Levodopa

Rev Neurol 1997 Dec;25(148):1957-63.
Madopar: more than 20 years.
Leiva C.
Servicio de Neurologia, Hospital General Universitario de Alicante, España..

OBJECTIVE: To review the main landmarks which led to the introduction of levadopa in the the treatment of Parkinson's disease and the impact of levadopatherapy. DEVELOPMENT: The introduction of levadopa was based on the results of basic scientific investigations in neurochemistry and neuropharmacology. In 1959 the possibility of dopamine being a neurotransmissor, and the role it plays in motor control, had been discovered. In 1960, Hornykiewiez and Ehringer published a paper on the existence of a marked deficit of dopamine in the caudate nucleus and putamen of patients with Parkinson's disease. Almost simultaneously, Birkmayer and Barbeau treated their patients with levadopa for the first time. However, levadopa was not introduced into clinical practice until 1967 and 1969 when Cotzias published papers establishing the principles of levadopatherapy as we now know it. Introduction of levadopa produced a markedly beneficial effect on the course and mortality of Parkinson's disease. However, it was soon seen that progression of the disease was not halted and that undesirable side effects appeared in patients on long-term treatment. This has led to the development of strategies to prolong the beneficial effects of levadopa and minimize its side effects. CONCLUSION: More than 25 years after the introduction of levadopatherapy, it is still the mainstay of the treatment of Parkinson's disease, in combination with other medical and surgical treatment. Definitive treatment, however, will have to wait until the cause of this illness is fully understood.

Schweiz Rundsch Med Prax 1995 Oct 24;84(43):1235-8.
Benefits of a new galenic form of levodopa and benserazide in the treatment of patients with Parkinson disease.
Dessibourg CA, Gachoud JP.
Roche Pharma Schweiz AG, Reinach.

We describe a new, water-soluble formulation of levodopa plus benserazide (Madopar LIQ) for the treatment of Parkinson's disease. Two dosage strengths are available: 100 mg levodopa plus 25 mg benserazide and 50 mg levodopa plus 12.5 mg benserazide. Pharmacokinetic data show that levodopa absorption is more rapid than with standard Madopar, resulting in a shorter time to peak plasma concentration. Other pharmacokinetic values are comparable to those obtained with the standard formulation. We discuss the clinical advantages of this new water-soluble formulation, particularly when the patient requires rapid onset of action for morning or circadian akinesia. The indications of this formulation in patients with dysphagia and in other clinical situations, e.g. during the postoperative period and for levodopa dosage adjustment in ambulatory care, are discussed.

GENERIC NAME: levodopa
BRAND NAME: Madopar

DRUG CLASS AND MECHANISM: Levodopa is a combination of two drugs, levodopa and carbidopa. Levodopa-carbidopa is used in the treatment of Parkinson's disease. Parkinson's disease is believed to be related to low levels of dopamine in certain parts of the brain. When levodopa is taken orally, it crosses through the "blood- brain barrier." Once it crosses, it is converted to dopamine. The resulting increase in brain dopamine concentrations is believed to improve nerve conduction and assist the movement disorders in Parkinson disease. Carbidopa does not cross the blood-brain barrier. Carbidopa is added to the levodopa to prevent the breakdown of levodopa before it crosses into the brain. The addition of carbidopa allows lower doses of levodopa to be used. This reduces the risk of side effects from levodopa such as nausea and vomiting. This combination medicine was approved by the FDA in 1988.

PREPARATIONS: Oval tablets (doses stated are for levodopa/carbidopa): 100mg/10mg, 200mg/20mg, 200mg/25mg, 250mg/ 25mg, and a sustained-release preparation (Sinemet CR) containing 200mg/50mg.

STORAGE: Tablets should be kept at room temperature, 15- 30°C (59-86°F).

PRESCRIBED FOR: Levodopa-carbidopa is indicated for the management of Parkinson's disease.

DOSING: Levodopa-carbidopa is taken several times per day. It may be administered with food to reduce the likelihood of nausea. However, a high-protein diet may reduce its absorption.

DRUG INTERACTIONS: The use of amantadine (Symmetrel), benztropine (Cogentin), procyclidine (Kemadrin), or trihexyphenidyl (Artane) with levodopa-carbidopa can enhance the anti- Parkinson's effects of levodopa. Droperidol, haloperidol (Haldol), loxapine (Loxitane), metoclopramide (Reglan), phenothiazines such as prochlorperazine (Thorazine); thioxanthenes as thiothixene (Navane) inhibit dopamine in the brain. These drugs, therefore, can worsen Parkinson's disease and reverse the beneficial effects of levodopa. Methyldopa (Aldomet) and reserpine also can interfere with the beneficial actions of levodopa- carbidopa and can increase the risk of side effects.

Phenytoin (Dilantin) can increases the break-down of levodopa- carbidopa, reducing its effectiveness.

Use of levodopa-carbidopa with monoamine oxidase inhibitors (MAOI's) antidepressants, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane), can result in severe and dangerous elevations in blood pressure. MAOI's should be stopped 2-4 weeks before starting levodopa-carbidopa therapy.

The side effects associated with levodopa, including dizziness upon rising, confusion, movement disorders, nausea, and hallucinations, all can be increased by selegiline (Eldepryl).

PREGNANCY: Although there are no human studies that have examined the effects of levodopa-carbidopa on the fetus, animal studies have shown adverse effects. Therefore, in prescribing levodopa- carbidopa for a pregnant woman, the physician must weigh the potential risks to the fetus against the potential benefits to the mother.

NURSING MOTHERS: Levodopa is distributed into breast milk. It also may inhibit production of milk. It is generally recommended that levodopa-carbidopa should not be given to women who are breast- feeding.

SIDE EFFECTS: Most patients receiving levodopa-carbidopa experience side effects, but these are usually reversible. Occasional involuntary movements are the most common of the serious side effects of levodopa-carbidopa therapy. These may include chewing, gnawing, twisting, tongue or mouth movements, head bobbing, or movements of the feet, hands, or shoulder. These may respond to a reduction in the dose. Muscle twitching, dizziness, muscle jerks during sleep, and hand tremor also may occur. Various psychiatric disturbances may occur during levodopa-carbidopa therapy. Such disturbances include memory loss, anxiety, nervousness, agitation, restlessness, confusion, inability to sleep, nightmares, daytime tiredness, mental depression or euphoria.

Gastrointestinal side effects are common in patients receiving levodopa-carbidopa. Nausea, vomiting, loss of appetite, and weight loss may occur. Patients may experience dizziness upon standing up, associated with a drop in blood pressure. Fortunately, the body develops tolerance to this side effect within a few months.

Infrequently, patients may develop a drop in white blood cell count during levodopa-carbidopa therapy. This is a cause to temporarily, if not permanently, stop treatment.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.

Madopar medicine is made up of benserazide and madopar levodopa and is used basically for treatment of Parkinson's disease. This medicine acts as a substitute for the required content in the nervous system which is lessen down due to the disease hence improving movement activities and muscle control in body. But, people under 25 years of age, pregnant women, persons who are highly reactive to allergies, the one who has heart, kidney, eye or any endocrine disease or someone who as taken MAO very recently should firmly avoid taking this medicine.

Antacids, anesthetics, opioids, blood pressure and mental disorder lowering drugs, metoclopramide and some other such medicines have a tendency to make this madopar tablets inactive toward body. Madopar Side Effects are like, red urine, dizziness, palpitations, looseness, confusion, skin rash or itching, tiredness, hallucination, agitation, nausea, vomiting and many more. But they are negligible if properly treated.

Madopar dosage is of 125 mg HBS and 250 mg. Carbidopa is also combiningly given with benseazide for the treatment. There are no such side effects of madopar but if in case you find any then you must consult you doctor without wasting any time. If you are suffering from glaucoma, diabetes, any psychological disorder, such as depression etc then also you should tell you doctor before taking these drugs. You want to be pregnant or you are pregnant in both the cases physician's advice is must, because there are possibilities that this drug will have bad effects on your health when they are combined with other medicines that you take during pregnancy time.

How much dosage you should take of madopar is to be asked by the doctor. You should not take medicines without doctor's advice. Until and unless it is prescribed by the doctor one should not take it.