Drug Metabolism D: Word Scramble
|
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
| Question | Answer |
| What is drug metabolism? | Drug metabolism is the transformation by the body of the administered drug into a different molecular entity. |
| How are drugs removed by the body? What organs are typically involved? | Drugs are eliminated by the body either by excretion of intact drug molecules (usually by kidney) or by metabolism (usually by liver). |
| Why are most drugs designed to be lipophilic? | To allow them to reach the site of action (pass through membranes) |
| Are lipophilic drugs excreted efficiently well by the kidneys? Why? | No; Because as water is extracted from tubular lumen of nephron, drug is concentrated in tubular lumen and therefore diffuses across epithelial membranes back into body. |
| What is the main route of elimination for lipophilic drugs? | DRUG METABOLISM is the main route of DRUG ELIMINATION from the body-->does so by (nearly always) metabolizing drug into hydrophilic molecule that is easily excreted by kidneys (or into bile) |
| What was evolutionary reason allowed animals to metabolize drugs for removal? Why does it matter clinically? | Animals that ate organisms with lipophilic toxins evolved metabolic machinery to eliminate toxins; different animals=different mechanisms-->lab animal metabolism poor predictor of human metabolism & explain differences metabolism across human populations |
| What are the major types of drug metabolism? | Phase I and Phase II reactions |
| What are Phase I reactions in drug metabolism? | Introduces or exposes a functionality group on parent molecule and increases water solubility. |
| What are Phase II reactions in drug metabolism? | Conjugates (attaches) a water soluble compound to functional group to further increase water solubility. |
| Is a Phase II reaction necessary for excretion via urine (or bile)? Is a phase I reaction necessary for Phase II reaction? | No, but increases solubility; USUALLY Phase I precedes Phase II; Phase I need not occur before Phase II; Phase II may also be followed by Phase I |
| What are the 3 major types of Phase I reactions? | Oxidation, reduction, and hydrolysis |
| What are the major types of oxidation reactions? | Dealkylation (N and O), hydroxylation (aliphatic or aromatic), deamination, dehydrogenation (alcohol and aldehyde), and oxidation (N, S, monoamine) |
| What are the major types of reduction reactions? | (Nitro and azo) group reduction |
| What are Cytochrome P450S? | Terminal oxidases in multi-component electron transport chain |
| What are microsomes? | In cell biology, microsomes are vesicle-like artifacts formed from the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; by definition, microsomes are not ordinarily present in living cells. |
| Describe how P450S works | In microsomes, electrons supplied by NADPH via cytochrome P450S reductase (closely associated with cytochrome P450S in lipid membrane of ER); P450S introduces single oxygen from molecular oxygen into substrate with other oxygen being reduced to H2O |
| How are CYPs classified? | According to amino acid sequence similaritie, e.g. CYP3A5: 3 = family # (40% identity within family); A = subfamily letter (55% identity within subfamily); 5=isoform #, each isoform given unique number) |
| More than 50% of all drugs are metabolized by which cytochrome family? Which groups are important due to genetic variations? | CYP3A; CYP2D6, CYP2C9, and CYP2C19 important due to genetic variations that result in inter-individual variations in rate of drug metabolism |
| What are the two major types of hydrolysis reactions in Phase I reactions? | Ester and amide hydrolysis |
| Where do Phase I reactions take place in body? In cell? | Mainly liver (though also lungs, kidneys, and GI tract); ER (also in cytosol, mitochondria, nuclear envelope, and plasma membrane) |
| What other enzymes besides cytochrome P450S can mediate phase I reactions? | Dehydrogenases, flavin containing monooxygenases, esterases, amidases |
| What results in individuals that are poor drug metabolizers? What about extensive and ultrarapid metabolizers? | Toxicity (buildup of drug) or too little active metabolites (if given pro-drug); Lack of efficacy (rapid loss of drug) or too many active metabolites |
| What is a prodrug? | Inactive parent drug that is activated by metabolism |
| Describe how codeine is metabolized | Codeine is an inactive prodrug that is metabolized by CYP2D6 to morphine; 2D6 PMs do not get pain relief from codeine-->give morphine or oxycodone (doesn't need metabolism for action) |
| What are he (6) major forms of phase II reactions? | Glucuronidation, sulfation, acetylation, glutathione, glycine, methylation |
| What is glucuronidation? | Conjugation of substrate (alcohol, carboxylic acid, amines, or thiols) with glucuronic acid via uridine diphosphate glucuronosyltransferases to give very soluble X-glucuronides (where X can be O, N, S) |
| What enzyme controls glucuronidation? | UGTs: uridine diphosphate glucuronosyltransferases |
| Where are UGTs found? | In the LIVER, intestines, kidney |
| What is sulfanation? | Conjugations with sulfate |
| What enzyme controls sulfation? Where are they found? | STs: Sulfotransferases (found in cytosol) |
| What is acetylation? | Conjugation with acetic acid |
| What enzyme mediates acetylation? Where are they found? How many isoforms are there of this enzyme? | NATs: N-acetyltransferases; cytosol; two isoforms (NAT1 and NAT2); most American are slow-acetylators |
| What is a risk of using drugs that have acetylated metabolites? | Acetylated metabolites are often less water soluble than parent drugs, and may result in crystalluria unless high urine flow rate is maintained |
| What enzyme mediates the conjugation with a glutathione? Where is it found? | GST: glutathione S-transferase; typically found in cytosol, but some are microsomial |
| What type of drug is particularly susceptible to conjugation with glutathione? | Anti-cancer drugs |
| Where do phase II reactions take place (body)? In cell? | Mainly in liver (also in lungs, kidneys, GI tract); mainly in cytosol (except for glucoronidation, which takes place in ER) |
| What are the main causes of variations in drug metabolism? | Genetic variations (change activity or expression of drug metabolizing enzymes); drug-drug interactions (can induce or inhibit metabolyzing enzymes); interactions with food, smoking, disease state, and environment |
| How does grapefruit juice interact with drug metabolism? | Inhibits CYP3A4 in gut-->increases bioavailability of drugs metabolized by this enzyme |
| How does smoking interact with drug metabolism? | Induces certain isoforms of CYPs resulting in enhanced drug metabolims-->stopping smoking may cause spike in drug levels as enzyme goes back to basal level |
| How can liver disease change drug metabolism? | Diseases that reduce liver blood flow or cause damage to hepatocytes will decrease drug metabolism |
Created by:
karkis77
Popular Pharmacology sets