Levodopa
When ATH:
N04BA01
Pharmacological action
Protivoparkinsonicescoe tool. It is levorotatory isomer dihydroxyphenylalanine – dopamine precursor, Levodopa is converted into that under the influence the enzyme of the rally-carboxy-lyases. Protivoparkinsonicescoe levodopa due to its transformation into dopamine in the central nervous system directly, that leads to fill the deficit of dopamine in the central nervous system. However, most of the information provided in the body of levodopa is transformed into dopamine in peripheral tissues. Formed in peripheral tissues dopamine does not participate in the realization of the protivoparkinsonicheskogo effect of levodopa, tk. It does not penetrate the CNS, Besides, He calls most of the peripheral side effects of levodopa. In this regard, it is advisable to l-dopa combined with inhibitors of peripheral rally-carboxy-lyases (Carbidopa, Benserazide), that makes it possible to substantially reduce the dose of levodopa and severity of side effects.
Pharmacokinetics
If ingestion is rapidly absorbed from the digestive tract. Absorption depends on the speed of the evacuation of the stomach contents and from pH in it. The presence of food in the stomach slows down the absorption of. Some amino acid foods can compete with levodopa for absorption from the intestine and transport through GEB. Cmax plasma levels achieved after 1-2 hours after ingestion.
Only 1-3% active substances penetrate into the brain, the remainder metabolised jekstracerebralno, mainly through decarboxylation with the formation of dopamine, that does not cross the Geb.
About 75% return with urine in the form of metabolites within 8 no.
Testimony
Parkinson's Disease, Parkinson's syndrome (except parkinsonism, caused by Neuroleptics).
Dosage regimen
Individual. Treatment starts with a small dose of, gradually increasing it to best for each patient. At the beginning of treatment dose is 0.5-1 g / day, the average therapeutic dose – 4-5 g / day. When treating drugs, containing l-dopa with inhibitors of peripheral rally-carboxy-lyases, converted to l-dopa apply much smaller daily doses.
The maximum daily dose: ingestion – 8 g.
Side effect
Cardio-vascular system: often – orthostatic hypotension, Arrhythmia.
From the digestive system: often – nausea, vomiting, anorexia, epigastric pain, dysphagia, ulcerogenic action (in predisposed patients).
CNS: often – spontaneous movement, sleep disorders, ažitaciâ, dizziness; rarely – depression.
From the hematopoietic system: rarely – leukopenia, thrombocytopenia.
When treating drugs, containing l-dopa with inhibitors of peripheral rally-carboxy-lyases, These side effects are less common.
Contraindications
Expressions of the liver, kidney, the cardiovascular and/or endocrine systems, severe psychosis, zakrыtougolynaya glaucoma, melanoma, hypersensitivity to levodope, childhood.
Pregnancy and lactation
We do not recommend the use of levodopa in pregnancy, except for the presence of strong evidence.
If necessary, the use of levodopa in lactation should decide on the termination of breastfeeding.
Cautions
To apply caution in patients with renal diseases, light, Endocrine, Cardiovascular, especially when the guideline history to myocardial infarction, abnormal heart rhythm; When mental disorders, liver diseases, peptic ulcer, osteomalacia; in patients with diseases, which may require the use of simpatomimeticakih funds (incl. bronchial asthma), antihypertensive agents.
You should avoid sudden discontinuation of levodopa.
When transferring a patient with treatment of levodopa in the treatment of levodopa with inhibitors of peripheral rally-decarboksilaza receiving levodopa should stop for 12 hours before the appointment of combined medication.
Simultaneous application of levodopa with MAO inhibitors (except MAO-B inhibitor) not recommended, because of the possibility of circulatory disorders, incl. arterial hypertension, excitation, heartbeat, redness of the face, dizziness.
Effects on ability to drive vehicles and management mechanisms
During the period of application of levodopa should avoid activities, at that require high concentration and speed of psychomotor reactions.
Drug Interactions
Together with the application antatidami increases the risk of side effects.
While the use of antipsychotics (neuroleptics) butyrophenone derivatives, dyfenylbutylpyperydyna, thioxanthen, phenothiazines, pyridoxine may oppression protivoparkinsonicheskogo activity.
Together with the use of beta-adrainomimetikami possible cardiac arrhythmia.
Together with the use of MAO inhibitors (except MAO-B inhibitor) possible circulatory disorders. This is due to the accumulation of under the influence of levodopa dopamine and norepinephrine, inactivation of which slows down under the influence of MAO inhibitors.
Together with the use of m-holinoblokatorami possible reduced action of protivoparkinsonicheskogo; with means for anesthesia – the risk of arrhythmia.
There is evidence of a decrease in bioavailability of levodopa, while the use of tricyclic antidepressants.
Together with the use of diazepam, klozepinom, methionine, clonidine, phenytoin may decrease protivoparkinsonicheskogo actions.
Together with the use of lithium salts may increase risk of dyskinesias and hallucinations.
If you are applying with papaverina hydrochloride, possibly significant decrease protivoparkinsonicheskogo rezerpinom actions; with suksametoniem – possible arrhythmias; with tubokurarinom – increased risk of arterial hypotension.
