Physostigmine is a carbamate that inhibits the enzyme acetylcholinesterase. Acetylcholinesterase is responsible for the degradation of acetylcholine at the nerve terminals.

Physostigmine Uses:

• It is indicated for the reversal of central nervous system anticholinergic syndrome.

Note:

• Because of the serious adverse effects of the drug, it is only indicated to reverse the toxic effects of anticholinergic agents including life-threatening delirium.
• Consultation from a poison control center and/or clinical toxicologist is required when considering physostigmine administration.
• Important anticholinergic agents include:
  • atropine
  • benztropine
  • scopolamine
  • dimenhydrinate
  • diphenhydramine
  • Atropa belladonna (deadly nightshade),
  • jimson weed (Datura spp).

Physostigmine dose in Adults

Physostigmine Dose in the Reversal of toxic anticholinergic effects:

Note:

• Intravenous administration should not exceed 1 mg/minute to avoid drug-induced bradycardia, respiratory distress, and seizures.
• IM or IV:
  • 0.5 to 2 mg initially.
  • The dose may be repeated every 10 to 30 minutes until clinical response.
  • In cases of life-threatening anticholinergic effects, subsequent doses may be administered.

Physostigmine dose in Childrens

Physostigmine dose in the reversal of toxic anticholinergic effects:

Note:

• It is reserved for life-threatening situations only
• IM or IV:
  • 0.02 mg/kg initially.
  • The dose may be repeated every 5 to 10 minutes until clinical response.
  • The maximum total dose is 2 mg/dose.

Note:

• Intravenous administration should not exceed 0.5 mg/minute in children (to avoid drug-induced bradycardia, respiratory distress, and seizures).

Pregnancy Risk Category: C

• If there is a clear indication, antidotes can be used for pregnant women.
• Because of the potential for teratogenicity, antidotes (and Physostigmine), should not be withheld.

Use of physostigmine during breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturers recommend weighing the risks to the infant from drug exposure and the benefits for the mother.

Dose in Kidney Disease:

The manufacturer has not recommended any adjustments in the dose.   

Dose in Liver disease:

The manufacturer has not recommended any adjustments in the dose.   

Side effects of Physostigmine:

• Cardiovascular:
  • Asystole
  • Bradycardia
  • Palpitations
• Central Nervous System:
  • Hallucination
  • Nervousness
  • Restlessness
  • Seizure
  • Twitching
• Dermatologic:
  • Diaphoresis
• Gastrointestinal:
  • Diarrhea
  • Frequent Bowel Movements
  • Nausea
  • Salivation
  • Stomach Pain
  • Vomiting
• Genitourinary:
  • Urinary Frequency
• Hypersensitivity:
  • Hypersensitivity Reaction
• Ophthalmic:
  • Lacrimation
  • Miosis
• Respiratory:
  • Bronchospasm
  • Dyspnea
  • Pulmonary Edema
  • Respiratory Distress
  • Respiratory Paralysis

Contraindication to Physostigmine Include:

• Gastrointestinal and genitourinary obstruction
• Asthma, bronchial hyperreactivity
• Gangrene
• Diabetes
• Cardiovascular disease
• Vagotonic states
• Combination of choline esters with depolarizing neuromuscular blocking agents (eg succinylcholine).

Notice:

• It should not be used in situations other than toxic effects from anticholinergic agents.

Warnings and precautions

• Arrhythmias
  • Before treatment can be initiated, it is necessary to have a baseline ECG and measurement of the QRS.
  • Patients who are taking concomitant medications, which may prolong intraventricular conduction, should not use it.
• Cholinergic effects
  • Treatment may be stopped if excessive cholinergic activity has been detected.
  • Cholinergic effects can manifest as vomiting, salivation, urinary or fecal incontinence and/or bronchospasm.
  • An overdose can lead to a cholinergic crises that is difficult to distinguish from a myasthenic crises.
  • Patients who experience nausea or excessive sweating should reduce their dose.
• Hypersensitivity/ Overdose reactions
  • It is important to have Atropine readily available in order to reverse its effects in the event of an overdose or hypersensitivity reaction.
  • It can lead to cholinergic crises.

Monitoring parameters:

• ECG,
• vital signs
• Follow institutional policies and procedures.

How to administer Physostigmine?

• It is intravenously administered at a rate of 1mg/minute or less Rapid intravenous administration may cause bradycardia and respiratory distress as well as seizures.
• You can also administer it intramuscularly, as per the manufacturer's label.   

Mechanism of action of Physostigmine:

• It is a carbamate which inhibits Acetylcholinesterase. 
• Acetylcholinesterase enzyme inactivates acetylcholine receptors.
• It does this by inhibiting the acetylcholinesterase and prolonging the central and peripheral effects acetylcholine.

The onset of action:

• Within 3 to 8 minutes

Duration of action:

• 45 to 60 minutes

Absorption following intramuscular administration:

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• Readily absorbed

Distribution:

• It is widely distributed throughout the body. It also crosses the blood-brain barrier readily and reverses both the central and peripheral anticholinergic effects.

Metabolism:

• It is metabolized via hydrolysis by cholinesterases.

Half-life elimination:

• 1 to 2 hours

International Brands of Physostigmine:

• Anticholium
• Fisostigmina Salicilato
• Fisostin
• Physostigmine Salicylate
• Physostigminum S

Physostigmine Brand Names in Pakistan:

No Brands Available in Pakistan.