Term
| Where in the body are reductases found? |
|
Definition
| ER, cytosol, anaerobic gut microorganisms |
|
|
Term
| What are the different types of reduction reactions? |
|
Definition
| azoreduction, nitroreduction, ketoreduction |
|
|
Term
| Where do hydrolysis reactions take place? |
|
Definition
| plasma, liver, kidney, and all tissues |
|
|
Term
| What types of enzymes catalyze hydrolysis reactions? |
|
Definition
| esterase, amidase, and epoxide hydrolase |
|
|
Term
| What is succinylcholine apnea? |
|
Definition
| dut to an esterase deficiency, enzyme appears to have an altered affinity for esters, affects about 1/3000 |
|
|
Term
| Where is epoxide hydrolase found? |
|
Definition
|
|
Term
| What are the two forms of epoxide hydrolase? |
|
Definition
| microsomal and soluble forms |
|
|
Term
| What induces epoxide hydrolase? |
|
Definition
| phenobarbital and 3 methylcholanthrene |
|
|
Term
| What induces epoxide hydrolase? |
|
Definition
| phenobarbital and 3 methylcholanthrene |
|
|
Term
| What types of reactions happen in phase 2 conjugation reactions? |
|
Definition
| glucouronidation, sulfate conjugation, acetylation, glutathione conjugation, methylation, glycine conjugation |
|
|
Term
| What enzyme is used for glucuronide conjugation? |
|
Definition
| UDP-glucuronyl-transferase |
|
|
Term
| What enzyme is used for sulfate conjugation? |
|
Definition
|
|
Term
| What enzyme and substrate are used for acetylation? |
|
Definition
| acetyl CoA, N-acetyltransferase |
|
|
Term
| What enzyme is used for glutathione conjugation? |
|
Definition
| glutathione S transferase |
|
|
Term
| What enzymes perform methylation? |
|
Definition
|
|
Term
| Where are methyltransferases located within the cell? |
|
Definition
|
|
Term
| What activated molecule is used for methylation? |
|
Definition
|
|
Term
| Which amino acid is most often used in conjugation reactions? |
|
Definition
|
|
Term
| Where in the cell does amino acid conjugation occur? |
|
Definition
| mitochondria and cytoplasm |
|
|
Term
| What factors of an organism will affect drug metabolism? |
|
Definition
| genetics, aging, species differences |
|
|
Term
| Why do the elderly have a lower drug clearance? |
|
Definition
| decreased absorption, altered distribution, decreased metabolism, decreased excretion |
|
|
Term
| What is the equation for the rate of elimination? |
|
Definition
|
|
Term
| What value is equal to the slope of the line plotted on a log [drug] over time? |
|
Definition
|
|
Term
| What functional groups does glucuronidation react with? |
|
Definition
| hydroxyl, amine, or carboxylic acid |
|
|
Term
| Where in the cell does glucuronidation occur? |
|
Definition
|
|
Term
| What fuctional groups does sulfate conjugation occur with? |
|
Definition
| alcohols, phenols, and aromatic amines |
|
|
Term
| Where does sulfate conjugation occur? |
|
Definition
|
|
Term
| Where does acetylation occur? |
|
Definition
|
|
Term
| Name 2 conjugation reactions that are saturable. |
|
Definition
| sulfate and glycine conjugation |
|
|
Term
| What functional groups does acetylation occur with? |
|
Definition
|
|
Term
| Are most people in the US slow or fast acetylators? |
|
Definition
|
|
Term
| What racial groups are rapid acetylators? slow acetylators? |
|
Definition
japanese are rapid acetylators
middle eastern, scandanavians, finns are slow |
|
|
Term
|
Definition
|
|
Term
| Slow acetylators are at risk for: |
|
Definition
| isoniazid-induced neurotoxicity, drug-induced SLE, and arylamine induced bladder cancer |
|
|
Term
| Fast acetylators are at risk for: |
|
Definition
| isoniazid induced hepatitis, and colorectal cancer (esp with rapid CYP1A2 type) |
|
|
Term
| What functional groups react in methylation reactions? |
|
Definition
| hydroxyl, sulfhydryl, and amine |
|
|
Term
| Where do glutathione conjugation reactions take place? |
|
Definition
| cytosol and mitochondria of liver and numerous other tissues |
|
|
Term
| Describe the structure of glutathione conjugation enzymes: |
|
Definition
|
|
Term
| What type of conjugation reactions can ultimately form mercapturic acids? |
|
Definition
|
|
Term
| What types of functional groups participate in glutathione conjugations? |
|
Definition
| aromatic hydrocarbons (epoxides), arylamines, organic halides, phenols, and ligand binidng cpabilities (ligandins) |
|
|
Term
| How do you induce alpha class GSTs? |
|
Definition
| ingestion of high levels of brussel sprouts |
|
|
Term
| What are the polymorphisms of glutathione conjugation? |
|
Definition
|
|
Term
|
Definition
| polymorphic (*0, 8a, and *b); null gene (increased risk of cancer), essentially absent in 20-50% of all individuals |
|
|
Term
| How many variants of GSTP1 are there? |
|
Definition
|
|
Term
| GSTM1 null phenotype is linked to what cancers? |
|
Definition
| pituitary adenomas, head and neck cancer, malignant melanoma, colorectal cancer, and bladder carcinoma |
|
|
Term
| Is GSTM1 null phenotype associated with lung cancer? |
|
Definition
| yes but only in heavy smokers |
|
|
Term
| What functional groups participate in glycine conjugation? |
|
Definition
| aliphatic acids and aromatic carboxylic acids |
|
|
Term
| Name a type of conjugation reaction that is developmentally induced |
|
Definition
|
|
Term
| What effect do ethanol and cimantidine have on drug metabolism |
|
Definition
|
|
Term
| Name drugs that induce P450 and other drug metabolizing enzymes. |
|
Definition
| phenobarbital and other drugs, polycyclic hydrocarbons and carcinogenesis |
|
|
Term
| What dietary elements can affect drug metabolism? |
|
Definition
| charcoal broiled beef, vitamin deficiencies, brussel sprouts, grapefruit |
|
|
Term
| What is the relationship between the half life and the elimination constant? |
|
Definition
|
|
Term
| What is the volume of distribution? |
|
Definition
| apparent volume into which a drug distributes in the body |
|
|
Term
| How do you calculate a volume of distribution? |
|
Definition
| inject a known quantity of drug as an IV bolus. take blood samples at various times after injection. Plot data on a semilogarithmic plot and extrapolate back to t=0 to calculate the concentration prior to elimination. VD= amount of drug/plasma concentration = X0/Cp |
|
|
Term
| List three equations that equal total clearance. |
|
Definition
ClT = Kel * VD
CLT = X0/area under the curve
CLT = Cl(liver) + CL(kidney) + Cl(other) |
|
|
Term
| Describe an equation for rate of absorption. |
|
Definition
|
|
Term
|
Definition
| area under the curve of drug [] over time |
|
|
Term
|
Definition
|
|
Term
| How do you calculate teh total clearance of a drug administered IV. |
|
Definition
|
|
Term
| How do you calculate total clearance in a drug that is administered extravascularly? |
|
Definition
|
|
Term
| What is the extraction ratio for hepatic clearance? |
|
Definition
|
|
Term
| What is the hepatic clearance for first order drugs? |
|
Definition
|
|
Term
| What is the hepatic clearance for zero order drugs? |
|
Definition
| ClH = Fu * Cl(int), where Cl(int) = Vmax/Km |
|
|
Term
| Renal clearance is related to the rates of... |
|
Definition
| glomerular filtration, passive reabsorption, and active secretion |
|
|
Term
| Which type of drug reaches a steady state faster, those with a long half life or those with a short half life? |
|
Definition
|
|
Term
| If renal clearance is greater than GFR, the the drug is being excreted by... |
|
Definition
|
|
Term
| If renal clearance is less than GFR then several mechanisms may be responsible such as... |
|
Definition
| protein binding, tubular reabsorption, depressed GFR |
|
|
Term
| T/F The area under the curve for a drug given IV is greater than the area under the curve of the same drug given extravenously. |
|
Definition
|
|
Term
| What is the equation for continuous IV infusion |
|
Definition
|
|
Term
| The inital dose of a medicine which is greater than the following doses is termed a ________. |
|
Definition
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