Neostigmine

Neostigmine induced (0.1-1 mM) positive inotropic effects on driven guinea pig isolated atria. Neostigmine also incr cardiac frequency of spontaneously beating atria. The positive inotropic effect of neostigmine was not caused by a nicotine-like action of the drug.

Morphological techniques were used to determine the acute and chronic effects of neostigmine on rat muscles. Transient calcium deposits were independent of fiber type and found at sites corresponding to neostigmine-induced focal lesions. Characteristic intermediate findings consisted of rod bodies and ribosomal clusters. Such clusters were frequently mingled and clumped sarcoplasmic reticulums, T-systems, or mitochondria. The focal myopathic changes were reversible with the exception of those in the synaptic region of the end plates.

1) ESTABLISH CLEAR AIRWAY & TISSUE OXYGENATION BY ASPIRATION OF SECRETIONS & IF NECESSARY, BY ASSISTED PULMONARY VENTILATION WITH OXYGEN. IMPROVE TISSUE OXYGENATION AS MUCH AS POSSIBLE BEFORE ADMINISTERING ATROPINE TO MINIMIZE THE RISK OF VENTRICULAR FIBRILLATION. /CARBAMATES, CHOLINESTERASE INHIBITORS/

2) ADMIN ATROPINE SULFATE IV, OR IM IF IV INJECTION IS NOT POSSIBLE... IN MODERATELY SEVERE POISONING: ADULT DOSAGE, INCLUDING CHILDREN OVER 12 YR: 0.4-2.0 MG REPEATED EVERY 15 MIN UNTIL ATROPINIZATION IS ACHIEVED (TACHYCARDIA, FLUSHING, DRY MOUTH, MYDRIASIS). MAINTAIN ATROPINIZATION BY REPEATED DOSES FOR 2-12 HR, OR LONGER, DEPENDING ON SEVERITY OF POISONING... DOSAGE FOR CHILDREN UNDER 12 YEARS: 0.05 MG/KG BODY WT REPEATED EVERY 15 MIN UNTIL ATROPINIZATION IS ACHIEVED. MAINTAIN ATROPINIZATION WITH REPEATED DOSAGE OF 0.02-0.05 MG/KG. SEVERELY POISONED INDIVIDUALS MAY EXHIBIT REMARKABLE TOLERANCE TO ATROPINE; TWICE THE DOSES SUGGESTED ABOVE MAY BE NEEDED... /CARBAMATES, CHOLINESTERASE INHIBITORS/

3. PRALIDOXIME (PROTOPAM-AYERST, 2-PAM) IS OF DOUBTFUL VALUE IN POISONINGS BY CARBAMATE INHIBITORS OF CHOLINESTERASE. ATROPINE ALONE IS ALMOST ALWAYS AN ADEQUATE ANTIDOTE. PRALIDOXIME IS PROBABLY CONTRAINDICATED IN POISONINGS BY CARBARYL, SPECIFICALLY. IF VICTIM OF CARBAMATE POISONING EXHIBITS SEVERE MUSCLE WEAKNESS &/OR RESPIRATORY DEPRESSION, OR IF POISONING INVOLVES A COMBINATION OF CARBAMATE & ORGANOPHOSPHATE, A DILUTE SOLUTION OF PRALIDOXIME (TOTAL DOSE IN 250 ML 5% GLUCOSE SOLN) MAY BE GIVEN CAUTIOUSLY IV. THE INFUSION SHOULD BE TERMINATED IF PATIENT'S CONDITION WORSENS. PRALIDOXIME DOSAGE: ADULTS, 1.0 G; FOR CHILDREN UNDER 12 YR, 20-50 MG/KG. 4. OBSERVE TREATED PATIENTS CLOSELY AT LEAST 24 HR TO INSURE THAT SYMPTOMS (POSSIBLY PULMONARY EDEMA) DO NOT RECUR AS ATROPINIZATION WEARS OFF. IN VERY SEVERE POISONINGS, METABOLIC DISPOSITION OF TOXICANT MAY REQUIRE SEVERAL HR OR DAYS DURING WHICH ATROPINIZATION MUST BE MAINTAINED. /CARBAMATES, CHOLINESTERASE INHIBITORS/

6. IF...INGESTED IN QUANTITY SUFFICIENT TO CAUSE POISONING, EMPTY THE STOMACH & INTESTINE. A. IF VICTIM IS ALERT & RESPIRATION IS NOT DEPRESSED, GIVE SYRUP OF IPECAC, FOLLOWED BY 1-2 GLASSES OF WATER TO INDUCE VOMITING; ADULTS (INCLUDING CHILDREN OVER 12), 30 ML; CHILDREN (UNDER 12 YR), 15 ML. CAUTION: OBSERVE VICTIM CLOSELY AFTER ADMIN IPECAC, IF CONSCIOUSNESS LEVEL DECLINES, OR IF VOMITING HAS NOT OCCURRED IN 15 MIN, PROCEED IMMEDIATELY TO INTUBATE THE STOMACH. FOLLOWING EMESIS, HAVE VICTIM DRINK A SUSPENSION OF /PRC: 30 G ACTIVATED CHARCOAL IN 3-4 OZ OF WATER (CHILDREN), 100 G IN 8-10 OZ OF WATER (ADULTS)/...TO BIND TOXICANT REMAINING IN THE GI TRACT. /CARBAMATES, CHOLINESTERASE INHIBITORS/

For more Antidote and Emergency Treatment (Complete) data for NEOSTIGMINE (6 total), please visit the HSDB record page.

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

The pharmacokinetics of neostigmine was evaluated in man after iv and oral admin. The mean plasma T/2 for neostigmine after iv admin was 0.89 hr. Following oral admin peak concn occurred 1-2 hr after intake, but biol availability was only 1-2% of the admin dose. In patients with myasthenia gravis, the decrement of the evoked electric muscle response of repetitive nerve stimulation correlated well with plasma concn of neostigmine.

Neostigmine undergoes hydrolysis by cholinesterase and is also metabolized by microsomal enzymes in the liver.

NEOSTIGMINE IS DESTROYED BY PLASMA ESTERASES, AND THE QUATERNARY ALCOHOL AND PARENT COMPOUND ARE EXCRETED IN THE URINE.

NEOSTIGMINE YIELDS 3-HYDROXYPHENYL TRIMETHYLAMMONIUM IN THE RAT. ROBERTS, JB ET AL; BIOCHEM PHARMAC 17: 9 (1968). /FROM TABLE/

3982TWQ96G

NEOSTIGMINE

Established Pharmacologic Class [EPC] - Cholinesterase Inhibitor

Mechanisms of Action [MoA] - Cholinesterase Inhibitors

Neostigmine is a Cholinesterase Inhibitor. The mechanism of action of neostigmine is as a Cholinesterase Inhibitor.

NEOSTIGMINE

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.

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

NEOSTIGMINE...IS ABSORBED POORLY AFTER ORAL ADMINISTRATION, SUCH THAT MUCH LARGER DOSES ARE NEEDED THAN BY THE PARENTERAL ROUTE. ...THE EFFECTIVE PARENTERAL DOSE OF NEOSTIGMINE IN MAN IS 0.5 TO 2.0 MG, THE EQUIVALENT ORAL DOSE MAY BE 30 MG OR MORE. LARGE ORAL DOSES MAY PROVE TOXIC IF INTESTINAL ABSORPTION IS ENHANCED FOR ANY REASON.

...THE EXCRETION OF NEOSTIGMINE IS RETARDED IN PATIENTS WITH SEVERE KIDNEY DISEASE, MAKING THIS ANTICHOLINESTERASE DRUG AN ACCEPTABLE CHOICE IN PATIENTS WITH RENAL FAILURE.

The pharmacokinetics of neostigmine in patients with normal renal function were determined and compared with those of patients undergoing renal transplantation or bilateral nephrectomy. Ten to 15 min prior to the end of operation and anesthesia, d-tubocurarine infusion was terminated and neostigmine, 0.07 mg/kg and atropine 0.03 mg/kg were given by infusion over a 2-min period. In anephric patients the elimination half-life was prolonged. Total serum clearance was decr from 16.7 ml/kg/min in patients with normal renal function to 7.8 ml/kg/min in anephric patients. Neostigmine pharmacokinetics following renal transplantation were not different from those in patients with normal renal function. Renal excretion accounts for 50% of neostigmine clearance.