Details About Overdose or Poisoning Generic Salt :: Physostigmine And Neostigmine
Physostigmine and Neostigmine
Drug Pharmacology ::
I. Pharmacology. Physostigmineand neostigmine are carbamates and reversible inhibitors ofacetylcholinesterase, the enzyme that degrades acetylcholine. Theyincrease concentrations of acetylcholine, causing stimulation of bothmuscarinic and nicotinic receptors. The tertiary amine structure ofphysostigmine allows it to penetrate the blood-brain barrier and exertcentral cholinergic effects as well. Neostigmine, a quaternary ammoniumcompound, is unable to penetrate the CNS. Owing to cholinergicstimulation of the brainstem’s reticular activating system,physostigmine has nonspecific analeptic (arousal) effects. Afterparenteral administration of physostigmine, the onset of action iswithin 3–8 minutes and the duration of effect is usually 30–90 minutes.The elimination half-life is 15–40 minutes. Neostigmine has a sloweronset of 7–11 minutes and longer duration of effect of 60–120 minutes.
Drug Indications ::
Physostigmineis used for the management of severe anticholinergic syndrome (agitateddelirium, urinary retention, severe sinus tachycardia, or hyperthermiawith absent sweating) from antimuscarinic agents (eg, benztropine,atropine, jimson weed or [Datura], diphenhydramine). SeeAnticholinergics for discussion of anticholinergic toxicity. Althoughthere are anecdotal case reports of its use to treat delirium and comaassociated with GHB, baclofen, and several atypical antipsychotic(olanzapine, clozapine, quetiapine) agents, its safety and efficacy areuncertain with these intoxications.
Physostigmine is sometimes used diagnostically to differentiate functional psychosis from anticholinergic delirium.
Neostigmine is used primarily to reverse the effect of nondepolarizing neuromuscular blocking agents.
Drug Contra-Indications ::
Physostigmine should notbe used as an antidote for cyclic antidepressant overdose because itmay worsen cardiac conduction disturbances, cause bradyarrhythmias orasystole, and aggravate or precipitate seizures.
Do not use physostigmine with concurrent use of depolarizing neuromuscular blockers (eg, succinylcholine).
Known hypersensitivity to agent or preservative (eg, benzyl alcohol, bisulfite).
Relativecontraindications may include: bronchospastic disease or asthma,peripheral vascular disease, intestinal and bladder blockade,parkinsonian syndrome, and cardiac conduction defects (AV Block).
Drug Adverse Effects ::
IV. Adverse effects
Bradycardia, heart block, and asystole.
Seizures (particularly with rapid administration or excessive dose of physostigmine).
Nausea, vomiting, hypersalivation, and diarrhea.
Bronchorrhea and bronchospasm (caution in asthmatics).
E. Fasciculations and muscle weakness.
F. Use in pregnancy. FDAcategory C (see Table III–1). Transient weakness has been noted inneonates whose mothers were treated with physostigmine for myastheniagravis.
Drug Lab Interactions ::
Drug or laboratory interactions
Maypotentiate agents metabolized by the cholinesterase enzyme (eg,depolarizing neuromuscular blocking agents—succinylcholine, cocaine,esmolol), cholinesterase inhibitors (eg, organophosphate and carbamateinsecticides), and other cholinergic agents (eg, pilocarpine).
Theymay inhibit or reverse the actions of nondepolarizing neuromuscularblocking agents (eg, pancuronium, vecuronium, etc). Neostigmine is usedtherapeutically for this purpose.
Theymay have additive depressant effects on cardiac conduction in patientswith cyclic antidepressant, beta-adrenergic antagonist, and calciumantagonist overdoses.
Physostigmine,through its nonspecific analeptic effects, may induce arousal inpatients with GHB, opioid, benzodiazepine, sedative-hypnoticintoxication, or ketamine and propofol-induced anesthesia.
Drug Dose Management ::
Dosage and method of administration
Physostigmine. Parenteral: 0.5–2 mg slow (1 mg/min as adverse effects may be related to rapid administration) IV push (children, 0.02 mg/kg and given 0.5mg/min) while a cardiac monitor is used to monitor the patient; repeatas needed every 10–30 minutes (symptoms may recrudesce due to the shorthalf-life of physostigmine). Usual adult total dose is 4 mg. Atropine(see Atropine and Glycopyrrolate) should be kept nearby to reverseexcessive muscarinic stimulation and given at ½ the physostigmine dose(adults: 1–4 mg; children: 1 mg). Do not administer physostigmine intramuscularly or as a continuous intravenous infusion.
Neostigmine.Parenteral: 0.5–2 mg slow IV push (children: 0.025–0.08 mg/kg/dose) andrepeat as required (total dose rarely exceeds 5 mg). Premedicate withglycopyrrolate (0.2 mg per mg of neostigmine; usual adult dose 0.2–0.6mg; child 0.004–0.02 mg/kg) or atropine (0.4 mg per mg of neostigmine;usual adult dose 0.6–1.2 mg; child 0.01–0.04 mg/kg) several minutesbefore or simultaneously with neostigmine to prevent muscarinic effects(bradycardia, secretions).
Drug Chemical Formulations ::
Parenteral. Physostigminesalicylate (Antilirium), 1 mg/mL in 2-mL ampules (contains benzylalcohol and bisulfite). Neostigmine methylsulfate (Prostigmine,others), 1:1000, 1:2000, 1:4000 in 1- and 10-mL ampules and vials(contains phenol or parabens).
The suggested minimum stocking levelto treat a 70-kg adult for the first 24 hours is 10 ampules (2 mL each)for physostigmine and one 10-mL vial of 1:2000 or equivalent forneostigmine.