NUSCTX Questions with Correct Answers
6. What are the key concepts of how storage affects the toxicity decrease toxicity: if
storage site is distant from site of action. increase toxicity: if storage site is site of action. change
effects of other substance: if displacement occurs of similar substance from storage site
7. The key concepts of excretion Kidney to urine - most important for quantity Liver to
bile - m.w. >350 D, metals Intestine to feces - mostly unabsorbed, some active Lung to expired
air - volatiles, gases Mammary gland to milk - lipid sol. xenobiotics Exocrine glands to sweat,
saliva etc.- water sol.xenobiotics
8. In biotransformation, what does phase I and Phase II reaction do? What type of enzymes are
responsible for phase I reaction? Phase I metabolism- a chemical "hook"is added to the
xenobiotics usually by oxidative enzymes in cells. Phase II metabolism- a water soluble "tag"
chemical is added to the hook from phase I metabolism to make the metabolite more water
soluble. The cytochrome p450 superfamily of enzymes (CYP)catalyze the oxidation of organic
substances (phase I reaction). The substrates for CYP include lipid metabolites, steroid
hormones, xenobiotics such as drugs and toxic chemicals.
, 9. Do phase I and II reactions always detoxify xenobiotics? No. Sometimes makes them
more toxic
10. Can xenobiotics and other less toxic substances modulate the expression and activities of
xenobiotic metabolism enzymes? (yes. Usually xenobiotics will induce the expression of
genes encoding enzymes that can metabolize themselves.
1. What is the difference between on- and off-target toxicities? On target: Toxic effect due
to the drug interacting with the intended therapeutic target. Usually dose is too high or there is
chronic activation effects. Off target: Toxic effect due to the drug interacting with an unintended
biological target or unintended tissue.
2. For non-steroidal anti-inflammatory drugs like aspirin and ibuprofen that block inflammation
and fever, how does it reduce fever and inflammation? What types of toxicity are associated with
these drugs? Is this on- or off-target toxicity? Inhibits COX 1 and 2 and reduces
proinflammatory eicosanoids such as prostaglandins, prostacyclins, and thromboxanes. These are
On-Target toxicities. Cox1 also mediates prostaglandins levels of the gut which mediates the
mucosal lining protecting your gut from the acid. Without this, you are prone to gastric bleeding.
Both therapeutic and toxic effect happen through the same receptors.
6. What are the key concepts of how storage affects the toxicity decrease toxicity: if
storage site is distant from site of action. increase toxicity: if storage site is site of action. change
effects of other substance: if displacement occurs of similar substance from storage site
7. The key concepts of excretion Kidney to urine - most important for quantity Liver to
bile - m.w. >350 D, metals Intestine to feces - mostly unabsorbed, some active Lung to expired
air - volatiles, gases Mammary gland to milk - lipid sol. xenobiotics Exocrine glands to sweat,
saliva etc.- water sol.xenobiotics
8. In biotransformation, what does phase I and Phase II reaction do? What type of enzymes are
responsible for phase I reaction? Phase I metabolism- a chemical "hook"is added to the
xenobiotics usually by oxidative enzymes in cells. Phase II metabolism- a water soluble "tag"
chemical is added to the hook from phase I metabolism to make the metabolite more water
soluble. The cytochrome p450 superfamily of enzymes (CYP)catalyze the oxidation of organic
substances (phase I reaction). The substrates for CYP include lipid metabolites, steroid
hormones, xenobiotics such as drugs and toxic chemicals.
, 9. Do phase I and II reactions always detoxify xenobiotics? No. Sometimes makes them
more toxic
10. Can xenobiotics and other less toxic substances modulate the expression and activities of
xenobiotic metabolism enzymes? (yes. Usually xenobiotics will induce the expression of
genes encoding enzymes that can metabolize themselves.
1. What is the difference between on- and off-target toxicities? On target: Toxic effect due
to the drug interacting with the intended therapeutic target. Usually dose is too high or there is
chronic activation effects. Off target: Toxic effect due to the drug interacting with an unintended
biological target or unintended tissue.
2. For non-steroidal anti-inflammatory drugs like aspirin and ibuprofen that block inflammation
and fever, how does it reduce fever and inflammation? What types of toxicity are associated with
these drugs? Is this on- or off-target toxicity? Inhibits COX 1 and 2 and reduces
proinflammatory eicosanoids such as prostaglandins, prostacyclins, and thromboxanes. These are
On-Target toxicities. Cox1 also mediates prostaglandins levels of the gut which mediates the
mucosal lining protecting your gut from the acid. Without this, you are prone to gastric bleeding.
Both therapeutic and toxic effect happen through the same receptors.
