Unit 1- Excretion Flashcards
Most important route of drug elimination
renal excretion
Factors determining renal excretion
Renal blood flow, active tubular secretion, tubular reabsorption
Total renal excretion of a drug
Rate of filtration + secretion - reabsorption
Glomerular Filtration
Determined by renal blood flow, drugs enter glomerulus from blood by bulk flow passively
Active Tubular Secretion
Transport proteins at the brush border and basolateral membrane move drugs rapidly, not limited by protein binding, susceptible to competition between drugs
Organic Anion Transporter
Secretory pathway in the renal tubules for acidic compounds
Organic Cation Transporter
Secretory pathway in the renal tubule for basic compounds
Competition in tubular transport
Many drugs compete for the same tubular transport sites, weak acids can inhibit secretion of other weak acids
Tubular Reabsorption
Passive reabsorption from renal tubules into renal capillaries slows renal excretion, depends on lipid solubility and ionization
Reabsorption and ionization
Weakly acidic drugs more likely to be reabsorbed in acidic urine but trapped and excreted in alkaline urine
Diet and pH
Carnivores have more acidic urine than herbivores. Acidic drugs have higher renal excretion in herbivores, basic drugs have higher renal excretion in carnivores
Modifying pH
Urinary pH can be altered to change renal excretion rate in cases of overdose or toxicity
Urine Drug Concentration
Drugs that are not reabsorbed will concentrate in the renal tubule, leading to nephrotoxicity
Polar Compounds and Reabsorption
Polar compounds have low lipid solubility and are not reabsorbed, many drug metabolites
Active Reabsorption
Systems used to recover essential nutrients, drugs that are actively reabsorbed have important tubular fluid concentration for predicting activity
Factors affecting Active Secretion
Renal blood flow, drug pKa
Factors affecting Glomerular Filtration
Molecular weight, protein binding, renal blood flow
Factors affecting Passive Reabsorption
Drug concentration, molecular weight, lipid solubility, drug pKa, urine pH
Renal Biotransformation
Phase I and phase II enzymes exist in the kidney, oxidative processes occur in proximal tubule
Relay Metabolism
The kidney metabolizes a drug already biotransformed by the liver
Other routes of excretion
Bile, milk, saliva, expired air, feces, sweat, tears
Biliary Excretion I
Drugs excreted in bile are in contact with intestine and its flora, causing adverse reactions, phase II drugs may undergo enterohepatic circulation, intestinal bacteria can unconjugate the drug
Enterohepatic Circulation
Drugs are conjugated in the liver and eliminated in the bile, bur unconjugated in the small intestine and reabsorbed, the drug then reenters systemic circulation and prolongs half-life
Saliva Excretion
Drugs enter saliva by passive diffusion from the blood, important in herbivores that have large amounts of saliva that can be swallowed and upset digestion
