3 - Drug Metabolism and Excretion Flashcards
What is the role of drug metabolism?
Drug metabolism protects the body from harmful substances while also being used to make essential molecules.
What are the therapeutic consequences of drug metabolism?
- Increase water solubility: Drugs are metabolized into more water-soluble forms for easier excretion.
- Inactivate drugs: Metabolism neutralizes a drug, preventing harmful side effects.
- Increase drug effectiveness: Drug metabolism can enhance therapeutic action.
- Activate prodrugs: Some medications are inactive until metabolized.
- Increase drug toxicity: Metabolism can produce toxic metabolites.
What is first-order kinetics?
First-order kinetics occurs when the concentration of a drug is lower than the body’s ability to metabolize it, leading to a rate of metabolism that is directly proportional to the concentration of free drug.
What is zero-order kinetics?
Zero-order kinetics occurs when the body’s enzymes are saturated, leading to a constant amount of drug being metabolized over time, regardless of drug concentration.
What is first-pass metabolism?
First-pass metabolism occurs when a drug taken orally is metabolized in the digestive system before reaching systemic circulation.
Which cells participate in first-pass metabolism?
- Hepatocytes in the liver: Primary organ for drug metabolism.
- Intestinal enterocytes: Absorptive cells in the intestine.
- Stomach: Can contribute to drug breakdown.
- Intestinal bacteria: Can metabolize drugs before they reach systemic circulation.
What are the types of biotransformations in Phase I metabolism?
Phase I metabolism involves reactions that add or expose functional groups to make drugs more polar, including oxidation, reduction, and hydrolysis.
What occurs in Phase II metabolism?
Phase II metabolism involves conjugation, where larger chemical groups are added to drug metabolites to enhance polarity for easier elimination.
What are the main enzymes involved in Phase I metabolism?
Cytochrome P-450 enzymes are the main type of Phase I drug metabolizing enzymes.
What are the renal processes involved in drug excretion?
- Glomerular Filtration: Small, unbound drug molecules are filtered from blood into the Bowman’s capsule.
- Tubular Secretion: Active transport of drugs into the nephron from the peritubular capillaries.
- Tubular Reabsorption: Lipophilic drugs may be reabsorbed back into circulation.
What cannot be filtered during glomerular filtration?
Drugs bound to plasma proteins and large drugs cannot be filtered.
What happens during tubular secretion?
Drugs that escape filtration can be actively secreted into the nephron using active transport mechanisms.
What factors affect tubular reabsorption?
Lipid solubility affects reabsorption; lipophilic drugs can diffuse back into blood, while hydrophilic drugs remain in urine.
What happens to lipophilic drugs in the renal tubule?
Lipophilic (non-polar, uncharged) drugs passively diffuse back into circulation, reducing renal clearance.
What happens to hydrophilic drugs in the renal tubule?
Hydrophilic (polar, ionized) drugs stay in the urine and are excreted.
What factor affects drug reabsorption related to lipid solubility?
Lipid solubility affects reabsorption; lipophilic drugs are reabsorbed, while hydrophilic drugs are excreted.
How does urine pH affect drug ionization and reabsorption?
Weak acids are reabsorbed in acidic urine, while weak bases are reabsorbed in alkaline urine.
What is the effect of increasing drug concentration in urine?
If drug concentration in urine is high and the drug is non-ionized, passive reabsorption increases, reducing drug excretion.
What is the process of drug secretion in the proximal convoluted tubule?
Drugs can be selectively secreted into nephron tubules via protein carriers on the basolateral membrane of tubule cells.
How are organic anions secreted in the proximal tubule?
Negatively charged organic anions are selectively secreted into the tubule lumen using organic anion transporters.
What is the role of organic cation transporters in drug secretion?
Organic cation transporters transport positively charged compounds into the tubule cells from the peritubular capillaries.
How does drug concentration affect reabsorption from nephrons?
In the distal tubule, if drug concentration is greater than blood concentration, reabsorption increases.
What is biliary excretion?
Drugs can be excreted through bile, especially if they are larger, amphipathic, or have glucuronic acid added.
What is enterohepatic recycling?
Bile salts are recycled from the intestine back to the liver via the hepatic portal vein.
