Dostimid

• Approved Indications:
• Myasthenia Gravis: Treatment of muscle weakness in patients with myasthenia gravis (both generalized and ocular forms).
• Reversal of Non-depolarizing Neuromuscular Blockade: Used postoperatively to reverse neuromuscular blockade induced by agents such as tubocurarine.
• Chronic Orthostatic Hypotension: Sometimes used off-label to improve symptoms associated with autonomic dysfunction.
• Off-label / Clinically Accepted Uses:
• Eaton-Lambert Syndrome (Lambert-Eaton Myasthenic Syndrome) for symptomatic improvement.
• Prophylaxis against nerve agent poisoning in military or emergency settings.

• Myasthenia Gravis (Adults):
• Initial oral dose: 60 mg every 6 hours.
• Maintenance: 60–150 mg every 4–6 hours, adjusted according to patient response.
• Maximum daily dose: Usually 600 mg.
• Children:
• Dosage individualized; typically 1–3 mg/kg/day divided into multiple doses.
• Adjust according to clinical response and tolerability.
• Reversal of Neuromuscular Blockade (IV route):
• Dose: 0.01 to 0.07 mg/kg intravenously; administered slowly.
• Special Populations:
• Renal impairment: Use with caution; dosage adjustment may be necessary.
• Hepatic impairment: Limited data; monitor carefully.
• Elderly: Start with lower doses and titrate based on tolerance.
• Administration:
• Oral tablets or syrup; intravenous injection for acute reversal.
• Tablets taken with or without food; syrup can be used for patients with swallowing difficulties.

Pyridostigmine bromide is a reversible acetylcholinesterase inhibitor that inhibits the breakdown of acetylcholine at the neuromuscular junction, thereby increasing acetylcholine concentration and prolonging its action on nicotinic receptors. This enhancement of cholinergic transmission improves neuromuscular transmission and muscle strength in conditions characterized by impaired acetylcholine signaling, such as myasthenia gravis.

• Absorption: Oral bioavailability approximately 15–20%; peak plasma concentration reached within 1–2 hours after oral administration.
• Distribution: Widely distributed; crosses the blood-brain barrier poorly.
• Metabolism: Partially metabolized by plasma cholinesterases; primarily hydrolyzed in the liver.
• Excretion: Mainly renal excretion of unchanged drug and metabolites.
• Half-life: Approximately 1.5 to 2 hours.
• Onset of Action: Oral – within 30–60 minutes; IV – within minutes.

• Pregnancy: Classified as FDA Pregnancy Category C. Animal studies have shown no teratogenic effects, but adequate and well-controlled studies in pregnant women are lacking. Use only if clearly needed.
• Lactation: Pyridostigmine is excreted in breast milk in small amounts; caution is advised when administered to breastfeeding mothers.

• Acetylcholinesterase inhibitor
• Parasympathomimetic agent

• Known hypersensitivity to pyridostigmine or formulation excipients.
• Mechanical intestinal or urinary obstruction.
• Peritonitis or asthma exacerbations without proper management.
• Use with caution in bradycardia or cardiac conduction disturbances.

• Monitor for signs of cholinergic crisis, which may mimic worsening myasthenia gravis.
• Use cautiously in patients with cardiovascular disease, bronchial asthma, hyperthyroidism, or epilepsy.
• Patients with renal or hepatic impairment require careful monitoring.
• Overdosage can cause severe muscle weakness and respiratory depression.
• Educate patients on recognizing early symptoms of overdose or insufficient dosing.

• Common:
• Gastrointestinal: nausea, vomiting, diarrhea, abdominal cramps, increased salivation.
• Musculoskeletal: muscle cramps, fasciculations.
• Nervous system: dizziness, headache.
• Serious (rare):
• Bradycardia, hypotension, bronchospasm, cholinergic crisis (excessive salivation, muscle weakness, respiratory failure).
• Allergic reactions including rash and urticaria.

• Anticholinergic drugs (e.g., atropine): May antagonize pyridostigmine’s effects.
• Neuromuscular blocking agents:
• Non-depolarizing blockers: pyridostigmine may antagonize effects.
• Depolarizing blockers (e.g., succinylcholine): effects may be enhanced.
• Cholinergic agents: Additive cholinergic effects and toxicity risk.
• Other interactions: Caution when combined with beta-blockers and calcium channel blockers due to potential additive cardiac effects.

• Guidelines continue to endorse pyridostigmine as first-line symptomatic treatment for myasthenia gravis.
• Recent recommendations emphasize individualized dosing and monitoring to balance efficacy and side effects.
• No significant changes in dosing or new black box warnings.
• Increased awareness of cholinergic crisis and differentiation from myasthenic crisis is emphasized.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Syrup should be shaken well before use.
• Keep out of reach of children.