Drug Metabolism

Question 1

Metabolite

Answer 1

the breakdown product of a xenobiotic. Can be more or less toxic than the ingested/inhaled/injected substance.

Question 2

Phase 1 metabolism

Answer 2

make a drug more hydrophilic so that it can be excreted in water. Involves oxidation, reduction, and hydrolysis reactions. Can go through multiple phase 1 reactions. Oxidation is the most common.

Question 3

Phase 2 metabolism

Answer 3

involves the conjugation of phase 1 metabolites to larger polar molecules for excretion from the body

Question 4

Cytochrome p450

Answer 4

large heme group, principally responsible for phase 1 metabolism. 20 different families, lots of different types. 5 major ones, CYP3A4(most common), CYP2D6, CYP2cs, CYP1A2, CYP2E1

Question 5

Where are most CYTs

Answer 5

liver, lung, kidney. Mostly in the liver.

Question 6

Smoking

Answer 6

affects cyt, may lower the dosages of each of these drugs.

Question 7

Nuclear Receptors

Answer 7

drug or toxicant enters cell and acts as ligands that bind to receptors. Work through positive feedback loop. Different drugs bind to different receptors and thus similulates different cytocromes

Question 8

Effects of P450 induction

Answer 8

If the specific cytochrome has already been induced, expect the amount of drug to last a much shorter time.

Question 9

Glucuronidation

Answer 9

most common phase 2 reaction. transferase transfers molecules to UDP-GT for help exceptions.

Question 10

Neonatal hyperbilirubinemia

Answer 10

babies fail to metabolize bilirubin to billirubin conjugate (UDP-GT), leading to CNS damage

Question 11

Chloramphenicol-Low GLucuronidaiton

Answer 11

a deficiency leads to build up drug in blood causing toxicities such as grey baby syndrome including grey teeth.

Question 12

Crigler-Naijar syndrome

Answer 12

genetic deficiency in hepatic UDP-GT, leads to jaundice and death in early childhood.

Question 13

N-acetylconjugation conjugation

Answer 13

biphasic distribution in the population. Slow aceytalators are susceptible to dose dependent toxicities, especially from isoniazid, sulfamethazine, p-aminosalicycilic acid, and hydralazine.

Question 14

What types of pathology is most detrimental to drug metabolism.

Answer 14

Diseases of the liver: Malaria, shcistosomyosis, cancer, cirrohosis, hepatitis, radiation, etc.

Question 15

Cellular efflux

Answer 15

ejection of drug from a cell, even it manages to enter the cell. Pgps transfer out parent molecules, while mrps transfer out conjugates. Big reason why drugs fail.

Question 16

Ethanol effects on drugs

Answer 16

can have opposite effects in acute vs chronic use settings. IN acute setting, inhibits cytochromes and thus prolongs effects of the drugs via competition. In chronic settings, metabolism is quicker since system is already primed to handle.

Question 17

Alcohol and phenobarbitol

Answer 17

alcohol has an additive effect on individuals who have just ingested phenobarbital, but a dampening effect 24 hours later.

Question 18

Metabolic Age

Answer 18

very young and very old have reduced metabolic efficiency, so dosages must be adjusted. metabolism slows, excretion slows, reduced receptors.

Question 19

Nutrition effects on drug metabolism

Answer 19

green vegetables, brussle sprouts, cabbage. Grapefruit Juice-inhibits CY3P4A metabolism of drugs, increases toxicity and bioavailability. Charcoal meat speeds up metabolism.