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Azidothymidine
Azidothymidine actively affects retroviruses (among them, HIV infection).
Pharmacodynamics
The drug is phosphorylated inside the cell with the help of cellular TK, thymidylate kinase, and with this nonspecific kinase. As a result, certain phosphate compounds (mono-, di-, and tri-) are formed. The substance zidovudine-triphosphate penetrates into the structure of the provirus and prevents further increase in the DNA chain of the virus. As a result, binding of parts of the virus DNA becomes impossible. The drug also helps increase the number of T4 cells in the body.
Zidovudine is active against herpes viruses of the 4th type, as well as hepatitis B in in vitro tests. But in the case of using drugs with monotherapy in people with AIDS or hepatitis B, it does not significantly inhibit viral replication of hepatitis B.
In vitro, it has been found that the substance in small concentrations can slow down the activity of most strains of enterobacteria (this includes strains of various types of Salmonella, Shigella, Klebsiella, Citrobacterium and enterobacter) and, with this, Escherichia coli (but it should be borne in mind that microbes rapidly acquire resistance to zidovudine).
In vitro tests, it was not possible to detect the activity of the substance with respect to the Pseudomonas aeruginosa. The drug in high concentrations (size 1.9 μg / ml) depresses the intestinal lamblia, but does not affect other protozoa.
Pharmacokinetics
The level of bioavailability of the substance is 60-70%.
The medicine penetrates through the BBB. The concentration index inside the cerebrospinal fluid reaches 50% of the plasma values of the substance. Exposed to hepatic metabolism.
Excretion occurs through the kidneys - approximately 30% of the drug is excreted unchanged, and 50 +% have the form of glucuronides.
Contraindications
The main contraindications:
- the presence of heightened sensitivity with respect to the components of drugs;
- leukopenia (neutrophil counts are <750 / mm 3 ), thrombocytopenia (decrease in platelet count to 2000 / μL), and anemia (hemoglobin level <7.5 g / dL);
- insufficiency of the liver or kidneys.
Side effects of the azidothymidine
Use of the drug may cause some side reactions:
- the development of anemia, neutropenic or leukopenia;
- the appearance of headaches, sensations of drowsiness, paresthesias, severe fatigue, asthenia, myalgia with cardialgia, and a disorder of taste buds;
- the emergence of diarrhea, vomiting, bloating and nausea, and in addition the development of gastralgia or pancreatitis and impaired appetite;
- the emergence of a secondary type of infection and the development of fever;
- the appearance of cough, insomnia, chills, increased frequency of urination, the development of depression;
- development of dyspeptic manifestations or hypercreatininaemia, as well as an increase in the activity of liver transaminases and amylase within the serum.
Dosing and administration
Oral administration. For adults, the initial dosage is 200 mg of the drug 6 times per day. The most suitable daily dosage is selected individually, it can fluctuate within 500-1500 mg.
For children: on average, the dosage is calculated in the range of 150-180 mg / m 2 every 6 hours (four times per day). The dosage is recalculated in accordance with special tables that take into account weight and height. Do this at least once every 2 months.
Interactions with other drugs
Paracetamol increases the incidence of neutropenia, because this substance suppresses the metabolism of zidovudine (both drugs undergo glucuronization).
Inhibitors of oxidative processes of microsomes inside the liver (among them morphine with oxazepam, codeine, ASA and clofibrate, and in addition indomethacin with cimetidine) increase the plasma values of zidovudine.
Drugs with nephrotoxic properties, as well as depressing bone marrow function (such as amphotericin, vinblastine with ganciclovir and pentamidine, and additionally vincristine), increase the likelihood of developing a toxic effect in zidovudine.
Drugs that slow the secretion of the tubules, prolong the half-life of zidovudine.
Zidovudine increases the fluconazole index in the body.
When combined with other medicines against the HIV virus (especially lamivudine), a synergistic effect occurs with respect to replication of HIV infection in the cell culture.
Ribavirin inhibits the process of zidovudine phosphorylation before the formation of triphosphate, so these drugs can not be used in combination.
Stavudine has antagonistic properties when the molar values of this substance with zidovudine have a proportion of 20k1. As a consequence, the combination with stavudine is prohibited.