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Dopamine receptor agonist with high selectivity and specificity associated with dopamine receptor subgroups D2, has a strong affinity for D3 receptors. It reduces sustanon the deficit of motor activity in Parkinson’s disease due to the stimulation of dopamine receptors in the striatum. Pramipexole inhibits the synthesis, release and metabolism of dopamine, protects dopamine neurons from degeneration that occurs in response to ischemia or methamphetamine neurotoxicity.

Reduces prolactin secretion (dose-dependent).
With prolonged use (more than 3 years) signs of declining efficacy not established.
Pharmacokinetics
Pramipexole after ingestion rapidly and completely absorbed. The absolute bioavailability is greater than 90% and the maximum plasma concentration observed 1-3 hours. The rate of absorption is reduced when having a meal, but at the total absorption does not affect food intake. For pramipexole characteristic linear kinetics and a relatively small variation in concentrations between individual patients.

Indications
Treatment of Parkinson’s disease symptoms (monotherapy or in combination with levodopa).
Contraindications
: Hypersensitivity to pramipexole or to any component of the formulation.
Precautions
Kidney failure, hypotension.
In the study of carcinogenicity in animals showed degeneration and loss of photoreceptor cells in the retina of albino rats. The potential significance of this effect in humans has not been established, but it can not be ignored due to a possible violation of the mechanism (blurring of the disc), universal for all vertebrates.

Maintenance treatment:
The individual dose should be in the range from 0.375 mg to 4.5 mg per day. Both early and late stages of the disease the drug was effective, starting with a daily dose of 1.5 mg. It is not ruled out that in some patients doses above 1.5 mg per day may provide an additional therapeutic effect, especially at the late stage of the disease when levodopa dose reductions shown.

Treatment discontinuation:
Pramipexole should be withdrawn gradually over several days.

Doses for patients receiving concomitant therapy with levodopa:
If concurrent therapy with levodopa, it is recommended as the dose, as well as during maintenance therapy with pramipexole reduce the dose of levodopa. This is necessary to avoid excessive dopaminergic stimulation.

Doses for patients with renal failure: For the initial therapy: patients with a creatinine clearance greater than 50 mL / min does not require reduction of the daily dose. If creatinine clearance 20 – 50 mg / ml initial drug dose administered daily in two steps, starting with 0.125 mg 2 times per day (0.25 mg daily). When creatinine clearance less than 20 ml / min the daily dose of the drug is prescribed once a day, starting at 0.125 mg.

If, during maintenance therapy of renal function decreases, the daily dose reduced by the same percentage by which the creatinine clearance decreased, i.e. If creatinine clearance is reduced by 30%, the daily dose should be reduced by 30%. The daily dose can be divided into two stages, if creatinine clearance is in the range of 20 – 50 ml / min, or taken once a day, if creatinine clearance less than 20 mL / min.

Doses for patients with hepatic insufficiency: there is no need to reduce the dose in patients with hepatic insufficiency.

Side effects of
the early stages of the disease more common adverse events were somnolence and constipation, and at a later stage of the disease when treatment in combination with levodopa were more common dyskinesia and hallucinations. These adverse events decreased with continued therapy; constipation, nausea and dyskinesia tended to disappear.

From the nervous system: confusion, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, altered mental status, akathisia, vegetative lability, abnormal thinking), insomnia, extrapyramidal syndrome, dizziness, fatigue, amnesia, hypoesthesia, dystonia, myoclonus, tremor, depression, anxiety, ataxia, hypokinesia, delusions, suicidal thoughts.

From the musculoskeletal system: hypertonus muscles, cramps in the leg muscles, muscle twitching, arthritis, bursitis, male, pain in the lumbosacral spine, chest pain, pain in the neck.

From the digestive system: loss of appetite, dysphagia, dyspepsia, abdominal pain, flatulence, diarrhea, dry mouth, vomiting.

The respiratory system: pharyngitis, sinusitis, rhinitis, flu-like symptoms, shortness of breath, increased cough, voice alteration.

With the genitourinary system: urinary tract infection, increased frequency of urination.

Since the cardiovascular system: orthostatic hypotension, tachycardia, increased creatine sustanon kinase activity, angina, arrhythmia.

From the senses: conjunctivitis, paralysis of accommodation, diplopia, cataract, increased intraocular pressure, impaired hearing.

Allergic reactions. Other: hyperthermia, retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, weight loss. increased sweating.

Hypotension in the treatment of drug mirapex did not develop more frequently than with placebo. For some patients hypotension may occur at the beginning of the treatment, especially if the dose is increased too quickly.

Cases of Insomnia and peripheral edema.

Reported cases of sleep during daily activities (including while driving), which sometimes resulted in accidents.

Application mirapex drug can cause a change (increase or decrease) libido.

The literature describes cases of pathological craving for gambling in patients receiving pramipexole (especially in high doses), which was stopped after discontinuation of the drug.

Overdose
Cases of severe overdose not described. Expected symptoms: nausea, vomiting, hyperkinesia, hallucinations, agitation, and decreased blood pressure.

Treatment: gastric lavage, symptomatic therapy. Assigned antidote does not exist. If there are indications of stimulation of the nervous system, it may be recommended by neuroleptics. The effectiveness of hemodialysis has not been established.

Drug interactions
Pramipexole a small extent (<20%) is bound to plasma proteins and undergoes biotransformation. Therefore, interactions with other medications affecting plasma protein binding or elimination due to biotransformation are unlikely.

Drugs that inhibit the secretion of cationic active agents through the renal tubules (e.g., cimetidine) or which themselves are derived by an active secretion by the renal tubules, may interact with pramipexole, resulting in reduction of clearance of one or both drugs. In the case of simultaneous use of these drugs (including amantadine) and pramipexole is necessary to pay attention to such sustanon signs of excessive dopamine stimulation as dyskinesias, agitation or hallucinations. In such cases it is necessary to reduce the dose. Diltiazem, triamterene, verapamil, quinidine, quinine, reduce the clearance of 20%.

Selegelin and levodopa do not influence the pharmacokinetics of pramipexole. Pramipexole increases levodopa concentration and reduces TSmax from 2.5 to 0.5 hours. Interaction with anticholinergic drugs and amantadine has not been studied. However, interaction with amantadine is possible because drugs have a similar mechanism of excretion. Anticholinergic drugs mainly output pathway, so interactions with pramipexole unlikely.

With increasing doses of pramipexole recommended dose reduction of levodopa dosage while other antiparkinsonian drugs should be maintained at a constant level. Dopamine antagonists (phenothiazines, butyrophenone, thioxanthenes, metoclopramide) decrease the effectiveness of treatment.

Because of the potential cumulative effects, patients should be advised to exercise caution when taking other sedating medicinal products or alcohol in combination with the drug mirapex, as well as while the reception of medicines, increasing the concentration of the pramipexole plasma (eg, cimetidine).

Cautions
hallucinations and confusion – known side effects in the treatment of dopamine agonists and levodopa. When applying mirapex drug in combination with levodopa in the later stages of the disease hallucinations were observed more frequently than pramipexole monotherapy in patients at early stages of the disease. Patients should be informed of the possibility of hallucinations (mostly visual), which may affect the ability to drive a car.

Care should be taken if the patient of severe cardiovascular disease. Because of the risk of orthostatic hypotension during dopaminergic therapy to control blood pressure, especially at the beginning of treatment.

Patients should be warned of the possible sedative effect of the drug. Reported cases of sleep during daily activities (including while driving), which sometimes resulted in accidents. In some cases, falling asleep was not preceded by a state of drowsiness, which are often observed in patients taking pramipexole doses higher than 1.5 mg / day, and that, in accordance with the latest knowledge in the field of sleep physiology, is always preceded by a sleep.

A clear relationship between the severity of sleepiness and duration of treatment was not traced. Some patients received both drugs with other potentially sedative properties. In most cases (according to available data) after dose reduction or discontinuation of treatment in the future episodes of falling asleep was not observed.

It was reported that the sudden cessation of therapy was observed symptom, which allows to assume neuroleptic malignant syndrome.

Effects on ability to drive and use machinery
Patients should be informed of the possibility of hallucinations (mostly visual), which may affect the ability to drive a car.

In applying the drug may develop sedative effects, including drowsiness and falling asleep during daily activities. Since drowsiness is a common adverse event with potentially serious consequences, patients should not drive a car or operate other complex machinery until such time until they gain sufficient experience of treatment mirapex to assess affects whether it is negative or not their mental and / or locomotor activity. Patients should be advised that if during the treatment they experience increased sleepiness or episodes of falling asleep during daily activities (ie during conversation, food, etc.), they have to give up driving, working with machinery, and sustanon seek medical advice. online anabolic steroids pharmacy

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