10.16 Pharmacokinetics

Question 1

_ refers to how the drug affects the body

Answer 1

Pharmacodynamics refers to how the drug affects the body

Question 1

_ refers to how the body affects the drug

Answer 1

Pharmacokinetics refers to how the body affects the drug

Question 2

Stages of pharmacokinetics (4)

Answer 2

Question 3

Drugs must be sufficiently _ to get through membranes and into our blood

Answer 3

Drugs must be sufficiently hydrophobic to get through membranes and into our blood
* Need to cross the epithelium and the endothelium

Question 4

Bioavailability (F) for IV drug is _

Answer 4

Bioavailability (F) for IV drug is 100% or “1”

Question 5

Calculate oral availability based on time vs. concentration curve

Answer 5

F= area under the curve (oral) / area under the curve (I.V)

Question 6

First pass metabolism

Answer 6

First pass metabolism: oral drugs face two hurdles before they get into the bloodstream:
1. Must pass the gut wall
2. Gets metabolized by the liver

Question 7

Phase I reactions make _ modifications to drugs

Answer 7

Phase I reactions make small modifications to drugs (makes them slightly more polar)
* They are still slightly active upon completion of phase I metabolism

Question 8

Phase I reactions include:

Answer 8

Phase I reactions include: oxidation, reduction, hydrolysis

Question 9

Phase II reactions add larger groups;
The main reaction is _

Answer 9

Phase II reactions add larger groups;
The main reaction is glutathionation
* Also glucuronidation, glycination, sulfation, methylation, acetylation

Question 10

After phase II reactions, drugs are no longer active; they are in a more _ form and can be excreted easily in the _

Answer 10

After phase II reactions, drugs are no longer active; they are in a more hydrophilic form and can be excreted easily in the urine

Question 11

How does hydrophilicity affect reabsorption in the kidney?

Answer 11

More hydrophilic metabolites are less likely reabsorbed in the kidney; which helps more of the drug get excreted into the urine

Question 12

The main enzymes involved in phase I reaction are the _ family

Answer 12

The main enzymes involved in phase I reaction are the CYP450 family

Question 13

How does ethanol affect acetominophen metabolism?

Answer 13

Ethanol activates CYP2E1 –>
Increases the intermediate NAPQI –>
NAPQI is toxic to the liver

Question 14

What happens if you take omeprazole & cefpodoxime together?

Answer 14

Cefpodoxime is a prodrug that must get activated by the stomach acid’s low pH –> gains a hydrogen in this process and becomes a neutral/absorbable form

When omeprazole is given for acid-reflux, it increases the pH of the stomach and blocks this activation of cefpodoxime

This is an example of a drug that blocks another drug’s absorption

Question 15

Why should you not take NSAIDs with warfarin?

Answer 15

NSAIDs will compete for albumin –> knocks warfarin off of albumin –> increases free warfarin –> increased bleeding risk

Question 16

How does probenecid interact with penicillin?

Answer 16

Probenecid blocks the anion transporters that normally transport penicillin across the nephron epithelial cells –> blocks the transport into urine –> accumulation of penicillin in the blood

Question 17

How does verapamil interact with digoxin?

Answer 17

Verapamil blocks inhibits the clearance enzyme that removes digoxin –> toxicity

Question 18

Fick’s law of diffusion

Answer 18

Question 19

Drugs must be _ enough to cross the BBB

Answer 19

Drugs must be hydrophobic enough to cross the BBB

Question 20

High Vd means:

Answer 20

High Vd:
* Drug can move out of the plasma and distribute to other tissues
* Drug is likely small and hydrophobic

Question 21

Low Vd:

Answer 21

Low Vd:
* Drug must stay in the plasma
* It is probably large and less hydrophobic

Question 22

How do we calculate the volume of distribution?

Answer 22

Vd = Q / Cp

Volume of distribution = dose/ plasma concentration

Question 23

Affect of plasma proteins on Vd?

Answer 23

Plasma proteins like to bind the drug and retain it in the plasma, lowering Vd

Question 24

As the concentration of drug decreases, the rate of clearance decreases; this describes _ order kinetics

Answer 24

As the concentration of drug decreases, the rate of clearance decreases: first order

Question 25

As the concentration of drug decreases, the rate of clearance remains constant; this describes _ order kinetics

Answer 25

As the concentration of drug decreases, the rate of clearance remains constant: zero order

Question 26

In first order the enzyme is (saturated/ not saturated)

Answer 26

In first order the enzyme is NOT saturated

Question 27

Drug half-life only applies to drugs cleared by _ order kinetics

Answer 27

Drug half-life only applies to drugs cleared by first order kinetics

Question 28

As Vd increases, clearance _

Answer 28

As Vd increases, clearance decreases

You have to be in the plasma to be cleared/excreted

Question 29

As Vd increases, clearance decreases, therefore half life _

Answer 29

As Vd increases, clearance decreases, therefore half life increases

Question 30

Equation for half life

Answer 30

Question 31

All drugs take _ half-lives to reach steady state concentration

Answer 31

All drugs take 4-5 half-lives to reach steady state concentration

Question 32

Equation for maintanence dose

Answer 32

Question 33

Equation for loading dose

Answer 33

Question 34

Relationship between Kd and potency

Answer 34

Lower Kd = higher potency

Question 35

What does Kd represent?

Answer 35

Kd = dissociation constant; it is the concentration of [s] that causes 50% receptor accupancy

Question 36

Question 37

Non-competitive antagonists are always (reversible/irreversible)

Answer 37

Non-competitive antagonists are always irreversible

Question 38

Competitive antagonists change (potency/efficacy)

Answer 38

Competitive antagonists decrease potency (curve shifts right)

Question 39

Non-competitive antagonists change (potency/ efficacy)

Answer 39

Non-competitive antagonists decrease efficacy

Question 40

Inverse agonists work on receptors that are _

Answer 40

Inverse agonists work on receptors that are constituitively active
* These receptors have agonist-independent activity
* Ex: histamine

Question 41

Equation for therapeutic index

Answer 41

Question 42

Equation for margin of safety

Answer 42

Question 43

A _ therapeutic index makes for a safer drug

Answer 43

A larger therapeutic index makes for a safer drug