Pyrazinamide
Systematic (IUPAC) name
pyrazine-2-carboxamide
Identifiers
CAS number	98-96-4
ATC code	J04AK01
PubChem	1046
DrugBank	APRD01206
Chemical data
Formula	C5H5N3O
Mol. mass	123.113 g/mol
Pharmacokinetic data
Bioavailability	>90%
Metabolism	Hepatic
Half life	9 to 10 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C Image File history File links This is a lossless scalable vector image. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... This article or section does not cite any references or sources. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is an organ present in vertebrates and some other animals. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
Legal status	? The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	Oral

Pyrazinamide is a drug used to treat tuberculosis in afflicted patients. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... For other meanings, see Drug (disambiguation). ... Tuberculosis (abbreviated as TB for Tubercle Bacillus) is a common and deadly infectious disease that is caused by mycobacteria, primarily Mycobacterium tuberculosis. ... Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and repoduction of the bacteria, though do not kill it, while bactericidal antibiotics kill bacteria. ... Bacteriocidal prevents and combats bacterial infection. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ...

Abbreviations

The abbreviations PZA and Z are standard, and used commonly in the medical literature. The abbreviation P stands for penicillin, or in the context of tuberculosis treatment, stands for para-aminosalicylic acid. Penicillin nucleus Penicillin (sometimes abbreviated PCN) refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ... Aminosalicylic acid (C7H7NO3) is also known as para-aminosalicylic acid, p-aminosalicylic acid or 4-aminosalicylic acid; abbreviated 4-ASA, PAS or P. It is sold in the US by Jacobus Pharmaceutical as Paser. ...

Dosing and presentation

• 20–25 mg/kg daily, or
• 50–70 mg/kg three times a week.

The British Thoracic Society guidelines are for 1.5 g daily for patients weighing less than 50 kg, and 2 g daily for patients weighing 50 kg or more. The British Thoracic Society (BTS) is a specialist medical society in the United Kingdom in the field of respiratory medicine. ...

Pyrazinamide is a generic drug and is available in a wide variety of presentations. Pyrazinamide tablets are usually 500 mg and form the bulkiest part of the standard tuberculosis treatment regimen. Pyrazinamide tablets are so large that some patients find them impossible to swallow: pyrazinamide syrup is an option for these patients. A generic drug (pl. ...

Pyrazinamide is also available as part of fixed dose combinations with other TB drugs such as isoniazid and rifampicin (Rifater® is an example). Isoniazid (also called isonicotinyl hydrazine or isonicotinic acid hydrazide); abbreviated INH or just H. Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. ... Rifampicin (INN) (IPA: ) or rifampin (USAN) is a bacteriocidal antibiotic drug of the rifamycin group. ... Rifater® is a fixed dose combination tablet manufactured by Aventis used in the treatment of tuberculosis. ...

Pharmacokinetics

Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an essential part of the treatment of tuberculous meningitis. It is metabolised by the liver and the metabolic products are excreted by the kidneys. Tuberculous meningitis is also called TB meningitis. Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges. ... The liver is an organ present in vertebrates and some other animals. ...

Pyrazinamide is routinely used in pregnancy in the UK and the rest of the world; the WHO recommend its use in pregnancy; and there is extensive clinical experience to show that it is safe. In the U.S., pyrazinamide is not used in pregnancy, citing insufficient evidence of safety.^[1] Pyrazinamide is removed by haemodialysis and therefore doses should always be given at the end of a dialysis session. For other meanings of the acronym WHO, see WHO (disambiguation) WHO flag Headquartered in Geneva, Switzerland, the World Health Organization (WHO) is an agency of the United Nations, acting as a coordinating authority on international public health. ... In medicine, dialysis is a method for removing waste such as urea from the blood when the kidneys are incapable of this, i. ...

Medical uses

Pyrazinamide is only used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis';' it is never used on its own. It has no other medical uses; in particular, it is not used to treat other mycobacteria: Mycobacterium bovis and Mycobacterium leprae are innately resistant to pyrazinamide. Pyrazinamide is used in the first two months of treatment to reduce the duration of treatment required.^[2] Regimens not containing pyrazinamide must be taken for nine months or more. Isoniazid (also called isonicotinyl hydrazine or isonicotinic acid hydrazide); abbreviated INH or just H. Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. ... Rifampicin (INN) (IPA: ) or rifampin (USAN) is a bacteriocidal antibiotic drug of the rifamycin group. ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ... Binomial name Mycobacterium tuberculosis Zopf 1883 Mycobacterium tuberculosis is the bacterium that causes most cases of tuberculosis[1]. It was first described on March 24, 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905. ... Species see text Mycobacterium is the a genus of actinobacteria, given its own family, the Mycobacteriaceae. ... Binomial name Mycobacterium bovis Karlson & Lessel 1970 Mycobacterium bovis is a slow-growing (16 to 20 hour generation time), aerobic bacterium and the causative agent of tuberculosis in cattle. ... Binomial name Mycobacterium leprae Hansen, 1874 Mycobacterium leprae, also known as Hansen’s bacillus, is the bacterium that causes leprosy (Hansens disease). ...

Pyrazinamide must not be used to treat latent tuberculosis because the rate of liver toxicity is unacceptably high. Also called latent tuberculosis infection, latent TB or LTBI. Latent tuberculosis is where a patient is infected with Mycobacterium tuberculosis, but does not have active tuberculosis disease. ...

Mechanism of Action

Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis. M. tuberculosis has the enzyme pyrazinamidase which is only active at acidic pH. Pyrazinamidase converts pyrazinamide to the active form, pyrazinoic acid. Pyrazinoic acid inhibits the enzyme fatty acid synthetase I, which is required by the bacterium to synthesise fatty acids.^[1] Mutations of the pyrazinamidase gene (pncA) are responsible for pyrazinamide resistance in M. tuberculosis.^[3] A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... Binomial name Mycobacterium tuberculosis Zopf 1883 Mycobacterium tuberculosis is the bacterium that causes most cases of tuberculosis[1]. It was first described on March 24, 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905. ... Acidity redirects here. ... The correct title of this article is . ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid often with a long unbranched aliphatic tail (chain), which is either saturated or unsaturated. ...

Side effects

The most common (approximately 1%) side effect of pyrazinamide is joint pains (arthralgia), but this is not usually so severe that patients need to stop taking the pyrazinamide.^[4][5] The arthralgia can be distressing to patients, but is never harmful. In medicine, arthralgia (literally: joint pain, from arthros = joint and -algia denoting pain) is the presence of painful joints in the absence of frank arthritis. ...

The most dangerous side effect of pyrazinamide is hepatitis, which is dose related. The old dose for pyrazinamide was 40–70 mg/kg daily and the incidence of drug-induced hepatitis has fallen significantly since the recommended dose has been reduced. In the standard four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol), pyrazinamide is the most common cause of drug-induced hepatitis.^[6] It is not possible to clinically distinguish pyrazinamide-induced hepatitis from hepatitis caused by isoniazid or rifampicin; test dosing is required (this is discussed in detail in tuberculosis treatment) Hepatitis (plural hepatitides) implies injury to liver characterised by presence of inflammatory cells in the liver tissue. ... A bacteriostatic antimycobacterial prescribed to treat Tuberculosis (Mycobacterium). ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ...

Other side effects include nausea and vomiting, anorexia, sideroblastic anemia, skin rash, urticaria, pruritus, hyperuricemia, dysuria, interstitial nephritis, malaise; rarely porphyria, and fever. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... For the Beck song, see Nausea (song). ... Vomiting (also throwing up or emesis) is the forceful expulsion of the contents of ones stomach through the mouth and sometimes the nose. ... Anorexia (deriving from the Greek α(ν)- (a(n)-, a prefix that denotes absence) + όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Sideroblastic anemia is caused by the abnormal production of red blood cells as part of myelodysplastic syndrome, which can evolve into hematological malignancies (especially acute myelogenous leukemia). ... For the manga by Tsukasa Hôjô, see Rash. ... An itch (Latin: pruritus) is a sensation felt on an area of skin that causes a person or animal to desire to scratch that area. ... Hyperuricemia is the presence of high levels of uric acid in the blood. ... In medicine, specifically urology, dysuria refers to any difficulty in urination. ... Interstitial nephritis (or Tubulo-interstitial nephritis) is a form of nephritis affecting the interstititum of the kidneys surrounding the tubules. ... Malaise is a term used to refer to a general state of discomfort, tiredness, or illness. ... It has been suggested that Acute intermittent porphyria be merged into this article or section. ... An analogue medical thermometer showing the temperature of 38. ...

Wikipedia articles

• Tuberculosis
• Mycobacterium tuberculosis
• Tuberculosis treatment

Tuberculosis (abbreviated as TB for Tubercle Bacillus) is a common and deadly infectious disease that is caused by mycobacteria, primarily Mycobacterium tuberculosis. ... Binomial name Mycobacterium tuberculosis Zopf 1883 Mycobacterium tuberculosis is the bacterium that causes most cases of tuberculosis[1]. It was first described on March 24, 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905. ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ...

References

1. ^ ^{a b} American Thoracic Society, Centers for Disease Control, Infectious Diseases Society of America (2003). "Treatment of Tuberculosis". Am J Respir Crit Care Med 167 (602–662). 
2. ^ Hong Kong Chest Service, Medical Research Council. "Controlled trial of four thrice weekly regimens and a daily regimen given for 6 months for pulmonary tuberculosis". Lancet 1 (8213): 171–4. PMID 6109855. 
3. ^ Sreevatsan S et al. (1997). "Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis". Antimicrob Agents Chemother 41: 636–40. 
4. ^ East and Central African/Medical Research Council Fifth Collaborative Study (1983). "Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 9-month) for pulmonary tuberculosis". Tubercle 64: 153–166. PMID 6356538. 
5. ^ British Thoracic Society (1984). "A controlled trial of 6 months chemotherapy in pulmonary tuberculosis, final report: results during the 36 months after the end of chemotherapy and beyond". Br J Dis Chest 78 (4): 330–336. PMID 6386028. 
6. ^ Yee D et al. (2003). "Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis". Am J Resp Crit Care Med 167 (11): 1472–7. PMID 12569078.