Elimination Flashcards
Drug Excretion HappensThrough
- Kidney: major excreting organ
- Bile
- Sweat
- Saliva
- Milk
- Lung (alcohol. Gaseous anesthetic)
The Kidney
- Removal of metabolic waste.
- Maintain normal fluid volume and electrolyte balance.
- Secretion of renin to regulate blood pressure.
- Secretion of erythropoietin to stimulate RBCs production.
Clearance
Definition: volume of fluid removed per unit time
- Unit: ml/min, L/h, L/h/Kg
- Calculated by:
Cl= Dose/ AUC 0-∞ (Model Independent)
Cl= kVd (In One compartment Model)
Renal Excretion
- Glomerular filtration
- Active tubular secretion
- Tubular reabsorption
* Type of drugs, pH, protein binding and rate of urine flow.
Renal Clearance
- Volume that is removed from the drug per unit time through the kidney.
- Cl= Cl Renal + Cl NonRenal
Glomerular Filtration Rate( GFR)
- • GFR= 120 to 125 mL/min.
- • 99% of the fluid volume filtered at the glomerulus is reabsorbed.
- • Filtrate contains ions, glucose and essential nutrients as well as waste products such as urea, phosphate, sulfate and other substances.
- • Measured by inulin and creatinine
Drug Clearance
- Pharmacokinetics term to describe drug elimination from the body without identifying the mechanism.
- • It assumes the body is ONE drug elimination system where many elimination processes take place.
- • It has a unit of volume/ unit time, and usually normalized per kg body weight.
- • Clearance is constant for first order clearance unlike the elimination rate constant.
- • Cl= (dDE/dt)/Cp
Filtration
- Energy Needed : No
- Drug form Ionized and nonionized
- Drug Protein Binding : Protein binding dependent
- Influenced by : Protein binding
- Application : Creatinine clearance 120 ml/min
Secretion
- Energy Needed : Yes. Because it is carrier mediated ( against concentration gradient, low to high )
- Drug form : Weak Acid and weak bases
- Drug Protein Binding : Protein binding independent
- Influenced by : carrier-mediated i.e. competitive inhibitors
- Application : competitive inhibitors actively secreted drugs Cl > 120 mL/min
Reabsorption
- Energy Needed : Depending on the transport
- Drug form : nonionized
- Drug Protein Binding : Drug in urine (i.e no protein binding )
- Influenced by : urinary pH and flow
- Application : urinary pH affects reabsorption
Drug elimination
- irreversible removal of drug from the body by all routes of elimination.
- Drug elimination is usually divided into two major components: excretion and biotransformation
an increase in blood flow to the kidney, which may be due to diuretic therapy or large alcohol consumption, decreases the extent of drug reabsorption in the kidney and ________ the rate of drug excreted in the urine.
increases
To prevent crystalluria and renal complications with sulfonamides , patients are instructed to take these drugs with a high amount of fluid intake and to keep the urine_______
alkaline.
the rate of urine flow
- influences the amount of filtered drug that is reabsorbed
- Drugs that increase urine flow, such as ethanol, large fluid intake, and methylxanthines (such as caffeine or theophylline), decrease the time for drug reabsorption and promote their excretion.
- Thus, forced diuresis through the use of diuretics may be a useful adjunct for removing excessive drug in an intoxicated patient, by increasing renal drug excretion.
If glomerular filtration is the sole process for drug excretion
- the drug is not bound to plasma proteins, and is not reabsorbed,
- the amount of drug filtered at any time (t) will always be Cp × GFR
- Renal Clearance = GFR
