Muscle Relaxants: Mechanism of Action and Applications

I. Neuromuscular Blocking Agents

1. General Mechanism:

• Neuromuscular blocking agents: act directly on the neuromuscular junction, where nerve signals are received to activate muscle contraction.

• Classification:

• Depolarizing agents: Bind to receptors at the neuromuscular junction, causing excessive depolarization, which paralyzes the neuromuscular junction, leading to muscle relaxation.

• Non-depolarizing agents: Compete with Acetylcholine (Ach) to bind to receptors at the neuromuscular junction, preventing Ach from activating muscle contraction, causing muscle relaxation.

2. Depolarizing Muscle Relaxants:

• Succinylcholine:

• Mechanism of action: Binds to receptors at the neuromuscular junction, causing excessive depolarization, leading to muscle relaxation.

• Characteristics: Short-acting (6-8 minutes) due to degradation by pseudocholinesterase.

• Side effects: Tremors, post-surgical muscle pain and stiffness, increased intraocular pressure, arrhythmias (due to hyperkalemia).

3. Non-Depolarizing Muscle Relaxants:

• Tubocurarine, Rocuronium, Pancuronium:

• Mechanism of action: Bind to receptors at the neuromuscular junction, competing with Ach, preventing muscle contraction.

• Characteristics: Cause pure muscle relaxation.

• Side effects: Histamine release, weakness.

• Overdose treatment: Use cholinesterase inhibitors.

• Antidote: Acetylcholine is the antidote for poisoning by non-depolarizing muscle relaxants.

4. Cholinesterase Inhibitors:

• Neostigmin: Used to reverse the effects of non-depolarizing muscle relaxants.

5. Complexing Agents for Muscle Relaxants:

• Sugammadex: Complexes with non-depolarizing muscle relaxants, helping to remove the drug from the body, restoring muscle function.

II. Centrally Acting Muscle Relaxants

1. General Mechanism:

• Action on the central nervous system: Temporarily suppress monosynaptic and polysynaptic reflexes, causing muscle relaxation.

2. Benzodiazepine Derivatives:

• Diazepam:

• Mechanism of action: Inhibits GABA binding to GABAa receptors, opening Cl- channels, causing neuronal inhibition.

• Effects: Muscle relaxation, sedation.

• Side effects: Drowsiness, cognitive impairment.

3. Other Medications:

• Baclofen:

• Mechanism of action: Stimulates GABAb receptors, inhibits the release of pain-inducing substances, reduces the effects of glutamate and aspartate.

• Effects: Muscle relaxation, pain relief.

• Side effects: Drowsiness, hypotension, weakness.

• Tizanidine:

• Mechanism of action: Stimulates alpha2-adrenergic receptors.

• Effects: Muscle relaxation.

• Side effects: Drowsiness, hypotension, dry mouth.

4. Muscle Relaxants Acting Directly on Muscle:

• Dantrolene:

• Mechanism of action: Inhibits Ca++ release from the sarcoplasmic reticulum of skeletal muscle, reducing actin-myosin interaction, leading to decreased muscle tone.

• Effects: Anti-spasmodic.

• Side effects: Fatigue, drowsiness, weakness, diarrhea.

• Indications: Chronic muscle spasticity due to neurological disorders, malignant hyperthermia.

• Contraindications: Heart failure, liver failure, acute muscle spasms.

5. Neurotoxins:

• Botulinum toxin type A:

• Mechanism of action: Inhibits Ach release at the presynaptic membrane, causing reduced skeletal muscle tone.

• Effects: Muscle relaxation for a specific period (3 months).

6. Other Medications:

• Eperison:

• Mechanism of action:

• Stabilizes cell membranes, reducing depolarization.

• Inhibits afferent nerve conduction and motor neurons.

• Decreases the sensitivity of muscle spindles.

• Inhibits neurotransmitter release.

• Inhibits the descending reticular system.

• Has vasodilating effects.

• Effects: Skeletal muscle relaxation, vasodilation, pain relief.

• Side effects: Dizziness, increased liver enzymes, anemia.

• Indications: Muscle spasms due to neurological, musculoskeletal, or peripheral circulatory disorders.

III. Conclusion:

Muscle relaxants are widely used in the treatment of skeletal muscle disorders, ranging from acute muscle spasms to chronic diseases. Understanding the mechanism of action of each type of drug helps to choose the appropriate one for each case. In addition, it is necessary to pay attention to the side effects and contraindications of the drugs.