Excretion - PK5 Flashcards
What are the two main processes involved in drug elimination?
Metabolism + Excretion
What is drug excretion?
The irreversible transfer of drugs/metabolites from the internal environment (body) to the external environment.
Why is drug excretion important?
It terminates pharmacological action and prevents toxicity.
What are the major routes of drug excretion?
- Renal (Kidneys – Urinary system) 2. Non-Renal (Biliary, GI, Pulmonary, Skin, Saliva, Mammary, Genital).
Which route is responsible for 25-30% of drug elimination?
Renal excretion (Urinary system).
What types of drugs are primarily excreted by the kidneys?
Water-soluble (hydrophilic) and low molecular weight drugs (<500 Da).
How are lipophilic drugs excreted?
Metabolized in the liver to more water-soluble metabolites, then excreted via kidneys.
What are the three main stages of renal excretion?
- Glomerular Filtration (F) 2. Tubular Secretion (S) 3. Reabsorption (R).
How is the total drug eliminated in urine calculated?
Total renal excretion = Filtration + Secretion - Reabsorption.
What is glomerular filtration?
Passive filtration of small molecules (<500 Da) into the renal tubule.
What factors affect glomerular filtration?
- Molecular weight (<500 Da filtered easily). 2. Protein binding (only free drugs pass).
What is tubular secretion?
Active transport of drugs from blood → renal tubule (requires energy).
Which transporters are involved in tubular secretion?
OAT (Organic Anion Transporter) for acidic drugs & OCT (Organic Cation Transporter) for basic drugs.
What is tubular reabsorption?
Movement of drugs from renal tubule back into blood (depends on lipid solubility & ionization).
How does urine pH affect drug excretion?
It affects ionization, influencing whether a drug is reabsorbed or excreted.
What is the pH partition theory?
Ionized drugs are poorly reabsorbed and excreted more easily.
How does urine pH influence weak acids?
Basic urine → ionized acid (A-) → more excretion.
How does urine pH influence weak bases?
Acidic urine → ionized base (BH⁺) → more excretion.
Give a clinical example of urine pH manipulation.
Aspirin overdose (weak acid, pKa = 3.5) → treated with urinary alkalinization (e.g., bicarbonate) to increase excretion.
What factors can affect renal drug excretion?
- Plasma protein binding 2. Urine pH 3. Drug competition at transporters 4. Renal function 5. Age & Sex.
How does plasma protein binding affect excretion?
High protein binding → less filtration → reduced excretion.
How does renal function affect excretion?
Poor renal function → reduced drug elimination → dose adjustment needed.
How does sex & age affect renal excretion?
Females excrete 10% less than males. Elderly & infants have lower renal function, requiring dose adjustments.
What are the main non-renal excretion routes?
- Biliary (Liver & Intestine) 2. Gastrointestinal (Feces) 3. Pulmonary (Lungs) 4. Skin (Sweat) 5. Salivary 6. Mammary (Breast Milk).
How does the biliary system contribute to excretion?
Drugs/metabolites are secreted into bile, enter the intestine, and can be excreted in feces.
What molecular weight drugs are excreted in bile?
> 500 Da → Biliary excretion <300 Da → Renal excretion 300-500 Da → Both routes.
What is enterohepatic circulation?
Drug is excreted in bile, hydrolyzed in intestine, reabsorbed, and recirculated (prolongs drug action).
What is an example of enterohepatic circulation?
Leflunomide (rheumatoid arthritis drug) → remains in blood for >2 weeks, requiring activated charcoal for washout.
What is pulmonary excretion?
Excretion via lungs (important for volatile drugs like anesthetics & alcohol).
Give an example of a drug excreted via lungs.
Halothane (anesthetic gas) & alcohol (breath test detection).
What is gastrointestinal excretion?
Drugs excreted in feces (unabsorbed drugs or those secreted into bile).
What drugs are excreted in feces?
Nicotine, quinine, corticosteroids, streptomycin.
What is mammary excretion?
Drugs excreted into breast milk (lipophilic, unionized drugs).
Why can weak bases accumulate in breast milk?
Milk is slightly acidic (pH 6.4-7.6), so basic drugs ionize and get trapped.
What drugs are excreted in saliva?
Caffeine, phenytoin, theophylline (causing a bitter taste).
How does skin excrete drugs?
Through sweat, hair follicles, and keratin (e.g., arsenic, mercury, ethanol, amphetamines).
What is the formula for total renal excretion?
F (filtration) + S (secretion) - R (reabsorption).
How can drug excretion be enhanced?
By manipulating urine pH (acidic urine → basic drugs excreted, basic urine → acidic drugs excreted).
How does enterohepatic circulation affect drug half-life?
It prolongs drug action by recirculating drugs.
Why must drug dosing be adjusted in renal disease?
Reduced renal clearance → risk of drug accumulation and toxicity.
