Pharmacology: Pyridostigmine, the active ingredient of Mestinon is a cholinesterase inhibitor. It is characterized by the gentle onset, smooth course, comparatively long duration and gradual decline of its cholinergic action. Pyridostigmine has an antagonistic effect on non-depolarising muscle relaxants only. It has a synergistic effect on depolarizing muscle relaxants.
Pharmacokinetics: Absorption: Pyridostigmine, like other medicines of the same type, is not fully absorbed from the intestinal tract. Bioavailability following oral administration is 3-8%. Considerably higher doses are therefore required for oral as opposed to parenteral administration.
Distribution: Peak plasma concentrations were reached in the fasting state approximately 1.5-2 hours after administration of 120 mg pyridostigmine. The increase in active ingredient is delayed when taken with food. The distribution volume averages 1.4 L/kg body weight. Pyridostigmine is not noticeably bound to plasma proteins and does not cross the blood-brain barrier. Blood plasma levels of 20-60 ng/ml are required in order to obtain the desired therapeutic effect with myasthenia gravis.
Metabolism: Pyridostigmine is metabolized to 3-hydroxy-N-methylpyridine and other unidentified metabolites.
Elimination: Mean values of around 1.5 hours are given for the elimination half life. This can, however, be prolonged up to three times over in individual cases. Mean plasma clearance in healthy volunteers is given as 0.36-0.65 L/kg/h. No confirmed data are available regarding the potential accumulation of unchanged pyridostigmine or active metabolites. Since the dosage must, in any case, be adjusted individually, this point is devoid of practical significance. Pyridostigmine is largely eliminated unchanged (75-81%) via the kidneys. One part (18-21%) appears as the 3-hydroxy-N-methyl-pyridine metabolite in urine. Other unidentified metabolites account for 1-4%.
Kinetics in Specific Clinical Situations: Impaired liver function has no relevant effect on the kinetics of pyridostigmine. The elimination half-life can increase approximately four fold and plasma clearance can fall by up to around one-fifth in the case of age or disease induced kidney failure.
Mestinon is useful in the treatment of myasthenia gravis.
When using Mestinon it is important to remember that the full effect appears gradually, usually within 15-30 minutes.
Use in Adult: 1-3 dragees (60-180 mg) 2-4 times daily, or higher doses if required.
The total daily dose is usually in the range of 5-20 dragees (300-1200 mg) but doses higher than these may be needed by some patients.
Use in Children: Children under 6 years old should receive an initial dose of 30 mg of Mestinon. Children 6-12 years old should receive 60 mg. Dosage should increase gradually, in increments of 15-30 mg daily, until maximum improvement is obtained. Total daily requirements are usually in the range of 30-360 mg.
Patients with swallowing difficulties can take tablets broken into pieces instead of the whole tablets or dragees. In myasthenia gravis, one dose is effective for approximately four hours during the day whilst at night (owning to reduced physical activity), a longer duration of effect of around 6 hours can be expected. It is recommended that times of administration be chosen so that the maximum effect coincides with the most strenuous physical exertion, e.g. when getting up and at mealtimes.
Special Dosage Instructions: The required dose must be carefully titrated when used in paediatrics. In case of neonatal myasthenia, generally one treatment with neostigmine (Prostigmin) is preferred. However, if this appears unsuitable due to excessively cholinergic side effects, then Mestinon can be administered. In these cases, the following serves as a rough guideline: 5-10 mg by mouth in tablet form, 30-60 minutes before food. Treatment over the eight week if life is required only in extremely rare cases of congenital and familial infantile myasthenia. Pyridostigmine is mainly eliminated unchanged via the kidneys. Lower doses may therefore be indicated in patients presenting with kidney disease. The dose should be adjusted in line with the desired effect.
Overdosage with Mestinon or other cholinesterase inhibitors may lead to cholinergic crisis that manifest themselves in, among other things, pronounced muscle weakness or exacerbated muscle weakness in patients with myasthenia.
If such a situation is overlooked, life is endangered due to paralysis of the respiratory muscles. Bradycardia and paradoxically, tachycardia are other possible effects. Counter measures include the immediate withdrawal of Mestinon or other cholinergics and the slow intravenous administration of 1-2 mg atropine sulphate. Depending on the pulse rate, this dose is to be repeated at intervals of two to four hours if required.
Mestinon is contraindicated in mechanical obstruction of the intestinal or urinary tract and known allergy to the preparation.
Although failure of patients to show clinical improvement may reflect under dosage, it can also be indicative of overdose. As is true of all cholinergic drugs, overdosage of Mestinon may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death. Myasthenic crisis due to an increase in the severity of the disease is also accompanied by extreme muscle weakness, and thus may be difficult to distinguish from cholinergic crisis on a symptomatic basis. Such differentiation is extremely important, since increases in doses of Mestinon or other drugs of this class in the presence of cholinergic crisis or of a refractory or "Insensitive" state could have a grave consequence. The different diagnosis of the two types of crisis may require the use of Tensilon (edrophonium chloride) as well as clinical judgment. The treatment of the two conditions obviously differs radically. Whereas the presence of myasthenia gravis suggests the need for more intensive anti-cholinergic therapy, the diagnosis of cholinergic crisis, calls for the prompt withdrawal of all drugs of this type. The immediate use of atropine in cholinergic crisis is also recommended.
Atropine may abolish or obtund gastrointestinal side effects or other muscarinic reactions: but such use, by masking the signs of overdose, can lead to inadvertent induction of cholinergic crisis.
Pyridostigmine is mainly excreted unchanged by the kidney. Therefore, lower doses may be required in patients with renal diseases, and treatment should be based on titration of drug dosage to effect.
Reproduction studies in laboratory animals have not indicated any risks to the foetus but no controlled studies have so far been conducted in pregnant women. Therefore, this medication should only be used during pregnancy strictly as directed, with careful dosing under medical supervision.
Since the possibility of pyridostigmine diffusing into breast milk cannot be ruled out, nursing mothers are advised to refrain from breast feeding their babies during treatment.
Like all cholinergic drugs, Mestinon can have undesirable functional effects on the autonomic nervous system.
Muscarine-type side effects can manifest themselves as nausea, vomiting, diarrhea, stomach cramps, increased peristalsis and bronchial secretion, salivation and lacrimation as well as bradycardia and miosis. Nicotine-type side effects consist mainly of muscle spasms, muscle twitches and muscle weakness.
Like other bromine-containing drugs, Mestinon can occasionally cause skin rash, although this generally disappears rapidly once medication has been discontinued. Further use of Mestinon or other bromine-containing preparations is the contraindicated.
Pyridostigmine antagonizes the action of curare-like non-depolarising muscle relaxants. Atropine counteracts the cholinergic effects of pyridostigmine.
N07AA02 - pyridostigmine ; Belongs to the class of anticholinesterase. Used as parasympathomimetics.
Mestinon drag 60 mg
150's
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