Metabolism affecting toxicity Flashcards
(30 cards)
Why is the liver highly susceptible to drug toxicity?
High metabolic activity via CYPs which can bioactivate drugs into toxic metabolites (paracetamol into NAPQI)
How does CCl4 cause liver damage?
CYPs metabolise CCl4 to CCl3. triggering lipid peroxidation and hepatocyte nercrosis
What role does glutathione play in liver toxicity?
Detoxifies reactive metabolites (NAPQI), depletion leads to oxidative stress and cell death
How do kidneys become targets of toxicity?
High blood flow concentrates drugs/metabolites; active transport in tubules increases exposure (cisplatin nephrotoxicity)
Why is cadmium toxic to kidneys?
Binds to metallothionein in liver, circulates to kidneys, and accumulates, causing tubular damage via oxidative stress.
How does mercury affect the brain?
Methylmercury crosses BBB, binds to thiol groups in proteins, disrupting neuronal calcium homeostasis and causing neurotoxicity
What makes lungs vulnerable to inhaled toxins?
Large surface area and CYPs (CYP2E1) bioactivate compounds like naphthalene into cytotoxic metabolites
How does arsenic cause systemic toxicity?
Methylation in liver produces MMA(III), a highly toxic metabolite that damages DNA and inhibits enzymes
Why is the skin susceptible to PAH toxicity?
Cutaneous CYP1A1 converts PAHs (benzo[a]pyrene) into DNA-reactive epoxides, increasing carcinogenicity
How does paraoxonase (PON1) influence organophosphate toxicity?
PON1 detoxifies organophosphates (parathion–>paraoxon). Low PON1 activity increases toxicity risk.
What causes “first-pass” lung toxicity?
Drugs absorbed via inhalation bypass liver metabolism allowing direct damage (bleomycin-induced pulmonary fibrosis)
How do vinka alkaloids cause neurotoxicity?
Disrupt microtubules in peripheral nerves. Metabolism in liver produces less toxic metabolites, but initial exposure damages neurons
Why is the brain vulnerable to MPTP toxicity?
MAO-B in astrocytes converts MPTP to MPP+ which destroys dopaminergic neurons - mimicking Parkinson’s
How does renal CYP contribute to toxicity?
Kidneys express CYPs that activate aflatoxin B1, causing renal tubular carcinoma
What makes the skin a site for contact dermatitis?
Cutaneous metabolism of allergens into reactive quinones, triggering immune response
How does ethanol exacerbate liver toxicity?
Induces CYP2E1, increasing conversion of acetaminophen to NAPQI. Chronic use depletes glutathione
Why are neonates more susceptible to chloramphenicol?
Immature liver UDP-glucuronosyltransferase reduces detoxification, causing gray baby syndrome
How does lead affect haem synthesis?
Inhibits ALAD in liver/kidneys causing anemia and neurotoxicity
What causes contrast-induced nephrotoxicity?
Iodinated contrast agents generate ROS in kidneys, exacerbated by preexisting renal impairment
How does CYP2D6 polymorphism affect codeine toxicity?
Ultra-rapid metabolisers convert codeine to morphine excessively, risking respiratory depression
Why is dermal absorption of CCl4 dangerous?
Skin metabolises CCl4 to free radicals, causing local necrosis and systemic liver/kidney damage
How does cisplatin causes ototoxicity?
Accumulates in cochlea, generating ROS that destroy hair cells. Limited metabolism in inner ear increases exposure
What protects against paraquat lung toxicity?
Polyamine uptake systems concentrate paraquat in lungs; NADPH oxidase generates superoxide, causing fibrosis. No known antidote
How does alcohol dehydrogenase influence methanol toxicity?
ADH in liver converts methanol to formaldehyde, then formic acid causing metabolic acidosis and blindness
