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Do drugs also cause liver diseases?

💊💊Drug induced liver injury💊💊

★Pattern of drug induced liver injury:

  1. Hepatitis.
  2. Cholestasis.
  3. Steatosis.
  4. Vascular lesion.
  5. Fibrosis.

āĻĒā§āϰāĻĨāĻŽā§‡āχ āφāϏāĻŋ, āϕ⧋āύ āϕ⧋āύ āĻ”āώāϧ Hepatitis āĻ•āϰ⧇?

  • āĻ…āύ⧇āĻ• āĻ”āώāϧāχ āĻ•āϰ⧇āĨ¤ āĻāϰ āĻŽāĻ§ā§āϝ⧇ āωāĻ˛ā§āϞ⧇āĻ–āϝ⧋āĻ—ā§āϝ ⧍ āϟāĻŋ āĻšāϞ⧋ Paracetamol āĻ“ Isoniazid.

★Mechanism of paracetamol induced hepatitis:
In normal state, paracetamol liver āĻ metabolized āĻšā§Ÿā§‡, toxic metabolite: N – acetyl – p – benzoquinone imine (NAPQI) āĻ āϰ⧁āĻĒāĻžāĻ¨ā§āϤāϰ āĻšā§ŸāĨ¤ āϝāĻž Glutathione āĻāϰ āϏāĻžāĻĨ⧇ bind āĻ•āϰ⧇ non-toxic metabolite āĻ āϰ⧁āĻĒāĻžāĻ¨ā§āϤāϰ āĻšā§ŸāĨ¤

**āĻ•āĻŋāĻ¨ā§āϤ⧁ āϝāĻ–āύ Overdose>10gm āĻšāĻŦ⧇ āϤāĻ–āύ āĻāϤ āĻŦ⧇āĻļāĻŋ NAPQI āϤ⧈āϰāĻŋ āĻšāĻŦ⧇ āϝ⧇ āĻāϗ⧁āϞ⧋āϰ āϏāĻžāĻĨ⧇ bind āĻ•āϰāĻžāϰ āϜāĻ¨ā§āϝ Glutathione āϘāĻžāϟāϤāĻŋ āĻĻ⧇āĻ–āĻž āĻĻāĻŋāĻŦ⧇āĨ¤ āĻĢāϞ⧇, Toxic NAPQI āϤāĻ–āύ hepatocyte āĻāϰ āϏāĻžāĻĨ⧇ bind āĻ•āϰāĻŦ⧇ āĻāĻŦāĻ‚
hepatocyte damage āĻ•āϰāĻŦ⧇āĨ¤

★Mechanism of isoniazid induced hepatitis:

          Metabolism of isoniazid
                             âŦ‡ī¸
          Hydrazine ➕ Acetyl hydrazine         
                       âŦ‚           âŦƒ
               Hepatocyte damage
                             âŦ‡ī¸
                     Inflammation     

★āĻāĻŦāĻžāϰ āφāϏāĻŋ Cholestasis liver injury āϕ⧋āύ āϕ⧋āύ āĻ”āώāϧ⧇āϰ āĻ•āĻžāϰāϪ⧇ āĻšā§Ÿ?
āĻ…āύ⧇āĻ• āĻ”āώāϧ⧇āϰ āĻ•āĻžāϰāϪ⧇āχ āĻšā§Ÿā§‡ āĻĨāĻžāϕ⧇āĨ¤ āϤāĻŦ⧇, āĻāϰ āĻŽāĻ§ā§āϝ⧇ āωāĻ˛ā§āϞ⧇āĻ–āϝ⧋āĻ—ā§āϝ ⧍ āϟāĻŋ āĻšāϞ⧋ Estrogen āĻ“ ChlorpromazineāĨ¤

★Mechanism of Estrogen induced Cholestasis:
Estrogen
âŦ‡ī¸
Inhibit:
(i) Bile salt export pump
(ii) Multidrug resistance protein – 2transporter
(iii) Na – taurocholate – cotransporter
âŦ‡ī¸
Impaired of
Bile secretion from hepatocyte to
bile canaliculus
âŦ‡ī¸
Cholestasis

★Chlorpromazine āĻ•āĻŋāĻ­āĻžāĻŦ⧇ Cholestasis āĻ•āϰ⧇?
Chlorpromazine, allergic-immune mediated bile duct injury āĻ“ inflammation āĻ•āϰ⧇āĨ¤

★Steatosis āĻ•āĻŋ ⧍ āϰāĻ•āĻŽ?

✓Microvesicular Steatosis:
Numerous small lipid vesicles that leave the nucleus in the centre of the cell and give the hepatocytes a ‘foamy’ appearanceāĨ¤

★Basic mechanism āĻ•āĻŋāσ
Impair the mitochondrial β-oxidation of fatty acids.

āϕ⧋āύ āϕ⧋āύ Drugs āĻ•āϰ⧇â€Ļ?
Tetracycline
Sodium valporate

✓Macrovesicular Steatosis:
Single large droplet of fat which displaces the nucleus to the periphery of the cell.

★Basic mechanism āĻ•āĻŋāσ

  1. Increased hepatic synthesis of fat.
  2. Moderate decrease in fat oxidation in liver.
  3. Impaired egress of lipids out of the liver.

★āϕ⧋āύ āϕ⧋āύ Drugs āĻ•āϰ⧇â€Ļ?
Tamoxifen
Amiodarone

★āĻāĻ–āύ āφāϏāĻŋ Vascular lesion āĻ•āĻŋāĻ­āĻžāĻŦ⧇ āĻšā§Ÿāσ
Drugs
âŦ‡ī¸
Damage to hepatic vascular endothelium
âŦ‡ī¸
Formation of thrombus
âŦ‡ī¸
Venous outflow obstruction

**Vascular lesion āĻ•āϰ⧇ āĻāĻŽāύ āĻāĻ•āϟāĻŋ āωāĻ˛ā§āϞ⧇āĻ–āϝ⧋āĻ—ā§āϝ āĻ”āώāϧ āĻšāϞ Anti-cancer drug “Busulfan”āĨ¤

★Hepatic Fibrosis: Methotrexate drugs hepatic fibrosis āĻ•āϰ⧇āĨ¤

★Mechanism:
Methotrexate
âŦ‡ī¸
Inhibit Production of
methionine from hemocystine
âŦ‡ī¸
Excess accumulation of hemocystine
âŦƒ âŦ‚
Oxidative stress Activation of
âŦ‡ī¸ Pro-inflammatory cytokine
âŦ‚ âŦƒ
Activation of hepatic stellate cells
âŦ‡ī¸
Fibrosis

(āϕ⧋āύ āϭ⧁āϞāĻ¤ā§āϰ⧁āϟāĻŋ āĻšāϞ⧇ āĻ•ā§āώāĻŽāĻžāϏ⧁āĻ¨ā§āĻĻāϰ āĻĻ⧃āĻˇā§āϟāĻŋāϤ⧇ āĻĻ⧇āĻ–āĻŦ⧇āύ)

Towhidul Islam Topu
Rajshahi medical college
Session:2016-17
Nirupuma /Platform Academia

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