đđDrug induced liver injuryđđ
â Pattern of drug induced liver injury:
- Hepatitis.
- Cholestasis.
- Steatosis.
- Vascular lesion.
- Fibrosis.
āĻĒā§āϰāĻĨāĻŽā§āĻ āĻāϏāĻŋ, āĻā§āύ āĻā§āύ āĻāώāϧ Hepatitis āĻāϰā§?
- āĻ āύā§āĻ āĻāώāϧāĻ āĻāϰā§āĨ¤ āĻāϰ āĻŽāϧā§āϝ⧠āĻāϞā§āϞā§āĻāϝā§āĻā§āϝ ⧍ āĻāĻŋ āĻšāϞ⧠Paracetamol āĻ Isoniazid.
â
Mechanism of paracetamol induced hepatitis:
In normal state, paracetamol liver āĻ metabolized āĻšā§ā§, toxic metabolite: N – acetyl – p – benzoquinone imine (NAPQI) āĻ āϰā§āĻĒāĻžāύā§āϤāϰ āĻšā§āĨ¤ āϝāĻž Glutathione āĻāϰ āϏāĻžāĻĨā§ bind āĻāϰ⧠non-toxic metabolite āĻ āϰā§āĻĒāĻžāύā§āϤāϰ āĻšā§āĨ¤
**āĻāĻŋāύā§āϤ⧠āϝāĻāύ Overdose>10gm āĻšāĻŦā§ āϤāĻāύ āĻāϤ āĻŦā§āĻļāĻŋ NAPQI āϤā§āϰāĻŋ āĻšāĻŦā§ āϝ⧠āĻāĻā§āϞā§āϰ āϏāĻžāĻĨā§ bind āĻāϰāĻžāϰ āĻāύā§āϝ Glutathione āĻāĻžāĻāϤāĻŋ āĻĻā§āĻāĻž āĻĻāĻŋāĻŦā§āĨ¤ āĻĢāϞā§, Toxic NAPQI āϤāĻāύ hepatocyte āĻāϰ āϏāĻžāĻĨā§ bind āĻāϰāĻŦā§ āĻāĻŦāĻ
hepatocyte damage āĻāϰāĻŦā§āĨ¤
â Mechanism of isoniazid induced hepatitis:
Metabolism of isoniazid
âŦī¸
Hydrazine â Acetyl hydrazine
âŦ âŦ
Hepatocyte damage
âŦī¸
Inflammation
â
āĻāĻŦāĻžāϰ āĻāϏāĻŋ Cholestasis liver injury āĻā§āύ āĻā§āύ āĻāώāϧā§āϰ āĻāĻžāϰāĻŖā§ āĻšā§?
āĻ
āύā§āĻ āĻāώāϧā§āϰ āĻāĻžāϰāĻŖā§āĻ āĻšā§ā§ āĻĨāĻžāĻā§āĨ¤ āϤāĻŦā§, āĻāϰ āĻŽāϧā§āϝ⧠āĻāϞā§āϞā§āĻāϝā§āĻā§āϝ ⧍ āĻāĻŋ āĻšāϞ⧠Estrogen āĻ ChlorpromazineāĨ¤
â
Mechanism of Estrogen induced Cholestasis:
Estrogen
âŦī¸
Inhibit:
(i) Bile salt export pump
(ii) Multidrug resistance protein – 2transporter
(iii) Na – taurocholate – cotransporter
âŦī¸
Impaired of
Bile secretion from hepatocyte to
bile canaliculus
âŦī¸
Cholestasis
â
Chlorpromazine āĻāĻŋāĻāĻžāĻŦā§ Cholestasis āĻāϰā§?
Chlorpromazine, allergic-immune mediated bile duct injury āĻ inflammation āĻāϰā§āĨ¤

â Steatosis āĻāĻŋ ⧍ āϰāĻāĻŽ?
âMicrovesicular Steatosis:
Numerous small lipid vesicles that leave the nucleus in the centre of the cell and give the hepatocytes a âfoamyâ appearanceāĨ¤
â
Basic mechanism āĻāĻŋāĻ
Impair the mitochondrial β-oxidation of fatty acids.
āĻā§āύ āĻā§āύ Drugs āĻāϰā§âĻ?
Tetracycline
Sodium valporate
âMacrovesicular Steatosis:
Single large droplet of fat which displaces the nucleus to the periphery of the cell.
â Basic mechanism āĻāĻŋāĻ
- Increased hepatic synthesis of fat.
- Moderate decrease in fat oxidation in liver.
- Impaired egress of lipids out of the liver.
â
āĻā§āύ āĻā§āύ Drugs āĻāϰā§âĻ?
Tamoxifen
Amiodarone
â
āĻāĻāύ āĻāϏāĻŋ Vascular lesion āĻāĻŋāĻāĻžāĻŦā§ āĻšā§āĻ
Drugs
âŦī¸
Damage to hepatic vascular endothelium
âŦī¸
Formation of thrombus
âŦī¸
Venous outflow obstruction
**Vascular lesion āĻāϰ⧠āĻāĻŽāύ āĻāĻāĻāĻŋ āĻāϞā§āϞā§āĻāϝā§āĻā§āϝ āĻāώāϧ āĻšāϞ Anti-cancer drug “Busulfan”āĨ¤
â Hepatic Fibrosis: Methotrexate drugs hepatic fibrosis āĻāϰā§āĨ¤
â
Mechanism:
Methotrexate
âŦī¸
Inhibit Production of
methionine from hemocystine
âŦī¸
Excess accumulation of hemocystine
âŦ âŦ
Oxidative stress Activation of
âŦī¸ Pro-inflammatory cytokine
âŦ âŦ
Activation of hepatic stellate cells
âŦī¸
Fibrosis
(āĻā§āύ āĻā§āϞāϤā§āϰā§āĻāĻŋ āĻšāϞ⧠āĻā§āώāĻŽāĻžāϏā§āύā§āĻĻāϰ āĻĻā§āώā§āĻāĻŋāϤ⧠āĻĻā§āĻāĻŦā§āύ)
Towhidul Islam Topu
Rajshahi medical college
Session:2016-17
Nirupuma /Platform Academia