Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
X-Phar410 Drug Bio
Drug Biotransformation
| Question | Answer |
|---|---|
| two primary ways in which drugs are eliminated from the body | excreted unchanged in the urine or feces; or metabolized or biotransformed and then excreted |
| second source of metabolism; second to liver | intestine |
| once in bloodstream, drugs are transported directly to | liver; first pass metabolism |
| Biotransformation | metabolism |
| drugs that are "foreign to body" | xenobiotics |
| metabolite | derivative of drug structure; usually inactive or less active |
| biotransformation result in a metabolite that is no longer able to produce a therapeutic response | also makes the drug more soluble for excretion |
| In some cases, the drug is inactive and the biotransformation results in | an active compound |
| want to make the xenobiotics more polar to excrete | excreted in urine or feces OR metabolized or biotransformed and then excreted; may also be eliminated through sweat or respiration |
| most drugs are biotransformed prior to excretion because they are not | polar enough to be excreted (not water soluble enough) |
| most often the product of biotransformation of body enzymes is | less active or inactive as compared to parent drug; metabolite can no longer produce therapeutic response |
| in some cases biotransformation results in | an active form of the initially inactive parent drug |
| inactive parent drug | prodrug; must be biotransformed to have therapeutic response |
| the liver can make more polar in order to excrete but it cannot | cant actually make more or less active |
| biotransformation occurs mainly in the | liver; sometimes in kidneys GI tract, skin or lungs |
| drugs that are ingested orally must first be absorbed in the | GI tract to enter bloodstream; once in bloodstream drugs are transported directly to liver via hepatic poral vein then to circulation |
| a considerable percentage of of an orally ingested dose is often metabolized | prior to reaching systemic circulation |
| the loss of drug due to GI tract biotransformation | "first pass"- through liver |
| an active drug can go two routes | directly to excretion or can be biotransformed to an inactive metabolite then excreted |
| at site of action the chemical structure is not active | prodrug; when metabolized it then becomes active |
| if something is in the small intestine it is technically | not "in the body" |
| orally ingested drugs go to --> | intestine --> portal vein --> liver --> circulation via hepatic vein |
| first pass may or may not happen | no way to tell; can be a barrier to get drug into bloodstream |
| enzymes found in high concentration in liver (lower concentrations in brain, kidneys, intestines, and lungs) | CYP450's; superfamily thats responsible for majority of all drug biotransformations |
| cytochrome P450's are heme containing proteins that are capable of the following rxn's | hydroxylations; N, O, and S dealkylations; N-oxidations Sulfoxidation; N- hydroxylation, and deamination(removal of amine) |
| enzyme involved in drug-drug interactions | CYP 450 (1-3) |
| a substance (drug) that stimulates synthesis of an enzyme; increases metabolic capacity for that isozyme is known as | Inducer; induction |
| competitive binding at an enzymes binding site | inhibition |
| a drug with a high affinity for an enzyme will slow the metabolism of any lower affinity drug at that enzyme | basically the high affinity drug will hog the active sites and the low affinity drugs wont be metabolized |
| when less enzymes are available what happens to drug concentration in bloodstream? | It increases because not enough enzymes to metabolize them |
| affected drugs | drugs that are affected by the actions of inhibitors and inducers |
| block enzymes; prevents other drugs from binding | inhibitors; less enzymes= less metabolism |
| increases amount of enzymes | inducers; leads to lower concentrations of the drug in the bloodstream |
| must abundant subfamily of human cytochrome enzymes | CYP3A |
| administered as inactive drugs | prodrugs; it is then transformed into an active substance either by chemical or metabolic means |
| designed to take advantage of absorption or metabolic properties to provide optimal drug therapy | Prodrugs; can be activated in various places (stomach, intestine, liver, inside cell) and in various ways (cleavage of groups, biotransformations, addition of phosphates) |
| esters in blood can activate prodrugs | true; ex:chloramphenicol succinate is chemically inactive until release into bloodstream (IV) |
| some inactive drugs that cause stomach upset can be matched up with enzymes in the liver that activate them | this helps keep the inactive form from stomach upset; it becomes active in the liver |
| EX: an increase in the plasma concentration of a drug occurs because of | inhibition; too many drugs and not enough enzymes |
| EX: a decrease in the active form of a drug occurs | when there is an inducer; more enzymes, more metabolism |
| EX: Increase in plasma concentration of the ACTIVE form of a PROdrug | Inducer; lots of enzymes to activate the prodrug |
| EX: a decrease in the plasma concentration of the active form of PROdrug | inhibitor; not enough enzymes to activate the inactive prodrug |
| If a genetic defect in a CYP3A4 that made it inactive would result in? | No metabolism because enzyme doesnt work |
| 2 types of biotransformations | Phase I and Phase II |
| Functional Phase | Phase I; introduce or expose a functional group on a compound to make more polar (hydrophilic) |
| Phase that generally results in loss of activity | Phase I; in some cases the reaction enhances activity of parent compound |
| BioSYNTHETIC reactions that result in covalent linkage; something is ADDED (conjugated) | Phase II; covalent linkage between functional group ON the parent drug and a highly polar conjugate; to make more hydrophilic |
| Phase I doesnt always happen, neither does Phase II | Not always in order of I then II |
| entero | intestine |
| Microflora in intestines can cleave the covalent bond made during Phase II biotransformations which does what? | the parent compound is cleaved and released/ reabsorbed in systemic circulation; enterohepatic recirculation |
| Reversal of Phase II rxn | enterohepatic recirculation; occurs with Glucuronides of drug taht are formed in the liver; excreted in intestine via bile |
| Phase I reactions (dealkylation)KNOW* | N and O- dealkylation (removal of alkyl attached to N or O) |
| Phase I reactions (hydroxylation) | Aliphatic and aromatic hydroxylation- addition of OH group; can also result in a doubly bonded O |
| Phase I reactions (oxidation) | N and S; addition of O to N or S |
| Phase I reaction (deamination) | remove amine; done via oxygen |
| Phase I reaction (hydrolysis) | breaking of a bond with addition of H2O |
| Phase II reactions Glucuronidation | O-UDP + ROH --> RO ; UDP is a transfer agent |
| Phase II- sulfation | add a sulfate (SO3--) |
| Phase II- Acetylation | SCoA + RNH2 --> NHR plus CoASH |
| Phase II Glutathione conjugation | a tripeptide of glutamate, cysteine, and glycine that picks things up to help them be excreted |
| Glutathione (GSH) is found where? | Primarily kidneys and liver in high concentrations; detoxification of xwnobiotics via Phase II conjugation |
| GSH is metabolized to what in order to be excreted? | Mercapturic acids |
| CSH conjugation is catalyzed by | glutathione S- transferases |
| Electrophilic substrate that wants electrons | "E", can be dangerous; we want to bind it to Glutathione and get rid of it |
| Glutathione Adduct or Conjugate is what | The "E" bound to the "S" of the Glutathione; rxn kicks off glutamyl AA and then Glycine AA to leave Cysteine with the E |
| Mercapturic Acid | urinary excretion product; cysteine with the "E" and C=O- CH3 |
| metabolism of acetaminophen | 60% Glucuronide, 30% Sulfate -->both go toward renal excretion |
| Oxidized Acetaminophen becomes | NAPQI; "E", can kill hepatic cells if not conjugated with Glutathione |
Created by:
angieryx