Pharmacological action Carbidopa Levodopa
Antiparkinsonian combination tool – a combination of carbidopa (an inhibitor of aromatic amino acid decarboxylase) and levodopa (a precursor doamina). Eliminates hypokinesia, rigidity, tremor, dysphagia, drooling. Antiparkinsonian action of levodopa is due to its conversion into dopamine directly into the CNS, which leads to a shortfall of dopamine in the CNS. Formed in peripheral tissue dopamine is not involved in the implementation of the antiparkinsonian effect of levodopa (does not penetrate the CNS) and is responsible for most of the side effects of levodopa. Carbidopa – an inhibitor of peripheral dopa-decarboxylase, reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the number of levodopa entering the CNS. Optimal combination of levodopa and carbidopa 4:1 or 10:1.
Effect of the drug appears on the first day since the beginning of the reception, sometimes – after the first dose. The full effect is reached within 7 days.
Pharmacokinetics Carbidopa Levodopa
Data on the pharmacokinetics of carbidopa limited. Levodopa ingestion is rapidly absorbed from the gastrointestinal tract. Removals – 20-30% of the dose, Tmax after oral administration – 2-3 hours absorption depends on the speed of the evacuation of stomach contents and the pH in it. The presence of food in the stomach slows absorption. Some amino acids the food can compete with levodopa for absorption from the intestine and transport across the BBB. In great quantity in the small intestine, liver and kidneys, only about 1-3% penetrates into the brain. Unchanged excreted by the kidneys (35% for 7 h) and through the intestines.
T1 / 2 – about 1 hour, when used in combination with carbidopa – about 2 hours
Metabolized in all tissues, mostly by decarboxylation to form dopamine, which does not penetrate the BBB, metabolites – dopamine, norepinephrine, epinephrine the kidneys. About 75% is excreted by the kidneys as metabolites within 8 hours
After oral administration of healthy individuals and patients with Parkinson’s disease carbidopa labeled with radioactive isotopes, a single dose of the maximum level of radioactivity in plasma is 2-4 hours after administration of healthy individuals and in 1.5-5 hours in patients with Parkinson’s disease.
Excretion of the drug in urine and feces is approximately the same in both groups.
Among the metabolites excreted in urine, the main ones being the alpha-methyl-3-methoxy-4-gidroksifenilpropionovaya acid and alpha-methyl-3 ,4-дигидроксифенилпропионовая acid. They make up about 14 and 10% of output metabolites, respectively. In smaller quantities are found the other 2 metabolite. One of them was identified as 3,4-digidroksifenilatseton, another – tentatively as N-metilkarbidopa. The content of each of these substances is not more than 5% of the total metabolites. The urine is also found unchanged carbidopa. Conjugates were not identified.
Statement Carbidopa Levodopa
- Parkinson’s disease;
- Parkinson’s syndrome (with the exception caused by antipsychotic drugs);
- Postentsefalitny, against the background of cerebrovascular disease, poisoning by toxic substances (including carbon monoxide or manganese).
Dosing regimen Carbidopa Levodopa
Inside, 1 / 4 tablets (250 mg/25 mg) 2-3 times a day. , Then increase the dose by 1 / 4 tablet every 2-3 days to achieve optimal effect. Typically, the optimal effect observed at a dose of 1-2 tablets (250 mg/25 mg) per day.
The maximum daily dose – 1.5 grams of levodopa and carbidopa 150 mg (6 tablets 250 mg/25 mg).
Side effect Carbidopa Levodopa
Cardio-vascular system: arrhythmia, and / or palpitations, orthostatic reactions, including the reduction or increase in blood pressure, fainting; phlebitis.
From the digestive system: vomiting, anorexia, diarrhea, constipation, dyspepsia, dry mouth, change in taste, dark saliva, gastrointestinal bleeding, duodenal ulcer.
On the part of hematopoiesis: leukopenia, thrombocytopenia, anemia, including hemolytic anemia, agranulocytosis.
The nervous system: dizziness, headache, drowsiness, neuroleptic malignant syndrome, episodes of bradykinesia (syndrome “on-off”), sleep disturbances, including nightmares, insomnia, psychotic reactions, including delirium, hallucinations and paranoid thinking, confusion, agitation, paresthesia, depression (including suicidal intentions), dementia, increased libido. Reported on the development of seizures, but a causal relationship with drug intake is not installed.
Allergic reaction: angioedema, hives, itchy skin, hemorrhagic vasculitis (Henoch-Schonlein purpura), bullous rashes (including reaction similar to pemphigus).
With the respiratory system: dyspnea, upper respiratory tract infection.
Dermatological reactions: skin rash, excessive sweating, dark with sweat, alopecia.
With the urinary system: urinary tract infections, frequent urination, dark urine.
Laboratory indicators: reduction in hemoglobin and hematocrit, increased ALT, AST, LDH, alkaline phosphatase, hyperbilirubinemia, increased urea nitrogen and positive Coombs test, hyperglycemia, leucocyturia, bacteriuria, and hematuria.
Other: chest pain, asthenia.
Other adverse reactions were observed when only levodopa, and therefore may occur when using a combination of levodopa and carbidopa:
With the cardiovascular system: myocardial infarction.
From the digestive system: gastrointestinal pain, dysphagia, excessive salivation, flatulence, bruxism, burning sensation language, heartburn, hiccups.
From a metabolism: edema, decrease or increase in body weight.
The nervous system: ataxia, extrapyramidal disorder, falling, anxiety, impaired gait, nervousness, reduced visual thinking, memory loss, disorientation, euphoria, blepharospasm, trismus, increased tremor, numbness, muscle twitching, activation of latent Horner’s syndrome, peripheral neuropathy.
With the respiratory system: pain in the throat, cough.
Dermatological reactions: malignant melanoma, the tides.
From the sensory organs: oculogyric crises, diplopia, blurred vision, mydriasis.
With the genitourinary system: urinary retention, urinary incontinence, priapism.
Other: abdominal pain, fatigue, weakness, pain in the lower extremities, dyspnea, nausea, hoarseness, excitement.
Laboratory findings: leukopenia, hypokalemia, and hyperuricemia hypercreatininemia, proteinuria and glucosuria.
Contraindications Carbidopa Levodopa
- Hypersensitivity;
- Angle-closure glaucoma;
- Melanoma and a suspicion on her, and skin disease of unknown etiology;
- Concomitant use of nonselective MAO inhibitors;
- The age of 18.
Precautions: myocardial infarction, arrhythmia (history), chronic heart failure and severe cardio-vascular system, severe lung disease (including asthma), epilepsy and seizures (in history), erosive and ulcerative lesions GIT (risk of bleeding from upper GIT), diabetes, and decompensated endocrine diseases, severe hepatic and / or renal failure, open-angle glaucoma, pregnancy and lactation.
Application of pregnancy and breastfeeding
Precautions: pregnancy, lactation
Use in hepatic dysfunction
Precautions: severe hepatic renal failure.
Use in renal impairment
Precautions: severe renal insufficiency.
Cautions
Unacceptably abrupt discontinuation of levodopa (with a sharp cancellation possible development of symptoms resembling neuroleptic malignant syndrome include muscle rigidity, fever, abnormalities in the psyche and the increased activity of CPK in serum).
Should be monitored for patients who took a sudden decrease dose or stop taking it, especially if the patient receives an antipsychotic medicine.
Not indicated for the removal of extrapyramidal reactions caused by drugs.
In the course of treatment is necessary to monitor the mental status of the patient’s pattern of peripheral blood.
Foods high in protein may interfere with absorption.
Glaucoma patients against taking the medication regularly to control intraocular pressure.
Recommended to be taken with food or with a small amount of liquid, capsules, swallowed whole.
During long-term treatment is appropriate periodic monitoring of liver function, blood, kidneys and cardiovascular system.
Before a planned general anesthesia drug can be taken up until the patient permitted oral intake.
After surgery, the usual dose may be appointed again as soon as the patient will be able to take the drug orally.
Effects on ability to drive vehicles and management mechanisms
During the period of treatment must be careful when driving vehicles and occupation of other potentially hazardous activities that require high concentration of attention and quickness of psychomotor reactions.
Overdose Carbidopa Levodopa
Treatment: gastric lavage, careful observation and ECG monitoring to detect arrhythmias, if necessary – antiarrhythmic therapy.
Drug Interactions Carbidopa Levodopa
With the simultaneous application of levodopa with beta-agonists, ditilina and medicines for inhalation anesthesia may increase the risk of cardiac arrhythmias; with tricyclic antidepressants – a decrease of bioavailability of levodopa, with diazepam, clozapine, phenytoin, clonidine, M-holinoblokatorami, antipsychotic drugs (neuroleptics ) – derivatives butirofenona, difenilbutilpiperidina, thioxanthenes, phenothiazines as well as pyridoxine, papaverine, reserpine may reduce antiparkinsonian action; with lithium therapy increases the risk of dyskinesias and hallucinations, with methyldopa – aggravating side effects.
With the simultaneous application of levodopa with inhibitors (except for MAO inhibitors type B) are possible circulatory disorders (receiving MAO inhibitors should be discontinued for 2 weeks). This is due to the accumulation under the influence of levodopa of dopamine and norepinephrine, which inhibited the inactivation of MAO inhibitors, and high probability of arousal, increased blood pressure, tachycardia, facial flushing and dizziness.
Patients receiving levodopa, the application of tubocurarine increases the risk of significant decrease of blood pressure.
Iron salts may decrease the bioavailability levodoy and carbidopa, the clinical significance of this interaction is unknown.
Although metoclopramide increases the bioavailability of levodopa, accelerating gastric emptying, however it may adversely affect disease control due to its antagonism of dopamine receptors.
