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14 Cards in this Set
- Front
- Back
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Describe Phase I Enzymes.
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They are Cytochrom P450's that add a hydroxyl group to the compound meant to be eliminated.
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What about Phase II Enzymes?
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They use the hydroxyl group from Phase I enzyme and modify it to make it easier to eliminate from the body. Recall how sterols cannot be degraded but their OH groups can be modified to make them more water soluble/excretable.
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Describe typical xenobiotics
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Nonpolar, lipophilic molecules that easily cross membranes but are poorly excreted.
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Where do P450 rxns take place?
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ER - that's why they're often called microsomal.
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Are P450s/Transferases highly specific and have high catalytic rates? Why or why not?
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No. Bc a small number of them can handle over 60,000 chemicals.
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What are the polar groups typically added to xenobiotics by P450s? (there are three) (p411)
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1. OH
2. NH2 3. SH |
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Unlike the P450s used to make cholesterols, those that deal with drugs work exclusively in the:
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ER
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Although P450s are found throughout the body, they are their highest concentration in the (3 places): (p413)
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1. Lung
2. Intestinal Mucosa 3. (especially the...) Liver |
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P450's could operate in Smooth ER or RER - which one?
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Smooth ER.
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Where/how do some xenobiotics get "activate" in their metabolism?
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When they are oxygenated in conformationally hindered positions that are inaccessible to Phase II enzymes. They can interact nonenzymatically with intracellular nucleophiles
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What is it called when one drug affects the activity of a P450 such that the therapeutic dose of another drug is too low? Too high?
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Induction. Repression
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What are the three ways P450 activity can be repressed?
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1. Mechanism-based inhibition - certain drugs that contain functional groups that are oxidized by P450s to metabolites that bind irreversibly to the enzyme
2. Disease States: Diseases with hepatic involvement, such as cirrhosis, are associated with impaired drug elimination 3. Multiple Drug therapy: drugs compete for same cytochrome P450 resulting in repression |
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What combination of drugs can result in unplanned pregnancies? What P450 enzyme does it induce?
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Rifampin (Antibiotic) and St. John's Wart. CYP 3A4
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What combination of drugs can result in increased risk of cardiac death? What happens?
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Erythromycin and Verapamil. BP drug slows down breakdown of erythromycin. It increases its concentration in blood. This increases salt retention in resting heart cells, prolonged time until next heart beat, increased likelihood of abnormal fatal rhythm.
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