Amostigmine

Uses

Amostigmine Methyl Sulphate is used for-

• Reversal of nondepolarising neuromuscular blockade for surgical anesthetic procedures
• The prevention and treatment of post-operative abdominal distention and urinary retention after mechanical obstruction has been excluded.
• Treatment of the systemic control of Myasthenia Gravis when oral therapy is impractical.

Amostigmine is also used to associated treatment for these conditions: Curarization therapy, Myasthenia Gravis, Neuromuscular Blockade, Ogilvie's syndrome, Postoperative Urinary Retention, Post-operative intestinal atony

How Amostigmine works

Amostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. The drug inhibits acetylcholinesterase which is responsible for the degredation of acetylcholine. So, with acetylcholinesterase inhibited, more acetylcholine is present By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors which are involved in muscle contraction.. It does not cross the blood-brain barrier.

Dosage

Amostigmine dosage

Reversal of the effects of Non-depolarizing Neurormuscular Blocking Agents: The usual dose is 0.5 to 2 mg given by slow intravenous injection over 60 seconds; repeated as required. Total dose should not exceed 5 mg (in exceptional cases). When Amostigmine is administered intravenously, it is recommended that Atropine Sulphate (0.6-1.2 mg) also be given intravenously using separate syringe.

Prevention of post-operative abdominal distention and urinary retention: 0.25 mg intramuscularly or subcutaneously as soon as possible after operation; repeat every 4 6 hours for 2-3 days.

Treatment of post-operative abdominal distention: 0.5 mg intramuscularly or subcutaneously or as required.

Treatment of urinary retention: 0.5 mg intramuscularly or subcutaneously. If urination does not occur within an hour, the patient should be catheterized. After the patient has voided, or the bladder has been emptied, continue the 0.5 mg injection every 3 hours, for at least 5 injections.

Symptomatic control of Myasthenia Gravis: 0.5 mg intramuscularly or subcutaneously. Subsequent dose should be based on the individual patient's response.

Neonates: 50-250 micrograms (0.1 to 0.5 ml) every 4 hours.

Children: 200-500 micrograms (0.4 ml to 1 ml) as recommended.

Side Effects

Nausea, vomiting, increased salivation, diarrhoea and abdominal cramps (more marked with high doses). Signs of overdose are increased gastrointestinal discomfort, bronchial secretions and sweating, involuntary defecation and micturition, miosis, nystagmus, bradycardia, hypotension, agitation, excessive dreaming and weakness eventually leading to fasciculation and paralysis.

Toxicity

Overdosage of Amostigmine can cause cholinergic crisis, which is characterized by increasing muscle weakness, and through involvement of the muscles of respiration, may result in death. The LD 50 of neostigmine methylsulfate in mice is 0.3 ± 0.02 mg/kg intravenously, 0.54 ± 0.03 mg/kg subcutaneously, and 0.395 ± 0.025 mg/kg intramuscularly; in rats the LD 50 is 0.315 ± 0.019 mg/kg intravenously, 0.445 ± 0.032 mg/kg subcutaneously, and 0.423 ± 0.032 mg/kg intramuscularly.

Precaution

Asthma, bradycardia, recent myocardial infarction, epilepsy, hypotension, parkinsonism, vagotonia, peptic ulceration. Atropine or other antidote to muscarinic effccts may be necessary (particularly when Amostigmine is given by injection), but it should not be given routinely as it may mask signs of overdose.

Interaction

Anti-arrhythmic Procainamide, Quinidine and possibly Propafenone antagonise effect of Amostigmine. Antibacterials, Aminoglycosides, Clindamycin, Lincomycin and Polymyxins antagonise effect of Amostigmine.

Food Interaction

Amostigmine Drug Interaction

Moderate: pyridostigmineUnknown: aspirin, epinephrine, RHO Immunoglobulin , calcium / vitamin d, Allergy , glucose, heparin, ipratropium, acetaminophen, procaine penicillin, phenytoin, valproic acid, multivitamin, thiamine, cyanocobalamin, pyridoxine, ascorbic acid, phytonadione, phytonadione

Amostigmine Disease Interaction

Major: bradycardia, bronchospasm, coronary artery disease, parkinsonism, PUD, seizuresModerate: hyperthyroidism

Elimination Route

Amostigmine bromide is poorly absorbed from the gastrointestinal tract following oral administration

Half Life

The half-life ranged from 42 to 60 minutes with a mean half-life of 52 minutes.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no adequate or well-controlled studies of Amostigmine in either laboratory animals or in pregnantwomen. It is not known whether Amostigmine can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Amostigmine should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects: Anticholinesterase drugs may cause uterine irritability and induce premature labor when given intravenously to pregnant women near term.

Nursing Mothers: It is not known whether Amostigmine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Amostigmine in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Amostigmine is contraindicated in patients with known hypersensitivity to the drug. It is also contraindicated in patients with peritonitis or mechanical obstruction of the intestinal or urinary tract.

Storage Condition

Store in a cool and dry place, protected from light.

Innovators Monograph

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