Tramadol
Description of the active substance Tramadol.
Formula: C16H25NO2, chemical name: trans-(±)-2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (in the form of hydrochloride).
Pharmacological group: neurotropic drugs, opioids, their analogues and antagonists, opioid non-narcotic analgesics.
Pharmacological action: analgesic (opioid).
Pharmacological properties
Tramadol has an activating effect on opiate receptors (delta-, mu- and kappa-) on the post- and presynaptic membranes of the afferent fibers of the nociceptive system, in the spinal cord and brain, as well as in the gastrointestinal tract. Tramadol promotes the opening of calcium and potassium channels, hyperpolarization of membranes and slows down the nerve impulse. Stabilizes the content of catecholamines in the central nervous system and slows down their destruction.
The analgesic effect of tramadol is due to a decrease in the activity of the nociceptive and an increase in the antinociceptive systems of the body. Tramadol has a sedative effect, depresses the cerebral cortex, respiratory and cough centers, excites the nuclei of the oculomotor nerve, the starting zone of the vomiting center; causes spasm of the smooth muscles of the sphincters.
When ingested, tramadol is fully (90%) and rapidly absorbed. The absolute bioavailability of tramadol is 68%. After 2 hours, the maximum concentration in the blood is reached. The volume of tramadol distribution depends on the method of its administration and amounts to 203 and 306 liters after intravenous or oral administration, respectively. It binds to plasma proteins by 20%. Tramadol penetrates through tissue barriers, including the placental and blood-brain barrier, and is excreted in breast milk. In the liver, tramadol is biotransformed with the participation of CYP3A4 and CYP2D6 isoenzymes by O- and N-demethylation with further conjugation. Tramadol has 11 metabolites, one of which is mono-O-desmethyltramadol, which has pharmacological activity. Tramadol is excreted mainly (90%) by the kidneys (unchanged 30%) and 10% by the intestines. With violations of the functional state of the kidneys (with creatinine clearance less than 80 ml / min) and the liver, tramadol elimination slows down.
Indications
Pain syndrome of severe and moderate intensity (including injuries, malignant neoplasms, in the postoperative period); for anesthesia during painful therapeutic or diagnostic measures.
Method of administration of tramadol and dose
Tramadol is taken orally (regardless of food intake), administered intramuscularly, intravenously, subcutaneously, rectally. The dosage is individual, depending on the nature and intensity of pain; the duration and regimen of therapy should be established only by a doctor. Inside, the usual initial dose for patients older than 14 years is 50 mg (repeatedly, in the absence of effect — after 0.5 – 1 hour). Parenterally, 50-100 mg is administered, rectally — 100 mg (repeated administration of candles is possible only after 4-8 hours). The maximum daily dose is 400 mg (in rare cases it can be increased to 600 mg). Children 1-14 years old parenterally or orally (drops) — a single dose is 1-2 mg / kg, the maximum daily dose is 4-8 mg / kg. Patients who have liver and kidney diseases, as well as elderly patients, it is necessary to increase the interval between the administration of single doses.
Contraindications to use
Hypersensitivity; risk of suicide, conditions that are accompanied by severe depression of the central nervous system or respiratory depression (poisoning with sleeping pills, alcohol, narcotic analgesics and other psychoactive drugs); simultaneous administration of MAO inhibitors (as well as a period of 14 days after their withdrawal), propensity to substance abuse, severe renal or / and liver failure, breast-feeding (with prolonged use), pregnancy (1 trimester), age up to 1 year (for parenteral route of administration) and up to 14 years (for oral administration).
Restrictions on use
Opioid addiction, increased intracranial pressure, disorders of consciousness of various origins, epilepsy, traumatic brain injury, disorders of the functional state of the liver or / and kidneys, abdominal pain of unknown origin (acute abdomen).
Use during pregnancy and lactation
Taking tramadol is contraindicated in the 1st trimester of pregnancy. In the 2nd and 3rd trimesters of pregnancy, while breastfeeding, the use of tramadol is possible, but if the expected effect of treatment is higher than the possible risk to the fetus and only under strict medical supervision.
Side effects of tramadol
Digestive system: nausea, dry mouth, vomiting, abdominal pain, flatulence, diarrhea/constipation, difficulty swallowing;
nervous system and sensory organs: dizziness, increased sweating, fatigue, weakness, lethargy, headache, paradoxical stimulation of the central nervous system (nervousness, anxiety, agitation, tremor, euphoria, muscle spasm, hallucinations, emotional lability), sleep disturbance, drowsiness, confusion, gait instability, impaired coordination of movements, seizures of central genesis, depression, paresthesia, cognitive impairment, amnesia, taste and vision disorders;
circulatory system: tachycardia, syncope, orthostatic hypotension, collapse;
genitourinary system: difficulty urinating, urinary retention, dysuria, menstrual disorders;
allergic reactions: itching, exanthema, urticaria, bullous rash;
other: shortness of breath;
with abrupt withdrawal — withdrawal syndrome, with prolonged use — drug dependence.
Interaction of tramadol with other substances
Tramadol enhances the effect of ethanol (alcohol) and drugs that depress the central nervous system (including tranquilizers, hypnotics, sedatives and anesthetics). Inducers of microsomal oxidation (including barbiturates, carbamazepine) reduce the severity of the analgesic effect of tramadol and the duration of its action. Since carbamazepine enhances tramadol metabolism and increases the likelihood of seizures, the combined use of tramadol and carbamazepine is not recommended. Prolonged use of barbiturates or opioid analgesics stimulates the appearance of cross-tolerance with tramadol. Anxiolytics increase the severity of the analgesic effect of tramadol; the duration of anesthesia increases with the combination of tramadol with barbiturates. Naloxone eliminates analgesia and activates respiration after using opioid analgesics. Furazolidone, MAO inhibitors, neuroleptics, procarbazine increase the likelihood of seizures when combined with tramadol. Quinidine increases the concentration of tramadol in plasma and reduces the metabolite (mono-O-desmethyltramadol) by inhibiting (competitively) the CYP2D6 isoenzyme. Inhibitors of CYP3A4 isoenzymes (such as erythromycin, ketoconazole) and CYP2D6 (such as paroxetine, fluoxetine and amitriptyline) can lower tramadol metabolism and increase the risk of serious adverse reactions, including seizures and serotonin syndrome. Serotonergic drugs, such as MAO inhibitors, SSRI antidepressants, linezolid (an antibiotic that is a reversible non-selective MAO inhibitor), anti-migraine drugs (triptans), as well as lithium preparations when used in combination with tramadol can lead to the development of serotonin syndrome. The activity of tramadol is reduced by psychostimulants and analeptics, completely blocked by naltrexone and naloxone.
Overdose
With an overdose of tramadol, respiratory depression develops (up to apnea), anuria, pupil constriction, convulsions, coma. Intravenous administration of naloxone is necessary (it is a specific antagonist), gastric lavage, maintenance of vital functions.
Trade names of drugs with the active substance tramadol
Protradon
Sintradon ®
Tramadol
Tramadol Lannacher
Tramadol retard
Tramadol STADA ®
Tramadol-Acri ®
Tramadol-GR Tramadol-Plethiko
Tramadol-ratiopharm
Tramadol-Slovakopharma
Tramadol Hydrochloride
Tramadol tablets 0.1 g
Tramaclosidol
Tramal ®
Tramal ® 50 Tramal ® retard
Tramal ® retard 100
Tramal ® retard 150
Tramal ® retard 200
Tramal ® 100
Tramolin ®
Tramundin retard
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