Adapun
daftar dibuat berdasarkan mekanisme hepatotoksik yang dimiliki suatu obat. Obat yang semakin sering
muncul adalah obat yang memiliki beberapa efek hepatotoksik sekaligus, sehingga secara umum lebih
hepatotoksik dibanding obat lain yang jarang muncul.
1. Obat yang mengakibatkan gejala mirip hepatitis viral akut
Allopurinol
Diklofenak
Fenobarbital
Kuinin
Piroksikam
Antidepresan trisiklik
Diltiazem
Halotan
Labetalol
Probenesid
Asam asetilsalisilat
Enfluran
Ibuprofen
Maprotilin
Ranitidin
Asam paraaminosalisilat
Etambutol
Indometasin
Simetidin
Metoprolol
Asam valproat
Etionamid
Isoniazid
Naproksen
Sulfonamid
Asebutolol
Fenelzin
Karbamazepin
Parasetamol
Sulindak
Atenolol
Fenilbutazon
Ketokonazol
Penisilin
Verapamil
Dantrolen
Fenitoin
Kuinidin Pirazinamid
Aminoglikosida
Pathogenesis dari penurunan GFR pada pasien yang menerima aminoglikosida secara predominan
menghasilkan kerusakan sel epitel tubulus proksimal yang akhirnya dapat memicu obstruksi lumen
tubular dan hasil filtrasi glumerulus berindah ke epitel tubular yang sudah rusak. Toksisitas dari beberapa
aminglikosida berkaitan dengan muatan kation , yang difasilitasi oleh ikatan aminoglikosiada yang telah
terfiltrasi pada membrane luminal sel epitel tubulus renal (DiPiro, 2002).
Sebagai contoh, neomisin mempunyai gugus amino kationik, merupakan aminogliksida yang sangat
nefrotoksik, dibandingkan streptomisin, dengan 3 gugus amino yang sedikit toksik.
Gentamisin dan tobramisin , dengan 5 gugus amino mempunyai toksisitas sedang dibandingkan amikasin
dan netilmisin, dengan 4 dan 3 gugus amino, yang biasanya sedikit toksik.
Pengikatan sel epitel tubular diikuti oleh transport intraseluler dan konsentrasi dalam lisosom. Ikatan
berikutnya dengan fosfolipid menyebabkan terjadinya agregasi dan penghambatan aktivitas fosfolipase
(DiPiro, 2002).
Disfungsi sel dan kematian yang disebabkan oleh pelepasan enzim lisosom kedalam sitosol, penambahan
rektif oksigen spesies, penurunan metabolisme sel, dan penurunan sifat alir dalam mebran sel memicu
penurunan dari aktivitas pengikatan membrane dengan enzim, termasuk Na+-K+- ATPase, dipeptidyl
peptidase IV, dan aminopeptidase netral. Meskipun ikatan aminoglikosida pada sel epitel tubular di
fasilitasi oleh jumlah gugus kation yang ada, resiko toksisitas juga merupakan faktor yang berpengaruh
(DiPiro, 2002).
Cisplatin/carboplatin
Kerusakan tubulus proksmal muncul secara akut setelah pengguaan senyawa mengandung platin,
sebahai hasil ke tidakseimbangan produksi energy sel, mungkin berpengaruh pada ikatan protein pada
sel tubulus proksimal dengan gugus sulfhidril dan gangguan aktivitas enzim sel dan fosforilasi oksidatif.
Kerusakan tubulus proksimal diikuti oleh penurunan GFR yang progresiv dan gangguan fungsi tubulus
distal (DiPiro, 2002).
Amphotericin B
Mekanisme disfungsi gnjal termasuk toksisitas sel epitel tubulus secara langsung dengan peningkatan
permeabilitas tubulus dan nekrosis, hingga terjadi vasokonstriksi arteri san iskemia. Permeabilitas
membrane tubulus meningkat tehadap Na dan K ketika amfoterisin berikatan dengan membrane dan
bekerja sebagai inophore. Vasokonstriksi ginjal terjadi dari mekanisme yang tidak sesuai, mungkin
termasukefek dari amfoterisin B pada influk Ca seluler dan aktivasi vasokonstriktor prostaglandin .
Diatas semua itu, kombinasi efek dari ditingkakanya energy sel dan kebutuhan oksigen menyebabkan
penigkatan permeabilitas membrane sel, dan pengurangan penghantaran oksigen pada saat
vasokonstriksi renal menghasilkan nekrosis sel epitel tubulus dan kerusakan renal (DiPiro, 2002).
2. Osmotic nephrosis
Mannitol
Mekanismenya adlah pinositosis manitol kedalam sel, menyebabkan penembangan sel dan obstruksi
tubulus ginjal. Manitol dapat menyebabkan vasokonstriksi renal secara langsung atau mengindksi diuretic
osmosis dengan peningkatan penghantaran cairan ke macula densa dan aliran balik tubloglomerular
memicu vasokonstriksi arteriole aferan pada glomerulus dan penurunan aliran darah ke ginjal (DiPiro,
2002).
Intravenous immunoglobulin
Larutan immunoglobulin intravena terdiri tari sukrosa hiperosmolar dan dapat menyebabkan nefrosis
osmotik dan gagal ginjal akut, yang bersifat reversiel denga terapi diskontinu (DiPiro, 2002).
s Mixed (Elevated ALP + Elevated ALT) Amitriptyline Azathioprine Captopril Carbamazepine Clindamycin
Cyproheptadine Enalapril Flutamide Nitrofurantoin Phenobarbital Phenytoin Sulfonamides Trazodone
Trimethoprimsulfamethoxazole Verapamil
Cholestatic (Elevated ALP + TBL) Amoxicillinclavulanic acid Anabolic steroids Chlorpromazine
Clopidogrel Oral contraceptives Erythromycins Estrogens Irbesartan Mirtazapine Phenothiazines
Terbinafine Tricyclics
Anticholinergics
Anisotropine
Atropine
Belladonna
Clidinium
Dicyclomine
Glycopyrrolate
Homatropine
Hyoscyamine
Ipratropium
Mepenzolate
Methantheline
Methscopolamine
Pirenzepine
Propantheline
Scopolamine
Other medications with anticholinergic activity
Antihistamines, H1-receptor (except for non-sedating ones)
Benztropine
Biperiden
Buclizine
Carbamazepine
Clozapine
Cyclizine
Cyclobenzaprine
Digoxin
Disopyramide
Dronabinol
Ethopropazine
Loxapine
Maprotiline
Meclizine
Molindone
Orphenadrine
Oxybutynin
Phenothiazines
Pimozide
Procainamide
Procyclidine
Quinidine
Trihexyphenidyl
Thioxanthenes
Acetazolamide
Alemtuzumab
Aminopyrine
Amodiaquine
Amphotericin B lipid complex
Angiotensin-converting enzyme (ACE) inhibitors
Anticonvulsants, hydantoin
Anticonvulsants, succinimide
Antidepressants, tricyclic
Antidiabetic agents, sulfonylurea
Anti-inflammatory drugs, nonsteroidal (NSAIDS), especially
phenylbutazone
Antithyroid agents
Bexarotene
Carbamazepine
Cetirizine and Pseudoephedrine
Chloramphenicol
Clozapine
Dapsone
Divalproex
Epirubicin
Felbamate
Flecainide
Foscarnet
Gemtuzubam Ozogamicin
Gold compounds
Levamisole
Loxapine
Maprotiline
Mirtazapine
Peginterferon alfa-2B
Penicillamine
Pentamidine
Phenothiazines
Pimozide
Primaquine
Primidone
Procainamide
Propafenone
Propylthiouracil
Pyrimethamine (with high doses)
Rifampin
Rifapentine
Rituximab
Sulfasalazine
Sulfamethoxazole and Trimethoprim
Sulfonamides, systemic
Temozolomide
Thioxanthenes
Ticlopidine
Tiopronin
Tocainide
Trastuzumab
Trimethobenzamide
Trimethoprim
Valproic acid
Alcohol
Aminoglutethimide
Anesthetics, general
Anesthetics, parenteral-local
Anticonvulsants
Antidepressants, monoamine oxidase (MAO) inhibitor
Antidepressants, tricyclic
Antidyskinetics (except amantadine)
Antihistamines, H1-receptor (except cetirizine, fexofenadine, and
loratadine)
Apomorphine
Azelastine
Baclofen
Barbiturates
Benzodiazepines
Beta-adrenergic blocking agents
Brimonidine
Buclizine
Carbamazepine
Cetirizine (dose related)
Cetirizine and Pseudoephedrine (dose related)
Chlophedianol
Chloral hydrate
Chlorzoxazone
Clonidine
Clozapine
Cyclizine
Difenoxin and atropine
Diphenoxylate and atropine
Disulfiram
Donepezil
Dronabinol
Ethchlorvynol
Ethinamate
Etomidate
Glutethimide
Guanabenz
Guanfacine
Haloperidol
Hydroxyzine
Ifosfamide
Interferons
Ketamine
Levomethadyl
Loratadine (dose related)
Loxapine
Magnesium sulfate, parenteral
Maprotiline
Meclizine
Meprobamate
Methyldopa
Methyprylon
Metoclopramide
Metyrosine
Mirtazapine
Mitotane
Molindone
Nabilone
Nefazodone
Olanzapine
Opioid (narcotic) analgesics
Oxcarbazepine
Paraldehyde
Paregoric
Pargyline
Peginterferon alfa-2B
Phenothiazines
Pimozide
Procarbazine
Promethazine
Propiomazine
Propofol
Quetiapine
Rauwolfia alkaloids
Risperidone
Scopolamine
Skeletal muscle relaxants (centrally acting)
Thalidomide
Thioxanthenes
Trazodone
Trimeprazine
Trimethobenzamide
Zolpidem
Amantadine
Amphetamines
Anesthetics, local
Appetite suppressants, sympathomimetic
Bronchodilators, theophylline
Bupropion
Caffeine
Chlophedianol
Cocaine
Corticosteroids (in moderate to large doses)
Doxapram
Dronabinol
Dyphylline
Fluoroquinolones
Meropenem
Methylphenidate
Modafinil
Nabilone
Pemoline
Selegiline
Sympathomimetics
Folate antagonists
Anticonvulsants, hydantoin
Anticonvulsants, succinimide
Divalproex
Methotrexate
Phenobarbital (with long-term use)
Pyrimethamine
Sulfonamides
Triamterene (with high doses or prolonged use)
Trimethoprim
Trimetrexate
Valproic acid
Hemolytics
Acetohydroxamic acid
Antidiabetic agents, sulfonylurea
Doxapram
Furazolidone
Mefenamic acid
Menadiol
Methyldopa
Nitrofurans
Primaquine
Procainamide
Quinidine
Quinine
Sulfonamides, systemic
Sulfones
Hepatotoxic medications
Hyperkalemia-causing medications
Amiloride
Angiotensin-converting enzyme (ACE) inhibitors
Anti-inflammatory drugs, nonsteroidal (NSAIDS), especially indomethacin
Anti-thymocyte globulin (rabbit)
Cyclosporine
Digitalis glycosides (with acute overdose)
Diuretics, potassium-sparing
Heparin
Penicillins, potassium-containing (with high doses)
Pentamidine
Phosphates, potassium-containing
Potassium citrate-containing medications
Potassium iodide
Potassium supplements (including OTC salt substitutes)
Succinylcholine chloride
Tacrolimus
Hypokalemia-causing medications
Alcohol
Amphotericin B, systemic
Amphotericin B cholestryl complex
Amphotericin B lipid complex
Amphotericin B liposomal complex
Bronchodilators, adrenergic, beta-2
Capreomycin
Carbenicillin, parenteral
Carbonic anhydrase inhibitors
Corticosteroids, systemic
Diuretics, loop
Diuretics, thiazide
Edetate disodium (with prolonged use)
Fludrocortisone
Foscarnet
Indapamide
Insulin
Insulin lispro
Laxatives (with acute overdose or chronic misuse)
Mannitol
Mezlocillin
Piperacillin
Piperacillin and Tazobactam
Salicylates
Sodium bicarbonate
Sodium polystyrene sulfonate
Ticarcillin
Ticarcillin and Clavulanate
Urea, systemic
Hypotension-producing medications
Alcohol
Aldesleukin
Alprostadil
Amantadine
Amifostine
Anesthetics, general
Angiotensin-converting enzyme (ACE) inhibitors
Antidepressants, monoamine oxidase (MAO) inhibitor
Antidepressants, tricyclic
Antihypertensives
Benzodiazepines used as preanesthetics
Beta-adrenergic blocking agents
Bretylium
Brimonidine
Bromocriptine
Cabergoline
Calcium channel blocking agents
Calcium supplements, parenteral
Carbidopa and levodopa
Clozapine
Contrast agents, radiopaque, water-soluble organic iodides (with intravascular use)
Contrast agents, paramagnetic
Contrast agents, superparamagnetic
Deferoxamine (when given IV at doses >15 mg/kg/hr)
Diuretics
Droperidol
Edetate calcium disodium
Edetate disodium
Gadopentetate
Haloperidol
Hydralazine
Levodopa
Lidocaine, systemic
Loxapine
Magnesium sulfate, parenteral
Mirtazapine
Molindone
Nabilone (with high doses)
Nefazodone
Nitrates
Nitric Oxide
Nitrites
Olanzapine
Opioid (narcotic) analgesics (including alfentanil, fentanyl, and sufentanil)
Paclitaxel
Pentamidine
Pentoxifylline
Phenothiazines
Pimozide
Pramipexole
Procainamide
Propofol
Protamine (with too rapid administration)
Quetiapine
Quinidine
Risperidone
Rituximab
Ropinirole
Sildenafil
Thioxanthenes
Thrombolytic agents
Tizanidine
Tocainide
Tolcapone
Hypothermia-producing medications
Alcohol, ethyl
Alpha-adrenergic blocking agents (dihydroergotamine, ergotamine, labetalol, phenoxybenzamine,
phentolamine, prazosin, tolazoline)
Anesthetics, general
Barbiturates (with high doses or acute overdose)
Beta-adrenergic blocking agents
Clonidine
Insulin
Minoxidil, systemic
Opioid analgesics (with overdose)
Phenothiazines
Polyethylene glycol and electrolytes (with large amounts of refrigerated solution)
Vasodilators
Methemoglobinemia-causing medications
Acetanilid
Aminosalicylic acid
Articaine
Benzocaine
Castellani solution
Cetrimide
Chloroquine
Coal tar
Dapsone
Flutamide
Lidocaine
Mafenide
Methylene blue (with high doses)
Nitrates
Nitric oxide
Nitrites
Nitrofurantoin
Nitroglycerin
Nitroprusside
Pamaquine
Phenacetin
Phenobarbital
Prilocaine
Primaquine
Quinine
Silver nitrate
Sulfonamides
Thiopental
Triclocarban
Nephrotoxic medications
Neurotoxic medications
Altretamine
Aminoglycosides, parenteral and topical irrigation (only on denuded surfaces or mucous membranes)
Anticonvulsants, hydantoin
Asparaginase
Capreomycin
Carbamazepine
Chloramphenicol, systemic
Chloroquine
Cilastatin
Ciprofloxacin
Cisplatin
Contrast agents (ionic and some nonionic; with intrathecal administration)
Cycloserine
Cyclosporine
Cytarabine
Didanosine
Disulfiram
Docetaxel
Ethambutol
Ethionamide
Fludarabine
Hydroxychloroquine
Imipenem
Interferon, gamma
Interferons, alpha
Isoniazid
Lincomycins
Lindane, topical
Lithium
Methotrexate, intrathecal
Metronidazole
Mexiletine
Nitrofurantoin
Oxamniquine
Pemoline
Penicillins, parenteral
Polymyxins, parenteral
Pyridoxine (with long-term, high-dose use)
Quinacrine
Quinidine
Quinine
Stavudine
Tacrolimus
Tetracyclines
Thalidomide
Vincristine
Zalcitabine
Ototoxic medications
Aminoglycosides, parenteral and topical irrigation (only on denuded surfaces or mucous membranes)
Anti-inflammatory drugs, nonsteroidal (NSAIDS)
Bumetanide, parenteral
Capreomycin
Carboplatin
Chloroquine
Cisplatin
Deferoxamine (with long-term, high-dose use)
Erythromycins (with high doses and renal function impairment)
Ethacrynic acid
Furosemide
Hydroxychloroquine
Quinidine
Quinine
Salicylates (especially with long-term, high-dose use or overdose)
Vancomycin, parenteral (with elevated plasma concentration)
Abciximab
Alprostadil, systemic
Anagrelide
Anti-inflammatory drugs, nonsteroidal (NSAIDS)
Aspirin
Clopidogrel
Contrast agents, radiopaque, water-soluble organic iodides (with intravascular administration)
Dextran
Dipyridamole
Divalproex
Epoprostenol
Eptifibatide
Mezlocillin
Pentoxifylline
Piperacillin
Plicamycin
Sulfinpyrazone
Thrombolytic agents
Ticarcillin
Ticlopidine
Tirofiban
Valproic acid
Serotonergics
Citalopram
Clomipramine
Fluoxetine
Fluvoxamine
Lysergic acid diethylamide (LSD)
Methylenedioxymethamphetamine (MDMA ["ecstasy"])
Moclobemide
Monoamine oxidase inhibitors, irreversible (furazolidone, phenelzine, procarbazine, selegiline,
tranylcypromine)
Nefazodone
Paroxetine
Sertraline
Sibutramine
Tryptophan
Venlafaxine
Ademetionine
Almotriptan
Amitriptyline
Bromocriptine
Buspirone
Dextromethorphan
Imipramine
Levodopa
Lithium
Marijuana
Meperidine
Naratriptan
Pentazocine
Sumatriptan
Tramadol
Trazodone
Zolmitriptan