Pharm Day 1: Equations and Definitions

What is bioavailability (F)?

Fraction of an administered dose that reaches systemic circulation unchanged; IV = 100%

What causes the first-pass effect?

Hepatic (and gut wall) metabolism of an oral drug before it reaches systemic circulation, lowering F

What does volume of distribution (Vd) represent?

Theoretical volume relating total drug in the body to plasma concentration; high Vd = extensive tissue distribution

What is clearance (CL)?

Volume of plasma cleared of drug per unit time (hepatic + renal)

What is half-life (t1/2)?

Time for plasma concentration to fall by 50%; determines dosing interval and time to steady state

How many half-lives does it take to reach steady state?

Approximately 4-5 half-lives, regardless of dose or infusion rate

What is therapeutic index (TI)?

TD50/ED50 (or LD50/ED50); narrow TI drugs need close monitoring (warfarin, digoxin, lithium, aminoglycosides, phenytoin)

What is the difference between an agonist and an antagonist?

Agonist binds and activates the receptor; antagonist binds but does not activate, blocking the agonist

What is affinity?

Strength of drug-receptor binding

What is efficacy?

Ability of a bound drug to produce a maximal biological response (Emax)

What is potency?

Amount of drug needed to produce a given effect; lower EC50 = more potent

Which transmembrane signaling mechanism do steroid hormones use?

Lipid-soluble ligand crosses the membrane and binds an intracellular/nuclear receptor, altering gene transcription (slow, sustained)

Which transmembrane signaling mechanism is fastest (milliseconds)?

Ligand-gated ion channels (e.g., nicotinic ACh, GABA-A)

Which transmembrane signaling mechanism does insulin use?

Receptor tyrosine kinase (RTK) — intrinsic enzymatic activity triggers a phosphorylation cascade

Which transmembrane signaling mechanism do GPCRs use?

7-transmembrane receptor coupled to a G-protein that activates an effector enzyme (adenylyl cyclase or phospholipase C), generating second messengers (cAMP, IP3/DAG)

Which transmembrane signaling mechanism do cytokine and EPO receptors use?

JAK/STAT — receptor dimerizes, cytoplasmic JAK phosphorylates STAT, which translocates to the nucleus

What is the formula for half-life?

t1/2 = 0.693 / ke

What is the formula for clearance?

CL = ke x Vd = Dose / AUC

What is the formula for loading dose?

LD = (Vd x Cp target) / F

What is the formula for maintenance dose during IV infusion?

MD (rate) = CL x Css target

What is the formula for bioavailability?

F = AUC(oral) / AUC(IV)

Does changing infusion rate change time to steady state?

No — time to steady state is always ~4-5 half-lives regardless of infusion rate

Which CYP450 isoenzyme handles about 50% of drug metabolism?

CYP3A4/5

Name two inhibitors of CYP3A4.

Azole antifungals and macrolides (not azithromycin), also grapefruit juice

Name three classic CYP450 inducers.

Rifampin, carbamazepine, phenytoin

Which CYP450 isoenzyme metabolizes warfarin (S-isomer)?

CYP2C9

Which CYP450 isoenzyme activates clopidogrel?

CYP2C19

What is the difference between Phase I and Phase II drug metabolism?

Phase I (oxidation/reduction/hydrolysis) exposes a polar group; Phase II (conjugation) attaches a polar moiety and almost always inactivates the drug while boosting water solubility