Pramipexole

Chemical name

(S)-2-Амино-4,5,6,7-тетраги��ро-6-(пропиламино)бенз отиазол

Gross

C10-H17-N3-S

Characteristics

White or almost white powder substance. Melting it is in the range of ^ 296 degrees to 301 degrees] and by corruption. Solubility in water of more than 20% in methanol-about 8%, in ethanol-about 0.5%, almost nerastvorim in dihlormetane.

Of drugs

The drugs - противопаркинсоничес кое. Neergotaminovy agonist dofamine receptors. Vsokoseleguo dofaminove stimulates receptors in the body polostom predominantly D_3-podtip family D_2-retseptorov (while delivering a lesser affinnostew to D_2- and D_4-podtipu D_2-retseptorov family). According to the электрофизиологическ их Studies on animals dofaminove activates receptors in the body polostom and black substance, thus affecting the level of impoulsation in neuron striped Tela.umenishaet gravity propulsion violations at any stage of the disease. Ters disease symptoms (bradikinesia, tremor, rigidity, etc.), reduces the severity motor fluctuations and diskinezi. Decreases the severity of depression and neiropsihologicakih violations, including Paul Funksii.v experimental work has been demonstrated neiroproteguoe Effects (stimulates production neirotroficskih factors, etc.), thus slowing degeneration dofaminergicakih Neironov.primenaetsa with Parkinson's disease, both in terms alone, and in combination with levodopa. Pramipeksola effectiveness has been shown in randomized controlled studies among patients with early stage Parkinson's disease, is not receiving treatment at the same time drug levodopa, as well as in patients with raised stage disease, while a drugs levodopa. Using pramipeksola combination therapies can reduce dose of levodopa (in a number of studies, almost one third), with the improving II ( "The day-to-day activity") and III ( "Motor function") of the scale of UPDRS (unified scale of the BP), and reducing the duration of the shutdown period. " Effectiveness pramipeksola use in the treatment of acquired troubled Nog.bystro and completely absorbed from the Digestive tract. C_max is about 2 hours Away increases the time of C_max at 1 h, but does not affect the completeness removals. Absolute bioavailability, more than 90% of the approximately 500 litres, linking a plasma protein is 15%. Collected in erythrocytes (the ratio of concentration in erythrocytes to the concentration in the plasma or 2). Equilibrium concentration in the blood is achieved within 2 days after the start of the reception. T_1/2 young healthy volunteers, 8 h, the older volunteers, 12 hours Excreted mainly kidneys (renal secretiruetsa kanalzami possibly via transport of organic cations), "90% imposed dose virtually unchanged to. Kidney klirens about 400 ml / min. Ground among women was 30% lower than that of men (which may be due to differences in body weight). In patients with Parkinson's disease klirens could be lowered by 30% as compared with healthy elderly volunteers. Older people (65 years and above) klirens 30% lower and T_1/2 increased by 40% compared with T_1/2 young healthy volunteers (age 40 years or more). Moderate violation of the kidney (Cl creatinine 40 ml / min) klirens reduced by 60% compared with healthy tested, with the express violation (Cl creatinine 20 ml / min) to 75%. Clearance is low in patients in Gemodialize.v 2-godichnykh studies on animals (mice and rats) have been detected cancer-causing. There has been mutagennogo actions tests in vitro and in Vivo.pri fertility study in rats receiving pramipexol dose of 2.5 mg / kg / day (5.4 times the therapeutic dose in mg / m ^ 2 for humans), the animals were chosen for estrus and inhibition of implantation. These effects were related to the reduction in the level of serum prolactin (necessary for implantation and preservation of early pregnancy in rats). Pregnant rats receiving pramipexol dose of 2.5 mg / kg / day (5.4 times the therapeutic dose in mg / m ^ 2 for humans), an inhibition of implantation. The pregnant rats at the dose of 1.5 mg / kg / day during organogeneza (from 7 to 16 day pregnancy) sopr

Indications

Parkinson disease.

Restrictions on the use of

Pregnancy, breast-feeding.

Pregnancy and lactation

Perhaps if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies on the use during pregnancy did not). At the time of treatment should stop breast-feeding (data on the penetration of breast milk in humans lacking).

Contraindications

Гиперчувствительност ь.

Side-Effects

From the nervous system and sensory organs : fatigue, drowsiness / insomnia, hallucinations, delirium, amnesia sputannosti consciousness, dizziness, anxiety, depression, disfagia, distonia, akatizia, violations thinking suizidalnaya spirit, ekstrapiramidnyi syndrome, diskinesia, tremor, gipostesia, hypokinesia, mioclonus, ataxy, the coordination of movements, diplopia, paralysis ccomodation, conjunctivitis, the weakening of hearing; in a few cases (with the rapid dose reduction or abolition of harsh), neirolepticeski malignant syndrome (hyperthermia, muscle rigidity, violation of consciousness, autonomic lability). From the circulatory system and blood (blood, gemostaz) : ortostatical gipotenzia, tachycardia, Aritmia.so the respiratory system : dizziness, rhinitis, pharyngitis, sinusit, grippopodobnyy syndrome, increased Kashl.so part of the intestine : nausea, vomiting, neuralgia, flatulence, diarrhea, dry mouth, anorexia, Zapor.so the musculoskeletal system : gipertonus muscles cramping muscles in the legs, muscle apnoea, male, arthritis, Bursit.prochie : fever; peripheral edema, sweating, increased vnutriglaznogo pressure decrease libido, impotence, decreased body mass index; increasing urination, infections urinary tract; pain syndrome, including pain in the chest, pain in the abdomen, pain in the sacral spine division, the pain in the neck; change of voice; Enhancement of CFC; allergic reactions.

Patient interaction

Increases C_max levodopa by 40% and reduces the time to achieve it from 2.5 to 0.5 hours Zimetidin increases pramipeksola AUC (50%) and T_1/2 (40%). Together admission PP, which secretiruyutza Ackermann transport system kidney (ranitidine, diltiazem, triamteren, verapamil, quinidine, and quinine, etc.) klirens pramipeksola reduced by about 20%. Dopamine antagonists, including neiroleptiki (fenotiazina, butirofenona, tioksantena) and metoclopramide, may reduce the effectiveness.

Overdosing

Treatment : washing stomach, maintenance therapy in / in a liquid ECG monitoring; If you see any signs of central nervous system can be displayed neiroleptiki (fenotiazina, butirofenona). Specific antidote unknown.

Precautions

Patients should be alerted to the risks of hallucinations (especially older patients), the development Orthostatic hypotension (at the beginning of treatment, or if the dose). Be wary appoint patients with renal failure in history. With very serious violation of the kidney (Cl creatinine less than 15 ml / min and in patients at gemodialise) Clinical applications pramipeksola inadequate. Pramipeksola lifting should be done gradually (within 1 week). It should not be used in conjunction with the drivers of vehicles and people skills relate to the high concentration of attention.

Dosing and Administration

Inside, 3 times a day. Initial dose at any stage of Parkinson's disease on the 0.375 mg / sut. The dose increase, but not more than once every 5-7 days (to achieve an optimal therapeutic effect, taking into account the emergence of side-effects) : 2nd week of treatment, 0.75 mg / day, the third week, 1.5 mg / day and further increasing the dose of 0.75 mg per week to a maximum of 4.5 mg / sut. Supporting - dose of 1.5-4.5 mg / day in 3 admission. In combination with levodopa dose of levodopa could be Snijena.u patients with renal insufficiency dose depends on creatinine clearance : if Cl creatinine greater than 60 mL / min for the 57 mg three times a day (maximum dose, 1.5 mg three times daily) 59 ml / min for 57 mg twice a day (maximum of 1.5 mg twice a day), 15-34 ml / min, 0,125 mg once a day (a maximum of 1.5 mg once a day).

Literature

1. Gecht AB Treatment for the disease Паркинсона//Фарматека .- 2001 - N 8 .- C. 33-38.2. Gorkov VA Prospects for the early release agonist at the time of Паркинсона//Фарматека .- 2001 - N 8 .- C. 39-42.3. Dr. Levin, Fedorov NV, Smolensev IG etc. Influence agonists dofamine receptors on the severity neiropsihologicakih disorders in patients with Parkinson's disease / / The Russian congress "New technologies in neurology and neurosurgery Millennium" 7-9 December 1999 .- C. 115-116.4. Dr. Levin, Fedorov NV, Smolensev IG Agonists dofamine receptors in the treatment of Parkinson's disease / / RMJ .- 2000 .- T. 8-N-16 S. 643-646.5. Nodel 17:29, tell DV, Ahno NN Treatment of propulsion in the latter stages of Parkinson's disease / / The Jubilee scientific conference with international participation, the Department 140-letiu mental and nervous diseases Military Academy "Contemporary approaches to the diagnosis and treatment of nervous and mental diseases" 14-16 June 2000 .- C. 418.6. Nodel 17:29, tell DV The Mirapexa with Parkinson's disease / / New drugs-1999-Volume 8 .- C. 3-6.7. Obukhov AV Syndrome troubled legs / / RMJ. Parkinson's Disease-2001 .- C. 16-19.8. Fedorov NV Treatment of Parkinson's disease / / RMJ. Parkinson's Disease-2001 .- C. 24-33.9. Shirokov EA Mirapex in the treatment of Parkinson's disease / / RMJ .- 2001 .- N 7-8 .- C. 328-329.10. Stock VN, Fedorov NV Current treatment guidelines parkinsonizma / / RMJ - SDA-N-13 C. 837-844.11. Ahno N., R. Nodel Current therapy for Parkinson's disease / / RMJ .- 2000 .- T. 8-N-10 C. 418-425.12. Ahno N., R. Nodel, tell DV and others showing agonist Mirapexa with Parkinson's disease / / RMJ. Parkinson's disease-2001 - C 34-38.

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