Array ( [0] => {{Short description|Antibiotic for treatment of tuberculosis}} [1] => {{redirect|Inah|"INAH"|Instituto Nacional de Antropología e Historia}} [2] => {{redirect|FSR 3|FidelityFX Super Resolution v3|GPUOpen#FidelityFX Super Resolution}} [3] => {{cs1 config |name-list-style=vanc |display-authors=6}} [4] => {{Drugbox [5] => |Watchedfields = changed [6] => |verifiedrevid = 459455986 [7] => |image = Isoniazid skeletal.svg [8] => |width = 160 [9] => |image2 = Isoniazid 3d.png [10] => |width2 = 220 [11] => |tradename = Hydra, Hyzyd, Isovit, others [12] => |Drugs.com = {{drugs.com|monograph|isoniazid}} [13] => |MedlinePlus = a682401 [14] => |DailyMedID = Isoniazid [15] => |pregnancy_AU = A [16] => |pregnancy_AU_comment = {{cite web | title=Isoniazid (Nydrazid) Use During Pregnancy | website=Drugs.com | date=7 October 2019 | url=https://www.drugs.com/pregnancy/isoniazid.html | access-date=24 January 2020}} [17] => |routes_of_administration = [[By mouth]], [[intramuscular]], [[intravenous]] [18] => |ATC_prefix = J04 [19] => |ATC_suffix = AC01 [20] => |ATC_supplemental = {{ATC|J04|AC51}} {{ATC|J04|AM01}} {{ATC|J04|AM02}} {{ATC|J04|AM03}} {{ATC|J04|AM04}} {{ATC|J04|AM05}} {{ATC|J04|AM06}} {{ATC|J04|AM07}} {{ATC|J04|AM08}} [21] => |legal_AU = [22] => |legal_BR = [23] => |legal_CA = Rx-only [24] => |legal_CA_comment = {{cite web | title=Drug and medical device highlights 2018: Helping you maintain and improve your health | website=[[Health Canada]] | date=14 October 2020 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | access-date=17 April 2024}} [25] => |legal_DE = [26] => |legal_NZ = [27] => |legal_UK = [28] => |legal_US = Rx-only [29] => |legal_UN = [30] => |legal_status = [31] => |protein_bound = Very low (0–10%) [32] => |metabolism = liver; CYP450: 2C19, 3A4 inhibitor [33] => |elimination_half-life = 0.5–1.6h (fast acetylators), 2-5h (slow acetylators) [34] => |excretion = urine (primarily), feces [35] => |synonyms = isonicotinic acid hydrazide, isonicotinyl hydrazine, INH, INAH, INHA [36] => |CAS_number_Ref = {{cascite|correct|??}} [37] => |CAS_number = 54-85-3 [38] => |PubChem = 3767 [39] => |DrugBank_Ref = {{drugbankcite|correct|drugbank}} [40] => |DrugBank = DB00951 [41] => |ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} [42] => |ChemSpiderID = 3635 [43] => |UNII_Ref = {{fdacite|correct|FDA}} [44] => |UNII = V83O1VOZ8L [45] => |KEGG_Ref = {{keggcite|correct|kegg}} [46] => |KEGG = D00346 [47] => |KEGG2_Ref = {{keggcite|correct|kegg}} [48] => |KEGG2 = C07054 [49] => |ChEBI_Ref = {{ebicite|correct|EBI}} [50] => |ChEBI = 6030 [51] => |ChEMBL_Ref = {{ebicite|correct|EBI}} [52] => |ChEMBL = 64 [53] => |NIAID_ChemDB = 007657 [54] => |IUPAC_name = Pyridine-4-carbohydrazide [55] => |C=6 | H=7 | N=3 | O=1 [56] => |SMILES = C1=CN=CC=C1C(=O)NN [57] => |StdInChI_Ref = {{stdinchicite|correct|chemspider}} [58] => |StdInChI = 1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10) [59] => |StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} [60] => |StdInChIKey = QRXWMOHMRWLFEY-UHFFFAOYSA-N [61] => }} [62] => [63] => '''Isoniazid''', also known as '''isonicotinic acid hydrazide''' ('''INH'''), is an [[antibiotic]] used for the [[Tuberculosis management|treatment of tuberculosis]]. For active tuberculosis, it is often used together with [[rifampicin]], [[pyrazinamide]], and either [[streptomycin]] or [[ethambutol]].{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free |page=136 }} For latent tuberculosis, it is often used alone. It may also be used for [[Nontuberculous mycobacteria|atypical types of mycobacteria]], such as ''[[M. avium]]'', ''[[Mycobacterium kansasii|M. kansasii]]'', and ''[[Mycobacterium xenopi|M. xenopi]]''. It is usually taken by mouth, but may be used by [[intramuscular|injection into muscle]]. [64] => [65] => ==Side effects and mechanism of action== [66] => Common side effects include [[elevated transaminases|increased blood levels of liver enzymes]] and [[paresthesia|numbness in the hands and feet]]. Serious side effects may include [[Hepatitis|liver inflammation]] and acute [[liver failure]].{{cite web|title=Isoniazid|url=https://www.drugs.com/monograph/isoniazid.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220231039/https://www.drugs.com/monograph/isoniazid.html|archive-date=20 December 2016}} It is unclear if use during [[pregnancy]] is safe for the fetus. Use during [[breastfeeding]] is likely safe.{{cite web|title=Isoniazid (Nydrazid) Use During Pregnancy|url=https://www.drugs.com/pregnancy/isoniazid.html|website=www.drugs.com|access-date=10 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220231059/https://www.drugs.com/pregnancy/isoniazid.html|archive-date=20 December 2016}} [[Pyridoxine]] may be given to reduce the risk of side effects.{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=49}} Isoniazid works in part by disrupting the formation of the bacteria's [[cell wall]] which results in [[bactericidal|cell death]]. [67] => [68] => ==History, society, and culture== [69] => Isoniazid was first made in 1952.{{cite book| vauthors = Walker SR |title=Trends and Changes in Drug Research and Development|date=2012|publisher=Springer Science & Business Media|isbn=9789400926592|page=109|url=https://books.google.com/books?id=FB_2CAAAQBAJ&pg=PA109|url-status=live|archive-url=https://web.archive.org/web/20170910151826/https://books.google.com/books?id=FB_2CAAAQBAJ&pg=PA109|archive-date=2017-09-10}} It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = [[World Health Organization]] | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free | last1 = Organization | first1 = World Health }} The World Health Organization classifies isoniazid as critically important for human medicine.{{cite book | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision | publisher = [[World Health Organization]] | location = Geneva | hdl=10665/312266 | isbn=9789241515528 | hdl-access=free}} Isoniazid is available as a [[generic medication]]. [70] => [71] => ==Medical uses== [72] => ===Tuberculosis=== [73] => Isoniazid is often used to treat latent and active tuberculosis infections. In persons with isoniazid-sensitive ''[[Mycobacterium tuberculosis]]'' infection, drug regimens based on isoniazid are usually effective when persons adhere to the prescribed treatment. However, in persons with isoniazid-resistant ''Mycobacterium tuberculosis'' infection, drug regimens based on isoniazid have a high rate of failure.{{cite journal | vauthors = Gegia M, Winters N, Benedetti A, van Soolingen D, Menzies D | title = Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 2 | pages = 223–234 | date = February 2017 | pmid = 27865891 | doi = 10.1016/S1473-3099(16)30407-8 }} [74] => [75] => Isoniazid has been approved as prophylactic therapy for the following populations: [76] => * People with HIV infection and a PPD (purified protein derivative) reaction of at least 5 mm induration [77] => * Contacts of people with tuberculosis and who have a PPD reaction at least 5 mm induration [78] => * People whose PPD reactions convert from negative to positive in a two-year period – at least 10 mm induration for those up to 35 years of age, and at least 15 mm induration for those at least 35 years old [79] => * People with pulmonary damage on their chest X-ray that is likely to be due to healed tuberculosis and also have a PPD reaction at least 5 mm induration [80] => * Injection drug users whose HIV status is negative who have a PPD reaction at least 10 mm induration [81] => * People with a PPD of greater than or equal to 10 mm induration who are foreign-born from high prevalence geographical regions, low-income populations, and patients residing in long-term facilities{{cite journal|title=The Use of Preventive Therapy for Tuberculosis Infection in the United States – Recommendations of the Advisory Committee for Elimination of Tuberculosis|journal=Morbidity and Mortality Weekly Report|date=May 18, 1990|volume=39 (RR-8)|pages=9–12|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00001643.htm|access-date=22 February 2016|url-status=live|archive-url=https://web.archive.org/web/20160302075630/http://www.cdc.gov/mmwr/preview/mmwrhtml/00001643.htm|archive-date=2 March 2016}} [82] => [83] => Isoniazid can be used alone or in combination with [[Ethambutol/isoniazid/pyrazinamide/rifampicin|Rifampin]] for treatment of latent tuberculosis, or as part of a four-drug regimen for treatment of active tuberculosis.{{cite book|title=Medical-surgical nursing : assessment and management of clinical problems| vauthors = Lewis SM, Dirksen SR, Heitkemper MM, Bucher L, Harding M |date=5 December 2013|isbn=978-0-323-10089-2|edition=Ninth|location=St. Louis, Missouri|oclc=228373703}} The drug regimen typically requires daily or weekly oral administration for a period of three to nine months, often under [[Directly observed therapy|Directly Observed Therapy]] (DOT) supervision. [84] => [85] => ===Non-tuberculous mycobacteria=== [86] => Isoniazid was widely used in the treatment of [[Mycobacterium avium complex|''Mycobacterium avium'' complex]] as part of a regimen including rifampicin and ethambutol.{{cite journal | title = First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol | journal = Thorax | volume = 56 | issue = 3 | pages = 167–172 | date = March 2001 | pmid = 11182006 | pmc = 1758783 | doi = 10.1136/thorax.56.3.167 | last1 = Research Committee Of The British Thoracic Society }} Evidence suggests that isoniazid prevents mycolic acid synthesis in ''M. avium'' complex as in ''M. tuberculosis''{{cite journal | vauthors = Mdluli K, Swanson J, Fischer E, Lee RE, Barry CE | title = Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium | journal = Molecular Microbiology | volume = 27 | issue = 6 | pages = 1223–1233 | date = March 1998 | pmid = 9570407 | doi = 10.1046/j.1365-2958.1998.00774.x | s2cid = 13764717 | doi-access = free }} and although this is not bactericidal to ''M. avium'' complex, it greatly potentiates the effect of rifampicin. The introduction of macrolides led to this use greatly decreasing. However, since rifampicin is broadly underdosed in ''M. avium'' complex treatment, this effect may be worth re-investigating.{{cite journal | vauthors = van Ingen J, Egelund EF, Levin A, Totten SE, Boeree MJ, Mouton JW, Aarnoutse RE, Heifets LB, Peloquin CA, Daley CL | title = The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment | journal = American Journal of Respiratory and Critical Care Medicine | volume = 186 | issue = 6 | pages = 559–565 | date = September 2012 | pmid = 22744719 | doi = 10.1164/rccm.201204-0682OC | author3-link = Adeera Levin }} [87] => [88] => ===Special populations=== [89] => It is recommended that women with active tuberculosis who are pregnant or breastfeeding take isoniazid. Preventive therapy should be delayed until after giving birth.{{cite web | title=Isoniazid tablet | website=DailyMed | date=18 October 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1553312b-ed76-421c-a055-2579bdcf366c | archive-url=https://web.archive.org/web/20190313234259/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1553312b-ed76-421c-a055-2579bdcf366c | archive-date=13 March 2019 | url-status=live | access-date=24 January 2020 }} Nursing mothers excrete a relatively low and non-toxic concentration of INH in breast milk, and their babies are at low risk for side effects. Both pregnant women and infants being breastfed by mothers taking INH should take [[vitamin B6]] in its [[pyridoxine]] form to minimize the risk of peripheral nerve damage.{{cite journal | vauthors = Bothamley G | title = Drug treatment for tuberculosis during pregnancy: safety considerations | journal = Drug Safety | volume = 24 | issue = 7 | pages = 553–565 | date = 2001 | pmid = 11444726 | doi = 10.2165/00002018-200124070-00006 | s2cid = 10479433}} [90] => Vitamin B6 is used to prevent isoniazid-induced B6 deficiency and neuropathy in people with a risk factor, such as pregnancy, lactation, HIV infection, alcoholism, diabetes, kidney failure, or malnutrition.{{cite journal | vauthors = Steichen O, Martinez-Almoyna L, De Broucker T | title = [Isoniazid induced neuropathy: consider prevention] | journal = Revue des Maladies Respiratoires | volume = 23 | issue = 2 Pt 1 | pages = 157–160 | date = April 2006 | pmid = 16788441 | doi = 10.1016/S0761-8425(06)71480-2}} [91] => [92] => People with liver dysfunction are at a higher risk for hepatitis caused by INH, and may need a lower dose. [93] => [94] => Levels of liver enzymes in the bloodstream should be frequently checked in daily alcohol drinkers, pregnant women, IV drug users, people over 35, and those who have chronic liver disease, severe kidney dysfunction, peripheral neuropathy, or HIV infection since they are more likely to develop hepatitis from INH.{{cite journal | vauthors = Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, Bernardo J, Venkataramanan R, Sterling TR | title = An official ATS statement: hepatotoxicity of antituberculosis therapy | journal = American Journal of Respiratory and Critical Care Medicine | volume = 174 | issue = 8 | pages = 935–952 | date = October 2006 | pmid = 17021358 | doi = 10.1164/rccm.200510-1666ST | s2cid = 36384722}} [95] => [96] => ==Side effects== [97] => Up to 20% of people taking isoniazid experience [[peripheral neuropathy]] when taking daily doses of 6 mg/kg of body weight or higher.{{cite book|title=Applied Therapeutics| vauthors = Alldredge B |date=February 12, 2013| publisher = Lippincott Williams & Wilkins |isbn=9781609137137}} Gastrointestinal reactions include nausea and vomiting.{{cite web|url=http://medlibrary.org/lib/rx/meds/isoniazid-10/|title=Isoniazid (package insert)|date=30 March 2023 }} [[Aplastic anemia]], [[thrombocytopenia]], and [[agranulocytosis]] due to lack of production of red blood cells, platelets, and white blood cells by the bone marrow respectively, can also occur. Hypersensitivity reactions are also common and can present with a [[maculopapular]] rash and fever. [[Gynecomastia]] may occur. [98] => [99] => Asymptomatic elevation of serum liver enzyme concentrations occurs in 10% to 20% of people taking INH, and liver enzyme concentrations usually return to normal even when treatment is continued.{{cite web|title=Latent Tuberculosis Infection: A Guide for Primary Health Care Providers|url=https://www.cdc.gov/tb/publications/ltbi/treatment.htm|website=cdc.gov|publisher=Center for Disease Control|access-date=25 March 2016|url-status=live|archive-url=https://web.archive.org/web/20160325150054/http://www.cdc.gov/tb/publications/ltbi/treatment.htm|archive-date=25 March 2016}} Isoniazid has a boxed warning for severe and sometimes fatal hepatitis, which is age-dependent at a rate of 0.3% in people 21 to 35 years old and over 2% in those over age 50.Trevor, A. & Katzung, B. (2013). Katzung & Trevor's Pharmacology: examination & board review (10th ed., p. 417). New York. McGraw-Hill Medical, Lange. Symptoms suggestive of liver toxicity include nausea, vomiting, abdominal pain, dark urine, right upper quadrant pain, and loss of appetite. Black and Hispanic women are at higher risk for isoniazid-induced hepatotoxicity. When it happens, isoniazid-induced liver toxicity has been shown to occur in 50% of patients within the first 2 months of therapy.{{cite web|url=http://www.uptodate.com/contents/isoniazid-an-overview|title=Isoniazid UpToDate|url-status=live|archive-url=https://web.archive.org/web/20151025175722/http://www.uptodate.com/contents/isoniazid-an-overview|archive-date=2015-10-25}} [100] => [101] => Some recommend that liver function should be monitored carefully in all people receiving it, but others recommend monitoring only in certain populations.{{cite web|title=Treatment of Tuberculosis – Guidelines (4th ed.)|url=http://apps.who.int/iris/bitstream/10665/44165/1/9789241547833_eng.pdf?ua=1&ua=1|website=who.int|publisher=World Health Organization|access-date=25 March 2016|url-status=live|archive-url=https://web.archive.org/web/20160404193153/http://apps.who.int/iris/bitstream/10665/44165/1/9789241547833_eng.pdf?ua=1&ua=1|archive-date=4 April 2016}}{{cite journal | vauthors = Joint T | title = Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society | journal = Thorax | volume = 53 | issue = 7 | pages = 536–548 | date = July 1998 | pmid = 9797751 | pmc = 1745276 | doi = 10.1136/thx.53.7.536 }} [102] => [103] => Headache, poor concentration, weight gain, poor memory, insomnia, and depression have all been associated with isoniazid use. All patients and healthcare workers should be aware of these serious side effects, especially if suicidal ideation or behavior are suspected.{{cite journal | vauthors = Alao AO, Yolles JC | title = Isoniazid-induced psychosis | journal = The Annals of Pharmacotherapy | volume = 32 | issue = 9 | pages = 889–891 | date = September 1998 | pmid = 9762376 | doi = 10.1345/aph.17377 | s2cid = 73122253}}{{cite journal | vauthors = Iannaccone R, Sue YJ, Avner JR | title = Suicidal psychosis secondary to isoniazid | journal = Pediatric Emergency Care | volume = 18 | issue = 1 | pages = 25–27 | date = February 2002 | pmid = 11862134 | doi = 10.1097/00006565-200202000-00008 | s2cid = 31383347 | doi-access = free }}{{cite journal | vauthors = Pallone KA, Goldman MP, Fuller MA | title = Isoniazid-associated psychosis: case report and review of the literature | journal = The Annals of Pharmacotherapy | volume = 27 | issue = 2 | pages = 167–170 | date = February 1993 | pmid = 8439690 | doi = 10.1177/106002809302700205 | s2cid = 28637999}} [104] => [105] => Isoniazid is associated with [[pyridoxine]] (vitamin B6) deficiency because of its similar structure. Isoniazid is also associated with increased excretion of pyridoxine. Pyridoxal phosphate (a derivative of pyridoxine) is required for δ-[[aminolevulinic acid synthase]], the enzyme responsible for the rate-limiting step in heme synthesis. Therefore, isoniazid-induced pyridoxine deficiency causes insufficient heme formation in early red blood cells, leading to [[sideroblastic anemia]]. [106] => [107] => Isoniazid was found to significantly elevate the in vivo concentration of [[GABA]] and [[homocarnosine]] in a single subject via [[magnetic resonance spectroscopy]].{{cite journal | vauthors = Landheer K, Prinsen H, Petroff OA, Rothman DL, Juchem C | title = Elevated homocarnosine and GABA in subject on isoniazid as assessed through 1H MRS at 7T | journal = Analytical Biochemistry | volume = 599 | pages = 113738 | date = June 2020 | pmid = 32302606 | doi = 10.1016/j.ab.2020.113738 | s2cid = 215809029 }} [108] => [109] => ==Drug interactions== [110] => People taking isoniazid and acetaminophen are at risk of acetaminophen toxicity. Isoniazid is thought to induce a liver enzyme which causes a larger amount of acetaminophen to be metabolized to a toxic form.{{cite journal | vauthors = Murphy R, Swartz R, Watkins PB | title = Severe acetaminophen toxicity in a patient receiving isoniazid | journal = Annals of Internal Medicine | volume = 113 | issue = 10 | pages = 799–800 | date = November 1990 | pmid = 2240884 | doi = 10.7326/0003-4819-113-10-799 }}{{cite journal | vauthors = Burk RF, Hill KE, Hunt RW, Martin AE | title = Isoniazid potentiation of acetaminophen hepatotoxicity in the rat and 4-methylpyrazole inhibition of it | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 69 | issue = 1 | pages = 115–118 | date = July 1990 | pmid = 2218067 }} [111] => [112] => Isoniazid decreases the metabolism of carbamazepine, thus slowing down its clearance from the body. People taking carbamazepine should have their carbamazepine levels monitored and, if necessary, have their dose adjusted accordingly.{{cite journal | vauthors = Fleenor ME, Harden JW, Curtis G | title = Interaction between carbamazepine and antituberculosis agents | journal = Chest | volume = 99 | issue = 6 | pages = 1554 | date = June 1991 | pmid = 2036861 | doi = 10.1378/chest.99.6.1554a | doi-access = free }} [113] => [114] => It is possible that isoniazid may decrease the serum levels of ketoconazole after long-term treatment. This is seen with the simultaneous use of rifampin, isoniazid, and ketoconazole.{{cite journal | vauthors = Baciewicz AM, Baciewicz FA | title = Ketoconazole and fluconazole drug interactions | journal = Archives of Internal Medicine | volume = 153 | issue = 17 | pages = 1970–1976 | date = September 1993 | pmid = 8357281 | doi = 10.1001/archinte.153.17.1970 }} [115] => [116] => Isoniazid may increase the amount of phenytoin in the body. The doses of phenytoin may need to be adjusted when given with isoniazid.{{cite journal | vauthors = Jonville AP, Gauchez AS, Autret E, Billard C, Barbier P, Nsabiyumva F, Breteau M | title = Interaction between isoniazid and valproate: a case of valproate overdosage | journal = European Journal of Clinical Pharmacology | volume = 40 | issue = 2 | pages = 197–198 | date = 1991 | pmid = 2065702 | doi = 10.1007/BF00280078 | s2cid = 22218366 }}{{cite journal | vauthors = Bass JB, Farer LS, Hopewell PC, O'Brien R, Jacobs RF, Ruben F, Snider DE, Thornton G | title = Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention | journal = American Journal of Respiratory and Critical Care Medicine | volume = 149 | issue = 5 | pages = 1359–1374 | date = May 1994 | pmid = 8173779 | doi = 10.1164/ajrccm.149.5.8173779}} [117] => [118] => Isoniazid may increase the plasma levels of [[theophylline]]. There are some cases of theophylline slowing down isoniazid elimination. Both theophylline and isoniazid levels should be monitored.{{cite journal | vauthors = Höglund P, Nilsson LG, Paulsen O | title = Interaction between isoniazid and theophylline | journal = European Journal of Respiratory Diseases | volume = 70 | issue = 2 | pages = 110–116 | date = February 1987 | pmid = 3817069}} [119] => [120] => [[Valproate]] levels may increase when taken with isoniazid. Valproate levels should be monitored and its dose adjusted if necessary. [121] => [122] => ==Mechanism of action== [123] => Isoniazid is a [[prodrug]] that inhibits the formation of the [[mycobacterium|mycobacterial]] cell wall. Isoniazid must be activated by KatG, a bacterial catalase-peroxidase enzyme in ''[[Mycobacterium tuberculosis]]''.{{cite journal | vauthors = Suarez J, Ranguelova K, Jarzecki AA, Manzerova J, Krymov V, Zhao X, Yu S, Metlitsky L, Gerfen GJ, Magliozzo RS | title = An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG) | journal = The Journal of Biological Chemistry | volume = 284 | issue = 11 | pages = 7017–7029 | date = March 2009 | pmid = 19139099 | pmc = 2652337 | doi = 10.1074/jbc.M808106200 | doi-access = free }} KatG catalyzes the formation of the isonicotinic acyl radical, which spontaneously couples with [[NADH]] to form the nicotinoyl-NAD adduct. This complex binds tightly to the [[enoyl-acyl carrier protein reductase]] InhA, thereby blocking the natural enoyl-AcpM substrate and the action of [[fatty acid synthase]]. This process inhibits the synthesis of [[mycolic acids]], which are required components of the [[mycobacterium|mycobacterial]] cell wall. A range of radicals are produced by KatG activation of isoniazid, including [[nitric oxide]],{{cite journal | vauthors = Timmins GS, Master S, Rusnak F, Deretic V | title = Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis | journal = Antimicrobial Agents and Chemotherapy | volume = 48 | issue = 8 | pages = 3006–3009 | date = August 2004 | pmid = 15273113 | pmc = 478481 | doi = 10.1128/AAC.48.8.3006-3009.2004 }} which has also been shown to be important in the action of another antimycobacterial prodrug [[pretomanid]].{{cite journal | vauthors = Singh R, Manjunatha U, Boshoff HI, Ha YH, Niyomrattanakit P, Ledwidge R, Dowd CS, Lee IY, Kim P, Zhang L, Kang S, Keller TH, Jiricek J, Barry CE | title = PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release | journal = Science | volume = 322 | issue = 5906 | pages = 1392–1395 | date = November 2008 | pmid = 19039139 | pmc = 2723733 | doi = 10.1126/science.1164571 | bibcode = 2008Sci...322.1392S}} [124] => [125] => [[Image:Activation of isoniazid with NAD.jpg|Isoniazid (INH) is activated by KatG to the isonicotinic acyl radical, which subsequently reacts with NAD to form the isonicotinic acyl-NADH complex.|500px]] [126] => [127] => Isoniazid is [[bactericidal]] to rapidly dividing [[mycobacterium|mycobacteria]], but is [[bacteriostatic]] if the mycobacteria are slow-growing.{{cite journal | vauthors = Ahmad Z, Klinkenberg LG, Pinn ML, Fraig MM, Peloquin CA, Bishai WR, Nuermberger EL, Grosset JH, Karakousis PC | title = Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig | journal = The Journal of Infectious Diseases | volume = 200 | issue = 7 | pages = 1136–1143 | date = October 2009 | pmid = 19686043 | doi = 10.1086/605605 | doi-access = free }} It inhibits the [[cytochrome P450 system]] and hence acts as a source of free radicals.{{cite book|title=Pharmacology| volume= 864| vauthors = Harvey RA, Howland RD, Mycek MJ, Champe PC | veditors = Harvey RA, Champe PC | publisher= Lippincott Williams & Wilkins| year= 2006| isbn= 9780781741187| edition= 4th}} [128] => [129] => Isoniazid is a mild [[monoamine oxidase inhibitor]](MAO-I).{{cite journal | vauthors = Judd FK, Mijch AM, Cockram A, Norman TR | title = Isoniazid and antidepressants: is there cause for concern? | journal = International Clinical Psychopharmacology | volume = 9 | issue = 2 | pages = 123–125 | date = 1994 | pmid = 8056994 | doi = 10.1097/00004850-199400920-00009}} [130] => [131] => ==Metabolism== [132] => Isoniazid reaches therapeutic concentrations in serum, [[cerebrospinal fluid]], and within [[caseous necrosis|caseous granulomas]]. It is metabolized in the liver via [[acetylation]] into acetylhydrazine. Two forms of the enzyme are responsible for acetylation, so some patients metabolize the drug more quickly than others. Hence, the [[half-life]] is [[Bimodal distribution|bimodal]], with "slow acetylators" and "fast acetylators". A graph of number of people versus time shows peaks at one and three hours. The height of the peaks depends on the ethnicities of the people being tested. The metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of [[renal failure]].{{cn|date=August 2022}} [133] => [134] => ==History== [135] => First synthesis was described in 1912.{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | language = de | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 393–414 | date = 1912-04-01 | pmid = 32166015 | doi = 10.1177/2045894020908782 | pmc = 7052475 }} A. Kachugin invented the drug against tuberculosis under name Tubazid in 1949. Three pharmaceutical companies unsuccessfully attempted to patent the drug at the same time,{{cite journal | vauthors = Rieder HL | title = Fourth-generation fluoroquinolones in tuberculosis | journal = Lancet | volume = 373 | issue = 9670 | pages = 1148–1149 | date = April 2009 | pmid = 19345815 | doi = 10.1016/S0140-6736(09)60559-6 | s2cid = 43789954}} the most prominent one being Roche, which launched its version, Rimifon, in 1952.{{cite web| url= http://www.rocheusa.com/about/history.html |title= History| website= rocheusa.com| publisher= Roche USA| archive-url= https://web.archive.org/web/20071212082842/http://www.rocheusa.com/about/history.html | archive-date=2007-12-12}} With the introduction of isoniazid, a cure for tuberculosis was first considered possible.{{cn|date=August 2022}} [136] => [137] => The drug was first tested at [[Many Farms, Arizona|Many Farms]], a [[Navajo Nation|Navajo]] community in [[Arizona]], due to the Navajo reservation's tuberculosis problem and because the population had not previously been treated with [[streptomycin]], the main tuberculosis treatment at the time.{{cite journal | vauthors = Jones DS | title = The health care experiments at Many Farms: the Navajo, tuberculosis, and the limits of modern medicine, 1952-1962 | journal = Bulletin of the History of Medicine | volume = 76 | issue = 4 | pages = 749–790 | year = 2002 | pmid = 12446978 | doi = 10.1353/bhm.2002.0186 | s2cid = 30166423 }} The research was led by [[Walsh McDermott]], an infectious disease researcher with an interest in public health, who had previously taken isoniazid to treat his own tuberculosis.{{cite book|chapter-url=https://www.nap.edu/read/1652/chapter/15#283|chapter=Walsh McDermott|pages=282–307|publisher=[[National Academies Press]]|title=Biographical Memoirs | volume = 59 |year=1990| vauthors = Beeson PB |doi=10.17226/1652|isbn=978-0-309-04198-0}} [138] => [139] => Isoniazid and a related drug, [[iproniazid]], were among the first drugs to be referred to as [[antidepressant]]s.{{cite journal | vauthors = Moncrieff J | title = The creation of the concept of an antidepressant: an historical analysis | journal = Social Science & Medicine | volume = 66 | issue = 11 | pages = 2346–2355 | date = June 2008 | pmid = 18321627 | doi = 10.1016/j.socscimed.2008.01.047 }} [140] => [141] => ==Preparation== [142] => Isoniazid is an [[isonicotinic acid]] [[derivative (chemistry)|derivative]]. It is manufactured using [[4-cyanopyridine]] and [[hydrazine hydrate]].{{cite book|last1=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia|date=2008|publisher=Elsevier Science|location=Norwich, NY|isbn=9780815515265|pages=1968–1970|edition=3rd|url=https://books.google.com/books?id=bRX8MwEACAAJ&q=9780815515265}} In another method, isoniazid was claimed to have been made from [[citric acid]] starting material.{{cite journal | vauthors = Baizer MM, Dub M, Gister S, Steinberg NG | title = Synthesis of isoniazid from citric acid | journal = Journal of the American Pharmaceutical Association | volume = 45 | issue = 7 | pages = 478–480 | date = July 1956 | pmid = 13345683 | doi = 10.1002/jps.3030450714}} [143] => [144] => It can in theory be made from [[methyl isonicotinate]], which is labelled a [[semiochemical]]. [145] => [146] => ==Brand names== [147] => Hydra, Hyzyd, Isovit, Laniazid, Nydrazid, Rimifon, and Stanozide.{{cite web|title=Drugs@FDA|url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm|website=fda.gov|publisher=United States Food and Drug Administration|access-date=22 August 2016|url-status=live|archive-url=https://web.archive.org/web/20120814072104/http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm|archive-date=14 August 2012}} [148] => [149] => ==Other uses== [150] => ===Chromatography=== [151] => Isonicotinic acid hydrazide is also used in [[chromatography]] to differentiate between various degrees of [[conjugated system|conjugation]] in [[organic compound]]s barring the [[ketone]] [[functional group]].{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 102–105 | date = 1959 | pmid = 32166015 | doi = 10.1021/ac60145a020 | pmc = 7052475 }} The test works by forming a [[hydrazone]] which can be detected by its [[bathochromic shift]].{{cn|date=December 2022}} [152] => [153] => ===Dogs=== [154] => Isoniazid may be used for dogs, but there have been concerns it can cause seizures.{{cite book | vauthors = Sykes JE |title= Canine and Feline Infectious Diseases |format= E-Book |date=2013 |publisher= Elsevier Health Sciences |isbn=978-0323241946 |page=425 |url= https://books.google.com/books?id=cb0kTIlb8HgC&pg=PA425 | via = Google Books}} [155] => [156] => == References == [157] => {{Reflist}} [158] => [159] => == Further reading == [160] => * {{cite journal | vauthors = Romero JA, Kuczler FJ | title = Isoniazid overdose: recognition and management | journal = American Family Physician | volume = 57 | issue = 4 | pages = 749–752 | date = February 1998 | pmid = 9490997 | url = http://www.aafp.org/afp/980215ap/romero.html | access-date = 2005-12-13 | archive-date = 2011-11-01 | archive-url = https://web.archive.org/web/20111101092427/http://www.aafp.org/afp/980215ap/romero.html | url-status = dead}} [161] => [162] => == External links == [163] => * {{Commonscatinline}} [164] => [165] => {{Antimycobacterials}} [166] => {{Cell wall disruptive antibiotics}} [167] => {{Monoamine metabolism modulators}} [168] => {{GABA metabolism and transport modulators}} [169] => {{Hydrazines}} [170] => {{Portal bar | Medicine}} [171] => {{Authority control}} [172] => [173] => [[Category:Anti-tuberculosis drugs]] [174] => [[Category:Antidepressants]] [175] => [[Category:CYP3A4 inhibitors]] [176] => [[Category:Disulfiram-like drugs]] [177] => [[Category:GABA transaminase inhibitors]] [178] => [[Category:Hepatotoxins]] [179] => [[Category:Hydrazides]] [180] => [[Category:4-Pyridyl compounds]] [181] => [[Category:Prodrugs]] [182] => [[Category:Vitamin B6 antagonists]] [183] => [[Category:World Health Organization essential medicines]] [184] => [[Category:Wikipedia medicine articles ready to translate]] [] => )
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Isoniazid

Isoniazid is an antibiotic medication primarily used for the treatment of tuberculosis (TB). It is included in the list of essential medicines by the World Health Organization (WHO) and is considered one of the most effective drugs for treating TB.

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It is included in the list of essential medicines by the World Health Organization (WHO) and is considered one of the most effective drugs for treating TB. Isoniazid works by inhibiting the growth and replication of the bacteria that cause the disease. The Wikipedia page on isoniazid provides comprehensive information about the drug, including its history, mechanism of action, uses, side effects, and contraindications. The medication was first discovered in the mid-20th century and has since played a crucial role in the global efforts to combat TB. The page explains that isoniazid is typically administered orally and is often used in combination with other antibiotics to form multidrug therapy regimens. It highlights the importance of patient adherence to the prescribed treatment, as incomplete dosing or premature discontinuation can lead to the development of drug-resistant strains of TB. Furthermore, the page addresses the potential side effects and adverse reactions associated with isoniazid. While the drug is generally well-tolerated, some individuals may experience liver toxicity or peripheral neuropathy. These risks are discussed in detail, along with recommendations for monitoring and management. The page also delves into the contraindications and precautions associated with the use of isoniazid. Individuals with liver disease, alcoholics, and those with certain genetic factors may be more susceptible to adverse effects and require careful monitoring during treatment. In addition to its role in TB treatment, the page also mentions other uses of isoniazid, such as in the preventative treatment of latent tuberculosis infection in high-risk individuals. It highlights the medication's importance in reducing the risk of developing active TB in these cases. Overall, the Wikipedia page on isoniazid provides a comprehensive overview of the drug, covering its history, mechanism of action, uses, side effects, contraindications, and precautions. It serves as a valuable resource for healthcare professionals, researchers, and individuals seeking information about the medication.

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