Drugs that enhance neuromuscular transmission
Anticholinesterase drugs enhance neuromuscular transmission in voluntary and involuntary muscle in myasthenia gravis. They prolong the action of acetylcholine by inhibiting the action of the enzyme acetylcholinesterase. Excessive dosage of these drugs can impair neuromuscular transmission and precipitate cholinergic crises by causing a depolarising block. This may be difficult to distinguish from a worsening myasthenic state. Muscarinic side-effects of anticholinesterases include increased sweating, increased salivary and gastric secretions, increased gastro-intestinal and uterine motility, and bradycardia. These parasympathomimetic effects are antagonised by atropine.
NEOSTIGMINE:
Indications: Myasthenia Gravis, Reversal of Neuromuscular Blockade, Urinary Retention.
Contraindications: Gastrointestinal Obstruction, Urinary Tract Infections, And Urinary Tract Obstructive Uropathy.
Dose and Administration: By subcutaneous or intramuscular injection, neostigmine metilsulfate 1–2.5 mg at suitable intervals throughout day (usual total daily dose 5–20 mg); neonate 50–250 micrograms every 4 hours half an hour before feeds; child 200–500 micrograms as required.
PYRIDOSTIGMINE BROMIDE:
Indications: Myasthenia Gravis, Prevention of Nerve Agent Poisoning.
Contraindications: Gastrointestinal Obstruction, Urinary Tract Infections, And Urinary Tract Obstructive.
Dose and Administration: By mouth, 30–120 mg at suitable intervals throughout day, total daily dose 0.3–1.2 g (but see also notes above); neonate 5–10 mg every 4 hours, 30–60 minutes before feeds; child up to 6 years initially 30 mg, 6–12 years initially 60 mg, usual total daily dose 30–360 mg.
Skeletal muscle relaxants
The drugs described below are used for the relief of chronic muscle spasm or spasticity associated with multiple sclerosis or other neurological damage; they are not indicated for spasm associated with minor injuries. They act principally on the central nervous system with the exception of dantrolene, which has a peripheral site of action. They differ in action from the muscle relaxants used in anaesthesia, which block transmission at the neuromuscular junction. The underlying cause of spasticity should be treated and any aggravating factors (e.g. pressure sores, infection) remedied. Skeletal muscle relaxants are effective in most forms of spasticity except the rare alpha variety. The major disadvantage of treatment with these drugs is that reduction in muscle tone can cause a loss of splinting action of the spastic leg and trunk muscles and sometimes lead to an increase in disability.
BACLOFEN:
Indications: chronic severe spasticity resulting from disorders such as multiple sclerosis or traumatic partial section of spinal cord. Trigeminal Neuralgia.
Contraindications: peptic ulceration.
Dose and Administration: By mouth, 10 mg 3 time’s daily, preferably with or after food, gradually increased; max. 100 mg daily (discontinue if no benefit within 6 weeks); child 0.75–2 mg/kg daily (over 10 years, max. 2.5 mg/kg daily) or 2.5 mg 4 times daily increased gradually according to age to maintenance: 1– 2 years 10–20 mg daily, 2–6 years 20–30 mg daily, 6–10 years 30–60 mg daily.
DANTROLENE SODIUM:
Indications: chronic severe spasticity of voluntary muscle; malignant hyperthermia.
Contraindications: hepatic impairment (may cause severe liver damage); acute muscle spasm; pregnancy and breast-feeding.
Dose and Administration: Initially 25 mg daily may be increased at weekly intervals to max. of 100 mg 4 times daily; usual dose 75 mg 3 times daily; child not recommended.
TIZANIDINE:
Indications: spasticity associated with multiple sclerosis or spinal cord injury or disease.
Contraindications: severe hepatic impairment.
Dose and Administration: adult over 18 years, initially 2 mg daily as a single dose increased according to response at intervals of at least 3–4 days in steps of 2 mg daily (and given in divided doses) usually up to 24 mg daily in 3–4 divided doses; max. 36 mg daily.
CHLORZOXAZONE-PARACETAMOL:
Indications: Pain relief and restoration of mobility in cases associated with sever and painful skeletal muscle spasms due to different etiology.
Contraindications: Drug-Induced Hepatitis.
Dose and Administration: 2 capsules (each 300mg paracetamol and 250mg chlorzoxazone) 3 times daily after meals.
