Hepatotoxicity causes: Difference between revisions

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Latest revision as of 20:20, 15 July 2016

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Drug Side Effect

Overview

More than 900 drugs have been implicated in causing liver injury^[1] and it is the most common reason for a drug to be withdrawn from the market. Chemicals often cause subclinical injury to liver which manifests only as abnormal liver enzyme tests. Drug induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.^[2]^[3]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Hepatotoxicity}}
-{{CMG}}
+{{CMG}} {{AE}}
-==Specific Drug or Toxin==
+{{PleaseHelp}}
-*Acetaminophen: [[Acetaminophen]] (paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and [[acute liver failure]] worldwide,<ref name="isbn0-443-06633-7"/> which is one of the most painful experiences patients report.  Reports of death from accute hepatotoxicity have been reported to be as low as 2.5 grams over a 24 hour period. Damage to the liver is not due to the drug itself but to a toxic metabolite (''N''-acetyl-''p''-benzoquinone imine NAPQI, or NABQI) which is produced by cytochrome P450 enzymes in the liver.<ref name="pmid15345657">{{cite journal |author=Wallace JL |title=Acetaminophen hepatotoxicity: NO to the rescue |journal=Br. J. Pharmacol. |volume=143 |issue=1 |pages=1–2 |year=2004 |pmid=15345657 |doi=10.1038/sj.bjp.0705781}}</ref> In normal circumstances this metabolite is detoxified by conjugating with [[glutathione]] in phase 2 reaction. In overdose large amount of NAPQI is generated which overwhelm the detoxification process and lead to damage to liver cells. [[Nitric oxide]] also plays role in inducing toxicity.<ref>{{cite journal |author=James LP, Mayeux PR, Hinson JA |title=Acetaminophen-induced hepatotoxicity |journal=Drug Metab. Dispos. |volume=31 |issue=12 |pages=1499–506 |year=2003 |pmid=14625346 |doi=10.1124/dmd.31.12.1499}}</ref> The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote etc. The dose toxic to liver is quite variable and is lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher level predicting worse prognosis. Administration of [[Acetylcysteine]], a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those who develop [[acute liver failure]] can still recover spontaneously,  but may require transplantation if poor [[prognostic]] signs such as [[encephalopathy]] or [[coagulopathy]] is present (see [[King's College Criteria]]). [[Image:Paracetamol-rod-povray.png|thumb|Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease]]
-*Nonsteroidal anti-inflammatory drugs: Although individual analgesics rarely induce liver damage, due to their widespread use NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose dependent and idiosyncratic reactions have been documented.<ref>{{cite journal |author=Manov I, Motanis H, Frumin I, Iancu TC |title=Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects |journal=Acta Pharmacol. Sin. |volume=27 |issue=3 |pages=259–72 |year=2006 |pmid=16490160 |doi= |doi=10.1111/j.1745-7254.2006.00278.x}}</ref> Aspirin and [[phenylbutazone]] are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac,  phenylbutazone, piroxicam, diclofenac and indomethacin.
+===Drug Side Effect===
+*[[Ado-trastuzumab emtansine]]
+*[[Ceritinib]]
+*[[clofarabine]]
+* [[Docetaxel]]
+* [[Eltrombopag]]
+* [[Eribulin]]
+* [[Fluoxymesterone]]
+* [[Hydrochlorothiazide]]
+* [[Idelalisib]]
+* [[Interferon alfa-2b ]]
+* [[Lapatinib]]
+* [[Lenvatinib]]
+* [[Losartan]]
+* [[Mercaptopurine]]
+* [[Pegaspargase]]
+* [[Potassium]]
+* [[rifapentin]]
+* [[Tipranavir]]
+* [[Zileuton]]
+==Overview==
+More than 900 drugs have been implicated in causing liver injury<ref name="isbn0-8385-1551-7">{{cite book |author=Friedman, Scott E.; Grendell, James H.; McQuaid, Kenneth R. |title=Current diagnosis & treatment in gastroenterology |publisher=Lang Medical Books/McGraw-Hill |location=New York |year=2003 |pages=p664-679 |isbn=0-8385-1551-7 |oclc= |doi=}}</ref> and it is the most common reason for a drug to be withdrawn from the market. Chemicals often cause [[subclinical]] injury to liver which manifests only as abnormal [[Liver function tests|liver enzyme tests]]. Drug induced liver injury is responsible for 5% of all hospital admissions and 50% of all [[acute liver failure]]s.<ref name="isbn1-56053-618-7">{{cite book |author=McNally, Peter F. |title=GI/Liver Secrets: with STUDENT CONSULT Access |publisher=C.V. Mosby |location=Saint Louis |year= |pages= |isbn=1-56053-618-7 |oclc= |doi=}}</ref><ref>{{cite journal |author=Ostapowicz G, Fontana RJ, Schiødt FV, ''et al'' |title=Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States |journal=Ann. Intern. Med. |volume=137 |issue=12 |pages=947–54 |year=2002 |pmid=12484709 |doi=}}</ref>
+==Causes==
+===Causes in Alphabetical Order===
+: List the causes of the disease in alphabetical order. You may need to list across the page, as seen [[Jaundice causes#Causes in Alphabetical Order|here]]
+{{col-begin|width=80%}}
+{{col-break|width=33%}}
+*[[5-fluorocytosine]]
+*[[Abacavir]]
+*[[Abiraterone]]
+*[[Acetaminophen]] (paracetamol)
+*[[Alcohol]]
+*[[Allopurinol]]
+*[[Amatoxins]]
+*[[Amiodarone]]
+*[[Amoxicillin]]
+*[[Amoxicillin–clavulanate]]
+*[[Amphotericin]]
+*[[Anabolic c-17]]
+*[[Anesthetic agent]]
+*[[Antianginal agents]]
+*[[Antiarrhythmics]]
+*[[Antibiotics]]
+*[[Anticoagulants]]
+*[[Anticonvulsives]]
+*[[Antifungals]]
+*[[Antihyperlipidemic agents]]
+*[[Antihypertensives]]
+*[[Antineoplastic agents]]
+*[[Antithyroid drugs]]
+*[[Antituberculous agents]]
+*[[Antiviral medication]]
+*[[Aspirin]]
+*[[Benzodiazepine]]
+*[[British anti-lewisite penicillamine]]
+*[[Bromfenac]]
+*[[Bromfenacb]]
+*[[Butyrophenone]]
+*[[Captopril]]
+*[[Carbamazepine]]
+*[[Carbimazole]]
+*[[Carbon tetrachloride]]
+*[[Carboplatin]]
+*[[caspofungin acetate]]
+*[[Cephalosporin]]
+*[[Ciclosporin]]
+*[[Chaparral]]
+*[[Chlorambucil]]
+*[[Chloramphenicol]]
+*[[Chlormethiazole]]
+*[[Chloroform]]
+*[[Cimetidine]]
+*[[Ciprofloxacin]]
+*[[Clindamycin]]
+*[[Cocaine]]
+*[[Colchicine]]
+*[[Comfrey]]
+*[[Cotrimoxazole]]
+*[[Crizotinib]]
+*[[Cyclopropane]]
+*[[Cycloserine]]
+*[[Cyproterone acetate]]
+*[[Cytarabine]]
+*[[Dantrolene]]
+*[[Dapsone]]
+*[[Diclofenac]]
+*[[Didanosine]]
+*[[Dideoxyinosine]]
+*[[Diflunisal]]
+*[[Disulfiram]]
+*[[Diuretic agents]]
+*[[Docetaxel]]
+*[[Doxycycline]]
+*[[Duloxetine]]
+*[[Ebrotidine]]
+*[[Ecarazine]]
+*[[Efavirenz]]
+*[[Enalapril]]
+*[[Endocrine agent]]
+{{col-break|width=33%}}
+*[[Enflurane]]
+*[[Erlotinib]]
+*[[Erythromycin estolate]]
+*[[Erythromycin ethyl succinate]]
+*[[Ethanol]]
+*[[Ether]]
+*[[Ethionamide]]
+*[[Etodolac]]
+*[[Felbamate]]
+*[[Fenoprofen]]
+*[[Fialuridine]]
+*[[Flucloxacillin]]
+*[[Flutamide]]
+*[[Gemcitabine]]
+*[[Gemtuzumab]]
+*[[Germander]]
+*[[Glucocorticoids]]
+*[[Gold]]
+*[[Greater celandine]]
+*[[Griseofulvin]]
+*[[Gyromitrin]]
+*[[Halothane]]
+*[[He shon wu]]
+*[[Herbal slimming aids]]
+*[[Herbalife®]]
+*[[Highly active antiretroviral treatment]]
+*[[Hydrazine sulfate]]
+*[[Hydroxycut®]]
+*[[Ibuprofen]]
+*[[Ibuprofen ]]
+*[[Idoxuridine]]
+*[[Imatinib mesylate]]
+*[[Indomethacin]]
+*[[Interferon beta]]
+*[[Interferons]]
+*[[Iodide ion]]
+*[[Iron compounds]]
+*[[Isoflurane]]
+*[[Isoniazid]]
+*[[Itraconazole]]
+*[[Kava 3,4- methylenedioxymethamphetamine]]
+*[[Kava kava]]
+*[[Ketoconazole]]
+*[[Labetalol]]
+*[[Lamotrigine]]
+*[[Leflunomide]]
+*[[Leflunomide ]]
+*[[Lipokinetix®]]
+*[[Lisinopril]]
+*[[Ma huang]]
+*[[Mdma (ecstasy)]]
+*[[Mephenytoin]]
+*[[Methamphetamine]]
+*[[Methotrexate]]
+*[[Methoxyflurane]]
+*[[Methyldopa]]
+*[[Minocycline]]
+*[[Monoamine oxidase inhibitors]]
+*[[Mushroom poisoning]]
+*[[Naltrexone]]
+*[[Naproxen]]
+*[[Nefazodone]]
+{{col-break|width=33%}}
+*[[Nevirapine]]
+*[[Nicotinic acid]]
+*[[Nimesulide ]]
+*[[Nitisinone]]
+*[[Nitrofuran]]
+*[[Nitrofurantoin]]
+*[[Nitrous oxide]]
+*[[Nonsteroidal anti-inflammatory drugs]]
+*[[Novobiocin]]
+*[[Ofloxacin]]
+*[[Omeprazole]]
+*[[Oral hypoglycemics]]
+*[[Oxaprozin ]]
+*[[P-aminosalicylic acid]]
+*[[Paracetamol]]
+*[[Pazopanib]]
+*[[Pemoline]]
+*[[Penicillin]]
+*[[Phenobarbital]]
+*[[Phenothiazines]]
+*[[Phenprocoumon]]
+*[[Phenylbutazone]]
+*[[Phenytoin]]
+*[[Ponatinib hydrochloride]]
+*[[Piroxicam ]]
+*[[Poison mushrooms (amanita phalloides)]]
+*[[Propylthiouracil]]
+*[[Psychotropic agents]]
+*[[Pyrazinamide]]
+*[[Quinolone]]
+*[[Ranitidine]]
+*[[Regorafenib]]
+*[[Rifampicin]]
+*[[Rifampin]]
+*[[Salicylate]]
+*[[Saramycetin]]
+*[[Senecio]]
+*[[Spectinomycin]]
+*[[Statins]]
+*[[Steroids]]
+*[[Sulfonamide]]
+*[[Sulfonamides]]
+*[[Sulfones]]
+*[[Sulindac]]
+*[[Suloctidil]]
+*[[Tacrine]]
+*[[Tamoxifen]]
+*[[Telithromycin]]
+*[[Terbinafine]]
+*[[Tetrabamate]]
+*[[Tetracycline]]
+*[[Thioxanthene]]
+*[[Thorotrast]]
+*[[Tienilic acid]]
+*[[Tolcapone]]
+*[[Toluene]]
+*[[Topiramate]]
+*[[Tricyclic antidepressant]]
+*[[Tricyclic antidepressants]]
+*[[Troglitazone]]
+*[[Trovofloxacin]]
+*[[Valproic acid]]
+*[[Vidarabine]]
+*[[Vitamin a]]
+*[[Xenylamine]]
+*[[Zafirlukast]]
+*[[Zalcitabine]]
+*[[Zoxazolamine]]
+{{col-end}}
+===Specific Drug or Toxin===
+*Acetaminophen: [[Acetaminophen]] (paracetamol, also known by the brand name Tylenol and Panadol) is usually well tolerated in prescribed dose but overdose is the most common cause of drug induced liver disease and [[acute liver failure]] worldwide,<ref name="isbn0-443-06633-7">{{cite book |author=Keeffe, Emmet B; Friedman, Lawrence M. |title=Handbook of liver diseases |publisher=Churchill Livingstone |location=Edinburgh |year=2004 |pages=104-123 |isbn=0-443-06633-7 |oclc= |doi= |accessdate=2007-09-07}}</ref> which is one of the most painful experiences patients report.  Reports of death from accute hepatotoxicity have been reported to be as low as 2.5 grams over a 24 hour period. Damage to the liver is not due to the drug itself but to a toxic metabolite (''N''-acetyl-''p''-benzoquinone imine NAPQI, or NABQI) which is produced by cytochrome P450 enzymes in the liver.<ref name="pmid15345657">{{cite journal |author=Wallace JL |title=Acetaminophen hepatotoxicity: NO to the rescue |journal=Br. J. Pharmacol. |volume=143 |issue=1 |pages=1–2 |year=2004 |pmid=15345657 |doi=10.1038/sj.bjp.0705781}}</ref> In normal circumstances this metabolite is detoxified by conjugating with [[glutathione]] in phase 2 reaction. In overdose large amount of NAPQI is generated which overwhelm the detoxification process and lead to damage to liver cells. [[Nitric oxide]] also plays role in inducing toxicity.<ref>{{cite journal |author=James LP, Mayeux PR, Hinson JA |title=Acetaminophen-induced hepatotoxicity |journal=Drug Metab. Dispos. |volume=31 |issue=12 |pages=1499–506 |year=2003 |pmid=14625346 |doi=10.1124/dmd.31.12.1499}}</ref> The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote etc. The dose toxic to liver is quite variable and is lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher level predicting worse prognosis. Administration of [[Acetylcysteine]], a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those who develop [[acute liver failure]] can still recover spontaneously,  but may require transplantation if poor [[prognostic]] signs such as [[encephalopathy]] or [[coagulopathy]] is present (see [[King's College Criteria]]). [[Image:Paracetamol-rod-povray.png|thumb|center|Acetaminophen (3D structure) overdose is the most common cause of drug induced liver disease]]
+*Nonsteroidal anti-inflammatory drugs: Although individual analgesics rarely induce liver damage, due to their widespread use NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose dependent and idiosyncratic reactions have been documented.<ref>{{cite journal |author=Manov I, Motanis H, Frumin I, Iancu TC |title=Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects |journal=Acta Pharmacol. Sin. |volume=27 |issue=3 |pages=259–72 |year=2006 |pmid=16490160 |doi=10.1111/j.1745-7254.2006.00278.x}}</ref> Aspirin and [[phenylbutazone]] are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac,  phenylbutazone, piroxicam, diclofenac and indomethacin.
 *Glucocorticoids: Glucocorticoids are so named due to their effect on carbohydrate mechanism. they promote glycogen storage in liver. Enlarged liver is a rare side effect of long term steroid use in children.<ref name="pmid3944744">{{cite journal |author=Iancu TC, Shiloh H, Dembo L |title=Hepatomegaly following short-term high-dose steroid therapy |journal=J. Pediatr. Gastroenterol. Nutr. |volume=5 |issue=1 |pages=41–6 |year=1986 |pmid=3944744 |doi=}}</ref> The classical effect of prolonged use both in adult and [[paediatric]] population is steatosis.<ref>
@@ Line 20: / Line 316: @@
 *Natural products like: Amanita mushroom, particularly the [[destroying angel]]s, aflatoxins
-*Industrial toxins like: Arsenic, Carbon tetraChloride, Vinyl Chloride
+*Industrial toxins like: Arsenic, carbon tetra chloride, vinyl chloride
+*Herbal and alternative remedies like: Ackee fruit, bajiaolian, camphor, copaltra, cycasin, kava, pyrrolizidine alkaloids, horse chestnut leaf, valerian, comfrey (often used in herbal tea)<ref name="pmid15264453">{{cite journal |author=Pak E, Esrason KT, Wu VH |title=Hepatotoxicity of herbal remedies: an emerging dilemma |journal=Progress in transplantation (Aliso Viejo, Calif.) |volume=14 |issue=2 |pages=91–6 |year=2004 |pmid=15264453 |doi=}}</ref>
-*Herbal and alternative remedies like: Ackee fruit, Bajiaolian, Camphor, Copaltra, Cycasin, Kava, Pyrrolizidine alkaloids, Horse chestnut leaf, Valerian, Comfrey (often used in herbal tea)<ref name="pmid15264453">{{cite journal |author=Pak E, Esrason KT, Wu VH |title=Hepatotoxicity of herbal remedies: an emerging dilemma |journal=Progress in transplantation (Aliso Viejo, Calif.) |volume=14 |issue=2 |pages=91–6 |year=2004 |pmid=15264453 |doi=}}</ref>
+*Chinese herbal remedies like: Jin Bu Huan, Ma-Huang, Sho-Wu-Pian
-*Chinese herbal remedies:
-:Jin Bu Huan, Ma-huang, Sho-wu-pian
 <gallery>
@@ Line 34: / Line 330: @@
 ==References==
+{{Reflist|2}}
-{{Reflist|2}}
 [[Category:Disease]]
+[[Category:Hepatology]]
 [[Category:Gastroenterology]]
-[[Category:Needs overview]]
+[[Category:Needs content]]
+[[Category:Needs causes]]
+{{WS}}
+{{WH}}

Hepatotoxicity causes: Difference between revisions

Latest revision as of 20:20, 15 July 2016

Drug Side Effect

Overview

Causes

Causes in Alphabetical Order

Specific Drug or Toxin

References

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