Basic Principles

Question 1

Define: pharmacology

Answer 1

• Study of substances that interact w/ living system
• Beneficial therapeutic effect
• Toxic effects

Question 2

Define: toxicology

Answer 2

• Undesirable effects of chemicals on systems

Question 3

Define: pharmacotherapeutics

Answer 3

Study of therapeutic uses & effects

Question 4

Define: pharmacokinetics

Answer 4

“What the body does to the drug”
- Absorption, distribution, metabolism, elimination =
“ADME”

Question 5

Define pharmacodynamics, & what is potency?

Answer 5

“What the drug does to the body”

• Study of the relationship btwn drug [ ] & response of pt
• Potency = Amt of drug needed to produce effect

Question 6

Define: Bioavailability, & what type of administration is equal to 100%?

Answer 6

• Fraction of dose administered that reaches circulation

- 100% for IV administration

Question 7

How is bioavailability reduced?

Answer 7

• Incomplete absorption

- 1st pass metabolism

Question 8

Oral bioavailability (What is the percentage?)

Answer 8

5 - < 100%

Question 9

Geriatric population (How are drugs & nutrients absorbed?)

Answer 9

• Most drugs absorbed via passive diffusion
• Nutrients absorbed by active transport
• Evidence of decreased 1st-pass effect on hepatic or gut wall metabolism –> increased bioavailability

Question 10

Define: 1st-pass effect

Answer 10

• [ ] of drug is reduced before reaching circulation

- Fraction lost during absorption

Question 11

Effect of protein binding

Answer 11

• Fraction unbound can be altered by variables
• Higher drug [ ] & decreased plasma protein can lead to higher fraction unbound
• Clearance increases

Question 12

Protein-bound molecules are not available to do what?

Answer 12

Exert pharmacologic effects

Question 13

Define: Volume of distribution (Vd)

Answer 13

Relates amt of drug in body to serum [ ]

Question 14

What is Vd used to calculate?

Answer 14

The loading dose of a drug that will immediately achieve a steady-state [ ]

Question 15

PK: Distribution in peds

Answer 15

• ↑ Total body water
• ↑ Extracellular fluid volume
• ↓ Binding of drugs to plasma proteins
• ↓ Amt of body fat

Question 16

PK: Distribution in pregnancy

Answer 16

• ↑ Body fat

- ↓ Plasma albumin [ ]

Question 17

PK: Distribution in geriatrics

Answer 17

• ↓ Total body water
• ↓ Lean body mass
• ↑ Body fat
• ↔ or ↓ Serum albumin
• ↑ α1-Acid glycoprotein
• ↓ CO

Question 18

Define: receptors

Answer 18

Molecules in which drugs interact to produce changes in fxn of the system

Question 19

Define: agonist

Answer 19

Drugs bind to & activate the receptor, which directly or indirectly brings about the effect

Question 20

Define: partial agonist

Answer 20

Binds to its receptor but produces a smaller effect at full dosage than a full agonist

Question 21

Define: antagonist

Answer 21

Drugs, by binding to a receptor, compete w/ & prevent binding by other molecules

Question 22

Define: allosteric

Answer 22

Drugs bind to the same receptor molecule but do not prevent binding of the agonist

Question 23

Define Irreversible antagonist

Answer 23

Antagonist that cannot be overcome by increasing the agonist

Question 24

What are sites of drug metabolism?

Answer 24

• Liver = most important organ for metabolism
• Kidney plays a role
• A few drugs are metabolized in many tissues bc of their enzymes

Question 25

Describe Phase I Reactions

Answer 25

Convert parent drug to a more polar or more reactive product by unmasking or inserting a polar functional group s/a —OH, —SH, or —NH2 - Usually changed to inactive

Question 26

Describe Phase II Reactions

Answer 26

- Increase H2O solubility by conjugation of the drug molecule w/ a polar moiety s/a glucuronate, acetate, or sulfate - Forms a highly polar conjugate

Question 27

Define: Cytochrome P450 (What phase? Responsible for what?)

Answer 27

- Part of Phase I reactions | - Enzyme species, responsible for much of drug metabolism

Question 28

Define: substrate

Answer 28

Drug metabolized by 1 of the CYP450 enzymes

Question 29

Define: inducer

Answer 29

Drug that increases activity of a CYP450 enzyme

Question 30

Define: inhibitor

Answer 30

Drug that decreases activity of a CYP450 enzyme

Question 31

What are some inhibitors of P-gp?

Answer 31

- Verapamil | - Furanocoumarin components of grapefruit juice

Question 32

What drugs are normally expelled by P-gp?

Answer 32

- Digoxin - Cyclosporine - Saquinavir * More toxic when given w/ a P-gp inhibitor

Question 33

Metabolism in peds

Answer 33

- Slower in infants than in older children & adults - Sulfation pathway is well developed in infants - Glucoronidation pathway is undeveloped in infants

Question 34

Metabolism in pregnancy

Answer 34

Hepatic perfusion increases

Question 35

Metabolism in geriatrics

Answer 35

- ↓ Hepatic size - ↓ Hepatic blood flow - ↓ Phase I metabolism

Question 36

Define: Steady state

Answer 36

Avg total amt of drug in the body does not change over multiple dosing cycles

Question 37

What do most drugs follow?

Answer 37

Linear pharmacokinetics | - steady-state serum drug [ ]s change proportionally w/ long-term daily dosing

Question 38

What kind of drugs follow nonlinear pharmacokinetics?

Answer 38

Those w/ serum [ ]s that change more or less than expected

Question 39

What is the most important pharmacokinetic parameter?

Answer 39

Clearance

Question 40

What does clearance determine?

Answer 40

- Steady-state [ ] for a given dosage rate - Efficiency of the organ extracting the drug from the bloodstream * Determined by blood flow to the organ that metabolizes/eliminates the drug

Question 41

What can reduce the clearance of drugs that depend on renal fxn?

Answer 41

- Renal disease - Reduced CO - Liver disease (less common)

Question 42

How does impairment of hepatic clearance occur?

Answer 42

When liver blood flow is reduced | - Ex. HF, severe cirrhosis

Question 43

Define: GFR

Answer 43

- Total filtration rates of functioning nephrons of kidney - Cannot be measured directly - Used for detection, severity, & tx of kidney disease

Question 44

What are variables of GFR?

Answer 44

- Gender - Age - Weight - Race

Question 45

Efficiency of renal excretion in pediatric pts is determined by what?

Answer 45

- Glomerular filtration - Tubular secretion - Tubular reabsorption * Processes may not develop fully for several weeks to 1 yr after birth

Question 46

Excretion in pregnancy

Answer 46

- Maternal plasma volume, CO, & glomerular filtration increase by 30% to 50% or higher - Higher levels of estrogen & progesterone alter liver enzyme activity

Question 47

Excretion in geriatrics

Answer 47

``` ↓ GFR ↓ Filtration fraction ↓ Tubular secretory function ↓ Renal mass ↓ Renal blood flow ```

Question 48

Describe the MDRD equation

Answer 48

- Estimates GFR adjusted for BSA - More accurate than Cockroft-Gault - Used by most laboratories as eGFR

Question 49

Cockroft-Gault equation

Answer 49

- Uses body weight | - Standard for drug dosing

Question 50

When is ABW (actual body weight) used?

Answer 50

If ABW is less IBW

Question 51

Define: efficacy

Answer 51

Greatest effect an agonist can produce if the dose is taken to the highest tolerated level *Partial agonists have lower efficacy than full agonists

Question 52

Define: P-glycoprotein (Where is it found? What is its fxn?)

Answer 52

ATP-dependent transport molecule - Found in epithelial & cancer cells - Expels drug molecules from the cytoplasm into the extracellular space - In epithelial cells, expulsion is via the external or luminal face

Question 53

Define: Half life (t1/2)

Answer 53

Time required for serum [ ] to decrease by 1/2 after absorption & distribution are complete

Question 54

What does half life determine?

Answer 54

Time required to reach steady state & dosage interval

Question 55

What variables usually alter the clearance of a drug?

Answer 55

Disease, age

Question 56

What is half life dependent upon?

Answer 56

Clearance & Vd

Question 57

What is the MAP equation?

Answer 57

(SBP x 1/3) + (DBP x 2/3)