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Pharm Lect 8
| Question | Answer |
|---|---|
| Elimination | Removal of a drug from the body. All processes involved including metabolism and urinary excretion |
| Clearance | Quantitative measure of elimination. **Typically just a measurement of renal excretion |
| Excretion | A process of drug elimination. **Main route: Kidney's involvement of Elimination of a drug |
| Capacity-limited elimination | Clearance can vary with concentration (it is saturable/ dose-dependent). With high doses and saturation, steady-state cannot be reached and BL concentrations keeping rising w/ every dose. **Ethanol, Phenytoin, and Aspirin |
| Flow-dependent elimination | Elimination occurs easily (usually on first pass) but is dependent on the rate at which the drug is delivered to the organ (BL flow). **Plasma protein binding is also important |
| Routes of Excretion | 1.Dialysis. 2.Pulmonary: lungs (gaseous anesthetics, volitle compounds). 3.Salivary: saliva. 4.Mammary: breast milk (most lipophilic drugs). 5.Skin: sweat. 6.Kidneys: urine (PRIMARY). 7.Biliary: bile (large, polar molecules). 8.Intestine: unabsorb |
| Enterohepatic circulation | (Free Drug)Intestine-> Portal vein-> Liver (glucuronide conjugate)-> Bile duct-> (glucuronide conjugate) duodenum. **Recirculation can occur if conjugate becomes free drug by bacteria in intestine (Prolongs duration of drug in body. Blocked by diarrhea |
| Glucuronidase in the intestine | released from bacteria and frees the drug from conjugation which can allow recirculation. **Increases 1/2 life of the drug |
| Drug entry and re-absorption in the urine | filtered in the Glomerulus and enters the urine in the Proximal tubule. It can also be actively secreted into the Proximal tubule. LS & unionized drugs can be reabsorbed out of the the proximal tubule. **Ionized & None LS drugs will stay in urine |
| Are protein-bound drugs filtered by the glomerulus? | NO |
| pH's effect on Tubular Re-absorption (back diffusion) | Acidic Urine: weak bases will be ionized and trapped in the urine (weak acids will be unionized and reabsorbed). Basic Urine: weak acids will become ionized and trapped in the urine and excreted (weak bases will be reabsorbed). |
| ABC transporters involved in active secretion of drugs | 1.P-glycoporteins & MRP2s: transport organic anions & conjugated metabolites. 2.Other ABCs: Organic cations. **Plasma protein binding doesn't slow the process. |
| Normal GFR | 120 ml/min |
| Normal Renal perfusion rate | >120 ml/min unles tubular reabsorption |
| Normal Hepatic perfusion rate | 1500 ml/min |
| Acidic Urine: drug with low clearance <120 m/min | drug is a weak acid because more is being re-absorbed. |
| Clearance (CL) equation | CL(L/hr) = Rate of elimination(mg/hr)/C(mg/L) **CL is additive so CLsystemic=CLrenal+CLliver |
| First-order Vs Zero-order Elimination | 1st: Rate=CLXC. 0: capacity-limited. Elimination of constant amount of drug per unit time is Independent of concentration. |
| Renal Clearance (CLr) | CLr = (U X V)/(Cp X T). V:urine volume. U:urine concentration. Cp:plasma concentration. T:time. **V/T can be flow rate (ml/min) |
| High-Excretion Ratio Drugs | Perfusion-limited drugs. Kidney clears a drug from the BL readily compared to the rate of delivery to the kidney. |
| Low-Excretion Ratio Drugs | Ability of kidney to clear/eliminate drug from BL is low compared to its delivery rate. |
| Factors influencing Drug renal excretion | 1.BL flow. 2.Plasma Protein Binding. 3.Drug-Drug interactions. 4.Disease. 5.Age |
Created by:
WeeG
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