Azidotothimidina – Wikipedia

L’ Azidotoimidina or abbreviated It , also known as Zidovudine O ZdV , introduced on the market with names Retrovir It is Got back , produced by the pharmaceutical house Glaxosmithkline, is a nucleosidic analogue of shy, initially proposed as an anti-neoplastic, but abandoned because it is not very easy to handle and too toxic. It is currently used as an antiretroviral drug to prevent and treat HIV/AIDS infection.

It is generally recommended for use with other antiretrovirali. It can be used to prevent the diffusion from mother to child during birth or after a need for needles or other potential exposure. It is sold both alone and together as Lamivudine/Zidovudine and Abacavir/Lamivudine/Zidovudine. It can be used orally or by slow injection in a vein. ^[2]

Zidovudine was described for the first time in 1964. ^[3] It was approved in the United States in 1987 and was the first treatment for HIV. ^[4] It is included in the list of essential medicines of the World Health Organization, the safest and most effective medicines necessary in a health system. ^[5] It is available as a generic drug. The wholesale cost in developing countries ranges from $ 5.10 to $ 25.60 per month. ^[6] Starting from 2015, the cost for a month of drugs in the United States was over $ 200. ^[7]

HIV treatment [ change | Modifica Wikitesto ]

The AZT is usually administered twice a day in combination with other antiretroviral therapies. This approach is indicated as highly active antiretroviral therapy (HAART) and is used to prevent the probability of resistance to HIV. ^{[8] [9]}

Post-exposure prophylaxis [ change | Modifica Wikitesto ]

It is used for post-exposure prophylaxis from infected material in medical and para-medical staff in combination with lamivudine. They contribute to substantially reduce the risk of HIV infection after the first single exposure to the virus. ^[ten] More recently, the AZT has been replaced by other antiretrovirals such as the tenofovir to provide PEP. ^[11]

The AZT proved to be very effective in preventing the maternal-fetal transmission of HIV infection, so much so that, compared, any side effects on the fetus are considered secondary. There are formulations in tablets, capsules, syrup and also for parenteral infusion. It is commonly used in pregnancy and seems to be safe for the child. ^[2]

Without AZT, up to 10-15% of the fetuses is infected with HIV ^[twelfth] ; AZT has shown to reduce this risk of up to 8% when administered to a 3-phase regime (post-control, childbirth and six weeks after childbirth). Consistent and proactive precautionary measures, such as the rigorous use of antiretroviral drugs, cesarean cut, facial masks, rubber gloves, disposable diapers and the prevention of contact with the mouth will further reduce the transmission of the HIV by the child to a minimum 1-2%. ^{[13] [14]}

In the period 1994-1999, AZT was the main form of prevention of the transmission of HIV from mother to child. AZT prophylaxis has prevented more than 1000 deaths from parents and children due to AIDS in the United States. In the United States of the 90s, the care standard accepted for HIV -positive mothers was known as regime 076 and involved five daily doses of AZT from the second quarter onwards, as well as AZT administered intravenously during labor. ^[15] Since this treatment is long and expensive, it is considered unrealizable in the south of the world, where transmission from mother to child is a significant problem. In the late 1990s, numerous studies were started who tried to test the effectiveness of a shorter and easier regime to use in “poor resources” countries ^[16] .

The ZDV belongs to the class of the nucleosidic inhibitors of reverse transcripts (NRI). ^[2] It acts as an inhibitor of the viral reverse transcriptasi inhibitor, blocking the function of DNA polymerase, the enzyme that HIV uses to produce DNA and therefore reduces the replication of the virus. The molecule is introduced into the guest cell and is phosphorylated in trifosphic form, by a nucleoside-chinase. In this form, the AZT has a high affinity for the reverse transcriptase of HIV and competes with the trifosphic timidine for the link with the enzyme. The AZT is incorporated into the nascent DNA chain and interrupts it, because it does not have the 3′-hydrospile group for the attack of the subsequent trifosphate nucleoside to be incorporated. Thus the production of viral genome is prevented. The DNA-Polimerase-γ involved in the replication of man’s mitochondrial DNA can also inhibit, therefore it can give mitochondrial toxicity, with lactic acidosis and liver toxicity; It can give muscle damage with an increase in creatinfosphochinases in serum and cardiomyopathy, with left heart failure. However, these manifestations are rarer.

Distribution [ change | Modifica Wikitesto ]

The AZT penetrates better than the other antiretrovirali in the cephalorachidian liquid and therefore better reaches the nervous tissue.

The most common side effects include nausea, vomiting, acid reflux (stomach burning), headache, reduction of abdominal fat, sleep disorders and loss of appetite.

The less common side effects include a slight discoloring of the nails and nails of the feet, increase in mood, occasional tingling or transitional numbness of the hands or feet and mild discoloring of the skin. Allergic reactions are rare. ^[17]

At the beginning, the therapy at higher doses long -term with AZT was initially associated with side effects that sometimes limited therapy, including anemia, neutropenia, hepatotoxicity, cardiomyopathy and myopathy. All these conditions were generally found reversible with the reduction of AZT dosages. These effects are attributable to different possible causes, including the transitory exhaustion of the mitochondrial DNA, the sensitivity of the γ-DNA polymerase in some mitochondrial champions ^[18] , the exhaustion of the trifosphate shy, oxidative stress, the reduction of intracellular L-carnitine or the apoptosis of muscle cells. ^[19]

Due to AZT, anemia has been successfully treated with erythropoietin to stimulate the production of red blood cells. ^[20] The AZT Association with drugs that inhibit liver glucuronidation, such as indometarcoline, northzapam, acetylsalicylic acid (aspirin) and trimetoprim decreases the clearance and increases the concentration of the drug. ^[17] Currently, the side effects are much less common with the use of lower doses than AZT. ^[21]

According to Iarc, there is sufficient evidence that experience the carcinogenicity of zidovudine in experimental animals: it is probably carcinogenic for humans (group drug 2b). ^[22]

The side effects of the IZT can occur in a very variable way from patient to patient.

Viral resistance [ change | Modifica Wikitesto ]

Even at the highest doses that can be tolerated in patients, AZT is not powerful enough to prevent all HIV replication and can only slow down the replication of the virus and the progression of the disease. The prolonged treatment of the IZT can lead to the HIV that develops resistance to the Izt by means of the change of its reverse transcript. ^[23] To slow down the development of the resistance, doctors generally recommend to administer AZT in combination with another inhibitor of reverse transcriptase and an antiretroviral of another group, as a protease inhibitor, a non -nucleosidic inhibitor of reverse transcriptase or an inhibitor of the integraits ; This type of therapy is known as HAART (highly active antiretroviral therapy). ^[24]

• G.Mandell, J.Bennett, R.Dolin, ed. Principles and practice of infectious diseases . 6th ed. Elsevier Churchill Livingstone, 2005.
• HIV-positive children of ZDV-treated mothers de Martino et al.