Pharmacology- Pharmacokinetics and Pharmacodynamics

Question 1

Michaelis-Menten kinetics

Answer 1

Km is inversely related to the affinity of the enzyme for its substrate.

Vmax is directly proportional to the enzyme concentration.

Most enzymatic reactions follow a hyperbolic curve;
however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (eg, hemoglobin).

Question 2

Effects of enzyme inhibition

Answer 2

¨Pag 228

Question 3

Lineweaver-Burk plot

Answer 3

The higher the y-intercept, the lower the Vmax.

The further to the right the x-intercept, the greater the Km and the lower the affinity.

Kompetitive inhibitors increase Km.

Question 4

Bioavailability (F)

Answer 4

Fraction of administered drug reaching systemic circulation unchanged. For an IV dose, F = 100%.
Orally: F typically < 100%.

Question 5

Volume of distribution (Vd)

Answer 5

Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration.

Vd = amount of drug in the body / plasma drug concentration

Low Vd: Intravascular
Medium Vd: ECF
High Vd: All tissues

Question 6

Clearance (CL)

Answer 6

The volume of plasma cleared of drug per unit time.

CL = rate of elimination of drug / plasma drug concentration = Vd × Ke (elimination constant)

Question 7

Half-life (t1/2)

Answer 7

The time required to change the amount of drug in the body by 1⁄2 during elimination.

In first-order kinetics, a drug infused at a constant rate takes 4–5 half-lives to reach steady state. It takes 3.3 half-lives to reach 90% of the steady-state level.

t1/2 = 0.7 × Vd / CL
*in first-order elimination

Question 8

Loading dose =

Maintenance dose=

Answer 8

Cp × Vd / F

Cp × CL × τ / F

Cp = target plasma concentration at steady state
τ = dosage interval (time between doses), if not
administered continuously

Question 9

Types of drug interactions

• Additive
• Permissive

Answer 9

Effect of substance A and B together is equal to the sum of their individual effects (Aspirin and acetaminophen).

Presence of substance A is required for the full effects of substance B (Cortisol on catecholamine responsiveness).

Question 10

Types of drug interactions

• Synergistic
• Tachyphylactic

Answer 10

Effect of substance A and B together is greater than the sum of their individual effects (Clopidogrel with aspirin)

Acute decrease in response to a drug after initial/repeated administration (Nitrates, niacin, phenylephrine, LSD, MDMA)

Question 11

Competitive antagonist (pag. 230)

Answer 11

Shifts curve right (Low potency), no change in efficacy. Can be overcome by increasing the concentration of agonist substrate.

Diazepam (agonist) + flumazenil (competitive antagonist) on GABA receptor.

Question 12

Noncompetitive antagonist (pag. 230)

Answer 12

Shifts curve down (Low efficacy). Cannot be
overcome by Increasing agonist substrate concentration.

Norepinephrine (agonist) + phenoxybenzamine
(noncompetitive antagonist) on α-receptors.

Question 13

Partial agonist (alone) (pag. 230)

Answer 13

Acts at same site as full agonist, but with lower maximal effect (Low efficacy). Potency is an independent variable.

Morphine (full agonist) vs buprenorphine (partial agonist) at opioid μ-receptors.

Question 14

Zero-order elimination

Answer 14

Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp decrease linearly with time.

PEA: Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations). *Capacity-limited elimination

Question 15

First-order elimination

Answer 15

directly proportional to the drug concentration (ie, constant Fraction of drug eliminated per unit time). Cp Decrease exponentially with time. Applies to most drugs.

*Flow-dependent elimination.

Question 16

Urine pH and drug elimination

• Weak Acids
• Weak Bases

Answer 16

Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to alkalinize urine.

Example: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride to acidify urine.
* TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channelblocking
activity of TCAs, but not for accelerating drug elimination.

Question 17

Drug metabolism

• I phase
• II phase

Answer 17

Reduction, Oxidation, Hydrolysis with cytochrome P-450. *Geriatric patients lose phase I first.

Conjugation (Methylation, Glucuronidation, Acetylation, Sulfation). *Patients who are slow acetylators have higher side effects from certain drugs

Question 18

Efficacy

Answer 18

Maximal effect a drug can produce. Represented by the y-value (Vmax). High y-value = high Vmax = high efficacy.

Question 19

Potency

Answer 19

Amount of drug needed for a given effect. Represented by the x-value (EC50).

Left shifting = Low EC50 = High potency = Low drug needed.

Question 20

Therapeutic index

Answer 20

Measurement of drug safety. TD50/ED50

TD50 median toxic dose
ED50 median effective dose

Drugs with lower TI values frequently require monitoring
(eg, Warfarin, Theophylline, Digoxin, Lithium;
Warning! These Drugs are Lethal!)

Question 21

Therapeutic window

Answer 21

dosage range that can safely and effectively treat disease