs (NMBDs) block the action of acetylcholine (ACh) at the neuromuscular junction by competing for binding sites on the nicotinic receptor.
• This competition prevents muscle contraction, leading to muscle paralysis.

Depolarizing NMBDs

• Succinylcholine (SCh) is an example of a depolarizing NMBD.
• Depolarizing NMBDs cause persistent depolarization of the muscle membrane, leading to muscle paralysis.
• Characteristics of depolarizing NMBDs:
  • Fast onset and short duration of action
  • Can cause muscle fasciculations, hyperkalemia, and cardiac arrhythmias
  • Not reversed by anticholinesterases

Non-Depolarizing NMBDs

• Examples of non-depolarizing NMBDs: Atracurium, Vecuronium, Rocuronium, Cisatracurium
• Non-depolarizing NMBDs work through competitive inhibition of ACh at the nicotinic receptor.
• Characteristics of non-depolarizing NMBDs:
  • Slower onset and longer duration of action compared to depolarizing blockers
  • Can be reversed by anticholinesterases (e.g., neostigmine)
  • May cause histamine release, leading to hypotension and bronchospasm

Pharmacokinetics and Pharmacodynamics

• NMBDs are highly protein-bound and have a large volume of distribution.
• Elimination half-lives of NMBDs vary among agents, ranging from minutes (SCh) to hours (Atracurium).
• Dose-response curves are steep, with significant interindividual variability.
• Factors affecting NMBDs: age, renal and hepatic function, and underlying medical conditions.

Clinical Uses and Adverse Effects

• Clinical uses of NMBDs: facilitating tracheal intubation and providing muscle relaxation during surgery.
• Adverse effects of NMBDs:
  • Respiratory: respiratory depression, bronchospasm
  • Cardiovascular: hypotension, tachycardia
  • Neuromuscular: postoperative residual curarization, muscle weakness
  • Other: anaphylaxis, malignant hyperthermia