| Term | Definition |
|---|
| aka Phase 1? | Fuctionalization reactions |
| What are three things that can happen in Phase one? | New polar fxn groups, INterchange eisiting fxn groups, nmask exisiting polar groups |
| What are three rxn included in Phase 1? | Oxidation, Reduction, Hydrolyses |
| Ex of rxn for "new fxn group" | Oxidation (Rh--> ROH) |
| Oxidation | RH--> ROH (New Fxn group) |
| Reducation | C=O---> CH-OH (Interchange groups) |
| Which is more polar? C=0 or CH-OH? | CH-OH because can accept and donate more H's |
| Example of interchaing fxn groups | reduction |
| Example of "unmasking" | R-CO2-CH3--> RCOOH + CH3OH (Hydrolyses |
| Hydroylese | R-CO2-CH3--> RCOOH + CH3OH (unmasking) |
| Two purpose for phase one | Enhance excretion because made more water soluble and polar or Prepare for phase two by adding the req fxn group needed for phase 2 |
| AKA phase 2? | Conjugation Rxn |
| What type of drug does phase 2 act on? | parent drug if the required fxn group is present of on the phase one metabolite |
| Describe the stuff that is added in conjugation rxn? | Endogenous, polar, ionizable |
| Purpose of Phase 2 | enhance excretion |
| TWo types of phase 2 rxn | Glucoronidation and Sulfate formation |
| Glucurondiation | Adds ionizable, polar sugar |
| ex of phase 2 rxn | Acetometophen |
| After which phase can excretion occur? | "Yes"- depending on polarity and the R group- the parent drug- phase one or two can all be excreted at their stages bc wen u look in ur urine, wll will be seen |
| 3 fxn of liver | xenobiotic and endobiotic metabolism "Presystemic First Pass effect" |
| what do Xenobiotic metabloize | Nonessential exogenous (FOREIGN) comppounds |
| What do endobiotic metabolize? | "endgogenous compouds" = natural |
| most drugs are considered ____biotic? | xenobiotic (foriegn) |
| Where do most of the drugs "dump" to ? | portal vien leading to the liver |
| What occurs when the drug goes from the stomach to the liver via the portal vien | significant portion is converted to inactive molecule |
| Significance of 1st pass effect | if too much of the drug is metabloized in the liver and deactivated before getting to the systemic circulation defeatst he puprose of the drug; but depends on the drug |
| Sources for first pass effect? | Hepatic (liver) and GI mucosa during abosrption |
| Two specific significance for first pass effect? | "Regular drugs" are active wen taken but are reduced and inactivated and "Pro drugs" has a huge conversion to the active drug |
| Four ways to over come first pass effect | Modify to make it more nonpolar- inject, suppository, tongue |
| What is the significant contirbutor for the GI tract in metabolism | oral bioavail |
| Two ways that the GI tract assist in metabolism | The enzyme rich epithlium and the Gut flora |
| What are three things the gut flora can do? | REducation, Deconjugation, Eneropatic recyclin (EHC) |
| Ex of gut flora reducation to active metabolite | azulfidine |
| EX of Deconjugation | premarin |
| Where does premerin come from? | Horse conjugates the estrogens whichi s releasein the urine- used as hormone replacement- but must be DEconjugated bc too polar to abosrb |
| pathway for EHS? | liver--> bile-->gallbladder--> duodum (small intestin)--> INSTEAD OF GOING TO FECES--> gut flora "yum yum sugar"--> reabsorbed--> conjugated again--> and starts over |
| what types of molecules does EHS occur and why? | molecules over 500 MW (ie conjugated) because doesn't want to start excrenting protiens and wat not- so doesn't pass thro kindeys and urine- goes to liver then ile then galbadder to small intesting gut flora eat sugar and starts over |
| Other than the liver and GI tract- wat are other loations for metabolism? | Kidney, Lungs, Brain etc |
| Two fxn of metabolism in the Kidney, Lungs, Brain, Etc | Localized bioactivation and toxicity |
| Ex of localized bioactivation in kidney lungs brain etc | PAH in cigarette smoke |
| Ex of localized toxicity in kidney lungs brain etc | MPTP (ie domamine) |
| When is EHC bad? | If parent drugs reapears- then thatll mean to more you take the drug, themore it'll be present in the bod |
| When is EHC not so bad? | If the inactive metabolite is reabosorbed bc nothing will happen as a result |
| What enzyme is responsible for Phase 1 oxidation | cytochrom p450 |
| What type of exymne is cytochrom p450 | heme enzyme |
| about how many ioforms are in the cytochrom p450 enzyme famiy? | about 50 |
| Where does the number "450" for cyp-450 ome from? | Binds CO at 450 nm |
| Why do cyp-450 cover a broad metabolic range? | There are multiple forms of p450 and its susually substrate non-specfic and a drug is typically a substrate for more than one p450 |
| Downside to cyp-450 | SLOW= drug interactions |
| what's so bad about cyp-450 being so slow? | the next drug to bind to the enzyme has to wait around and still exhibits its drug action |
| Overall rxn for cyp450? | RH + NADPH + H + 02 --> ROH + NADP + H2O DECEPTIVE |
| Monooxygenase | One O in the product and one in the water |
| At the active site- wat type of Fe? | Ferric (+3) |
| What happens to the substrate in the cyp450 cycle? | nothing until "11 o clock" when then now active oxygen oxidiazesthe substrate |
| characteristics of the active oxygen species in the cyp450 cycle | highly electrophilic and wants elections hence "oxidation" because the sustrate loses electrons |
| what types of molecules bind at the substrate binding site? | Hydrophobic/lipophilic (ie alkly groups) |
| Example of cyp450 oxidation | para hydroxyation of anisole |
| how to determine if the cartoon is actually the mechanism? | replace an H with a D at the para postionbecause it should just get kicked out but it doesn't |
| what actually happens to the D in the cyp450 mechanism? | Shifted over meta postion |
Combine with other sets
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