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39 Cards in this Set
- Front
- Back
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1. What is drug metabolism?
What are some other names for metabolism? |
Interaction of a drug with the biological system causing a chemical change in the drug
**resultant compound is called the metabolite or metabolic product Detoxification or biotransformation |
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2. Are all drugs inactivated by being metabolized?
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No
Not all drugs are metabolized **may be excreted unchanged such as NO or some penicillins |
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3. How are drugs and their metabolic products related?
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Some metabolic products are inactive
Some are pharmacological activity *some valium products are still active Some are even more toxic *methanol and Tylenol Sometimes drugs are inactive and metabolized to active form *Parkinson disease drugs |
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4. What is the pro-drug?
What is an example of this? |
Inactive form of a drug
Pro-form of dopamine is given orally for Parkinson disease b/c it will cross the blood-brain barrier **dopamine given orally will not cross the blood-brain barrier |
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5. What is the purpose of drug metabolism?
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Metabolism makes the drug less lipid soluble and more water soluble
Therefore drug is more readily excreted in the body's aqueous excretions 1. Increase water solubility 2. Decrease lipid solubility 3. Increase excretion |
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6. What are the two categories of metabolic reactions?
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1. Phase I (non-synthetic) reactions
2. Phase II (synthetic) reactions |
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7. What happens in phase I reactions?
What happens to the metabolites if they are sufficiently polar? What are three examples of phase I (non-synthetic) reactions? |
Convert the parent drug to a more polar metabolite
Metabolites are excreted 1. Oxidation 2. Reduction 3. Hydrolysis |
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8. What happens in phase II (synthetic) reactions?
What else are these called? What does conjugate formation involve? What do most conjugate reactions yield? |
Add a group to the structure
*more likely to detoxify drugs Conjugation reactions Involves high-energy intermediates and specific transfer enzymes (transferase) Inactive products |
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9. What are examples of phase II (synthetic) reactions?
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1. Glucuronidation
2. Sulfate conjugation 3. Acetylation 4. Amino acid conjugation 5. Methylation 6. Glutathione conjugation |
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10. Where is the major site of drug metabolism?
Following oral administration may drugs are absorbed in the small intestine and the transported where? What is this process called? |
Liver
Transported via portal system to liver where undergo extensive metabolism First pass effect / first pass metabolism **some drugs may also be partially metabolized in the intestines |
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11. How does first pass metabolism affect bioavailability?
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Greatly limits oral bioavailability of a drug
**Therefore it limits its effectiveness by the oral route |
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12. Where are many drug-metabolizing enzymes located?
What is the microsomal mixed function oxidase system? |
Lipophilic membranes of the smooth ER
Metabolic enzymes that remain associated with the fraction of membrane that was homogenized and fractionated into microsomes |
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13. What do the activity of these enzymes requires?
(two things) What two microsomal enzymes play a key role? |
1. NADPH (reducing agent)
2. Molecular oxygen 1. HADPH-cytochrom P450 reductase 2. Cytochrome P450 *serves as a terminal oxidase |
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14. What happens in the cytochrome P450 mediated reaction?
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Substrates bind with the oxidized cytochrome
Resulting complex is reduced by the reductase Reduce complex combines with molecular oxygen Yield.. -oxidized substrate -water -oxidized cytochrome |
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15. What are two non-cytochrome P450 mediates phase I reactions?
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1. Xanthine oxidase
2. Alcohol dehydrogenase |
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16. What factors influence drug metabolism?
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1. Rate of blood flow to the liver (CO)
2. Rate of entry into the liver *free drug gets there so if highly bound to plasma protein may not enter liver 3. Enzyme induction/inhibition 4. Drug-drug interactions |
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17. What factors influence drug metabolism?
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5. Individual differences
6. Genetic (polymorphisms) 7. Diet, exercise, environmental factors 8. Tissue pathology 9. Age and gender |
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18. What is an inducer?
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Drug whose metabolism is enhanced
"Induce" cytochrome P450 activity by increasing the rate of synthesis or reducing the rate of degradation of the enzymes **Increase metabolism of some drugs |
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19. How is rifampin an inducer of warfin?
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Rifampin increases the metabolize of warfarin
This leads to excessive clotting so can have stroke |
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20. What is an inhibitor?
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Drug whose metabolism is inhibited
Inhibits cytochrome P450 activity by |
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21. How does an inhibitor inhibit cytochrome P450 activity?
Two ways... |
1. Compete with another drug for the same metabolic enzyme
2. Form a complex with the enzyme which inactivates it |
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22. What does acute ethanol inhibit?
What does cimetidine do? |
Reduces metabolism of methanol
Inhibits metabolism of warfarin so have excessive bleeding b/c not metabolizing warfarin |
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23. How do genetic polymorphisms affect drug metabolism?
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Different populations metabolize drugs differently
Example - Isoniazid -have two normal distributions: fast and slow -slow is more likely to get peripheral neuropathy |
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24. What is drug excretion?
Why is drug excretion important? |
Removal of a drug or its metabolites from the body to the external environment
Important in preventing or minimizing toxic effects of drugs |
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25. How are volatile drugs (i.e. inhalation general anesthetics) eliminated?
How are non-volatile, water-soluble or their metabolites eliminated? |
Via lungs (exhaled air)
Principally in urine or bile |
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26. What are five ways drugs are excreted?
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1. Lungs
2. Tears, sweat, saliva 3. Breast milk 4. Renal excretion 5. Biliary excretion |
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27. What are the two criteria for soluble substance to be filtered in the glomerulus?
If nothing else happens to the drug as it progresses through the nephron how is the drug excreted? |
1. MW less than 5,000
2. Free in plasma Drug (water soluble, ionized) is excreted in urine |
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28. What are several process that can occur in the nephron?
Five things... |
1. Glomerular filtration (125 mL/min)
2. Active tubular secretion (650 mL/min) 3. Active tubular resorption 4. Passive resorption 5. Ion trapping |
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29. What is active tubular secretion?
What form of the drug can undergo tubular secretion? |
Carrier mediated active transport process in the proximal tubule by which organic acids and bases may enter the nephron
Both bound and free drug **drugs can compete w/ each other or endogenous compounds for transport |
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30. What is active tubular resorption?
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Active transport in process in the proximal tubule by which drugs may be reabsorbed back into the general circulation
**very few drugs undergo active tubular resorption |
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31. What is passive resorption?
Which type of drugs will be reabsorbed instead of excreted? |
Process in the proximal and distal tubules in which a drug can re-enter the circulation by passive diffusion
Lipid-soluble, non-ionized drugs |
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32. What is ion-trapping?
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Pharmacologically changing the pH of the tubular filtrate you alter the excretion of the drug
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33. What is the rate at which a drug is filtered by glomerular filtration related to?
What does excretion by active secretion depend upon? How can the renal excretion of some drugs be altered? |
It free concentration in plasma
The total plasma concentration (free and bound) By changing the urine flow and pH of the urine |
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34. How can excretion of weak acids be increased?
How can excretion of weak bases be increased? |
Primarily excreted in alkaline urine
Acidify urine (more ionized) |
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35. What is biliary excretion?
How much bile is excreted a day? What is the MW requirement for biliary excretion? |
Drugs from general circulation may enter the liver and be excreted into the bile
1 L bile/day MW > 450 **phase II metabolism can increase MW of a drug so it's excreted in bile |
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36. How does biliary excretion occur?
In some cases what can occur? What is this? |
1. Oral
2. Small intestines 3. Feces Enteroheptatic recirculation Drug re-enters circulation and prolongs its half life in the body |
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37. What are the three main phases in the overall transfer from plasma into bile?
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1. Active uptake into the hepatocytes
**saturable, active transport process 2. Storage and/or biotransformation in the hepatocyte 3. Release into bile |
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38. What are some factors that alter the rate of elimination?
Six things... |
1. Age (pediatric/geriatric)
2. Environmental factors 3. Disease 4. Gender 5. Individual variation 6. Drug-drug interaction |
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39. What is first order kinetics rate of elimination?
What is zero order kinetics rate of elimination? |
Rate of elimination is proportional to plasma concentration
*plasma half-life can be determined Constant amount of drug is eliminated per unit time *rate of elimination doesn't increase or decrease w/ changes in plasma concentration |
