Intro to Pharm Sciences Therapeutic Variability

Question 1

Intensity of drug response

Answer 1

Varies among patients due to individual differences in pharmacokinetics, pharmacodynamics, or immune responses

Question 2

Pharmacokinetic variability

Answer 2

Caused by differences in ADME of the drug in patients, differing concentrations of drug at the target site, and alterations in efficacy and/or toxicity

Question 3

Sources of pharmacokinetic variability

Answer 3

Body weight and composition

Age

Gender

Health status

Question 4

Typical dose

Answer 4

ED50 for an effect in 70 kg male, 18-65 years

Question 4

Adjustment based on body weight

Answer 4

(Typical dose / 70 kg) * Weight of individual (kg)

Question 5

Does body weight formula for dosing work for everyone?

Answer 5

Not reliable for extremely lean or obese individuals because dramatically altered body composition

Question 6

Normal body water and fat percentages

Answer 6

~60% and 19-25%

Question 7

Obese body water and fat percentages

Answer 7

~50% and 33%+

Question 8

Lipophilic drugs

Answer 8

More fat available for drug distribution in obese patients

Increase in Vd

Lower plasma drug concentration

Question 9

Differences in body composition

Answer 9

Large differences in drug distribution and PK variability

Question 10

Therapeutic variability with age

Answer 10

Variability in very old and young cannot be explained by body size or composition alone

People at age extremes are generally more sensitive to drugs, due to differences in ADME

These people fall on extreme left on a quantal dose-response curve

Question 11

Infants and children variability statistics

Answer 11

Absorption: Increased due to higher permeability of tissues, skin, and blood-brain barrier

Metabolism: Decreased due to metabolic enzymes being under-developed

Excretion: Decreased due to lower rate of blood flow to kidneys

Question 11

Elderly variability statistics

Answer 11

Absorption: Slightly decreased due to reduced absorption efficiency

Metabolism: Decreased due to decreased hepatic mass, blood flow, and enzyme activity

Excretion: Decreased due to reduced number of nephrons, functioning glomeruli, and renal blood flow

Question 12

Pregnancy variations

Answer 12

Small molecular weight drugs can cross the placenta by passive diffusion

Drug concentration in fetus can be equal to mother, can be deadly and cause birth defects

Question 12

Gender differences

Answer 12

Higher body fat %

Lower metabolic rates

Question 13

Health status variability

Answer 13

Impaired liver or renal function can cause drug toxicity

Edema vs. dehydration

Acidosis vs. alkalosis

Question 14

Pharmacodynamic variability

Answer 14

Variability in drug effects caused by differences in the structure or function of target receptors

Question 15

Two major factors of PD variability

Answer 15

Drug resistance

Drug tolerance

Question 16

Drug resistance

Answer 16

Lack of or decreased responsiveness to a drug that normally inhibits cell growth or causes cell death

Question 17

Intrinsic resistance

Answer 17

A cell or organism is inherently insensitive

Question 18

Acquired resistance

Answer 18

Cells or organisms initially respond to the drug but eventually fail to respond because of acquired property

Question 19

Drug resistant microbes and cancer cells

Answer 19

Transfer genes to other microbes and cancer cells, spreading resistance

Question 20

Drug resistance mechanisms

Answer 20

Production of drug-inactivating enzymes

Alteration of the drug target or binding site

Decreased permeability of drug

Increased efflux of the drug

Question 21

Production of inactivation enzymes

Answer 21

Some bacteria make them naturally, making them inherently resistant

Some bacteria express them only in the presence of the inducer, making them acquired resistant

Question 22

Decreased permeability of drug

Answer 22

Decreased rate of passive diffusion

Decreased carrier-mediated transport

Question 23

Increased efflux of drug

Answer 23

More drug leaving the cells

Resistance to a broad range of drugs that are often structurally and functionally distinct

Question 24

Drug Tolerance Overall

Answer 24

Condition of decreased responsiveness acquired after repeated exposure to a drug

Need increased dose to get the same effect

Develops slowly

Pharmacodynamic and pharmacokinetic

Question 25

Pharmacodynamic drug tolerance

Answer 25

Due to alteration of target site

Decreased receptor number, receptor affinity, and receptor sensitivity

Question 26

Pharmacokinetic drug tolerance

Answer 26

Due to reduction in drug concentration at the site of action

Example: Ethanol and barbiturates increase own metabolism and need higher dose to get same effect

Question 27

Drug tolerance special cases

Answer 27

Cross tolerance: Tolerance to different drugs of the same pharmacological class

Tachyphylaxis: Acute tolerance following rapid, repeated drug administration (few hours to few days) Rapid pharmacodynamic tolerance

Question 28

Immunologic variability

Answer 28

Drug allergy: Adverse drug response to previous exposure to the drug

Different from drug toxicity and unrelated to usual effects of drug

Not dose dependent

Antagonists do not inhibit allergic reaction

Question 29

Drug allergy mechanism

Answer 29

Caused by false recognition of drugs as antigens by the immune system

Can be very onset symptoms or delayed