Levodopa absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out by active mechanisms. Barriers to absorption of levodopa is the presence of dopa decarboxylase in the intestinal wall. Levodopa anastrozole 1mg is absorbed from the stomach in a limited amount. The rate of gastric emptying plays a key role in the absorption of the drug. Factors that slow gastric emptying (food, m-anticholinergic agents), delaying the passage of the drug into the duodenum, and slow its absorption. The maximum concentration of the drug in the blood observed after 1-2 hours after administration. Distribution: The volume of distribution of levodopa is 0.9-1.6 l / kg. While maintaining the total clearance dopa decarboxylase activity in plasma levodopa is 0.5 l / kg / hr.
Levodopa penetrates through the blood-brain barrier by facilitated diffusion. The endothelium of the brain capillaries also contains a dopa decarboxylase as a second potential barrier to receipt of levodopa to the brain, however, in these capillaries is decarboxylated a small portion of the administered dose of levodopa. Metabolism: Approximately 70-75% of input into the levodopa is metabolized in the gut wall (the effect of “first pass “). Liver first-pass metabolism does not substantially participate. With increasing doses of levodopa, the amount of drug in the intestine undergoes decreases.Levodopa is not bound to plasma proteins. The of levodopa-dopa decarboxylase is the main way of the formation of dopamine levodopa. A large anastrozole 1mg number of this enzyme in the intestine, liver and kidneys.
Methoxylation levodopa influenced by catechol-O-methyltransferase to form a 3-O-is the second metildofy by metabolism of levodopa. With long-term treatment of this metabolite may accumulate. Transamination is an additional route of metabolism of levodopa. The end product of this pathway is vanilpiruvat, vanilatsetat and 2,4,5-trigidroksifeniluksusnaya acid. All pathways except transamination are irreversible. Selection: In combination with carbidopa, levodopa half-life is increased to 3 hours. Up to 69% of levodopa can be detected in the urine of a human dopamine and its metabolites – vinilinmindalnoy acid, norepinephrine, homovanillic acid digidrofeniluksusnoy acid.
At recommended doses, carbidopa does not penetrate the blood-brain barrier. The maximum plasma concentration is reached after 4.2 hours. Approximately 50% of carbidopa is excreted in the urine and feces. 35% of carbidopa are excreted renally, it appears unchanged.
Hypersensitivity to the drug, a form-closure glaucoma, severe psychosis or neurosis, pregnancy and lactation, melanoma or suspected it, skin disease of unknown etiology, Huntington’s disease, essential tremor. It should not be used for the treatment of secondary parkinsonism caused by the use of antipsychotic drugs (neuroleptics). Do not assign patients up to 18 years.
The drug is taken with caution in patients with erosive and ulcerative lesions of gastric and / or duodenal ulcer, epileptic seizures in history of myocardial infarction with cardiac arrhythmias in the history of, heart failure, diabetes, asthma, diseases of the endocrine system, mental disorders, as well as heavy violations of liver and kidney function.
Dosing and Administration
With a small amount of food or after a meal, with water and without chewing. Since there is competition between the aromatic amino acids and levodopa by sucking, while anastrozole 1mg use of the drug should avoid consuming large amounts of protein. The average daily dose of carbidopa needed to inhibit peripheral conversion of levodopa, is 70-100 mg. Exceeding 200 mg carbidopa does not entail further enhance the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg.
The starting dose – 1/2 tablets 2 times a day, can be increased by half pill daily as needed. Typically, at the beginning of substitution therapy, the daily dose should not exceed 3 tablets per day (1st tablet 3 times a day). The use of this dosage is recommended in the early treatment of severe cases of Parkinson’s disease. The daily dose of the drug as an exception may be raised during monotherapy, but should not exceed 8 tablets (1 tablet minutes 8 times a day). The use in an amount of more than 6 tablets per day should be carried out with great care.
Tidomet Forte when replacing levodopa
levodopa discontinued 12 hours prior to start of treatment Tidometom Forte, and in the case of receiving prolonged forms levokarbidopy – 24 hours. Dosage Tidometa Forte in this case should be no more than 20% of the previous dose of levodopa. The maintenance dose is 3-6 tablets per day for most patients.
Nervous system: Dyskinesia, including choreoathetosis, focal dystonia, with prolonged use – “on-off” syndrome, dizziness, ataxia, seizures, anorexia, sedation, drowsiness, nightmares, nervousness, irritability, anxiety, insomnia, psychotic reactions, hallucinations, depression, paranoid state, hypomania, increased libido, euphoria, dementia. Gastrointestinal tract: loss of appetite, nausea, vomiting, constipation, epigastric pain, dysphagia, ulcerogenic action in predisposed patients. Cardiovascular system: orthostatic hypotension, collapse, heart arrhythmia, tachycardia. hemopoiesis system: moderate leukopenia, thrombocytopenia, hemolytic anemia. The change in laboratory parameters: changes in the level glutumatoksalattransaminazy, glutamatpiruvatoksalazy, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, iodine-related protein, positive direct Coombs’ test . Others: blepharospasm, mydriasis, diplopia, a slight increase in body weight during long-term use. Side effects are usually dependent on the dose received and the individual patient’s sensitivity. Side effects can be eliminated temporary dose reduction without interruption in treatment. If side effects do not regress, the treatment should be stopped gradually.
Symptoms: The first increase and then decrease in blood pressure, sinus tachycardia, confusion, agitation, insomnia, anxiety. It may also develop orthostatic hypotension. Symptoms of anorexia and insomnia may persist for several days. Treatment: gastric lavage, activated charcoal. If necessary, carrying out symptomatic treatment in a hospital. There is no specific antidote.
- Simultaneous with the appointment of antihypertensive drugs requires special attention due to the risk of postural hypotension.
- when combined with tricyclic antidepressants may cause hypertension and dyskinesia, and reduced bioavailability of levodopa.
- the combined use of phenothiazines, and butirofenonov Tidometa Forte reduces the effect of the latter.
- Tidomet Forte should not be administered in conjunction with non-selective monoamine oxidase inhibitors, as can develop hypertensive crisis. monoamine oxidase inhibitors, treatment should be discontinued for at least 14 days prior to drug administration. The exception is selegiline (a selective inhibitor of monoamine oxidase – B) that can be used as an adjuvant in the treatment of levodopa.
- may increase the effects of sympathomimetics, and therefore it is recommended to reduce the dose. With simultaneous use of levodopa with β-adrenostimulyatorov, means for inhalation anesthesia may increase the risk of cardiac arrhythmias.
- when used with levodopa amantadine marked potentiating effect.
- methyldopa and levodopa may potentiate the side effects of each other.
- pyridoxine is a cofactor dopa decarboxylase – an enzyme responsible for peripheral decarboxylation of levodopa and dopamine education. When his appointment in patients receiving levodopa (without dopa decarboxylase inhibitors), there is a growing peripheral metabolism of levodopa and a smaller amount of it penetrates through the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of levodopa, dopa decarboxylase peripheral inhibitors if not assigned additionally.
- when supplemental dopa decarboxylase inhibitors, the daily dose of levodopa can be reduced by 70-80% while maintaining the same clinical outcome.
- when combined with diazepam, phenytoin, clonidine, thioxanthene derivatives, papaverine, reserpine, may decrease the antiparkinsonian action.
- while the use of drugs anastrozole 1mg increases the risk of dyskinesias and hallucinations.
Should not be used in cases of secondary parkinsonism, caused by the use of antipsychotic drugs (neuroleptics).
Discontinuation of therapy should be gradual, since the sudden discontinuation of the drug may develop symptom complex resembling neuroleptic malignant syndrome (muscular rigidity, increased body temperature, increased content serum ). Requires monitoring of patients who took a sudden reduce the dose or interrupt reception. The absorption of levodopa in elderly patients is higher than in the young. These data confirm the information on the reduction of the activity of dopa decarboxylase in tissues with age, as well as long-term administration of levodopa.
When erosive and ulcerative lesions of gastric and / or duodenal ulcer, epileptic seizures in history of myocardial infarction, rhythm disturbances in the history of, heart disease, diabetes , bronchial asthma, diseases of the endocrine system, mental disorders, as well as severe liver or kidney function should take the drug with caution. In such cases, patients should be under close medical supervision.
In long-term treatment is necessary to carry out periodic monitoring of liver function, kidney, hematopoietic system and the cardiovascular system are also necessary to monitor the patient’s mental status.
In general anesthesia during surgical operations Tidomet Forte administered without reducing the dose if the patient is able to take drugs and fluids inside. When using halothane and cyclopropane use of the drug is stopped for at least 8 hours before surgery. Treatment continued after the operation at the same dose.
Patients with glaucoma in patients receiving the drug should regularly monitor the intraocular pressure.
The impact on driving: anastrozole 1mg you must refrain from transport management, as well as activities requiring psychomotor speed reactions.