Neostigmine
Risk Factor: CM
Class: AUTONOMICS
/ Parasympathomimetics (Cholinergics)
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Neostigmine is a quaternary ammonium compound with anticholinesterase activity used in the diagnosis and treatment of myasthenia gravis and to reverse muscle relaxation from competitive (nondepolarizing) muscle relaxants.
Although neostigmine is ionized at physiologic pH, the low molecular weight (about 223) is low enough that transfer of the nonionized fraction to the fetus should be expected. Circumstantial evidence for neostigmine placental transfer was presented in a 1996 case report (1). A woman at 31 weeks' gestation, undergoing surgery for a fractured elbow, was given IV neostigmine (5 mg) and glycopyrrolate (1 mg) to reverse muscle paralysis at the end of the procedure. The fetal heart rate immediately decreased from 115130 beats/minute to 90110 beats/minute and then gradually returned to 130 beats/minute within 1 hour. Four days later, surgical repair of the elbow was again required. At the end of this surgery, neostigmine (5 mg) and atropine (0.4 mg) were given IV and no change in the fetal heart rate was observed. The authors attributed the different effects on the fetal heart rate to the greater placental transfer of atropine in comparison to glycopyrrolate (see also Glycopyrrolate), that resulted in blocking the transplacental muscarinic effects of neostigmine (1).
The safe use of neostigmine in the treatment of maternal myasthenia gravis or other conditions has been reported (2,3,4,5,6,7,8,9,10,11 and 12). One study described 22 exposures to neostigmine in the 1st trimester (2). No relationship to congenital defects was found. A 1973 study reported the use of IM neostigmine (0.5 mg/day) for 3 days as a pregnancy test in 27 women with uncertain pregnancies at 514 weeks' gestation (3). Although vaginal bleeding occurred in seven (26%) patients, only one aborted and the remaining 26 went to term without complications. In a 1983 report, two women with myasthenia gravis were treated throughout gestation with neostigmine, 105 mg/day (combined with pyridostigmine and ambenonium) and 300 mg/day (combined with pyridostigmine), respectively, without apparent fetal harm (12).
One investigator considers neostigmine to be one of the drugs of choice for pregnant patients with myasthenia gravis (4). This author also cautioned that IV anticholinesterases should not be used in pregnancy because of the potential for inducing premature labor and suggested that IM neostigmine be used in place of IV edrophonium for diagnostic purposes (4). This recommendation, however, should be approached with caution in view of the high rate of vaginal bleeding following IM neostigmine described above.
Transient muscular weakness has been observed in about 20% of newborns of mothers with myasthenia gravis (10). The neonatal myasthenia is caused by transplacental passage of antiacetylcholine receptor immunoglobulin G antibodies (10).
Breast Feeding Summary
No reports describing the use of neostigmine, a quaternary ammonium compound, during lactation have been located. Two publications have stated that the drug is not excreted into breast milk (11,13). However, pyridostigmine, another quaternary ammonium compound, is found in breast milk (see Pyridostigmine). Thus, although neostigmine is ionized at physiologic pH, the low molecular weight (about 223) is low enough that the nonionized fraction should be excreted into milk. The effects, if any, on a nursing infant from exposure to neostigmine in milk are unknown.
References
- Clark RB, Brown MA, Lattin DL. Neostigmine, atropine, and glycopyrrolate: does neostigmine cross the placenta? Anesthesiology 1996;84:4502.
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:34556.
- Brunclik V, Hauser GA. Short-term therapy in secondary amenorrhea. Ther Umsch 1973;30:496502.
- McNall PG, Jafarnia MR. Management of myasthenia gravis in the obstetrical patient. Am J Obstet Gynecol 1965;92:51825.
- Foldes FF, McNall PG. Myasthenia gravis: a guide for anesthesiologists. Anesthesiology 1962;23:83772.
- Chambers DC, Hall JE, Boyce J. Myasthenia gravis and pregnancy. Obstet Gynecol 1967;29:597603.
- Hay DM. Myasthenia gravis and pregnancy. J Obstet Gynaecol Br Commonw 1969;76:3239.
- Blackhall MI, Buckley GA, Roberts DV, Roberts JB, Thomas BH, Wilson A. Drug-induced neonatal myasthenia. J Obstet Gynaecol Br Commonw 1969;76:15762.
- Eden RD, Gall SA. Myasthenia gravis and pregnancy: a reappraisal of thymectomy. Obstet Gynecol 1983;62:32833.
- Plauche WC. Myasthenia gravis in pregnancy: an update. Am J Obstet Gynecol 1979;135:6917.
- Fraser D, Turner JWA. Myasthenia gravis and pregnancy. Proc R Soc Med 1963;56:37981.
- Lefvert AK, Osterman PO. Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children. Neurology 1983;33:1338.
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Wilson JT. Pharmacokinetics of drug excretion. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia: ADIS Press, 1981:17.
Questions and Answers
what effects do neostigmine have on cardiac function?,
Clinically, Neostigmine is used as first-line treatment in ocular myasthenia gravis and as an adjunct to immunosuppressant therapy for generalised myasthenia gravis.
It has got a many effects on various systems of our body. Effects in particular to cardiac functions are bradycardia(slow heart rate), arrythmias(abnormal heart rhythm), hypotension and in extreme case it can also cause heart block.
Hence, the dosage need to be titrated carefully to avoid untoward complications.
Hope, this helps.
why neostigmine is not given in succinylcholine poisoning?,
Previous answer is a bit off.
Neostigmine is an anti-acetylcholinesterase. It blocks the enzyme that breaks down acetylcholine in the body. As the acetylcholine builds up, it can displace the muscle relaxant at the motor end plate and the person can once again move. All of the various muscle relaxants are metabolized by the body, with or without the introduction of neostigmine as a reversal agent.
In general, Succ wears off so fast it does not need reversal. In fact the half life of the neostigmine is considerably greater than the Succ. Since neostigmine is a weak "nerve agent" and can cause paralysis itself the view is, if you do not need it, do not give it.
There are people out there who can not break down Succ, so the proper treatment is to give fresh frozen plasma which contains the enzyme needed to break it down. (If you give neostigmine you might see a very temporary improvement but if you do not get the Succ metabolized, when the neo wears off, you will be right back where you started.)
There is only one instance where neostigmine is indicated after the use of Succ. As Succ gets broken down, one of the products of the break down is succ MONO choline. That is a very weak non-depolarizer muscle relaxant. In cases where a person got a lot of Succ, such as in the "olden days" when a constant drip of Succ was used, or when the anesthesia provider gives repeated doses, the build up of succ MONO choline could cause prolonged paralysis. And for THAT you could use neostigmine, but the provider had better make sure he is correct in his assessment.
what is neostigmine?,
Neostigmine belongs to the group of medicines called anticholinesterases. It works by prolonging the action acetylcholine, which is found naturally in the body. It does this by inhibiting the action of the enzyme acetylcholinesterase. Acetylcholine stimulates a type of receptor called muscarinic receptors. When stimulated, these receptors have a range of effects.
Muscarinic receptors are found throughout the body, especially on muscle. Stimulation of these receptors causes to muscle contraction.
In myasthenia gravis the body's immune system destroys many of the muscarinic receptors, so that the muscle becomes less responsive to nervous stimulation. Neostigmine bromide increases the amount of acetylcholine at the nerve endings. Increased levels of acetyl choline allow the remaining receptors to function more efficiently. This medicine usually restores mucle function to near-normal levels.
What is it used for?
Abnormal muscle weakness (myasthenia gravis)
Difficulty in passing urine (urinary retention)
Failure of function of part of the gut causing an obstruction (paralytic ileus)
Use with caution in
Asthma
Decreased kidney function
Epilepsy
Low blood pressure (hypotension)
Parkinson's disease
People who have recently had a heart attack
Peptic ulcer
Slow heart rate of less than 50 beats per minute (bradycardia)
Not to be used in
Blockage of the gut (intestinal obstruction)
Known sensitivity or allergy to any ingredient
Obstruction of the urinary tract (urethra)
to restore BP in hypotensive crisis......Prostigmin (Neostigmine)?, 2 Intropin
3 Bonamine
4 Procainamide HCL (Pronestyl)
I wish I knew!
