Pyrazinamide is a drug used to treat tuberculosis (tuberculostat). The substance has been used since the 1950s to combat the lung disease as part of a combination therapy.
What is pyrazinamide?
Pyrazinamide (PZA for short) is an antibiotic that has been used since the 1950s to fight tuberculosis disease. The drug is also often referred to as pyrazine carboxamide, is water-soluble, and is white in color. Due to its intended use as a tuberculosis drug, it is classified as a tuberculostat. In chemistry, the molecular formula C5-H5-N3O is used to designate the substance. The moral mass of pyrazinamide is 123.11 g-mol-1. The active ingredient pyrazinamide is marketed under the trade names Pyrafate, Rifater, Rimstar and Tebesium Trio, among others. PZA acts exclusively on the causative agent of tuberculosis (Mycobacterium tuberculosis). Thus, there is no efficacy with respect to the bovine form of the bacterium (Mycobacterium bovis) or forms deviating from the basic type (atypical mycobacteria).
Pharmacologic action
Although PZA has been used to combat tuberculosis since the 1950s, the exact mechanism of action of the compound was not clear for a long time. Reliance was placed solely on treatment efficacy. The mechanism of action of pyrazinamide was only almost completely elucidated in 2011. While conventional antibiotics primarily kill bacteria that are still growing, PZA primarily kills growing bacteria. Its mechanism of action thus represents a deviation from the norm. This is because growing bacteria (known as persisters) are generally far less sensitive to antibiotics than those that are already in a dormant stage. However, pyrazinamide exerts its effect exclusively in the body. No effect could be detected in test tubes, which contributed to the mechanism of action remaining unknown for so long. Even before 2011, however, it was known that PZA acts as a prodrug. The substance converts pyrazinoid acid in the body and acts in an acidic environment. Pyranizide binds to a cell protein (RspA S1) and thus prevents trans-translation in the tuberculosis bacterium. As a result, the bacterium is no longer able to protect itself against toxic protein fragments. These fragments are formed by the bacterium itself when it is under stress. Because of this mechanism of action, PZA shortens the treatment of tuberculosis disease from 9 to 12 months to usually 6 months.
Medical application and use
Pyrazinamide has been used since the 1950s to combat the pulmonary disease tuberculosis. The substance is one of the antibiotics and is a tuberculostatic agent. An indication exists exclusively for tuberculosis disease in humans. Pyrazinamide is not applicable to atypical forms of the bacteria (atypical mycobacteria) or the bovine form of the bacteria (MYcobacterium bovis). When taken early, it shortens the average duration of treatment for tuberculosis from about 9 to 12 months to 6 months. The drug is usually used in combination therapy. Patients often also take isoniazid, ethambutol and rifampicin as part of their therapy. However, the exact combination may vary depending on the form of therapy chosen. The form of therapy depends on the duration and severity of the disease as well as the age of the patient. The average duration of treatment also depends on these factors.
Risks and side effects
Pyrazinamide may cause side effects. However, this is not necessarily the case. Before the first use, it should be checked whether there is an intolerance to pyrazinamide or substances related to it. In the event of an allergy, use or ingestion is prohibited. In addition, pyrazinamide is contraindicated in cases of severe liver dysfunction, kidney dysfunction, acute gout attacks, and during existing pregnancy and lactation. Increased caution is also advised in patients who regularly consume high amounts of alcohol. Since pyrazinamide may have effects on liver and kidney function, organ function monitoring should be performed at regular intervals during therapy. This monitoring should continue for several weeks after treatment.Furthermore, the following side effects are known:
Frequently (less than 1 in 10 patients but more than 1 in 100): loss of appetite, nausea, nausea, weight loss, damage to the liver, heartburn, sensitivity to light, and an increase in blood uric acid levels. Rare side effects include headache, excitability, insomnia, and dizziness. Rare side effects are those that occur in less than 1 in 1,000 people treated but in more than 1 in 10,000. In less than 1 in 10,000 cases, disorders of the blood formation system (e.g., anemia) and thrombocytopenia (very rare) also occurred. It is mandatory to follow the instructions of a physician as well as a pharmacist. They should be contacted immediately in case of occurrence of these and other side effects.
