Skeletal Muscle Relaxants

18th April, 2013

Classification I

• Centrally acting• Baclofen • Diazepam

• Direct acting• Dantrolene

Classification II

• Peripherally acting (Neuromuscular blockers)– Presynaptic neuromuscular blockers• Inhibit Ach synthesis

– Triethylcholine – Hemicholinium

• Inhibit Ach release – Mg– Aminoglycosides– Botulinum toxin

Classification III

– Postsynaptic neuromuscular blockers• Competitive (non depolarizing blockers)

– Long acting» Pancuronium

– Intermediate acting» Atracurium» Vecuronium» Rocuronium» Cisatracurium

– Short acting» Mivacurium

• Depolarizing blockers » Succinylcholine

Nicotinic ACh Receptor

NMJ

Pharmacodynamics

Non-depolarizing

• Important Features– Nicotinic antagonists– Reversibility with Ach E Inhibitors (↑conc. of ACh)– Cause progressive paralysis (face, eye, fingers, limbs, neck,

trunk muscles, intercostal, diaphragm)– No effects on heart , smooth muscles, or CNS– D-Tubocurarine is the prototypical drug– Polar compounds – Orally inactive ~ so taken parenterally – Don’t cross placenta or CNS

Non-depolarizing Specific Drugs I

• Gallamine– Less potent than curare– Tachycardia

• d –Tubocurarine– 1-2hr duration of action– Histamine releaser (Bronchospasm, Hypotension)– Blocks autonomic ganglia (Hypotension)

• Atracurium– Rapid recovery– Safe in hepatic & renal impairment– Spontaneous inactivation to laudanosine (seizures)

Non-depolarizing Specific Drugs II

• Mivacurium– Metabolized by pseudocholinesterases– Fast onset and short duration

• Pencuronium– Long duration of action– Tachycardia (Anti M, ↑NE release)

• Vecuronium– Intermediate duration of action– Fewer side effects (no histamine release, no ganglion

blockade, no antimuscarinic action)

Depolarizing Neuromuscular Blockers : Dynamics

• Phase I ( Depolarizing )– Binds with nicotinic receptors →depolarization of motor end

plate → initial muscle twitching → Persistent depolarization→ paralysis.

– Phase I block is augmented not reversed by anticholinestrases.

• Phase II ( Desensitization Block )– Continuous exposure to succinylcholine → depolarization

decreases and the membrane become repolarized, but the membrane cannot be depolarized by Ach as long as succinylcholine present → desensitization of the membrane.

Succinylcholine

• Rapid onset/Short duration ~ hydrolyzed by psuedocholinesterases

• Cause Hyperkalemia, Malignant Hyperthermia, bradycardia, ↑intraocular pressure

Therapeutic Uses

• Control convulsion electroshock therapy in psychotic patient .

• Relieve of tetanus and epileptic convulsion.• facilitate endoscopy• As adjuvant in general anesthesia to induce

muscle relaxation• Orthopedic surgery.

Centrally Acting

• Baclofen– GABAB agonist

• Diazepam• Dantrolene

• It interferes with the release of calcium from its stores in sk. muscles (sarcoplasmic reticulum).• It inhibits excitation-contraction coupling in the muscle

fiber.• Used in malignant hyperthermia & spastic states.

Uses of Spasmolytics

• Reduce muscle spasm in – Spinal cord injury– Stroke– Cerebral palsy