Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
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
Pharm Lect 6 & 7
| Question | Answer |
|---|---|
| Back diffusion in the Nephron | Drugs that are lipid soluble (LS) easily cross membranes and when a high concentration of drug builds up in a nephron, some can be reabsorbed back into the BL. **This is why metabolism of drugs is important because it decreases LS and Inc ionization |
| Prodrug concept (Bioactivation) | A drug that cannot be absorbed can be taken as a prodrug, which will become the active form of the drug after metabolized. |
| Drug metabolites after biotransfermation | 1.Less LS. 2.More Aq soluble. 3.more ionized at phys pH. 4.Less bound to plasma proteins. 5.Less able to cross membranes. 6.more readily excreted by urine. **Ends its pharmaco effects. |
| The duration and intensity of a Lipid soluble drug is limited by what? | Rate of its metabolism. |
| Biotransformation can create reactive, toxic intermediates that can covalently bind to protein or DNA and cause | 1.Injury/necrosis. 2.Hapten/antigen. 3.mutation/cancer. |
| Acetaminophen toxicity | 1.saturation of glucuronidation/sulfation pathway by excess drug. 2.Inc metabolized by CYP450 (toxic metabolite). 3.Depletion of Glutathione conjugation (makes intermediate non-toxic). 4.Inc toxic metabolite -> Hepatotoxicity & necrosis. |
| Major pathway of Metabolism: Phase 1 (CYP450 commonly involved) | Small changes to LS and biological activity to make a more polar metabolite. Redox and hydrolysis/hydroxylation reactions occur. Usually precede/prepares phase II. **Metabolites may be inactive & may not be eliminated rapidly. |
| Major Pathway of Metabolism: Phase II | LARGE changes in structure, LS, and biological activity. CONJUGATION: 1.Acetylation. 2.glucuronidation. 3.sulfation. 4.Methylation. **Forms highly polar, inactive metabolite that is excreted. |
| Microsomal mixed function oxidase enzyme system (monooxygenases) | Oxidation by the membrane bound enzymes within the ER. Need NADPH and O2 in order to add a -OH to the drug. |
| CYP3A4 | 30-60% of hepatic CYP. Most clinically significant enzyme in drug metabolism. Broadest specificity (susceptable to drug-drug interactions). **Very susceptable to induction (st johns wort) and inhibitors. |
| What inhibits Intestinal CYP3A4 | Grapefruit Juice. Decreases enzyme activity by 50% up to 72hrs. Drug classes affected: 1.statins. 2.Ca channel blockers. 3.antiarrythmics. 4.immunosuppressants. |
| 3 Main CYPs of the liver | 1.CYP3A4. 2.CYP2D6 (met 30% of drugs 4 polymorphic types, met antipsych, antidepress, B-blockers, opiates). 3.CYP2C9 3. |
| Phase 1: Oxidation reactions/enzymes | CYP450 Dependent: 1.Aromatic hydroxylations. 2.Deaminations. 3.Desulfonations. CYP450 Independent: 1.Alc Dehydrogenase. 2.Xanthine Oxidase |
| Phase 1: Hydroxylation reactions/enzymes | Microsomal mixed-funciton oxidase: 1.Hydroxylation. |
| Phase 1: Reduction reactions/enzymes | 1.Dehalogenation. 2.Carbonyl. **some are mediated by CYP450 |
| Phase II: Glucuronidation | Most frequent of phase II reactions. Enzyme involved: UDP glucuronosyl transferase (UGT). Transfers UDP-glucuronic acid to a drug inc polarity and aq solubility |
| Age and liver disease's effect on metabolism | Mostly effects phase 1 P450s (therefore lower doses are required). |
| How would INDUCTION of liver enzymes effect drug BL levels? | They would be lower due to increased drug metabolism and faster clearance. |
| Phenobarbital | An inducer chronically can cause induction of its own met: Autoinduction. Inducers like this can cause: 1.Tolerance (via autoind. need higher doses). 2.Drug interactions (effect Cpo, first pass, and bioavail. may need Inc dose). 3.De novo protein synt |
Created by:
WeeG
Popular Pharmacology sets