Acetaminophen (APAP) poisoning is caused by ________. - The usual liver
conjugation routes are saturated, and there is insufficient glutathione to
conjugate the metabolite NAPQI, which binds to hepatocellular proteins,
causing oxidative damage, mitochondrial malfunction, and hepatocellular
apoptosis.
What is the first step in responding to an acute paracetamol overdose? -
ANSWER The conjugation metabolism becomes saturated, and excess APAP is
oxidatively metabolised by the CYP enzymes (CYP2E1, 1A2, 2A6, and 3A4) to
the hepatotoxic reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
Glutathione's role in acetaminophen biotransformation. Conjugates the
hepatotoxic reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI), which
is then eliminated renally.
A lack of glutathione or high NAPQI synthesis can result in _______. -
ANSWER NAPQI binds to cysteinyl sulfhydryl groups in hepatocellular
proteins, creating NAPQI-protein adducts. This results in a cascade of oxidative
damage and mitochondrial malfunction. The following inflammatory ANSWER
promotes hepatocellular damage and mortality.
True or false: The amount of APAP that might cause toxicity may be lower in
the presence of chronic ethanol use, malnutrition, fasting, or viral infection. -
The answer is true.
yes or false: co-ingestion of drugs or treatments known to enhance the activity
of the APAP-metabolizing cytochrome P (CYP) oxidative enzymes increases
the risk of hepatotoxicity - ANSWER yes
What is the antidote to paracetamol poisoning? - ANSWER NAC is a
glutathione precursor that enhances glutathione concentrations accessible for
NAPQI conjugation. It also improves the sulphate conjugation of unmetabolized
, APAP, acts as an anti-inflammatory and antioxidant, has beneficial inotropic
effects, and raises local nitric oxide levels to improve blood circulation.
A drug is _______. - ANSWER an agent that influences biological processes
and is used to prevent or treat diarrhoea; the most are weak acids or bases.
Pharmacokinetics - Answer The quantitative study of drug absorption,
distribution, metabolism, and excretion (ADME), and their mathematical
relationship; what the body does with the drug once it is taken.
The absorption of a medication is determined by its ______. - ANSWER
solubility (lipid or water-soluble)
A protonated acid is non-ionized and lipid-soluble.
A non-protonated acid is ______. - ANSWER: Ionised and water soluble.
A protonated base is _____. - ANSWER: Ionised and water soluble.
A non-protonated base is _____. - ANSWER: non-ionized and lipid-soluble
Polar medicines work similarly to _____ medications. - ANSWER: Ionised,
water soluble
What decides whether a medication is ionised or not? - ANSWER 1) Whether it
is an acid or a basic, and 2) the pH of the solution in which it is found.
pKa is the pH at which 50% of the medication is ionised.
When the pH is less than the drug's pKa, it is referred to be a _____
environment, and the reaction favours the _____. - ANSWER acidic, left
When the pH exceeds the drug's pKa, it is considered a _____ environment, and
the reaction favours the _____. - ANSWER simple, right
When the pH is less than pKa, acid medications are ______ and base drugs are
_____. - ANSWER: Non-ionized, lipid-soluble; ionised, water-soluble
conjugation routes are saturated, and there is insufficient glutathione to
conjugate the metabolite NAPQI, which binds to hepatocellular proteins,
causing oxidative damage, mitochondrial malfunction, and hepatocellular
apoptosis.
What is the first step in responding to an acute paracetamol overdose? -
ANSWER The conjugation metabolism becomes saturated, and excess APAP is
oxidatively metabolised by the CYP enzymes (CYP2E1, 1A2, 2A6, and 3A4) to
the hepatotoxic reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
Glutathione's role in acetaminophen biotransformation. Conjugates the
hepatotoxic reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI), which
is then eliminated renally.
A lack of glutathione or high NAPQI synthesis can result in _______. -
ANSWER NAPQI binds to cysteinyl sulfhydryl groups in hepatocellular
proteins, creating NAPQI-protein adducts. This results in a cascade of oxidative
damage and mitochondrial malfunction. The following inflammatory ANSWER
promotes hepatocellular damage and mortality.
True or false: The amount of APAP that might cause toxicity may be lower in
the presence of chronic ethanol use, malnutrition, fasting, or viral infection. -
The answer is true.
yes or false: co-ingestion of drugs or treatments known to enhance the activity
of the APAP-metabolizing cytochrome P (CYP) oxidative enzymes increases
the risk of hepatotoxicity - ANSWER yes
What is the antidote to paracetamol poisoning? - ANSWER NAC is a
glutathione precursor that enhances glutathione concentrations accessible for
NAPQI conjugation. It also improves the sulphate conjugation of unmetabolized
, APAP, acts as an anti-inflammatory and antioxidant, has beneficial inotropic
effects, and raises local nitric oxide levels to improve blood circulation.
A drug is _______. - ANSWER an agent that influences biological processes
and is used to prevent or treat diarrhoea; the most are weak acids or bases.
Pharmacokinetics - Answer The quantitative study of drug absorption,
distribution, metabolism, and excretion (ADME), and their mathematical
relationship; what the body does with the drug once it is taken.
The absorption of a medication is determined by its ______. - ANSWER
solubility (lipid or water-soluble)
A protonated acid is non-ionized and lipid-soluble.
A non-protonated acid is ______. - ANSWER: Ionised and water soluble.
A protonated base is _____. - ANSWER: Ionised and water soluble.
A non-protonated base is _____. - ANSWER: non-ionized and lipid-soluble
Polar medicines work similarly to _____ medications. - ANSWER: Ionised,
water soluble
What decides whether a medication is ionised or not? - ANSWER 1) Whether it
is an acid or a basic, and 2) the pH of the solution in which it is found.
pKa is the pH at which 50% of the medication is ionised.
When the pH is less than the drug's pKa, it is referred to be a _____
environment, and the reaction favours the _____. - ANSWER acidic, left
When the pH exceeds the drug's pKa, it is considered a _____ environment, and
the reaction favours the _____. - ANSWER simple, right
When the pH is less than pKa, acid medications are ______ and base drugs are
_____. - ANSWER: Non-ionized, lipid-soluble; ionised, water-soluble