What is the difference between non-depolarizing (Non-Depolarizing Neuromuscular Blockers) and depolarizing (Depolarizing Neuromuscular Blockers) neuromuscular blockers (NMBs)?

From the Guidelines

Neuromuscular blocking agents (NMBs) are classified into two main types: non-depolarizing and depolarizing, which differ in their mechanism of action and clinical properties. Non-depolarizing NMBs, such as rocuronium, vecuronium, pancuronium, and cisatracurium, work by competitively binding to acetylcholine receptors at the neuromuscular junction without activating them, preventing muscle contraction. These agents have a slower onset (1-5 minutes) but longer duration of action (30-90 minutes depending on the specific drug), and can be reversed with neostigmine or sugammadex 1. They typically cause minimal histamine release and have few cardiovascular effects, making them suitable for most surgical procedures. In contrast, depolarizing NMBs, primarily succinylcholine, initially stimulate acetylcholine receptors, causing muscle fasciculations before paralysis. Succinylcholine has a rapid onset (30-60 seconds) and short duration (5-10 minutes), making it ideal for rapid sequence intubation 2. However, it cannot be pharmacologically reversed and has several potential side effects including hyperkalemia, malignant hyperthermia in susceptible individuals, increased intracranial and intraocular pressure, and muscle pain. The choice between these agents depends on the clinical scenario, with succinylcholine preferred when rapid airway control is needed, while non-depolarizing agents are better for longer procedures requiring sustained muscle relaxation with fewer side effects 3.

Some key differences between non-depolarizing and depolarizing NMBs include:

• Onset time: Non-depolarizing NMBs have a slower onset (1-5 minutes) compared to depolarizing NMBs (30-60 seconds) 4
• Duration of action: Non-depolarizing NMBs have a longer duration of action (30-90 minutes) compared to depolarizing NMBs (5-10 minutes) 5
• Reversibility: Non-depolarizing NMBs can be reversed with neostigmine or sugammadex, while depolarizing NMBs cannot be pharmacologically reversed 1
• Side effects: Depolarizing NMBs have several potential side effects, including hyperkalemia, malignant hyperthermia, and increased intracranial and intraocular pressure, while non-depolarizing NMBs typically cause minimal histamine release and have few cardiovascular effects 6, 7

Overall, the choice of NMB depends on the specific clinical scenario and the needs of the patient. Non-depolarizing NMBs are generally preferred for longer procedures requiring sustained muscle relaxation with fewer side effects, while depolarizing NMBs are preferred when rapid airway control is needed.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Atracurium besylate is a nondepolarizing skeletal muscle relaxant. Nondepolarizing agents antagonize the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. CLINICAL PHARMACOLOGY Succinylcholine is a depolarizing skeletal muscle relaxant. As does acetylcholine, it combines with the cholinergic receptors of the motor end plate to produce depolarization.

The main difference between non-depolarizing (e.g. atracurium) and depolarizing (e.g. succinylcholine) neuromuscular blockers (NMBs) is:

• Mechanism of action: Non-depolarizing NMBs antagonize the action of acetylcholine, while depolarizing NMBs mimic the action of acetylcholine, producing depolarization.
• Effect on the motor end-plate: Non-depolarizing NMBs competitively bind to cholinergic receptor sites, while depolarizing NMBs combine with the cholinergic receptors to produce depolarization. Key differences include:
• Onset of action: Depolarizing NMBs have a faster onset of action compared to non-depolarizing NMBs.
• Duration of action: Non-depolarizing NMBs have a longer duration of action compared to depolarizing NMBs. 8 9

From the Research

Difference between Non-Depolarizing and Depolarizing Neuromuscular Blockers

• Non-depolarizing neuromuscular blockers (NMBs) work by binding to the same receptors as acetylcholine, but instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade 10.
• Depolarizing NMBs, such as succinylcholine, attach to receptors in the motor end plate and depolarize the neuromuscular junction, making the end plate refractory to acetylcholine 10.
• The main difference between the two types of NMBs is their mechanism of action, with non-depolarizing agents competing with acetylcholine for receptor sites and depolarizing agents mimicking the action of acetylcholine 10, 11.
• Non-depolarizing NMBs have a slower onset of action compared to depolarizing agents, but they provide a more controlled and sustained paralysis 11, 12.
• Depolarizing agents, such as succinylcholine, have a rapid onset of action, but they can cause muscle fasciculations, hyperkalemia, and other adverse effects 10, 13.

Characteristics of Non-Depolarizing and Depolarizing NMBs

• Non-depolarizing NMBs:
  • Have a slower onset of action
  • Provide a more controlled and sustained paralysis
  • Can be reversed with anticholinesterase agents
  • Examples: vecuronium, pancuronium, rocuronium, and cisatracurium 14, 11
• Depolarizing NMBs:
  • Have a rapid onset of action
  • Can cause muscle fasciculations and hyperkalemia
  • Are often used for short procedures, such as endotracheal intubation
  • Examples: succinylcholine 10, 13

Clinical Use of Non-Depolarizing and Depolarizing NMBs

• Non-depolarizing NMBs are commonly used in surgical procedures, such as cardiac surgery, to provide a controlled and sustained paralysis 14.
• Depolarizing NMBs are often used in emergency situations, such as rapid sequence intubation, where a rapid onset of action is required 13.
• The choice of NMB depends on the specific clinical situation, the patient's medical history, and the desired duration of action 11, 12.