A nucleoside analog is a substance that resembles a natural nucleoside. In particular, these are drugs used for antiviral treatment (known as nucleoside reverse transcriptase inhibitors, NRTIs). Nucleoside analogues therefore play a significant role in the treatment of infectious diseases such as HIV, hepatitis B (HBV), and hepatitis C (HBC).
What are nucleoside analogues?
The term nucleoside analog is a collective term used in human medicine and pharmacology. It refers to various substances that have similarities to natural nucleosides. A nucleoside is a compound consisting of a nucleic base and pentose, which is an important component of nucleic acid (an essential element of DNA). Nucleoside analogues therefore resemble the building blocks of genetic material. Because of these properties, they succeed in suppressing viral replication. They thereby reduce the viral load in the body, leading to noticeable improvements in specific disease symptoms. The most important nucleoside analogues include the drugs ribavirin, zidovudine, abacavir, tenofovir, didanosine, stavudine and lamivudine. They are used to treat HIV, hepatitis B (HBV), or hepatitis C (HBC).
Pharmacologic effects on the body and organs
The efficacy of nucleoside analogues builds substantially on their structural similarity to the components of the genetic material. The corresponding substances are taken up by the cell and only develop a relevant effect through a phosphorylation that takes place within the cell. During this process, the cell gradually converts the nucleoside analog to phosphate residues. The analogues become part of the generated DNA as “false” components. This leads to an interruption of an otherwise properly constructed DNA chain and thus causes the termination of polymerization. The reverse transcription of the cell is stopped and the virus cannot reproduce further. After some time, this results in a significant reduction of the viral load in the body.
Medical application and use for treatment and prevention.
The field of application of nucleoside analogues forms the therapy of viral infections. The most important area here is the treatment of HIV and hepatitis B (HBV). They were first administered as part of HIV therapy in 1987. The development of nucleoside analogues marked the beginning of modern combination treatment, which led to considerable therapeutic success. Modern preparations of the younger generation are administered once daily in the form of film-coated tablets for oral administration. Nucleoside analogues are thus easy for patients to take themselves. The nucleoside analogues staduvin, cytidine, zidovudine, lamivudine, abacavir, and inosine are currently available for the treatment of HIV infection. Nucleoside analogues have only been available for the treatment of hepatitis B (HBV) since the early 2000s. Prior to that, the active ingredient lamivudine, developed for the treatment of HIV infection, and the somewhat younger adefovir were administered. Modern treatment approaches, on the other hand, rely on nucleoside analogues. The drugs tenofovir and entecavir are administered. Doctors hope that this will reduce the development of resistance and lead to greater success in long-term therapy. Nucleoside analogues are combined with other substances to combat HBV. Within the European Union and the United States of America, there is a strict prescription and pharmacy requirement, so that they can only be obtained after a doctor’s prior prescription.
Risks and side effects
Although nucleoside analogues are considered well tolerated, their use is not without risks and side effects. Gastrointestinal discomfort is common after use. Patients report an unwarranted feeling of fullness, nausea, vomiting, and diarrhea. In addition, general malaise and headache may also occur. In addition, long-term side effects are also conceivable, which only become apparent after several years of use. Common is the occurrence of pancreatitis, myelotoxicity, polyneuropathy, lactic acidosis and lipoatrophy. This is probably due to the fact that nucleoside analogues are toxic toward mitochondria. However, the intensity of the toxic effects depends on the particular preparation used.Patients who are allergic to the particular nucleoside analogue being used must refrain from taking it, as there is a medical contraindication.
