Drug Excretion & Pharmacokinetics Summary - PK6 Flashcards
What are the two major processes of drug elimination?
Metabolism & Excretion.
What is metabolism in drug elimination?
The conversion of a drug into an inactive form or metabolites.
What is excretion in drug elimination?
The irreversible removal of a drug or its metabolites from the body.
Can drugs be excreted unchanged?
Yes, some drugs are excreted without metabolism.
What is drug clearance?
The efficiency of irreversible elimination of a drug.
How is clearance (CL) defined?
The volume of plasma completely cleared of drug per unit time.
What is the unit of clearance?
Volume/time (e.g., mL/min, L/hr).
What does a high clearance value indicate?
The drug is rapidly eliminated from the body.
What does a low clearance value indicate?
The drug is slowly eliminated from the body.
What is total body clearance (CL_total)?
The sum of renal clearance, hepatic clearance, and other clearance pathways.
What is the formula for total body clearance?
CL_total = CL_renal + CL_hepatic + CL_lung + …
What is renal clearance?
The volume of plasma completely cleared of drug per unit time by the kidneys.
What factors affect renal clearance?
Urine pH, protein binding, drug solubility, kidney function.
How does urine pH affect weak base excretion?
Acidic urine → Increased excretion.
How does urine pH affect weak acid excretion?
Alkaline urine → Increased excretion.
Example: How does urine pH affect diethylcarbamazine (pKa 10)?
Acidic urine: CL = 38 L/hr (high excretion). Alkaline urine: CL = 1 L/hr (low excretion)
What is the elimination rate constant (Kel)?
The rate at which a drug is removed from the body.
What is the unit of Kel?
Time⁻¹ (e.g., h⁻¹ or 1/h).
How does Kel relate to clearance?
Kel = CL / Vd.
What does a high Kel indicate?
The drug is eliminated quickly.
What does a low Kel indicate?
The drug is eliminated slowly.
What is the definition of drug half-life (t1/2)?
The time required for the plasma concentration of a drug to decrease by 50%.
What happens after 1 half-life?
50% of the drug remains in the body.
What happens after 2 half-lives?
25% of the drug remains.
How many half-lives are required for a drug to be almost fully eliminated?
10 half-lives.
What is the formula for half-life?
t1/2 = 0.693 × (Vd / CL).
What is the half-life of adrenaline?
2-3 minutes (very short).
What is the half-life of lidocaine?
~2 hours.
What is the half-life of amiodarone?
Up to 107 days (longest half-life)
What factors increase drug half-life?
- Decreased metabolism (liver disease, enzyme inhibitors). 2. Decreased clearance (renal failure). 3. High plasma protein binding. 4. High tissue binding (high Vd). 5. Enterohepatic circulation.
What factors decrease drug half-life?
- Increased metabolism (enzyme inducers). 2. Increased clearance (alkaline urine for weak acids). 3. Low plasma protein binding. 4. Low tissue binding (low Vd)
How does half-life affect dosing frequency?
Short t1/2 → More frequent doses. Long t1/2 → Less frequent doses.
How does half-life affect drug accumulation?
Drugs with long half-lives accumulate in the body with repeated dosing.
Why is half-life important in overdose management?
Determines how long the drug stays in the body and whether dialysis is effective
What is AUC in pharmacokinetics?
The total amount of active drug that reaches systemic circulation.
What does AUC represent?
Drug exposure over time.
What is the unit of AUC?
Concentration × Time (e.g., mg/L × h).
How is AUC calculated?
Using the trapezoidal rule (sum of small trapezoidal areas under the curve).
What is the main determinant of drug elimination?
Clearance (CL).
How does Vd affect half-life?
Higher Vd → Longer half-life. Lower Vd → Shorter half-life.
How does half-life impact steady-state drug levels?
Steady-state is reached after ~5 half-lives.
What is the relationship between CL, Vd, and t1/2?
t1/2 = 0.693 × (Vd / CL).
How can urine pH be modified for drug excretion?
Sodium bicarbonate (alkaline urine) → Increases weak acid excretion.
