2010/06/05

Tramadol+Paracetamol

Group Affiliation:
Analgesic (analgesic with a mixed mechanism of action of non-narcotic analgesic + vehicle)

Description of the active substance (INN):
Tramadol + Paracetamol

Dosage form:
coated tablets

Mode of action:
Combined analgesic containing tramadol and acetaminophen. Tramadol - has a central action and the action on the spinal cord (promotes opening of K + and Ca2 +-channels, causing hyperpolarization of the membrane and inhibits the conduct pain impulses), increases the effects of sedative drugs. Activates opioid receptors (mu, delta, kappa) on the pre-and postsynaptic membranes of nociceptive afferent fibers in the brain and GI tract, inhibits reverse neuronal capture of catecholamines in the CNS. Paracetamol - non-opioid analgesics, blocks COX mainly in the central nervous system, affecting pain centers and thermoregulation. Does not cause gastrointestinal irritation, no effect on water-salt metabolism, since no effect on the synthesis of Pg in the peripheral tissues. With paracetamol there is a rapid analgesia, whereas tramadol provides prolonged effect. Synergism analgesic effect of two active ingredients reduces the risk of side effects.

Indications:
Pain (moderate to severe intensity of various etiologies, including inflammatory, traumatic, vascular origin). Pain relief during painful diagnostic or therapeutic interventions.

Contraindications:
Hypersensitivity, acute alcohol intoxication or drugs depressing the central nervous system, hypnotics, narcotic analgesics and psychotropic drugs, simultaneous reception of MAO inhibitors (and within 2 weeks after withdrawal), severe hepatic and / or renal failure (CC <10 mL / min) uncontrolled epilepsy therapy, the syndrome of "cancellation" of narcotic drugs, children's age (14 years), pregnancy, laktatsii.C caution. Schoch, head injury, intracranial hypertension, susceptibility to convulsions (with controlled epilepsy drug may be used only emergencies), confusion of unknown etiology, respiratory failure, simultaneous reception of psychotropic and other analgesic drugs of the central action of local anesthetics, biliary tract disease, benign bilirubinemia, hepatitis, lack of glucose-6-phosphate dehydrogenase, alcoholic liver disease, alcoholism, drug addiction, symptoms of "acute" abdomen of unknown origin, advanced age (older than 75 years).

Side effects:
Allergic reactions: rash, itching, Quincke's edema, rash, bullous eruption. On the part of the nervous system: dizziness, headache, lethargy, paradoxical CNS stimulation (nervousness, agitation, anxiety, tremors, muscle spasms, euphoria, emotional lability, hallucinations), drowsiness, sleep disturbances, confusion, poor coordination of movements, spasms of central origin (while the appointment of antipsychotic drugs), depression, amnesia, violation of cognitive function, paresthesias, unsteadiness of gait. On the part of the digestive system: dry mouth, nausea, vomiting, flatulence , abdominal pain, constipation, diarrhea, difficulty swallowing, increased activity of "liver" enzymes, usually without the development of jaundice. On the part of the SSA: tachycardia, orthostatic hypotension, syncope, collapse. From the Endocrine: hypoglycemia, hypoglycemic coma until . mochevydelitelnoy the part of the system: difficulty urinating, dysuria, urinary retention. Chronic administration at doses considerably higher than recommended - Nephrotoxicity (interstitial nephritis, papillary necrosis). On the part of the senses: blurred vision, taste. The respiratory system: dyspnea. On the part of the skin: erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome). From the side of hematopoiesis: sulfgemoglobinemiya. Chronic administration at doses considerably higher than recommended - aplastic anemia, pancytopenia, agranulocytosis. Other: Sweating, weakness, fatigue, menstrual disorders. When long-term use - the development of drug dependence (irritability, phobias, nervousness, sleep disturbances, psihotomotornaya activity tremor, discomfort in the stomach or intestine). In sharp end of reception may develop - syndrome "cancel." Overdose. Symptoms of overdose of tramadol: miosis, vomiting, collapse, coma, convulsions, depression of the respiratory center, sleep apnea. Symptoms of an overdose of paracetamol: (acute overdose develops within 6-14 h after administration of paracetamol, chronic - after 2-4 days in case of excess dose). Symptoms of acute overdose: diarrhea, loss of appetite. Symptoms of chronic overdose: cerebral edema, hypocoagulation, the development of DIC-syndrome, hypoglycemia, metabolic acidosis, arrhythmia, collapse; rare - abnormal liver function, which is developing at lightning speed and can be complicated by kidney failure (renal tubular necrosis). Treatment: gastric lavage and reception Enterosorbents (activated carbon, polyphepan), the maintenance functions of the SSA, to ensure the airway. When respiratory depression (symptom overdose tramadol) - naloxone, in convulsions - diazepam. Hemodialysis or hemofiltration during intoxication tramadol ineffective. If symptoms of overdosage of paracetamol: An Introduction donators of SH-groups and precursors of glutathione synthesis - through methionine 8-9 h after the overdose, and N-acetylcysteine have - after 12 pm The need for further introduction of methionine in / introduction N-acetylcysteine is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after the reception.

Dosage and administration:
Inside, regardless of the meal, swallow a whole (not crush or chew), washed down with liquid. Dosage regimen and duration of treatment are selected individually depending on the severity of pain. For adults and children over 14 years, the recommended initial single dose - 1-2 tablets with an interval between doses of the drug - at least 6 hours maximum daily dose - 8 tablets (300 mg tramadol and 2.6 g of paracetamol). In elderly patients (aged 75 years and older) can be used usual doses. However, with the possibility of a delayed launch, the interval between taking the drug may be increased. In patients with renal insufficiency (CC 10-30 ml / min) interval between doses must be at least 12 h. Since Tramadol very slowly excreted during hemodialysis or hemofiltration, the use of the drug after the dialysis session to maintain the analgesic effect is required. For a moderate abnormal liver function should be to increase the interval between doses of the drug.

Cautions:
Patients who are prone to abuse drugs or of drug addiction must be treated under close medical supervision in a short period. During drug treatment is recommended to avoid receiving ethanol. The risk of developing hepatotoxicity and overdose of paracetamol increases in patients with alcoholic hepatosis. During the long-term care necessary to monitor patterns of peripheral blood and liver functional state. At the time of treatment should refrain from driving motor vehicles and classes of potentially hazardous activities that require high concentration and quickness of psychomotor reactions.

Interaction:
The combined use of opioid agonist-antagonists (buprenorphine, nalbufinom, pentazocine), reduces the analgesic effect as a result of competing actions on the receptors, but also raises the risk of the syndrome of "cancel." Drugs, CNS depressants (including sleeping pills, tranquilizers), ethanol - increases the side effects characteristic of tramadol. Inductors microsomal oxidation (including carbamazepine, phenytoin, ethanol, barbiturates, rifampicin, fenilbutazon, tricyclic antidepressants) reduce the analgesic effect and its duration. naloxone activates respiration, eliminating the analgesia caused by taramadolom. Prolonged use of barbiturates reduce the effectiveness of paracetamol. Ethanol contributes to the development of acute pancreatitis. Prolonged joint use of paracetamol and other NSAIDs increases the risk of nephropathy and renal papillary necrosis, onset of end-stage renal failure. Simultaneous long-term assignment in high doses of paracetamol and salicylates increases the risk of kidney cancer or bladder. Diflunisal increases the plasma concentrations of paracetamol by 50% - the risk of hepatotoxicity. Concomitant use with drugs that reduce epileptic threshold (including selective inhibitors of reverse serotonin, tricyclic antidepressants, antipsychotics) - the risk of seizures. Drugs that inhibit CYP3A4 (ketoconazole and erythromycin) may slow the metabolism of tramadol (N-demethylation), and active O-demethylated metabolite. Quinidine increases the concentration in blood plasma tramadol and reduces the concentration of O demethylated metabolite due to competitive inhibition of isoenzyme CYP2D6. microsomal oxidation inhibitors (cimetidine) decrease the risk of hepatotoxicity. the rate of absorption of paracetamol is increased when taking metoclopramide or domperidone and decreases when receiving kolestiramina. preparation for admission to a long time increases the effect of indirect anticoagulants (warfarin, etc. coumarin), which increases the risk of bleeding.