Flupirtine
When ATH:
N02BG07
Pharmacological action
Centrally acting analgesic. It is a selective activator of neuronal potassium channel. Not applicable to opioids, is not addictive and habituation.
Renders analgesic, muscle relaxant and neuroprotective effect, based on indirect NMDA antagonism (N-methyl-D-aspartate)-Receptor, activation of the descending pain modulation mechanisms and GABA-ergic processes.
At therapeutic concentrations, flupirtine does not bind to α1-, a2-adrenoreceptor, serotonin 5HT1-, 5NT2-receptors, dopamine, benzodiazepine, opioid, central m- and n- holinoretseptorami.
Antispasmodic effect on the muscle to block the transfer of excitation in the motor neurons and intermediate neurons, leading to the removal of muscle tension. This action is manifested flupirtine for many chronic diseases, accompanied by painful muscle spasms (musculoskeletal pain in the neck and back, artropatii, tension headaches, fibromyalgia).
Thanks neuroprotective properties protects neural structures from the toxic effect of high concentrations of intracellular calcium ions, due, flupirtine with the ability to cause a blockade of neuronal ion channels and calcium to reduce intracellular calcium ion current.
Pharmacokinetics
After oral administration almost completely (to 90%) and rapidly absorbed from the gastrointestinal tract.
It is metabolized in the liver (to 75% of the dose) to form the active metabolite M1 (2-amino-3-acetamino-6-[4-fluorine]-ʙenzilaminopiridin). Metabolite M1 is formed by the hydrolysis of the urethane structure (1 phase reaction) and subsequent acetylation (2 phase reaction). This provides an average metabolite 25% analgesic activity of flupirtine. Color Other metabolite (M2 – biologically inactive) formed by the oxidation reaction (I phase) p-fluorobenzyl followed by conjugation (2 phase) p-fluorobenzoic acid with glycine.
T1/2 is about 7 no (10 h for the main substance and metabolite M1), that is sufficient to provide an analgesic effect. The concentration of active substance in plasma is proportional to dose.
Write mainly kidneys (69%): 27% excreted unchanged, 28% – It saw in the metabolite M1 (acetyl metabolite), 12% – It saw in the metabolite M2 (para-acid ftorgippurovaya) and the remaining third consists of several metabolites of unknown structure. A small part of the dose excreted in the bile and feces.
Patients over the age of 65 years, compared with younger patients, an increase T1/2 (to 14 h in single dose and up 18.6 h when administered within 12 days) and Cmax respectively in plasma above 2-2.5 times.
Testimony
Acute and chronic pain syndrome in the following diseases and conditions: muscle spasm, malignant neoplasms, Primary algomenorrhea, headache, post-traumatic pain, pain in trauma / orthopedic surgery and interventions.
Dosage regimen
Dose set individually depending on the severity of pain and the patient's sensitivity to flupirtine.
Duration of use is also determined individually and depends on the dynamics of pain and treatment.
Side effect
CNS: often weak at the beginning of treatment; possible depression, sleep disorders, Sweating, anxiety, nervousness, tremor, headache; rarely – confusion, visual impairment.
From the digestive system: possible dizziness, heartburn, nausea, vomiting, constipation or diarrhea, flatulence, stomach ache, dry mouth, loss of appetite; in some cases – increase in liver transaminases, hepatitis (acute or chronic, flowing with jaundice or without jaundice, elements with or without cholestasis).
Allergic reactions: rarely – fever, rash and itching.
Contraindications
Liver failure with symptoms of encephalopathy, cholestasis, myasthenia gravis, Saint Martin's evil, pregnancy, childhood and adolescence up 18 years, Hypersensitivity to flupirtine.
Pregnancy and lactation
Contraindicated during pregnancy.
If necessary, use during lactation should decide the issue of termination of breastfeeding during treatment, tk. shows, that a small amount of flupirtine is excreted in breast milk.
Cautions
Be wary of hepatic dysfunction and / or kidney, older patients 65 years. Patients of these groups requires correction mode.
Side effects depend mainly on the dose. In many cases they disappear on their own as of the treatment, or after treatment.
In the treatment of flupirtine may be false-positive test results with diagnostic strips for bilirubin, urobilinogen and protein in the urine. A similar reaction is possible for the quantitative determination of bilirubin in the blood plasma.
When used in high doses, in some cases there may be a urine staining green, that there is clinical evidence of any pathology.
Patients with impaired hepatic or renal function should be monitored liver enzymes and creatinine in the urine.
With simultaneous use of flupirtine with drugs, which are also metabolized by the liver, It requires regular monitoring of liver enzymes.
Avoid combination use and medicaments of flupirtine, soderzhashtih paracetamol and carbamazepine.
Effects on ability to drive and operate machinery
Considering, that flupirtine can attenuate the attention and slow responses of the body recommended during treatment with refrain from driving and transport activities potentially hazardous activities, require high concentration and speed of psychomotor reactions.
Drug Interactions
Flupirtine increases the effects of sedatives, muscle relaxants, and ethanol.
Because, that flupirtine is bound to plasma proteins, to consider the possibility of displacement of the connection with the other proteins simultaneously receive drugs. At the same time show, that flupirtine displace warfarin and diazepam from its association with proteins, that while admission to flupirtine could increase their activity.
With simultaneous use of flupirtine and coumarin derivatives may increase the anticoagulant action.
