Sinemet

Sinemet (carbidopa + levodopa) is an antiparkinsonian drug with a complex effect.

Indications

• Parkinson’s disease;
• Parkinsonism syndrome (except caused by antipsychotic drugs);
• symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

How does it work?

Sinemet is an anti-Parkinsonian combination drug. It contains carbidopa (an aromatic amino acid decarboxylase inhibitor) and levodopa (a precursor of doamine). The drug eliminates hypokinesia, stiffness, tremors, dysphagia, salivation. The anti-Parkinsonian effect of levodopa is due to its conversion into dopamine directly in the central nervous system, which leads to the replacement of dopamine deficiency in the central nervous system. Dopamine formed in the peripheral tissues is not involved in the implementation of the antiparkinsonian effect of levodopa (does not penetrate the central nervous system) and is responsible for most of the side effects of levodopa. Carbidopa is an inhibitor of peripheral dopa-decarboxylase, it reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the amount of levodopa entering the central nervous system. The optimal combination of levodopa and carbidopa is 4:1 or 10:1.

Instructions for use

The dosage and the frequency of administration are selected individually for each patient. According to studies, the average dose recommended for use ranges from 70-100 mg per day. In the standard scheme, the course of treatment starts with 1-2 tablets per day. The dose can be increased every few days. The maximum allowable dose is up to 8 tablets per day. The medicine can be taken with or after meals, there is no significant difference. You can talk about the first effect a week after the start of the course.

Contraindications

Do not take Sinemet if you have any of the following conditions/diseases:

• hypersensitivity;
• angle-closure glaucoma;
• melanoma and suspicion of it;
• skin diseases of unknown etiology;
• concomitant use of non-selective MAO inhibitors;
• age under 18 years.

With caution: myocardial infarction with rhythm disturbances (in the anamnesis), chronic heart failure and severe diseases of the cardiovascular system, severe lung diseases (including bronchial asthma); epilepsy and convulsive seizures (in the anamnesis), erosive and ulcerative lesions of the gastrointestinal tract (risk of bleeding from the upper gastrointestinal tract), diabetes mellitus and decompensated endocrine diseases, severe hepatic and / or renal failure, open-angle glaucoma, pregnancy, lactation.

Side effects

• Cardiovascular system: arrhythmia and / or palpitations, orthostatic reactions, including a decrease or increase in blood pressure, fainting; phlebitis;
• Digestive system: vomiting, anorexia, diarrhea, constipation, dyspepsia, dry mouth, taste change, darkening of saliva, gastrointestinal bleeding, duodenal ulcer;
• Hemopoietic organs: leukopenia, thrombocytopenia, anemia, including hemolytic, agranulocytosis;
• Nervous system: dizziness, headache, drowsiness, malignant antipsychotic syndrome, episodes of bradykinesia (on-off syndrome), sleep disturbance, including nightmares, insomnia; psychotic reactions, including delusions, hallucinations and paranoid thinking, confusion, agitation, paresthesias, depression (including with suicidal intentions), dementia, increased libido. Reported on the development of seizures, but a causal relationship with the drug has not been established;
• Allergic reactions: angioedema, urticaria, pruritus, hemorrhagic vasculitis (Shenlein-Genoch purpura), bullous rashes (including reactions similar to pemphigus);
• Respiratory system: dyspnea, upper respiratory tract infection;
• Dermatological reactions: skin rash, excessive sweating, darkening of sweat, alopecia;
• Urinary system: urinary tract infections, frequent urination, dark urine;
• Laboratory indicators: decreased hemoglobin and hematocrit, increased activity of ALT, AST, LDH, alkaline phosphatase, hyperbilirubinemia, increased urea nitrogen, positive Coombs test, hyperglycemia, leukocyturia, bacteriuria and hematuria;
• Other: chest pain, asthenia.

Overdose

Symptoms: muscle twitching, convulsive closing of the eyelids, nausea, vomiting, diarrhea, irregular and frequent pulse, loss of consciousness, cramps, anxiety arousal, hallucinations, coma.

Treatment: gastric lavage, close monitoring and ECG monitoring for the timely detection of arrhythmias; antiarrhythmic therapy (if necessary).

Drug interaction

The simultaneous use of Sinemet with beta-adrenostimulants and drugs for inhalation anesthesia may cause heart rhythm disturbances; with tricyclic antidepressants – a decrease in the bioavailability of levodopa; with diazepam, clozapine, phenytoin, clonidine, m-anticholinergics, antipsychotic drugs (antipsychotics) – derivatives of butyrophenone, diphenylbutylpiperidine, thioxanthene, phenothiazine, as well as with pyridoxine, papaverine, reserpine – a decrease in the effect; with lithium preparations – dyskinesias and hallucinations; with methyldopa – aggravation of side effects.

The simultaneous use of Sinemet with MAO inhibitors (with the exception of MAO inhibitors of type B) can cause circulatory disorders (taking MAO inhibitors should be stopped after 2 weeks). This is due to the accumulation of dopamine and norepinephrine under the influence of levodopa, the inactivation of which is inhibited by MAO inhibitors, and a high likelihood of developing excitation, increased blood pressure, tachycardia, facial redness and dizziness.

Patients taking Sinemet with tubocurarine have an increased risk of a pronounced decrease in blood pressure.

Iron salts may decrease the bioavailability of levodopa and carbidopa; the clinical significance of this interaction is unknown.

Although metoclopramide increases the bioavailability of levodopa by accelerating gastric emptying, it can nevertheless adversely affect control of the disease due to its antagonism with dopamine receptors.