toxicology

Question 1

○ Methanol

Answer 1

§ Metabolised by alcohol dehydrogenase to formic acid

Question 2

§ Formic acid

Answer 2

□ Has no further metabolic pathway so it accumulates
□ Acidosis
□ Moves across mitochondrial inner membrane and ruins electron gradient Inhibits mitochondrial respiration
® Person dies of asphyxia even with abundance of oxygen

Question 3

○ Paracetamol

Answer 3

§ Readily eliminated
§ Sulphated and glucuronidated allowing renal elimination
□ short half life
§ A small amount undergoes cytochrome P450 transformation

Question 4

paracetamol CYP450 metabolism

Answer 4

□ Produces a radical species with an unpaired electron
□ Reacts with glutathione with is present in liver tissue
® Tripeptide
□ Renally eliminated

Question 5

paracetamol hepatotoxicity

Answer 5

□ Supplies of sulphate and glucuronide are depleted
□ More ingested drug has to go through CYP450
□ More reactive intermediate made
□ Glutathione will be used up
□ Derivatising capacity will be used against other structures in the cell
□ Causes hepatotoxicity which may be lethal

Question 6

DILI

Answer 6

drug induced liver injury

Question 7

opiods

Answer 7

§ heroin, morphine, methadone, oxycodone, codeine, fentanyl etc

Question 8

opioids toxidrome

Answer 8

§ Drowsy leading to coma, hypoventilation of apnoea, miosis

Question 9

• Non opioid sedatives

Answer 9

§ Benzodiazepines, zolpidem, ethanol etc

Question 10

• Non opioid sedatives toxidrome

Answer 10

§ Drowsy leading to coma, staggering, slurred speech

Question 11

• Cholinesterase inhibitors

Answer 11

§ Organophosphate, and carbamate insecticides

Question 12

anticholinesterase toxidrome

Answer 12

§ Bradycardia, bronchoconstriction, small pupils, sweating

Question 13

muscarinic agonists

Answer 13

§ Atropine belladonna berries, tricyclic antidepressants

Question 14

muscarinic agonist toxidrome

Answer 14

Mad as a hatter, blind as a bat, hot as a brick, red as a beet, dry as a bone

Question 15

stimulants

Answer 15

§ Cocaine, methylamphetamine, amphetamine

Question 16

stimulants toxidrome

Answer 16

§ Tachycardia, hypertension, agitation, dilated pupils, seizures

Question 17

• Serotonergic syndrome

Answer 17

§ MDMA, designer amphetamine analogues

Question 18

Serotonergic syndrome toxidrome

Answer 18

§ Confusion, unstable blood pressure and cardiac rhythm, epileptiform seizures, hyperpyrexia, multi organ failure

Question 19

glutathione made of

Answer 19

glutamate, cysteine, glycine

Question 20

cysteine

Answer 20

§ The only necessary one
§ We can make our own glutamate and glycine
§ Replaced using intravenous infusion

Question 21

how to replace cysteine

Answer 21

□ Too reactive to anything else it meets to administer purely
□ N-acetyl cysteine used instead

Question 22

□ N-acetyl cysteine

Answer 22

® More stable but still taken up by the liver and formed into glutathione
® Glutathione used to prevent hepatotoxicity of paracetamol

Question 23

• Methanol

Answer 23

is metabolised into formic acid which builds up and causes acidosis

Question 24

antidote for methanol

Answer 24

○ Ethanol competitively inhibits oxidation to formic acid

Question 25

antidote for opioids

Answer 25

naloxone
○ Opioid drugs exert their lethal toxicity through agonism at u-opioid receptors
○ Naloxone is an antagonist at the u-opioid receptor

Question 26

• Metal poisoning

Answer 26

Succimer has high affinity for As, Pb and Hg, by virtue of coordinated -SH groups