North American Pharmacist Licensure Examination (NAPLEX) Pharmacokinetics, Pharmacodynamics, and Calculations Syllabus

Pharmacokinetics, Pharmacodynamics, and Calculations syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for Pharmacokinetics, Pharmacodynamics, and Calculations in North American Pharmacist Licensure Examination (NAPLEX), not a summary of it.

1. 1

   Core Pharmacokinetic Principles

   5 topics

   • Absorption, bioavailability, and first-pass metabolism
   • Volume of distribution and protein binding
   • Clearance and half-life relationships
   • Linear vs nonlinear (Michaelis-Menten) kinetics
   • Compartmental models and elimination order
2. 2

   Clinical Dosing and Therapeutic Drug Monitoring

   5 topics

   • Loading and maintenance dose calculations
   • Aminoglycoside dosing and monitoring
   • Vancomycin AUC-guided dosing
   • Steady-state and trough interpretation
   • Dose adjustment in renal and hepatic impairment
3. 3

   Pharmaceutical Calculations

   5 topics

   • Concentration, dilution, and alligation
   • Millimoles, milliequivalents, and osmolarity
   • IV flow rates and infusion calculations
   • Body surface area and weight-based dosing
   • Tonicity and isotonicity adjustments
4. 4

   Pharmacodynamics

   4 topics

   • Dose-response relationships and efficacy/potency
   • Agonists, antagonists, and receptor theory
   • Therapeutic index and margin of safety
   • Concentration- vs time-dependent killing

Pharmacokinetics, Pharmacodynamics, and Calculations flashcards for North American Pharmacist Licensure Examination (NAPLEX)

21 of 55 cards from the Pharmacokinetics, Pharmacodynamics, and Calculations deck — real questions with worked answers.

1. What is oral bioavailability (F) and how is it calculated relative to IV administration?

   $F$ is the fraction of an administered dose that reaches systemic circulation unchanged. Relative to IV: $$F = \frac{AUC_{oral}/Dose_{oral}}{AUC_{IV}/Dose_{IV}}$$ IV administration is defined as $F = 1$ (100%).

2. Define the first-pass effect and name the two organs primarily responsible.

   First-pass effect is the metabolism of an orally absorbed drug before it reaches systemic circulation, reducing bioavailability. It occurs primarily in the gut wall (intestinal enterocytes) and the liver via the portal circulation.

3. How does first-pass metabolism affect oral bioavailability for high-extraction-ratio drugs?

   Drugs with a high hepatic extraction ratio undergo extensive first-pass metabolism, giving low oral $F$. Their bioavailability is flow-limited and can change markedly with liver blood flow or cirrhosis. Examples: propranolol, morphine, lidocaine, nitroglycerin.

4. What factors influence the rate and extent of drug absorption from the GI tract?

   Drug lipophilicity and ionization (pH-partition), dissolution rate and formulation, gastric emptying and GI motility, surface area, blood flow, presence of food, active transporters (e.g., P-glycoprotein), and first-pass metabolism.

5. Define volume of distribution ($V_d$) and give its formula.

   $V_d$ is the apparent volume into which a drug distributes to produce the observed plasma concentration. $$V_d = \frac{\text{Amount of drug in body}}{C_p}$$ It is a proportionality constant, not a real physiologic volume.

6. How does plasma protein binding affect volume of distribution?

   Extensive plasma protein binding (e.g., to albumin) keeps drug in the vasculature, giving a small $V_d$. Extensive tissue binding gives a large $V_d$. Decreased protein binding increases free fraction and generally increases $V_d$.

7. What is the approximate $V_d$ for a drug confined to plasma vs. total body water in a 70 kg adult?

   Plasma volume $\approx 3\ \text{L}$; blood volume $\approx 5\ \text{L}$; extracellular fluid $\approx 14\ \text{L}$; total body water $\approx 42\ \text{L}$ ($\approx 0.6\ \text{L/kg}$). $V_d$ much greater than $42\ \text{L}$ implies extensive tissue binding.

8. Which plasma protein binds acidic drugs vs. basic drugs?

   Acidic and neutral drugs (e.g., warfarin, phenytoin) bind primarily to albumin. Basic drugs (e.g., lidocaine, propranolol, quinidine) bind primarily to $\alpha_1$-acid glycoprotein (AAG).

9. Why does phenytoin require a free-level adjustment in hypoalbuminemia, and what is the Sheiner-Tozer equation?

   Low albumin raises the free (active) fraction, so total levels underestimate effect. Corrected total concentration: $$C_{adj} = \frac{C_{obs}}{(0.2 \times \text{albumin}) + 0.1}$$ (use $0.275$ factor in patients with $CrCl < 10\ \text{mL/min}$).

10. Define clearance (CL) and state its fundamental relationship to elimination.

    Clearance is the volume of plasma cleared of drug per unit time. $$CL = \frac{\text{Rate of elimination}}{C_p}$$ Total $CL$ is the sum of organ clearances: $CL_{total} = CL_{hepatic} + CL_{renal} + \dots$

11. Write the relationship among half-life, volume of distribution, and clearance.

    $$t_{1/2} = \frac{0.693 \times V_d}{CL}$$ Half-life is directly proportional to $V_d$ and inversely proportional to $CL$. The elimination rate constant $k = \frac{CL}{V_d} = \frac{0.693}{t_{1/2}}$.

12. How many half-lives are needed to reach steady state and to eliminate a drug?

    It takes approximately $4$–$5$ half-lives to reach $\approx 94$–$97\%$ of steady state, and likewise $4$–$5$ half-lives to eliminate $\approx 94$–$97\%$ of the drug. After $1\ t_{1/2}$, $50\%$; $2$, $75\%$; $3$, $87.5\%$; $4$, $93.75\%$.

13. Distinguish first-order from zero-order elimination kinetics.

    First-order: a constant fraction is eliminated per unit time; rate $\propto$ concentration; constant $t_{1/2}$; linear pharmacokinetics. Zero-order: a constant amount is eliminated per unit time (saturated enzymes); rate is independent of concentration; $t_{1/2}$ varies with concentration.

14. State the Michaelis-Menten equation for the rate of drug elimination.

    $$\text{Rate} = \frac{V_{max} \cdot C}{K_m + C}$$ where $V_{max}$ is maximum elimination rate and $K_m$ is the concentration at half $V_{max}$. When $C \ll K_m$ kinetics are first-order; when $C \gg K_m$ they approach zero-order.

15. Name three drugs that exhibit nonlinear (Michaelis-Menten / capacity-limited) kinetics at therapeutic doses.

    Phenytoin, ethanol, and aspirin (salicylates) at high doses; theophylline at high concentrations. Small dose increases can cause disproportionately large increases in serum concentration.

16. In a one-compartment model, how does plasma concentration decline after an IV bolus?

    Monoexponentially: $$C_t = C_0 \, e^{-kt}$$ A semilog plot of $\ln C$ vs. time is a straight line with slope $-k$. There is no distinct distribution phase.

17. In a two-compartment model, what do the alpha and beta phases represent?

    The $\alpha$ (distribution) phase is the initial rapid decline as drug distributes from central to peripheral tissue. The $\beta$ (elimination) phase is the slower terminal decline reflecting elimination; the terminal $t_{1/2}$ is calculated from $\beta$.

18. What is the loading dose formula and why is a loading dose used?

    $$LD = \frac{V_d \times C_{target}}{F}$$ (also $\times$ salt factor $S$). A loading dose rapidly achieves therapeutic concentration without waiting $4$–$5$ half-lives that maintenance dosing alone would require.

19. What is the maintenance dose (dosing rate) formula at steady state?

    $$\text{Dosing rate} = \frac{CL \times C_{ss,avg} \times \tau}{F \times S}$$ where $C_{ss,avg}$ is target average steady-state concentration, $\tau$ is the dosing interval, $F$ is bioavailability, and $S$ is the salt factor. Maintenance dose replaces drug eliminated per interval.

20. Define the salt factor (S) and give the value for aminophylline (theophylline).

    $S$ is the fraction of the salt form that is active drug. For aminophylline, $S = 0.8$ (theophylline is $80\%$ of aminophylline). It is included in loading/maintenance dose calculations: doses must be multiplied/divided by $S$.

21. What are conventional (traditional) target peak and trough levels for gentamicin/tobramycin?

    For conventional dosing of gentamicin/tobramycin: peak $5$–$10\ \mu g/mL$ (higher, $8$–$10$, for serious infections) and trough $< 2\ \mu g/mL$ (ideally $< 1$) to minimize nephro-/ototoxicity. Amikacin: peak $20$–$30$, trough $< 10\ \mu g/mL$.

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