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L-DOPA

L-DOPA

Information about L-DOPA drug, how to use, dosage and side effects:

Naturally the lack of dopamine in the brain should be compensated by using the dopamine; however that is not possible because this biogenic amine after systemic implementation does not pass through the hematoencephalic barrier. L-DOPA, an amino acid and a dopamine precursor, penetrates into the brain where it is metabolized to active dopamine.

The mechanism of action

Dopamine activates the dopaminergic system in the large brain, acts on dopamine receptors. The most important two receptors of these receptors are D1 and D2

  • D1: related to the adenylate cyclase. Dopamine stimulates this enzyme and enhances synthesis of cyclic AMP, which as a second messenger realizes many effects of dopamine. Receptors of this type are localized in the zone compacta substantia nigrae, then in the presynaptic striatnim axioms which are based from the cortical neurons and dopaminergic substantia nigra cells.
  • D2: receptors are not associated with adenylate cyclase, and the effects of dopamine occurs through this type of receptor. These receptors are localized to the postsynaptic foreign neurons and Presynaptic axons of substances nigra that emanate from neurons in the basal ganglia. Affordable anti parkinsonic effects of dopamine released by stimulation likely depends on D2 receptor. Dopamine agonists used to treat Parkinson’s disease are powerful stimulators of D2-receptors.

Pharmacokinetics

L-DOPA is rapidly absorbed from the small intestine. Already 1-2 h hours after taking the medicine, the maximum concentration is achieved in blood. Half retention is 1-3h, but this time can vary significantly from person to person. About two thirds of the dose occurs within eight hours in the form of metabolites HVA (Homovanil acid) and DOPAC (hydroxy-phenyl-acetic acid).

Only a small percentage of the dose, only 1-3%, enters the brain where it is dekarbolized into dopamine, which is also the goal of therapy. The highest part of the dose dose is decarbolized into dopamine in the peripheral circulation and gastrointerstinalnokm tract, thus generated dopamine does not cross the hematoencephalic barrier. That is why L-DOPA in the treatment must be applied in large doses, if used alone. However, if it is applied with some of the DOPA-is decarbolized inhibitor such as carbidopa, benserazide, a peripheral metabolizing decreases and a larger quantity remains free and available for entry into the brain. In this way, the daily dose can be reduced to 75 percent.

Clinical use: L-DOPA is given orally and the initial dose is 1g, and then gradually increases to 5g a day. To achieve the optimal therapeutic effect several months of treatment are needed. Best results are achieved in the first years of the treatment. Later side effects occur, and the daily dose should be reduced.

At the start of the treatment the amount of dopamine increases in the striatum, what is manifested by a positive therapeutic effect. However, after an extended increase of the amount of dopamine, causing the dopamine receptor desensitization, as well as reducing their number. It is known that the usual constant increased concentrations of agonist to level of receptor occurs a low regulation of receptors ie, reducing their number. In practice, the efficacy of therapeutic effect manifests itself as an “on-off” (on-off phenomenon). In the period “off” period akinesia occurs a significant lasting several hours, and after that, during the “on period” occurs a significant improvement in motility, but sometimes with severe dyskinesia. That is when they are used the drug after 1 hour, the patient may be moving normally and that performs all functions but when effects of the drug stop, the patient suddenly gets back akiney and symptoms of Parkinson’s disease.

In order to avoid unpleasant phenomenon three procedures are applied:

  • L-DOPA is applied at shorter intervals,
  • L-DOPA is used in smaller doses but more often

The patient gives a short break from medicine Drug holiday* in a few days.

Interactions (The usage of other medicines)

A large number of drugs can significantly change the function and effect of L-DOPA and thereby reduce its therapeutic effect or provoke side effects. So for example pyridoxine accelerates decarboxylation of L-DOPA in the blood, thus reduces to a minimum amount of acid that remains to pass to the brain. During therapy with L-DOPA a reaction to is strengthened to simpatikomimetics. The combination of L-DOPA with antihypertensive drugs can cause a stronger effect of postural hypotension. Phenothiazines butyrophenone blocks central dopamine receptors, and significantly reduces the effects of L-DOPA. Giving L-DOPA with MAO inhibitors cause hypertensive crisis (due to the reduction of ozone creation dopamine). Reserpine empty depots of dopamine and thus antagonises the effect of L-DOPA. That is why you should avoid using other drugs while you are taking L-DOPA.

Side effects

  1. The most common side effects are anorexia, nausea and vomiting. Almost 80% of patients experiencing these side effects, although L-dopa is used alone. However, the percentage is much lower than 20, if L-DOPA is used on decarboxylased inhibitors.
  2. The cardiovascular system can occur as side effects, tachycardia, arrhythmias and rarely atrial fibrillation. All these undesirable effects are occurring due to the production of catecholamines in the periphery. It is possible that postural hypotension occurs, and if the patient is also taking MAO inhibitors hypertension may occur. After an extended treatment the dyskinesia occurs (Chaotic movements, athetosis, dystonia, myoclonus, and tics) on the face or extremities. These harmful effects are more often born when the L-DOPA is used together with decarboxylased inhibitors, but rather if used alone. In order to avoid this unwanted effect, patient is prescribed a break from drugs, but fewer passes on that option, because after the break of the drug in many cases can appear much heavier unwanted effects.
  3. In the course of treatment are possible mental side effects such as depression, anxiety, insomnia, confusion, illusions, hallucinations, euphoria. Here is a therapeutic measure a drug rest. But the rest of the drug is not always convenient especially with heavy parkinsonism where there is a complete immobility, may occur the venous thrombosis, pulmonary embolism and mental depression. At the start of L-DOPA treatment, one third of patients respond well to all, one third less well, while others cannot tolerate treatment or not react favorable effect.

Contraindications

L-DOPA cannot be applied among patients with any psychosis because it can get worsen. This drug should not be used either in closed-angle glaucoma. L-DOPA is also a precursor of melanin in the skin, so its application is contraindicated if the patient already has melanoma, or there is a serious doubt that it exists. Great caution is also required among patients with peptic ulcer, because L-DOPA can cause bleeding.

This drug is also known as: Dopar, Larodopa, Levodopa

For more information about drug L-DOPA visit Wikipedia: http://en.wikipedia.org/wiki/L-DOPA

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