Flashcards-Pharmacokinetics (PK) vs. Pharmacodynamics (PD)

Pharm Lecture 1

What is the definition of a drug?

A drug is any substance that acts at the molecular level on a biological system, causing a functional change.

Give examples of natural vs. synthetic drugs.

Natural drugs: plant/microorganism-derived (e.g., morphine). Synthetic drugs: lab-created (e.g., benzodiazepines).

Define pharmacokinetics (PK) and pharmacodynamics (PD).

PK = what the body does to the drug (ADME). PD = what the drug does to the body.

What is the fundamental hypothesis of PK?

Drug effect correlates with drug concentration at receptors, which reflects free plasma concentration.

Define zero-order kinetics and provide examples.

zero-order kinetics: constant amount eliminated regardless of concentration. Examples: phenytoin, ethanol, aspirin (high doses).

Define first-order kinetics and provide examples.

First-order kinetics: constant fraction eliminated; exponential decline. Most drugs follow this.

 What are the assumptions of the one-compartment model?

Assumptions: first-order kinetics + one-compartment distribution model.

 List routes of drug administration.

Routes: oral, IV, IM, subcutaneous, transdermal, inhalation, rectal, et

Compare passive diffusion, active transport, aqueous diffusion, and transporter proteins.

Passive diffusion (down gradient), active transport (ATP needed), aqueous diffusion (interstitial space), transporter proteins (uptake/efflux).

What physiochemical factors affect drug absorption?

Size, polarity, partition coefficient, ionization state, pH.

How does ionic character affect drug crossing?

 Uncharged drugs cross membranes more easily than charged ones.

Explain weak acid vs. weak base ionization at different pH levels.

Weak acids absorb in acidic pH; weak bases absorb in alkaline pH.

How does altering urine pH affect excretion of weak acids vs. weak bases?

 Alkaline urine favors weak acid excretion;

acidic urine favors weak base excretion.

Define bioavailability (F) and how it is calculated.

F = \frac{\text{AUC(route X)}}{\text{AUC(IV)}} Bioavailability (F) measures the fraction of an administered drug that reaches systemic circulation. It is calculated by comparing the area under the curve (AUC) for a given route of administration to the AUC for intravenous administration.

 What factors reduce oral bioavailability?

Factors: incomplete absorption, gut metabolism, first-pass liver metabolism.

What factors affect drug distribution?

 Blood flow, capillary structure, protein binding, tissue binding, physiochemical properties,age/disease.

How do reservoirs (plasma proteins, fat, tissues) affect drug action?

Reservoirs (plasma proteins, fat, tissues) store drugs, prolonging action.

Define volume of distribution (Vd)

Vd = amount of drug in body ÷ plasma concentration (theoretical volume)

 Compare drugs with high vs. low Vd

High Vd → tissue distribution; Low Vd → plasma-bound.

Define the first-pass effect.

 Drugs absorbed in GI tract undergo metabolism in gut wall + liver before circulation.

Compare phase I vs. phase II metabolism.

Phase I = oxidation/reduction/hydrolysis (CYP450).

Phase II = conjugation (glucuronidation,sulfation, acetylation).

Which CYP enzymes metabolize the majority of drugs?

CYP3A4 and CYP2D6 (also CYP2C9, CYP1A2).

Give examples of phase II conjugation reactions.

Glucuronidation, sulfation, methylation, acetylation, glutathione conjugation

Why are prodrugs used? Give an example.

Prodrugs improve absorption, reduce toxicity, target tissues. Example: loratadine → active metabolite

What are the three renal processes of excretion?

Glomerular filtration, proximal tubular secretion, distal tubular reabsorption.

 Which drugs are filtered at the glomerulus?

Small, unbound drugs are filtered at the glomerulus.

Why are lipophilic drugs reabsorbed?

Lipophilic drugs are reabsorbed because they diffuse back across membranes.

How is half-life (t½) calculated?

t½ = 0.693 × Vd / CL.

 What is the 4–5 half-life rule?

4–5 half-life rule: ~4–5 half-lives to reach steady state or eliminate drug.

The 4–5 half-life rule states that approximately 4 to 5 half-lives of a drug are needed to achieve steady state concentration or to eliminate the drug from the system.

What is the relationship between Vd, clearance (CL), and half-life?

Longer t½ if Vd ↑ or CL ↓.

The half-life (t½) of a drug is inversely related to clearance (CL); as volume of distribution (Vd) increases or clearance decreases, the half-life becomes longer, making the drug stay in the system for an extended period.

Calculate t½ if CL = 630 mL/min and Vd = 32 L

t½ = 0.693 × (32 L ÷ 0.63 L/min) ≈ 35 min.

 How do you calculate a loading dose?

LD = Cp × Vd / F.

How do you calculate a maintenance dose?

MD = Cp × CL × τ / F.

Example: Cp = 3.5 mg/L, Vd = 35 L, CL = 70 mL/min. Calculate LD and MD (q8h).

LD = 122.5 mg; MD = 117.6 mg q8h.

Define a drug interaction.

one drug modifies the action of another.

How do inhibitors vs. inducers affect CYP-mediated metabolism?

Inhibitors ↑ drug concentration; inducers ↓ concentration.

Which CYP enzymes are most clinically significant?

CYP3A4 and CYP2D6 are most clinically significant.

CYP3A4 and CYP2D6 are the most clinically significant due to their involvement in metabolizing a vast number of drugs. CYP3A4 metabolizes approximately 50-60% of all therapeutic drugs, while CYP2D6 metabolizes about 25%.