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57 Cards in this Set
- Front
- Back
List 5 fluid compartments that are sites of exclsuion to drugs
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Cerebral fluid
Ocular fluid Lymph fluid Fetal Fluid Pleural fluid CLOPF |
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2 major drug binding plasma proteins
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1. Albumin
2. Orosomucoid = alpha1 acid glycoprotein |
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What is the "negative acute phase plasma protein"?
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Albumin
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Name 2 drugs that decrease in the body if albumin is at a lower concentration
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Phenytoin
Salicylates |
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What is the "Positive acute phase plasma protein"?
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Orosomucoid
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When does Orosomucoid increase its concentration?
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with Inflammation
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Name two drugs that increase in concentration in the body when Orosomucoid increases
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Quinidine
Propranolol |
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What 3 things can alter the concentration of free drug in plasma?
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1. Dose
2. Disease (albuminemia, uremia) 3. Co-administration of other drugs |
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During which semester is the fetus most vulnerable to the teratogenic effects of drugs?
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1st semester
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How do drugs enter mammary milk?
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passive diffusion
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List 3 general drugs that accumulate in milk and why they do so
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1. Weak organic bases = milk is more acidic than plasma = "ion trap"
2. Tetracyclines = chelate with calcium 3. Lipid-soluble drugs = milk has high fat content |
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Explain Thiopental Redistribution
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-Thiopental is IV administered
-initally distributed to areas of highest blood flow: brain, liver, kidneys -drug is then redistributed to and stored in muscle and adipose tissue = terminated by redistribution |
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The action of what group of drugs are terminated by redistribution?
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Lipid soluble CNS active drugs
**The duration of action of an initial dose may depend more on the redistribution rate rather than on the half-life **With repeated doses, fat and other tissue depots become saturated, resulting in longer durations of action than the first dose |
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List 5 things that contribute to the blood brain barrier
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1. tight jxns
2. glia wrappings 3. low CSF protein = lower than plasma causes drugs to want to stay in plasma 4. Enzymes 5. Transporters |
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List the 5 factors affecting distribution
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1. blood flow to the organ
2. the solubility of the drug 3. level of binding to substances in the blood versus binding to substances in tissues 4. transporters 5. ion-trapping |
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What do Phase 1 reactions do to drugs?
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change the functionality of the drug
-metabolite with modified activity -inactive metabolite |
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What do Phase 2 reactions do to drugs?
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Synthesis = add something on to the molecule = make drug more hydrophilic
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What are sometimes referred to as Phase 3 clearance?
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Tranporters
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3 important Phase 1 reactions
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1. Oxidation = loss of electron
2. Reduction = gain of electron 3. Hydrolysis **HOR |
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6 important Phase 2 reactions
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1. Glucuronidation
2. Sulfate conjugation 3. Acetylation 4. Glutathione conjugation 5. Methylation 6. Glycine conjugation *1 and 2 are most important |
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Where are Phase 1 drug-metabolizing enzymes (mixed function oxidases or monooxygenases) located?
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in lipophilic membranes of SER
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Phase 1 biotransformation oxidation usually occurs by what?
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Cytochrome P450 isozyme
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What are the 4 Oxidation requirements for Phase 1 biotransformation?
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1. Cytochrome P450
2. Cytochrome P450 reductase 3. NADPH 4. Molecular Oxygen |
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CYP's that encode enzymes for most drug biotransfomations
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CYP 1, 2, and 3
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CYP that is extensively express in GI responsible for poor oral bioavailability (first-pass)
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CYP-3A4
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Drugs that induce CYP2C9 (3)
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Phenobarbital
Phenytoin Rifampin **To See 9 Fen-Fen Rif's** |
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Drugs that induce CYP2C19 (4)
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Barbiturates
Carbamazepine Phenytoin Rifampin To See 19 "Barbs, Carbs, Fins, and Rifs" |
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What CYP do the following drugs induce?
Polycyclic aromatic compounds 3-methylcholanthrene Benzo-a-pyrene |
1A2
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Drugs that induce CYP3A4 (2)
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1. Glucocorticoids
2. Anticonvulsants -barbs -phenytoin -Carbamazepine -Primidine |
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Drugs that induce CYP2E1 (3)
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1. Chronic Alcohol
2. Isoniazid 3. Activates carcinogenic nitrosamines **2 Erick's = Chronic Alcoholic -> Must "ISO"late them **Erick should not take Acetaminophen |
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CYP that when induced converts Acetominophen to a toxic metabolite
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CYP-2E1
*induced by Isoniazid and Chronic Alcohol |
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What CYP metabolizes Terfenadine and Astemizole?
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CYP-3A4
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List 2 drugs that markedly increase the toxicity of Terfenadine, why, and the physiologic effect
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-Erythromycin and Ketoconazole
-They inhibit CYP3A4 which causes Terfenadine to accumulate -QT prolongation -> -> -> Torsade de points *Terfenadine must be metabolized to be activated (active product is Fexofenadine) |
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List 8 inducers of phase 1 biotransformation (cause other drugs to be metabolized more quickly)
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1. Phenobarbital
2. Phenytoin 3. Carbamazepine 4. Polycyclic aromatics 5. Glucocorticoids 6. Chronic Alcohol 7. Rifampin 8. St. John's Wort *1-3 are Anticonvulsants **St. John, the Chronic Alcoholic, Smokes, eats Carbs, takes Phen-Phen, and gets shots of Cortisol, all while playing Rifs on the guitar |
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List 6 inhibitors of phase 1 biotransformation (decrease the metabolism of drugs)
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1. Cimetidine
2. Ketoconazole 3. Chloramphenicol 4. Erythromycin 5. Acute Alcohol 6. Grapefruit juice CAGE-CK |
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2 possible ways a Phase 2 drug conjugate can be formed
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1. via high energy intermediate and the parent compound
2. Phase 1 metabolite by a transfer enzyme |
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Phase 2 major route of metabolism for both drugs and endogenous compounds
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Glucuronide conjugation
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Glucuronide transferase activity is localized to this organelle and organ
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ER
Liver |
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By what process are glucuronides secreted in the kidney and liver
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ACTIVE transport = against their concentration gradient with use of ATP
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2 Phase-2 reactions that especially make compounds more water-soluble and excretable
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1. Sulfation
2. Glucuronidation |
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2 Phase 2 rxns that often make drugs less water-soluble
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1. Methylation
2. Acetylation |
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Crystalluria results when __1__(rxn) products of __2__(compound) precipitate in __3__(pH) tubular urine
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1. acetylated
2. sulfonamides 3. acidic |
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Which Phase reactions are more likely to be preserved in the elderly, Phase 1 or 2?
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Phase 2 reactions
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6 liver diseases that can cause decreased drug metabolism
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1. Fatty liver
2. Hepatitis 3. Cirrhosis 4. Hemochromatosis 5. Liver tumors 6. Drug-induced liver damage |
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2 CYP polymorphisms that can affect biotransformation in different races
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CYP-2D6
CYP-2C19 |
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Do not give this drug if a person has 2 non-functional alleles of Thiopurine S-methytransferase
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6-mercaptopurine b/c will cause toxicity
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20% of asians and blacks have a polymorphism of this CYP that has POOR METABOLISM (PM)
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CYP 2C19
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If prescribing for Warfarin, you should genetically test for these genes (2)
What would be the ADR? |
1. CYP 2C9
2. Vitamin K Epoxide Reductase ADR = bleeding |
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If giving Isoniazid (anti-TB) what gene should be tested for?
What would be the ADR? |
N-acetyltransferase (Phase II Conjugation)
Hepatoxicity |
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If prescribing 6-Mercaptopurine what gene should be tested for?
ADR? Therapeutical use of Mercaptopurine? |
Thiopurine S-methytransferase
Hematological toxicity Acute Lymphoblastic Leukemia |
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If prescribing Irinotecan, what metabolic gene should be tested for?
ADR? Irinotecan therapeutical use? |
1. UDP-Glucuronosyltransferase (UGT1A1)
2. Diarrhea or neutropenia 3. colon cancer |
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If giving Codeine, what gene should be tested for?
ADR? Codeine therapeutical use? |
CYP2D6
lack of analgesic effect Analgesic |
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The reactive metabolite of Acetaminophen may induce this adverse response
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Hepatotoxicity
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Reactive metabolites of Aflatoxin may induce this adverse response
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Tumors
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Reactive metabolites of Cyclophosphamide may induce this adverse response
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Cystitis
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What are 2 Weak Organic Base drugs that can accumulate in Milk and cause harm to babies who are breast-feeding?
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Amphetamines
Cocaine |
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CYP that when induced activates Carcinogenic Nitrosamines
What induces it? (2) |
CYP 2E1
Isoniazid & Chronic Alcohol |