đđDrug induced liver injuryđđ
â Pattern of drug induced liver injury:
- Hepatitis.
- Cholestasis.
- Steatosis.
- Vascular lesion.
- Fibrosis.
āĻĒā§āĻ°āĻĨāĻŽā§āĻ āĻāĻ¸āĻŋ, āĻā§āĻ¨ āĻā§āĻ¨ āĻāĻˇāĻ§ Hepatitis āĻāĻ°ā§?
- āĻ āĻ¨ā§āĻ āĻāĻˇāĻ§āĻ āĻāĻ°ā§āĨ¤ āĻāĻ° āĻŽāĻ§ā§āĻ¯ā§ āĻāĻ˛ā§āĻ˛ā§āĻāĻ¯ā§āĻā§āĻ¯ ā§¨ āĻāĻŋ āĻšāĻ˛ā§ 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 āĻ°ā§āĻĒāĻžāĻ¨ā§āĻ¤āĻ° āĻšā§āĨ¤ āĻ¯āĻž Glutathione āĻāĻ° āĻ¸āĻžāĻĨā§ bind āĻāĻ°ā§ non-toxic metabolite āĻ āĻ°ā§āĻĒāĻžāĻ¨ā§āĻ¤āĻ° āĻšā§āĨ¤
**āĻāĻŋāĻ¨ā§āĻ¤ā§ āĻ¯āĻāĻ¨ Overdose>10gm āĻšāĻŦā§ āĻ¤āĻāĻ¨ āĻāĻ¤ āĻŦā§āĻļāĻŋ NAPQI āĻ¤ā§āĻ°āĻŋ āĻšāĻŦā§ āĻ¯ā§ āĻāĻā§āĻ˛ā§āĻ° āĻ¸āĻžāĻĨā§ bind āĻāĻ°āĻžāĻ° āĻāĻ¨ā§āĻ¯ Glutathione āĻāĻžāĻāĻ¤āĻŋ āĻĻā§āĻāĻž āĻĻāĻŋāĻŦā§āĨ¤ āĻĢāĻ˛ā§, Toxic NAPQI āĻ¤āĻāĻ¨ hepatocyte āĻāĻ° āĻ¸āĻžāĻĨā§ bind āĻāĻ°āĻŦā§ āĻāĻŦāĻ
hepatocyte damage āĻāĻ°āĻŦā§āĨ¤
â Mechanism of isoniazid induced hepatitis:
Metabolism of isoniazid
âŦī¸
Hydrazine â Acetyl hydrazine
âŦ âŦ
Hepatocyte damage
âŦī¸
Inflammation
â
āĻāĻŦāĻžāĻ° āĻāĻ¸āĻŋ Cholestasis liver injury āĻā§āĻ¨ āĻā§āĻ¨ āĻāĻˇāĻ§ā§āĻ° āĻāĻžāĻ°āĻŖā§ āĻšā§?
āĻ
āĻ¨ā§āĻ āĻāĻˇāĻ§ā§āĻ° āĻāĻžāĻ°āĻŖā§āĻ āĻšā§ā§ āĻĨāĻžāĻā§āĨ¤ āĻ¤āĻŦā§, āĻāĻ° āĻŽāĻ§ā§āĻ¯ā§ āĻāĻ˛ā§āĻ˛ā§āĻāĻ¯ā§āĻā§āĻ¯ ā§¨ āĻāĻŋ āĻšāĻ˛ā§ 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 āĻāĻ°ā§?
Chlorpromazine, allergic-immune mediated bile duct injury āĻ inflammation āĻāĻ°ā§āĨ¤
â Steatosis āĻāĻŋ ā§¨ āĻ°āĻāĻŽ?
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§āĻ¨ āĻā§āĻ¨ Drugs āĻāĻ°ā§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§āĻ¨ āĻā§āĻ¨ Drugs āĻāĻ°ā§âĻ?
Tamoxifen
Amiodarone
â
āĻāĻāĻ¨ āĻāĻ¸āĻŋ Vascular lesion āĻāĻŋāĻāĻžāĻŦā§ āĻšā§āĻ
Drugs
âŦī¸
Damage to hepatic vascular endothelium
âŦī¸
Formation of thrombus
âŦī¸
Venous outflow obstruction
**Vascular lesion āĻāĻ°ā§ āĻāĻŽāĻ¨ āĻāĻāĻāĻŋ āĻāĻ˛ā§āĻ˛ā§āĻāĻ¯ā§āĻā§āĻ¯ āĻāĻˇāĻ§ āĻšāĻ˛ Anti-cancer drug “Busulfan”āĨ¤
â Hepatic Fibrosis: Methotrexate drugs hepatic fibrosis āĻāĻ°ā§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§āĻ¨ āĻā§āĻ˛āĻ¤ā§āĻ°ā§āĻāĻŋ āĻšāĻ˛ā§ āĻā§āĻˇāĻŽāĻžāĻ¸ā§āĻ¨ā§āĻĻāĻ° āĻĻā§āĻˇā§āĻāĻŋāĻ¤ā§ āĻĻā§āĻāĻŦā§āĻ¨)
Towhidul Islam Topu
Rajshahi medical college
Session:2016-17
Nirupuma /Platform Academia