USMLE Step 1 - General Principles of Pharmacology Flashcards

Question 1

Clinical Trial Phases: Phase 0

Accepted Answer

Very small dose testing (microdosing) in a small group of healthy human subjects ($n < 15$) to assess initial pharmacokinetics (PK) and pharmacodynamics (PD) before full Phase 1 trials.

Question 2

Clinical Trial Phases: Phase 1

Accepted Answer

Assesses **safety, toxicity, pharmacokinetics, and pharmacodynamics** in a small number of **healthy volunteers** (or patients with advanced cancer). Primary question: *Is it safe?*

Question 3

Clinical Trial Phases: Phase 2

Accepted Answer

Evaluates **treatment efficacy, optimal dosing, and adverse effects** in a moderate number of **patients with the target disease**. Primary question: *Does it work?*

Question 4

Clinical Trial Phases: Phase 3

Accepted Answer

Compares new treatment to standard of care or placebo in a large number of randomized, double-blinded patients to confirm **efficacy and monitor adverse reactions**. Primary question: *Is it better or as good?*

Question 5

Clinical Trial Phases: Phase 4

Accepted Answer

**Post-marketing surveillance** of patients after FDA approval to detect rare, long-term, or unexpected adverse drug reactions (ADRs) and drug-drug interactions. Primary question: *Can it stay on the market?*

Question 6

Potency vs. Efficacy

Accepted Answer

**Potency**: Amount of drug needed to produce 50% of maximal effect ($EC_{50}$). Shifts curve horizontally (left = more potent).

**Efficacy**: Maximal effect a drug can produce ($V_{max}$). Represented by the height of the curve on the $Y$-axis.

Question 7

Competitive Reversible Antagonist Effect on Dose-Response Curve

Accepted Answer

Shifts the dose-response curve **to the right** (increases $EC_{50}$, decreases potency). **Efficacy ($V_{max}$) remains unchanged** because high agonist concentrations can overcome the inhibition.

Question 8

Noncompetitive Antagonist Effect on Dose-Response Curve

Accepted Answer

**Decreases efficacy ($V_{max}$)** by binding irreversibly or allosterically. Cannot be overcome by increasing agonist concentration. $EC_{50}$ typically remains unchanged or increases.

Question 9

Partial Agonist (Alone vs. + Full Agonist)

Accepted Answer

**Alone**: Acts as an agonist with lower intrinsic activity ($V_{max}$) than a full agonist.

**In presence of full agonist**: Acts as a **competitive antagonist**, shifting the full agonist's curve down and to the right.

Question 10

Therapeutic Index (TI) Equation & Clinical Significance

Accepted Answer

Formula:
$$	ext{Therapeutic Index} = \frac{TD_{50}}{ED_{50}}$$
*(Median Toxic Dose / Median Effective Dose)*

**High TI** = Safe drug. **Low TI** = Narrow therapeutic window; requires frequent serum level monitoring (e.g., Warfarin, Digoxin, Lithium, Theophylline).

Question 11

Zero-Order vs. First-Order Elimination Kinetics

Accepted Answer

**Zero-Order**: Constant **amount** of drug eliminated per unit time. Rate is independent of drug concentration (e.g., Ethanol, Aspirin at toxic doses, Phenytoin).

**First-Order**: Constant **percentage/fraction** of drug eliminated per unit time. Rate is proportional to concentration.

Question 12

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

Accepted Answer

Formula:
$$t_{1/2} = \frac{0.693 	imes V_d}{CL}$$
where $V_d$ = Volume of Distribution and $CL$ = Clearance. It takes approximately **4 to 5 half-lives** to reach steady-state ($C_{ss}$) or complete elimination.

Question 13

Loading Dose Formula

Accepted Answer

Formula:
$$	ext{Loading Dose} = \frac{C_p 	imes V_d}{F}$$
where $C_p$ = target plasma concentration, $V_d$ = volume of distribution, and $F$ = bioavailability fraction.

Question 14

Maintenance Dose Formula

Accepted Answer

Formula:
$$	ext{Maintenance Dose} = \frac{C_p 	imes CL 	imes 	au}{F}$$
where $C_p$ = target concentration, $CL$ = clearance, $	au$ = dosage interval, and $F$ = bioavailability fraction.

Question 15

Volume of Distribution ($V_d$) Calculation

Accepted Answer

Formula:
$$V_d = \frac{	ext{Amount of drug in body}}{	ext{Plasma drug concentration } (C_p)}$$

- **Low $V_d$** (3-5 L): Plasma restriction (large/charged/protein-bound molecules).
- **High $V_d$**: Extravascular tissue accumulation (lipophilic/unbound molecules).

Question 16

G-Protein Signaling Pathways ($G_s, G_i, G_q$)

Accepted Answer

- **$G_s$**: Activates adenylyl cyclase $\rightarrow \uparrow$ cAMP $\rightarrow \uparrow$ Protein Kinase A (PKA).
- **$G_i$**: Inhibits adenylyl cyclase $\rightarrow \downarrow$ cAMP.
- **$G_q$**: Activates Phospholipase C $\rightarrow \uparrow IP_3 + DAG \rightarrow \uparrow Ca^{2+}$ and PKC activation.

Question 17

Receptor Tyrosine Kinase (RTK) Signaling

Accepted Answer

Transmembrane receptors that dimerize and autophosphorylate tyrosine residues upon ligand binding, initiating downstream cascades (e.g., Ras/MAPK pathway).

**Examples**: Insulin, IGF-1, PDGF, EGF, VEGF.

Question 18

Intracellular (Nuclear) Receptor Mechanism

Accepted Answer

Lipophilic ligands cross cell membrane and bind cytoplasmic or nuclear receptors. The ligand-receptor complex directly binds DNA response elements to alter gene transcription.

**Examples**: Glucocorticoids, Estrogen, Testosterone, Thyroid hormone, Vitamin D.

Question 19

Type I Adverse Drug Reaction (Hypersensitivity)

Accepted Answer

**IgE-mediated** immediate hypersensitivity. Pre-formed IgE cross-links on mast cells and basophils, causing degranulation and histamine release.

**Example**: Anaphylaxis or urticaria from Penicillin.

Question 20

Type II Adverse Drug Reaction (Hypersensitivity)

Accepted Answer

**Cytotoxic antibody-mediated** reaction. IgM or IgG antibodies bind antigen on cell surfaces, activating complement and cytotoxic cells.

**Example**: Penicillin- or Methyldopa-induced Coombs-positive autoimmune hemolytic anemia.

Question 21

Type III Adverse Drug Reaction (Hypersensitivity)

Accepted Answer

**Immune complex-mediated** reaction. Circulating Ag-Ab complexes deposit in tissue and microvasculature, activating complement.

**Example**: Serum sickness (fever, rash, arthralgias) from Cefaclor, monoclonal antibodies, or antitoxins.

Question 22

Type IV Adverse Drug Reaction (Hypersensitivity)

Accepted Answer

**T-cell-mediated delayed** hypersensitivity (occurs 24–48+ hours after exposure). Activated T-lymphocytes release cytokines.

**Examples**: Contact dermatitis, Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) (e.g., Allopurinol, Lamotrigine, Sulfa drugs).

Question 23

Cytochrome P450 Inducers vs. Inhibitors Impact

Accepted Answer

- **CYP Inducers**: Increase enzyme activity $\rightarrow$ increased drug clearance $\rightarrow$ reduced therapeutic plasma level of substrate drugs.
- **CYP Inhibitors**: Decrease enzyme activity $\rightarrow$ reduced drug clearance $\rightarrow$ increased risk of substrate drug toxicity.

USMLE Step 1 - General Principles of Pharmacology

Cards in this deck

Related Flashcard Sets

HSK 2 - Intermediate Chinese Vocabulary & Grammar

Genetics - Mendelian Inheritance & Population Genetics

Melbourne COMP90043 - Cryptography and Security

JLPT N5 - Essential Japanese Vocabulary & Grammar