Pharmacology - Pharmacokinetics & Pharmacodynamics (ADME Principles) Flashcards

Question 1

Pharmacokinetics (PK) vs. Pharmacodynamics (PD)

Accepted Answer

**Pharmacokinetics (PK)** is what the body does to a drug, encompassed by **ADME** (Absorption, Distribution, Metabolism, Excretion).

**Pharmacodynamics (PD)** is what the drug does to the body, including receptor interactions, biochemical actions, and physiological effects.

Question 2

Bioavailability ($F$)

Accepted Answer

The fraction of an administered drug that reaches systemic circulation unchanged.

* **Intravenous (IV):** $F = 100\%$ ($F = 1.0$)
* **Oral (PO):** $F < 1.0$ due to incomplete absorption and first-pass hepatic metabolism.
* **Formula:** $F = \frac{	ext{AUC}_{oral}}{	ext{AUC}_{IV}} 	imes 100\%$

Question 3

First-Pass Metabolism

Accepted Answer

The initial metabolic breakdown of an orally administered drug in the intestinal wall and liver before it reaches the systemic circulation, which significantly decreases bioavailability ($F$).

Question 4

Volume of Distribution ($V_d$)

Accepted Answer

A theoretical volume relating the total amount of drug in the body to its plasma concentration:

$$V_d = \frac{	ext{Amount of drug in body}}{	ext{Plasma drug concentration } (C_0)} = \frac{	ext{Dose}}{C_0}$$

* **Low $V_d$ (~3–5 L):** Confined to plasma (large/charged molecules, high plasma protein binding).
* **High $V_d$ (>41 L):** Distributed widely into tissues (small, lipophilic molecules).

Question 5

Clearance ($CL$)

Accepted Answer

The volume of plasma cleared of a drug per unit time (e.g., mL/min or L/hr):

$$CL = \frac{	ext{Rate of elimination}}{C_p} = V_d 	imes k_e$$

where $C_p$ is plasma concentration and $k_e$ is the elimination rate constant. Total clearance equals renal clearance plus hepatic clearance plus other clearances.

Question 6

Elimination Half-Life ($t_{1/2}$)

Accepted Answer

The time required for the plasma drug concentration to decrease by $50\%$.

$$t_{1/2} = \frac{0.693 	imes V_d}{CL}$$

* **Steady-State ($C_{ss}$):** Reached after approximately **4 to 5 half-lives** of continuous dosing or infusion.
* **Complete Elimination:** Takes approximately **4 to 5 half-lives** after stopping the drug.

Question 7

First-Order Elimination Kinetics

Accepted Answer

A **constant fraction (percentage)** of drug is eliminated per unit time. The elimination rate is directly proportional to plasma drug concentration ($C_p$).

* $t_{1/2}$ remains constant.
* Applies to the vast majority of therapeutic drugs.

Question 8

Zero-Order Elimination Kinetics

Accepted Answer

A **constant amount** of drug is eliminated per unit time, independent of plasma drug concentration because metabolic processes are saturated.

* $t_{1/2}$ is variable and increases with higher concentration.
* **Classic examples:** Ethanol, Aspirin (at high doses), Phenytoin.

Question 9

Phase I Drug Metabolism

Accepted Answer

Non-synthetic reactions (**Oxidation, Reduction, Hydrolysis**) that introduce or expose functional groups (e.g., $-	ext{OH}$, $-	ext{NH}_2$) to make drugs more polar.

* Primarily carried out by **Cytochrome P450 (CYP450)** enzymes in the liver.
* Converts active drugs to active/inactive metabolites or pro-drugs to active drugs.

Question 10

Phase II Drug Metabolism

Accepted Answer

Synthetic or **conjugation reactions** (e.g., Glucuronidation, Acetylation, Sulfation, Glutathione conjugation) that attach large, hydrophilic endogenous groups.

* Yields inactive, highly polar metabolites rapidly excreted in urine or bile.
* Patients with slow acetylation phenotypes (e.g., for Isoniazid, Hydralazine) have a higher risk of toxicity.

Question 11

Maximal Efficacy ($E_{max}$) vs. Potency ($EC_{50}$)

Accepted Answer

* **$E_{max}$ (Efficacy):** The maximum response achievable by a drug. Represented by the height of the dose-response curve.
* **$EC_{50}$ (Potency):** The concentration of drug required to produce $50\%$ of its maximal effect. A lower $EC_{50}$ indicates greater potency (curve shifted to the left).

Question 12

Full Agonist vs. Partial Agonist

Accepted Answer

* **Full Agonist:** Binds to a receptor and produces the maximal possible biological response ($E_{max} = 100\%$).
* **Partial Agonist:** Binds to the same receptor but produces a submaximal response ($E_{max} < 100\%$) even at full receptor saturation. Can act as a competitive antagonist in the presence of a full agonist.

Question 13

Inverse Agonist

Accepted Answer

Binds to the same active receptor site as an agonist, but stabilizes the **inactive state** of the receptor, thereby reducing constitutive (basal) activity below baseline.

Question 14

Competitive Reversible Antagonist

Accepted Answer

Binds **reversibly** to the agonist active site.

* Shifts the dose-response curve to the **right** (increases $EC_{50}$, decreases potency).
* **$E_{max}$ remains unchanged** because the antagonism can be overcome by increasing agonist concentration.

Question 15

Non-Competitive Antagonist

Accepted Answer

Binds to an **allosteric site** (or binds irreversibly to the active site), reducing the maximal capability of the receptor.

* **Reduces $E_{max}$** (decreases efficacy).
* **$EC_{50}$ remains unchanged**.
* Cannot be overcome by increasing agonist concentration.

Question 16

Irreversible Antagonist

Accepted Answer

Forms **covalent bonds** with the active receptor site, permanently preventing agonist binding.

* Reduces $E_{max}$ (acting functionally like a non-competitive antagonist).
* Effect persists until new receptors are synthesized by the body.

Question 17

Therapeutic Index ($TI$)

Accepted Answer

A quantitative measurement of a drug's relative safety:

$$TI = \frac{TD_{50}}{ED_{50}} \quad \left(	ext{or } \frac{LD_{50}}{ED_{50}} 	ext{ in animal studies}ight)$$

* $TD_{50}$: Median toxic dose; $ED_{50}$: Median effective dose.
* **High $TI$:** Safe drug (e.g., Penicillin).
* **Low $TI$:** Narrow therapeutic window requiring blood monitoring (e.g., Warfarin, Digoxin, Lithium, Theophylline).

Question 18

Loading Dose ($LD$)

Accepted Answer

An initial larger dose given to rapidly reach therapeutic steady-state plasma concentration ($C_{ss}$):

$$LD = \frac{C_{ss} 	imes V_d}{F}$$

Dependent primarily on **Volume of Distribution ($V_d$)** rather than clearance.

Question 19

Maintenance Dose ($MD$)

Accepted Answer

The ongoing dose required to maintain steady-state plasma concentration ($C_{ss}$) within the therapeutic window:

$$MD = \frac{C_{ss} 	imes CL 	imes 	au}{F}$$

where $	au$ is the dosing interval. Dependent primarily on **Clearance ($CL$)**.

Question 20

Ion Trapping & Renal Excretion

Accepted Answer

Uncharged (non-ionized) drugs cross cell membranes freely; charged (ionized) drugs are trapped.

* **Weak Acids** (e.g., Aspirin): Trapped in basic urine. Treat overdose with sodium bicarbonate ($	ext{NaHCO}_3$) to alkalinize urine and enhance renal excretion.
* **Weak Bases** (e.g., Amphetamines): Trapped in acidic urine. Acidify urine with ammonium chloride ($	ext{NH}_4	ext{Cl}$) or vitamin C to accelerate excretion.

Pharmacology - Pharmacokinetics & Pharmacodynamics (ADME Principles)

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