toxicology Flashcards
○ Methanol
§ Metabolised by alcohol dehydrogenase to formic acid
§ Formic acid
□ 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
○ Paracetamol
§ Readily eliminated
§ Sulphated and glucuronidated allowing renal elimination
□ short half life
§ A small amount undergoes cytochrome P450 transformation
paracetamol CYP450 metabolism
□ Produces a radical species with an unpaired electron
□ Reacts with glutathione with is present in liver tissue
® Tripeptide
□ Renally eliminated
paracetamol hepatotoxicity
□ 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
DILI
drug induced liver injury
opiods
§ heroin, morphine, methadone, oxycodone, codeine, fentanyl etc
opioids toxidrome
§ Drowsy leading to coma, hypoventilation of apnoea, miosis
- Non opioid sedatives
§ Benzodiazepines, zolpidem, ethanol etc
- Non opioid sedatives toxidrome
§ Drowsy leading to coma, staggering, slurred speech
- Cholinesterase inhibitors
§ Organophosphate, and carbamate insecticides
anticholinesterase toxidrome
§ Bradycardia, bronchoconstriction, small pupils, sweating
muscarinic agonists
§ Atropine belladonna berries, tricyclic antidepressants
muscarinic agonist toxidrome
Mad as a hatter, blind as a bat, hot as a brick, red as a beet, dry as a bone
stimulants
§ Cocaine, methylamphetamine, amphetamine
stimulants toxidrome
§ Tachycardia, hypertension, agitation, dilated pupils, seizures
- Serotonergic syndrome
§ MDMA, designer amphetamine analogues
Serotonergic syndrome toxidrome
§ Confusion, unstable blood pressure and cardiac rhythm, epileptiform seizures, hyperpyrexia, multi organ failure
glutathione made of
glutamate, cysteine, glycine
cysteine
§ The only necessary one
§ We can make our own glutamate and glycine
§ Replaced using intravenous infusion
how to replace cysteine
□ Too reactive to anything else it meets to administer purely
□ N-acetyl cysteine used instead
□ N-acetyl cysteine
® More stable but still taken up by the liver and formed into glutathione
® Glutathione used to prevent hepatotoxicity of paracetamol
- Methanol
is metabolised into formic acid which builds up and causes acidosis
antidote for methanol
○ Ethanol competitively inhibits oxidation to formic acid
antidote for opioids
naloxone
○ Opioid drugs exert their lethal toxicity through agonism at u-opioid receptors
○ Naloxone is an antagonist at the u-opioid receptor
- Metal poisoning
Succimer has high affinity for As, Pb and Hg, by virtue of coordinated -SH groups
