Orphenadrine
·
Orphenadrine is a tertiary amine
antimuscarinic agent closely related to diphenhydramine.
■■ Orphenadrine is used
in the treatment of painful skeletal muscle disorders.
■■ It is also used to
treat drug induced extrapyramidal reactions and Parkinson's disease.
■■ Orphenadrine
is rapidly and completely absorbed from the stomach and intestines, peak plasma
levels are reached in 2 to 4 hours, and after undergoing an enterohepatic cycle
is almost entirely metabolised by first-order kinetics to eight metabolites,
the most important among which is N-demethylorphenadrine (NDO). Absorption may
be delayed due to the drug’s anticholinergic effects on gastric motility.
■■Approximately 50 to 60% is excreted as metabolites in the urine, about 8% is excreted unchanged, while the remainder gets eliminated in the faeces. Elimination half-life is 14 hours after therapeutic doses.
·
Orphenadrine has certain central
effects on muscle tone, and is anticholinergic and antihistamininc, with some
local anaes-thetic effects.
·
The usual oral dose of orphenadrine
is 100 mg twice a day, while the usual parenteral dose is 60 mg IV or IM twice
a day.
·
Dry mouth, nausea, blurred vision,
mydriasis, tachycardia, urinary retention, headache, vertigo, agitation,
tremors, and mental confusion. Constipation is a common anticholin- ergic side
effect.
·
Rarely aplastic anaemia or
anaphylactic reactions may occur.
·
Potentiation of the effects of
alcohol, anticholinergics, antidepressants, MAOIs, and CNS depressants.
·
Propoxyphene may aggravate tremors
and confusion.
·
There is synergistic effect with
levodopa.
·
Overdose results in mydriasis,
tachycardia, dry hot skin, decreased gastrointestinal motility, athetoid
movements, agitation, confusion, hallucinations, convulsions, urinary
retention, hypokalaemia, hypoglycaemia, hypotension, ventricular arrhythmias,
respiratory depression, and cardiac arrest.
·
Bradycardia has been reported with
severe overdose.
·
Therapeutic blood levels should be
below 0.2 mg/L. Blood levels of over this are associated with toxicity, and
levels over 4 to 8 mg/L may be fatal.
·
In a review of orphenadrine
toxicity, the minimum lethal dose was between 2 to 3 grams for adults.
·
Death has been reported in children
ingesting as little as 400 mg of orphenadrine.
·
Continuous ECG monitoring, pulse,
respiration, and temperature measurements.
·
Monitor blood glucose; follow serum electrolytes, renal
function and CPK levels in patients with prolonged seizures or hypotension.
·
Stomach wash can be beneficial upto 4–6 hours of inges-tion.
·
Activated charcoal is said to help in the prevention of
absorption of orphenadrine, and is administered in the usual dose.
·
Correct hypoglycaemia with intravenous dextrose, 50 ml of
50% dextrose in adults; 2 to 4 ml/kg of 25% or 10% dextrose in children. Follow
blood glucose carefully and repeat as needed.
·
Physostigmine is the antidote and effectively reverses the
anticholinergic manifestations. However it should be used with caution, since
its cardiotoxic effects can aggravate the cardiac depressant property of
orphenad-rine. The dose recommended is 2 mg IV for an adult and 0.5 mg for a
child. Dilute the dose of physostigmine in 10 ml of dextrose 5% in water or
normal saline. Give over 5 minutes. This can be repeated after 15–20 minutes if
required. Atropine at a dose of 0.5 mg per 1 mg of physo-stigmine (of the last
dose administered) should be avail-able to reverse life-threatening
physostigmine induced, toxic cholinergic effects such as bronchoconstriction.
·
Attempt initial control of convulsions with a
benzodi-azepine (diazepam or lorazepam). If seizures persist or recur administer
phenobarbitone.
·
For hypotension: Infuse 10 to 20 ml/kg of isotonic fluid and
place in Trendelenburg position. If hypotension persists, administer dopamine
or noradrenaline. Consider central venous pressure monitoring to guide further
fluid therapy.
·
Lignocaine, phenytoin, esmolol, isoproterenol, amio-darone,
or magnesium sulfate may be used to treat cardiac conduction disorders.
Quinidine, disopyramide, and procainamide are contraindicated as their effects
on myocardial conduction are similar to that of other sodium blocking drugs.
Because orphenadrine has sodium blocking properties arrhythmias may respond to
administration of sodium bicarbonate. An initial dose of 1 mEq/kg is
appropriate, repeated as needed with careful monitoring of blood pH.
·
Convulsions usually respond to IV diazepam. Barbitu-rates
are best avoided.
·
Hypokalaemia may require potassium replacement under strict
ECG monitoring.
■■ Orphenadrine has
mood elevating effects at therapeutic doses, and has been chronically abused for
its euphoric effects.
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