drug induced liver toxicity-final.ppt

8/17/2019 Drug Induced Liver Toxicity-final.ppt

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Drug Induced Liver

Toxicity(DILT)By:

Mahmoud Mahmoud, MD,PhD


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Illustration of the proposed mechanism of DILI, which involves drugmetabolism, hepatocyte damage, activation of innate immune cells, andproduction of tissue-damaging and tissue-protective mediators. C !indicates cytochrome !"#$% I&', interferon% IL, interleu(in% '), natural(iller cell% ')*, natural (iller * cell% *'&, tumor necrosis factor.


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Liver in ury occurs with manydrugs through a variety ofmechanisms .

*he annual incidence is generallyfelt to be between one in 1$,$$$ to1$$,$$$%


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It is responsible for

It accounts for up to 1$ percent of all adverse drugreactions.

It is seen in up to +$ percent of patients whopresent with acute hepatitis and represents up to1$ percent of consultations by hepatologists, andabout 1 percent of all general medical admissions.

It is the cause of acute aundice in up to #$ percentof patients.

It is the most common cause of acute liver failure inthe nited tates, and is the most fre/uently citedreason for withdrawal of medications from themar(etplace.


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Classi0cations of drug-induced liver i

Type of classification Examples

Clinical laboratory

Hepatocellular

Cholestatic

Mixed hepatocellular/cholestatic

Mechanism of hepatotoxicity

Direct hepatotoxicity

Idiosyncratic

Immune-mediated

Metabolic

Histologic findings

Cellular necrosis or apoptosis

CholestasisSteatosis

Fibrosis

Phospholipidosis

ranulomatous

Sinuoidal obstruction syndrome


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SPECT !M "# D !$%I&D!CED LI'E I& !

Classi0cation is based upon *he clinical presentation and laboratoryfeatures, the mechanism of to3icity, and4or the histological 0ndings.5cute presentations range from asymptomatic mild biochemicalabnormalities to an acute illness with aundice that resembles viralhepatitis to acute liver failure.

*cute Pre+entation: aundice 6serum bilirubin 7+ times the upper limit of normal8 9aminotransferase elevations is associated with a worse prognosisthan isolated aminotransferase abnormalities.some drugs are associated with chronic histologic in:ammatorychanges and a clinical syndrome resembling autoimmune hepatitiswhile others cause endothelial damage or thrombosis leading tovascular complications such as veno-occlusive disease or ;udd-Chiari syndrome.

ithdra-a. o/ the o0ending drug u+ua..y .ead+ to rever+a. o/the in1ury2 3o-ever, +ome ty4e+ o/ toxicity can 5e a++ociated-ith a 4rogre++ive cour+e, 4o++i5.y .eading to 65ro+i+ orcirrho+i+, de+4ite di+continuation o/ the drug2


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Su5c.inica.

=any drugs can induce asymptomatic elevations inliver en>ymes without producing overt clinical disease. Drug-induced liver in ury 6DILI8 is generallyconsidered subclinical or insigni0cant if the serumalanine aminotransferase 65L*8 is ?+ times the upperlimit of normal.

ubclinical liver disease has been described with certain antibiotics, antidepressants, lipid-lowering drugs,sulfonamides, salicylates, sulfonylureas, and /uinidine .5 higher percentage of asymptomatic 5L* elevations canbe seen with other medications, including isonia>id 6upto 2$ percent8 and tacrine 6up to #$ percent8.

=ost subclinical 5L* elevations are benign and resolveonce the o@ending agent has been discontinued.

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1- 5cute liver in ury

*he patterns of acute in ury may presentas hepatocellular 6cytoto3ic8 damage,cholestasis, a mi3ed pattern or, lesscommonly, steatosisever+i5.e and i+ getting -or+e-hen com5ined -ith 1aundice

*he most common drugs in nited tatesare

acetaminophen followed by antibiotics.Borldwide, amo3icillin-clavulanate is one ofthe most commonly reported antibiotics thatcause DILI. Its classic pattern ofhepatoto3icity is cholestatic.

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epatitis

Drug-induced acute hepatocellular in ury issimilar to that seen in viral hepatitis andincludes hepatocellular necrosis or apoptosis,

steatosis, and cellular degeneration.5 characteristic 0nding on laboratory testingis an elevation in serum aminotransferases .5 hepatocyte that has become sensiti>ed tothe immune system dies by apoptosis viadeath receptors at the cell surface.=oderate degrees of o3idative stress result inapoptosis at the intracellular level whilesevere o3idative stress leads to necrotic celllysis 6necrosis8.


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Liver is divided histologically into lobules. *he center of thelobule is the central vein. 5t the periphery of the lobule areportal triads. &unctionally, the liver can be divided into three>ones, based upon o3ygen supply. Eone 1 encircles the portaltracts where the o3ygenated blood from hepatic arteries enters.Eone + is located around central veins, where o3ygenation is

poor. Eone 2 is located in between.7one 8: ha+ P9 ;2 Mo+t +u+ce4ti5.e area /or drug toxicity

!"#$

Drug to3icity


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epatocellular necrosis can be >onal or non>onal,depending upon the o@ending agent.Eonal necrosis

Eone + carbon tetrachloride , acetaminophen Eone 2 yellow phosphorusEone 1 iron sulfate.

*here may be little or no in:ammatory response% however,damaged cells may accumulate fat 6triglycerides8.

'on>onal necrosis appears in a viral hepatitis-li(epattern. It is more often seen with compounds thatproduce unpredictable idiosyncratic in ury 6eg,phenytoin , methyldopa , isonia>id , and diclofenac 8.Certain medications, such as aspirin , produce anonspeci0c pattern of in ury,-hich i+ com4.ete.y rever+i5.e 5ut rare.y may5e a++ociated -ith 4rogre++ive he4atic /ai.ure 2

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!i"er needle biopsy sho#ing se"ere recurrent hepatitis C$cholestatic type% &his photomicrograph sho#s centrilobularcholestasis causing feathery degeneration of hepatocytes 'longarro#(% In addition$ there are foci of parenchymal necrosisincluding acidophilic bodies 'short arro#s(% H)* stain$ originalmagnification +,,x

http://www.medsci.org/v03/p0079/ijmsv03p0079g01.jpg


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Cholestatic

Cho.e+tatic G 5cute cholestatic in ury oftenresembles e3trahepatic obstructive aundice.Cholestatic in ury is typically recogni>ed bypredominant elevations in al(aline phosphatase and

bilirubin.Compounds that have been associated with acutecholestatic in ury include amo3icillin-clavulanate ,chlorproma>ine , nafcillin ,trimethoprim-sulfametho3a>ole , rifampin ,erythromycin estolate, captopril , estradiol , and rarely,amiodarone .

!atients rarely feel ill, with the most commonsymptoms being pruritus and aundice. erumaminotransferases are only mildly elevated 6usuallyless than eightfold8. *he overall prognosis for purelycholestatic in ury is better than for hepatocellularin ury, although fatalities have been reported.

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=i3ed !atterns

=i3ed patterns of in ury are common, andshow elevations in both aminotransferases

and al(aline phosphatase.5n e3ample of this pattern is seen in patientswith hepatoto3icity due to !henytoin . uchpatients may be at increased ris( to developchronic liver disease compared with otherforms of hepatoto3icity.

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*ype of in ury epatocellular Cholestatic =i3ed

5L* H *wofold rise 'ormal H *wofold rise

5L! 'ormal H *wofoldrise H *wofold rise

5L* 5L! ratio igh, H# Low, 2 2-#

J3amples K1

5cetaminophen

5llopurinol5miodarone55M*

' 5ID

5nabolic steroid

Chlorproma>ine

ClopidogrelJrythromycin

ormonal co

5mitryptyline ,JnalaprilCarbama>epine

ulfonamide!henytoin

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liver steatosis (Fat accumulation)

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teatosis

Drugs that disrupt beta-o3idation of lipids ando3idative energy production lead to steatosis.

istologically, acute steatosis tends to bemicrove+icu.ar and 4redominant.ytrig.yceride2

*his is especially true of steatohepatitis relatedto

MeyeNs syndrome,high-dose intravenous tetracycline , and amiodarone. Other drugs associated with microvesicularsteatosis include camphor, cocaine, piro3icam ,tolmetin , valproic acid , and the antiretroviral agents>idovudine 65E*8, stavudine , and didanosine 6ddI8.

erbal remedies are being increasingly identi0ed ascauses of steatosis and other forms of in ury.

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Extrahe4aticmani/e+tation+

ome drugs causing liver in ury may be associatedwith clinical features dominated by e3trahepaticmanifestations. 5s e3amples

Drugs causing hypersensitivity reactions 6eg, penicillin

and procainamide 8 may be associated with fever, rash,and peripheral eosinophilia.ome drugs 6eg, dapsone , phenytoin , sulfonamides8

may be associated with a mononucleosis-li(e illness 6pseudomononucleosis8 including lymph nodeenlargement, lymphocytosis, and atypical lymphocytes.

*o3icity to multiple organs 6eg, bone marrow, (idney,lung, s(in and vessels8 may be seen with some drugs6eg, chlorproma>ine , augmentin, erythromycin , andsulindac 8.

erologic mar(ers of autoimmunity may be seen inpatients with to3icity related to procainamide andhydrochlorothia>ide , although their relationship tohepatic in ury is unclear.

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Chronic he4atic in1ury

Drugs associated with chronic liverin ury can resemble other causes of

chronic liver disease such asautoimmune hepatitis or alcoholic liverdisease.Chronic in ury generally resolves upondiscontinuation of the o@ending drug,but this pattern of liver in ury mayprogress to cirrhosis and liver failure .


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Chronic he4atiti+ ine,and ticrynafen.+-Mrare type of in ury leads to a syndrome with the histologic characteristics of

chronic hepatitis, but without autoimmune serologic mar(ers. *his is a morenondescript type of in ury, which can be seen in association with lisinopril ,sulfonamides, and tra>odone ."- Marely, drugs may lead to chronic to3icity without active necroin:ammatorydisease. J3amples include dantrolene , aspirin , and isonia>id .

Chronichepatitis

Diclofenac

Methyldopa

Minocycline

itrofurantoin

&ra.odone

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Type Autoantibodies

1 6classic8

ntinuclear

nti-smooth muscle

nti-actin

nti-soluble li"er/ li"er pancreas antigen' nti-S! /!P(

ntimitochondrial

+nti-!0M-1

nti-li"er cytosol -1 ' nti-!C1(

ass ca on o an au o-antibodies in autoimmune

hepatitis


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Steato+i+

Drug-induced chronic steatosis is predominantly macrove+icu.ar ,in contrast to the microvesicular steatosis usually seen in acute drugin ury. *he clinical picture of macrovesicular steatosis tends to beless severe than that seen with acute microvesicular steatosis withthe most common manifestation being hepatomegaly.

erum aminotransferases are typically moderately elevated.Drug-induced steatohepatitis may also resemble alcoholic liverdisease. istologic changes include mallorys hyaline, neutrophilicin:ammation, variable steatosis, and cirrhosis% phospholipidosis mayalso be present.Drugs associated with these types of in ury include diethylstilbestrol,glucocorticoids , griseofulvin , methotre3ate , nifedipine , tamo3ifen ,

total parenteral nutrition , mercury, and ethanol .teatosis may remain asymptomatic, or may evolve intosteatohepatitis with progression to cirrhosis within wee(s to monthsfollowed by development of chronic liver failure and subse/uenthepatic insuPciency 6 L-asparaginase , valproate, perhe3ilenemaleate, and amiodarone 8

Chronicinjury

Steato-hepatitis

miodarone

*thanol

&amoxifen

2alproiccid

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#i5ro+i+ and cirrho+i+

!rogressive liver in ury leads to scarring withsubse/uent cirrhosis.Clinical manifestations are typical of those seen withcirrhosis and portal hypertension from other causes.Drug-induced cirrhosis may result from steatosis 6amiodarone 8 or chronic hepatitis. Qradual progressionto cirrhosis can be seen without any manifestation ofclinical illness 6as with methotre3ate or methyldopa 8Cirrhosis may also result from lesions of chronicintrahepatic cholestasis, chronic cholestasis 6:o3uridine 8, chronic congestive hepatopathy withsinusoidal obstruction syndrome 6 a>athioprine ,mercaptopurine oral contraceptives8 or hepatic veinthrombosis 6oral contraceptives8, and noncirrhoticportal hypertension 6inorganic arsenic, copper sulfate,vinyl chloride, and vitamin 5 8.

http://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/162031&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/163197&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/224567&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/24656&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/157311&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/279832&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/13985&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/13985&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/279832&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/157311&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/24656&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/224567&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/163197&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/162031&drug=true


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Pho+4ho.i4ido+i+

!hospholipidosis is rare. It may develop acutely,but is more commonly seen after prolongedadministration of the o@ending agent.

*his condition has been described in animalmodels and in patients ta(ing amiodarone ,amitriptyline , chloro/uine , perhe3ilene maleate,chlorpheniramine , chlorproma>ine , or thiorida>ine .

*he lesions consist of .y+o+ome+ which areengorged with phospholipid, resulting in foamy

hepatocytes. It is believed that an interactionbetween the phospholipid and the drug leads tothe formation of a comple3 which preventsdegradation of the phospholipid molecules.

http://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/14215&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/53949&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/203389&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/54959&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/260780&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/14215&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/14215&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/260780&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/54959&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/203389&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/53949&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/14215&drug=true


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Chronic cho.e+ta+i+

Chronic intrahe4atic cho.e+ta+i+ G Drugs causing chronicintrahepatic cholestasis may produce a syndrome resemblingprimary biliary cirrhosis. owever, unli(e primary biliary cirrhosis,serum antimitochondrial antibodies are usually not seen.

Drugs which have been reported to cause chronic intrahepaticcholestasis include amitriptyline , ampicillin ,amo3icillin-clavulanate , carbama>epine , chlorproma>ine ,cyproheptadine , erythromycin estolate, haloperidol , imipramine ,organic arsenicals, prochlorpera>ine , phenytoin ,trimethoprim-sulfametho3a>ole , thiabenda>ole , tolbutamide ,tetracycline , oral contraceptives, and anabolic steroids.

*hose drugs implicated in chronic intrahepatic cholestasis andalso ductopenia include carbama>epine, chlorproma>ine,chlorpropamide , co-trimo3a>ole, haloperidol, thiabenda>ole, andtricyclic antidepressants.

http://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/17350&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/15929&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/42421&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/54959&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/68987&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/94465&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/120995&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/129925&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/211521&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/199700&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/20387&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/259459&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/265188&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/258546&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/55263&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/224567&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/224567&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/55263&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/258546&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/265188&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/259459&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/20387&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/199700&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/211521&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/129925&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/120995&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/94465&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/68987&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/54959&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/42421&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/15929&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/17350&drug=true


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Bi.iary +c.ero+i+ G *o3icity predominantlyinvolving the biliary tree is most commonlyseen after therapy of metastatic carcinomawith :o3uridine .

*he lesions resemble primary sclerosingcholangitis on cholangiography. 5@ectedpatients present with right upper abdominalpain, anore3ia , weight loss, and aundice.

http://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/24656&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/24656&drug=true


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'a+cu.ar di+ea+e


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2A

'a+cu.ar di+ea+e

3e4atic vein throm5o+i+ G epatic venousout:ow obstruction (Budd%Chiari +yndrome 8may arise from drug-induced thrombosis of

the hepatic veins or inferior vena cava.Bhile often associated with myeloproliferativeor coagulative disorders, the most prominentmedications associated with this syndromeare the oral contraceptives.

Bithout treatment, hepatic vein thrombosiswill progress to portal hypertension, liverfailure, and ultimately, death.


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2

Sinu+oida. o5+truction +yndrome (veno%occ.u+ive di+ea+e) G

hepatic venous out:ow obstruction in sinusoidal

obstruction syndrome 6 O 8 is due to occlusion ofthe terminal hepatic venules and hepatic sinusoidsrather than the hepatic veins and inferior venacava.

Drugs that have been associated with O includepyrroli>idine al(aloids 6found in herbal remedies8a>athioprine , mercaptopurine , vitamin 5 , oralcontraceptives, cyclophosphamide , tetracycline ,and a number of chemotherapeutic agents.

http://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/157311&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/279832&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/68161&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/258546&drug=truehttp://www.answers.com/topic/pyrrolizidine-alkaloidhttp://www.answers.com/topic/pyrrolizidine-alkaloidhttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/258546&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_a_k/68161&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/279832&drug=truehttp://www.uptodate.com/online/content/topic.do?topicKey=drug_l_z/157311&drug=true


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&eo4.a+ia

3e4atic adenoma G epatic adenoma is abenign tumor of the liver, which may rupturecausing hemoperitoneum or may be

associated with malignant transformation. *he ris( of hepatic adenoma is increased in-omen ta=ing ora. contrace4tive+ ("CP)and in men ta=ing ana5o.ic +teroid+2


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*ngio+arcoma G *his e3tremely rare tumorhas been associated with use of thorotra+t 6aradiographic contrast agent used in the 1 +$sto 1 #$s8, ar+enic, 4ota++ium ar+enite,radium, inorganic co44er, and 4o.yviny.ch.oride, and ana5o.ic +teroid+ . *heprognosis is poor with a mean life e3pectancyof si3 months following diagnosis.

3e4atoce..u.ar carcinoma G *he mainchemical associations with the developmentof hepatocellular carcinoma includea?atoxin, ora. contrace4tive+, anda.coho.2


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Indu+tria. toxinJ3ample 5rsenic, Carbon tetraChloride,Rinyl Chloride

3er5a. and a.ternative remedie+5c(ee fruit, ;a iaolian, Camphor, Copaltra,Cycasin, )ava, pyrroli>idine al(aloids ,

orse chestnut leaf, Ralerian, Comfrey

6often used in herbal tea8Chinese herbal remedies Sin ;u uan, =a-huang, ho-wu-pian

http://www.answers.com/topic/troglitazonehttp://www.answers.com/topic/troglitazone


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++

&D5 strong withdrawal

Drug+ -ithdra-n /or he4atotoxicity *roglita>one , Diabetes

bromfenac, ' 5ID trova:o3acin, antibiotics--:uoro/uinolonesebrotidine, 2 receptor bloc(ernimesulide, ' 5IDnefa>odone, 5ntidepressantTimelagatran, 5nticoagulant!emoline, psychotropic agent 65D D8

http://www.answers.com/topic/bromfenachttp://www.answers.com/topic/bromfenac


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+"

*he following are the most common symptoms ofdrug-induced hepatitis. owever, each individualmay e3perience symptoms di@erently. ymptomsmay include fever

rash or itchy red hives on s(in oint painsore muscles:u-li(e symptomsnauseavomitingdecreased appetitesore muscles

aundice - yellowing of the s(in and eyes.


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3o- i+ drug%induced he4atiti+ diagno+ed@In addition to complete medical history andphysical e3amination, diagnostic procedures fordrug-induced hepatitis may include the following+4eci6c .a5oratory 5.ood te+t+ , such as thefollowing

liver function studiescellular blood counts

bleeding timeselectrolyte teststests for other chemicals in the bodydrug screening tests


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C.a++i6cation o/ .iverte+t a5norma.itie+

Hepatitis 'hepatocellular( !& 3 x 4! 5 6

Cholestasis !& + x 4! 5 +Mixed !& 3 x 4! !P + x 4!

5 7+ to 86

5L* alanine aminotransferase% 5L! al(aline phosphatase% L' upperlimit normal% : *LTA!L& divided 5y *LPA!L& .


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+A

Treatment /or drug%inducedhe4atiti+:

*he goal of treatment for drug-induced hepatitis isto

1- discontinue ta(ing the causative agent2- monitor the liver closely while it recovers.+- ome drugs may cause a slight increase in liveren>ymes without symptoms. It may not benecessary to discontinue using these medications."- '-acetylcysteine for acetaminophen to3icity#- L-carnitine for cases of valproic acide overdose

- Corticosteroids are of unproven bene0t for most forms ofdrug hepatoto3icity,


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Meferences

1. !rinciple of pharmacology2. ;asic and clinical !harmacology

6)at>ung8+. Internet resources for diagrams

drug induced liver toxicity-final.ppt

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