Phase A

Question 1

Michaelis-Menten kinetics

Answer 1

K_m= [S] at (1/2)V_max

K_m is inversely related to the affinity of the enzyme for its substrate. Decreased K_m means an increased enzyme affinity V_max is directly proportional to the enzyme concentration, it is when all enzyme is saturated. Most enzymatic reactions follow a hyperbolic curve, but those that follow cooperative kinetics (hemoglobin) have a sigmoidal curve

Question 2

Competitive Inhibition

Answer 2

Competitive inhibitors increase K_m (lowering affinity), but do not affect V_max, meaning they can be overcome by increased substrate.

Competitive inhibitors often resemble substrates, and bind to the active site.

Decreases potency

Question 3

Noncompetitive Inhibition

Answer 3

Does not resemble substrate, does not bind active site, and cannot be overcome by increased substrate.

They decrease effective V_max, while leaving K_m unchanged.

They decrease pharmacological efficacy

Question 4

Michaelis-Menten Equation

Answer 4

V= (V_max [S])

(K_m + [S])

Question 5

Lineweaver-Burke Equation

Answer 5

(1/V) = K_m / (V_max [S]) + (1 / V_max)

Question 6

Bioavailabilty (F)

Answer 6

Fraction of administered drug that reaches systemic ciculation unchanged. For an IV dose, F = 100%.

Orally: F typically <100% due to incomplete absorption and first-pass metabolism

Question 7

Volume of Distribution

Answer 7

Theoretical fluid volume required to maintain the total absorbed drug amount at the plasma concentration.

V_d of plasma protein -bound drugs can be altered by liver and kidney disease (decreased protein binding, increased V_d)

V_d = Dose / concentration

Question 8

Examples of Volume of Distribution

Answer 8

Low V_d means mostly in blood, includes large/charged molecules; plasma protein bound

Medium V_d is in ECF, includes small hydrophilic molecules.

High V_d is in all tissues; small lipophilic molecules, especially if bound to tissue protein

Question 9

Half Life

Answer 9

The time required to change the amount of drug in the body by (1/2) during elimination (or constant infusion).

Property of first-order elimination.

A drug infused at a constant rate takes 4-5 half lives to reach steady state.

t_(1/2) = (0.7 x V_d) / CL

Question 10

Clearance (CL)

Answer 10

Relates the rate of elimination to the plasma concentration.

Clearance may be impaired with defects in cardiac, hepatic, or renal function.

CL = (rate of elimination of drug / plasma concentration of drug) = V_d x K_e (elimination constant)

Question 11

Loading Dose

Answer 11

C_p = target plasma concentration; = C_p x V_d / (F)

In renal or liver disease, maintenance dose decreases and loading dose is unchanged

Question 12

Maintenance dose

Answer 12

C_p = target plasma concentration = C_p x CL / (F)

Time to steady state depends primarily on t_(1/2) and is independent of dosing frequency or size

Question 13

Zero-order Elimination

Answer 13

Rate of elimination is constant regardless of C_p (constant amount of drug eliminated per unit time).

C_p decreases linearly with time.

Examples of drugs: PEA: Penytoin, ethanol, aspirin (at high dose)

Question 14

First Order Elimination

Answer 14

Rate of elimination is directly proportional to the drug concentration (constant fraction of the drug eliminated per unit time).

C_p decreases exponentially with time.

Question 15

First Order vs. Zero Order

Answer 15

Zero order: 5 units per hour

First order: half of the dose per hour

Question 16

Urine pH and drug elimination

Answer 16

Ionized species are trapped in urine and cleared quickly.

Neutral forms can be reabsorbed

Question 17

Weak Base Elimination

Answer 17

Trapped in acidic environments.

Treat overdose with ammonium chloride.

Example: amphetamines RNH₃⁺ (trapped) <==> RNH₂ + H⁺ (lipid soluble)

Question 18

Weak Acid Elimination

Answer 18

Trapped in basic environments.

Treat overdose with bicarbonate

Examples: methotrexate, aspirin, phenobarbitol

RCOOH (lipid solube) <==> RCOO^- (trapped) + H⁺

Question 19

Drug Metabolism: Phase I

Answer 19

Reduction, oxidation, hydrolysis with cytochrome P-450 usually yield slightly polar, water-soluble metabolites (often still active).

Geriatric patients lose Phase I first

Question 20

Drug Metabolism: Phase II

Answer 20

Conjugation (GAS: Glucuronidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites that are renally excreted.

Geriatric patients have GAS, patients who are slow acetylators have greater side effects from certain drugs because of decreased rate of metabolism

Question 21

Efficacy

Answer 21

Maximal effect a drug can produce.

High-efficacy drug classes are analgesic medications, antibiotics, antihistamines, and decongestants.

Partial agonists have less efficacy than full agonists

Question 22

Potency

Answer 22

Amount of drug needed for a given effect.

Increases potency means increases affinity for a receptor.

Highly potent drug classes include chemotherapeutics, antihypertensives, and antilipid drugs

Question 23

Receptor Binding: Agonist plus competitive antagonist

Answer 23

Increases the amount of dose needed for same maximum effect.

Does not interfere with the potential maximal effect.

Decreases potency, no change in efficacy

Question 24

Receptor Binding. Agonist plus noncompetitive antagonist

Answer 24

Decreases the maximal effect of the agonist.

Does not shift the maximal dosage of the agonist needed for maximum effect, just lowers the maximum effect.

Decreased efficacy.

Cannot be overcome with increased substrate.

Question 25

Therapeutic Index

Answer 25

Measurement of drug safety.

LD₍₅₀₎ / ED₍₅₀₎ = median lethal dose divided by median effective dose.

TILE: Therapeutic Index = L / E

The safer the drug, the higher the TI

Question 26

Therapeutic Window

Answer 26

Measure of clinical drug safety.

Range of minimum effective dose to minimum toxic dose

Question 27

Formulas to Know

Answer 27

Dosing Rate (steady state) = rate of elimination

Dosing Rate = clearance x target concentration

Dosing Rate (maintenance dosing rate) = CL x TC

Question 28

Half Life Formulas

Answer 28

Conc at time t C_(t) = C_(i) e^(-kt), where t is the time elapsed since initial dosage K= 0.7 / t_(1/2)