Term
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Definition
To get a drug into the body it must be relatively...?
a. ionized
b. unionized |
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Term
1. sweating
2. pulmonary
3. biliary/fecal
4. renal
5. breast milk |
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Definition
| What are the 5 ways for excretion? |
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Term
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Definition
| During which phase of metabolism is there a relatively minor chemical modification of the parent compound? |
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Term
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Definition
| Phase I reactions may result in the formation of functional groups which serve as sites for what? |
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Term
a. more polar
*more water soluble, less lipid soluble |
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Definition
The metabolite formed from Phase I reactions is...?
a. more polar
b. less polar |
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Term
Phase II
*conjugation: synthetic reactions with addition of another molecule |
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Definition
| Which phast of metabolism is conjugation in? |
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Term
More polar
*less lipid soluble |
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Definition
| Does the drug turn more or less polar in Phase II reactions? |
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Term
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Definition
| During which phase are the metabolites rendered physiologically inactive? |
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Term
1. hydrolysis
2. oxidations
3. reductions |
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Definition
| What are the three typical Phase I reactions? |
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Term
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Definition
| Cytochrome P450 is linked to which Phase I reaction? |
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Term
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Definition
| Alcohol, aldehyde dehydrogenase, xanthine oxidase, monoamine oxidase are all linked to which Phase I reaction? |
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Term
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Definition
| Which bonds are split in half during hydrolysis? |
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Term
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Definition
| Which compounds are associated with reduction reactions? |
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Term
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Definition
| Which reaction makes the molecule more polar, more water soluble and less lipid soluble? |
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Term
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Definition
| What mediates oxidation reactions? |
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Term
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Definition
| How many Cytochrome P450 gene families are in humans? |
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Term
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Definition
| What does the first number of CYP3A4 stand for? |
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Term
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Definition
| What does the second number of CYP3A4 stand for? |
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Term
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Definition
| What does the last number in CYP3A4 stand for? |
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Term
|
Definition
| What abbreviation stands for Cytochrome P450? |
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Term
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Definition
| CYP is characterized by what type of reactions? |
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Term
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Definition
| The mixed-function-oxidase reaction is dependent on what molecules? |
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Term
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Definition
| Which amino acid in the liver has a short electron transport chain? |
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Term
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Definition
Various isoforms of CYP catalyze the oxidation reaction with a ____ degree of substrate specificity?
a. high
b. low |
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Term
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Definition
Substrates of a CYP oxidation reaction must be
______ ______?
a. water soluble
b. lipid soluble |
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Term
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Definition
| After the CYP oxidation reaction, what type of product do you end up with? |
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Term
| Everyone has different Cytochrome P450s |
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Definition
| Why won't a drug that gets metabolized in the liver be metabolized the same way in everyone? |
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Term
Liver - 100
Intestine - 40
Lung - 15 |
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Definition
| What are the three most common area's for CytP450's? |
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Term
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Definition
| P450's located in the mytochondria are involved in _____ synthesis. |
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Term
| NADPH-cytochrome P450 reductase |
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Definition
| In humans, CYP's are largely associated with what 2nd membrane protein? |
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Term
| NADPH-cytochrome P450 reductase |
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Definition
| What is the source of the electron(s) required for the oxidation reaction of drugs in humans? |
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Term
1. genetic variation
2. environmental determinants
3. disease factors
4. age
5. sex
6. nutritional status
7. adrenal and thyroid status |
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Definition
| What 7 things influence drug metabolism? |
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Term
| Inhibition of P450 isoforms |
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Definition
| What is due to competition for enzyme active site, inactivation, or interactions with the heme group? |
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Term
drug toxicity
*P450 inhibition causes more drug in the plasma concentration |
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Definition
| What could result if P450 isoforms are inhibited? |
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Term
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Definition
| What type of nutritional diet will slow the metabolism? |
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Term
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Definition
| Do males or females metabolize faster? |
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Term
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Definition
| Which CYP's are normally used in drug reactions? |
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Term
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Definition
| Which CYP do a number of people not have? |
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Term
Glucuronidation
*donor: UDP-glucornonic acid |
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Definition
| Which phase II reaction is quantitatively most important and is a pharmacogenetic variation? |
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Term
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Definition
| The amino acid phase II drug reaction uses what donor? |
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Term
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Definition
| The amino acid Phase II drug reaction depends on the availability of what? |
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Term
| Glucuronidation, acetylation, thiopurine methyltransferase |
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Definition
| What are the three phase II reactions that are pharmacogenetic variations? |
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Term
ribosylation
*Donor: Ribose |
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Definition
| What is the normal reaction involved in purine and pyrimidine metabolism? |
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Term
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Definition
| Which Phase II reaction's substrates generally contain a hydroxy or primary amine group? |
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Term
Thiopurine methyltranserase
*donor: SAM |
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Definition
| What phase II reaction is the S-methylation of aromatic and heterocyclic sulphydryl compounds? |
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Term
| Glutathione-S-transferase |
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Definition
| What phase II reaction serves to protect cellular macromolecules from reactive substances? |
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Term
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Definition
| Which layer of the liver are the transport systems located? |
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Term
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Definition
| Lipid-soluble, conjugated metabolites must have a MW greater than what number to be excreted by the liver into the bile? |
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Term
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Definition
| What is the ability of the liver to eliminate a drug in the absence limitations imposed by blood flow? |
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Term
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Definition
| In biochemical terms, intrinsic clearance is a measurement of what kinetic parameters? |
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Term
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Definition
| What is high intrinsic clearance determined by? |
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Term
| unbound fraction of the drug |
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Definition
| What is low intrinsic clearance be proportional to in the blood? |
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Term
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Definition
Drugs with high hepatic extraction ratios or drugs which are metabolized rapidly compared to their rate of absorption demonstrate reduced or low bioavailability.
This is also known as what? |
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Term
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Definition
| Glomerular filtration will filtrate what part of the drug? |
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Term
| Tubular secretion (active transport) |
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Definition
| Where cells of the proximal tubule actively transport a wide variety of organic acids and bases from the plasma directly into the tubular fluid bypassing filtration? |
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Term
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Definition
| In tubular reabsorption what kind of urine will increase the excretion of weak acids? |
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Term
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Definition
| In tubular reabsorption what kind of urine will increase the excretion of weak bases? |
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Term
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Definition
| What number will the renal clearance be if the drug is filtered an completely reabsorbed? |
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Term
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Definition
| What will the average renal clearance be if the drug is filtered and not reabsorbed? |
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Term
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Definition
| What will the average renal clearance be if the drug is filtered and maximally secreted? |
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