Week 2: Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

What the body does to the drug

• absorption
• distribution
• metabolism
• excretion

Question 2

What is absorption

Answer 2

The rate at which a drug leaves the site of administration and passes into systemic circulation

Question 3

What is distribution

Answer 3

The transport of drugs in body fluids from the site of absorption to the receptor site on the cell, a storage site, and the elimination site

Question 4

How is the drug broken down after distribution?

Answer 4

Metabolism - the drug may be biotransformed through metabolism by the liver or the tissues

Question 5

How does the drug leave the body?

Answer 5

Excretion - the drug and its metabolites are eliminated from the body in urine, bile, or feces

Question 6

What are some factors that can impact pharmacokinetics

Answer 6

Age, preganancy, hepatic or renal disease, drug interactions, ethnicity, the rate of metabolism, GI surgeries, nutritional status

Question 7

Factors that can affect bioavailability of a drug

Answer 7

• how a drug is transported across the membrane
• how a drug interacts with the gastric acid and enzymes in the GI tract
• drug formulations - particle size, the salt form, the crystal polymorphisms, enteric coatings, what binders were used by the manufacturer - influences how a drug dissolves in the system
• *#1 factor that affects bioavailability of a drug - route of administration**

Question 8

The rate at which the drug leaves the site(s) of administration and passes into systemic circulation

Answer 8

absorption

Question 9

What is bioavailability?

Answer 9

measure of how much of the drug gets absorbed and into systemic circulation (blood)
F value = fraction of unchanged drug that reaches systemic circulation
F value = 0.25 this means that 1/4 of the dose get to systemic circulation

Question 10

3 factors that increase absorption and distribution of a drug

Answer 10

1) Lipophilic
2) Low protein binding
3) Low molecular weight

Question 11

3 factors that decrease absorption and distribution of a drug

Answer 11

1) Hydrophilic
2) High protein binding
3) High molecular weight

Question 12

A molecule that is un-ionized, uncharged, non-polar is considered:

Answer 12

lipophilic - are more lipid soluble allowing for increased absorption

Question 13

A molecule that is ionized, charged, polar is considered:

Answer 13

hydrophilic

Question 14

Where is a basic drug absorbed?

Answer 14

In the more basic environment of the small intestines

Question 15

Where is an acidic drug absorbed?

Answer 15

In the more acidic environment of the stomach

Question 16

What is the first pass effect?

Answer 16

Drugs taken orally are absorbed and goes into portal circulation/liver where is may be extensively metabolized before reaching systemic circulation - decreased the bioavailability of oral drugs - limits the efficacy of many oral medications

Question 17

What affects distribution of a drug?

Answer 17

• cardiac output & local blood flow
• capillary permeability
• Tissue volume
• amount of the drug that become bound to plasma and tissue proteins
• relative lipophilicity of the drug

Question 18

What is Volume of Distribution (Vd)?

Answer 18

The measure of the apparent space in the body available to contain the drug - theoretical - lipophilic drugs will have a larger Vd (larger concentration in the tissues) - hydrophilic drugs will have a smaller Vd (higher concentration in the plasma because it cannot pass as readily into the tissues/cells)

Question 19

Properties affecting distribution

Answer 19

• molecular size (large MW - lower distribution; small MW - greater distribution)
• Lipid solubility
• pH of the environment - acidic stays ionized in a basic environment - basic stays ionized in an acidic environment
• Ionization - polar molecules are hydrophilic
• Protein binding - albumin - drug bound to protein is inactive - only unbound drug is active and can exert an effect

Question 20

Your patient has had HTN for 5 years and has been taking an anti-hypertensive that is 90% protein bound since his diagnosis without any ADR. Recently, he was diagnosed with a DVT and started on Warfarin which is 99% protein bound. What will happen to his blood pressure?

Answer 20

Because Warfarin has a higher affinity to be bound to protein, more of the free antihypertensive medication in the plasma causing the patient’s blood pressure to drop significantly. (went from 10% free HTN medication to 99% free HTN medication)

Question 21

What enzymes are responsible for Phase 1 drug metabolism?

Answer 21

CYP450 (cytochrome P450)

Question 22

What is happening during Phase 1 of drug metabolism?

Answer 22

Oxidation (lose an electron), reduction (gain an electron), and hydrolysis (making something hydrophilic more hydrophilic) - oxidation is the most common enzyme reaction in Phase 1

Question 23

What do oxidation, reduction and hydrolysis do to a drug?

Answer 23

prepares the drug for further metabolism by making it more polar - this can increase or decrease the pharmacologic activity of a drug

Question 24

What P450 enzyme is responsible for metabolizing close to 50% of drugs?

Answer 24

CYP3A4

Question 25

Phase 1 enzymes are responsible for:

Answer 25

the first pass effect

Question 26

What is a prodrug?

Answer 26

An inactive drug that must go through the first pass effect in order to be activated - examples: Codeine and Plavix

Question 27

If a drug is a CYP 450 inducer, what could it do to another drug that is also processed by the same enzyme?

Answer 27

the inducing drug causes an increase in the rate of metabolism of the first drug, causing the first drug to be less effective

Question 28

If a drug is a CYP 450 inhibitor, what could it do to another drug that is also processed by the same enzyme?

Answer 28

The inhibiting drug causes a decrease in the rate of metabolism of the first drug, causing an increase in the concentration of the first drug in the blood because it is not being metabolized as quickly - causes the first drug to hang around longer in systemic circulation

Question 29

Your patient is taking an ace inhibitor which is a CYP3A4 substrate. She volunteers at a homeless shelter and recently contracted TB from working there. She was started on Ryfampin which is a CYP450 inducer. What will this drug-to-drug interaction cause to happen?

Answer 29

The metabolism of the ace inhibitor will be increased, which will cause it to be used up more quickly and will have decreased effectiveness, causing the patient’s blood pressure to go up (LESS DRUG=LESS EFFECTIVE)

Question 30

Your patient is currently taking an antihypertensive medication that is a CYP3A4 substrate. He goes to the gym and gets a severe case of athlete’s foot. He is prescribed Econazole which is an CPY3A4 inhibitor. What will this drug-to-drug interaction cause to happen?

Answer 30

The metabolism of the antihypertensive will be decreased which will cause an increase in the concentration of free antihypertensive medication in the bloodstream leading to a potentially significant drop in the patient’s blood pressure or hypotension. (MORE DRUG=MORE EFFECTIVE)

Question 31

What happens during Phase II of drug metabolism?

Answer 31

a conjugation reaction in which something is added to the drug to synthesize it into a new compound which will make it easier to excrete.

Question 32

The proximal tubule of the kidney is the site of elimination for:

Answer 32

Drugs with low molecular weight including conjugated metabolites, many of which are produced by phase 1 and phase 2 metabolism in the liver

Question 33

What types of drugs are reabsorbed in the kidneys back into the blood stream?

Answer 33

Lipophilic drugs

Question 34

You are working in the ER and a patient presents with a heroin overdose. Heroin is an acidic drug. What medication can be given in order to trap the heroin in the urine causing increase excretion?

Answer 34

Sodium bicarbonate - causes the urine to become more basic which traps acidic molecules of heroin in the urine. (ION TRAPPING)

Question 35

What medication can be given when you have a patient who has overdosed on a basic drug which causes the urine to be more acidic leading to increased excretion of the drug in the urine?

Answer 35

Ammonium chloride

Question 36

What things do you need to know about your patient in order to figure their creatinine clearance?

Answer 36

Weight in kg
sex
age
serum creatinine level

Question 37

The time it takes the peak drug level in the bloodstream to drop by half is known as the drug’s:

Answer 37

Half life

Question 38

At what level of creatinine clearance should you start thinking about the need for dosage adjustments because of decreased kidney function?

Answer 38

Less than 50mL/min - at or less than 30mL/min would definitely need dosage adjustment or possibly not giving that drug

Question 39

What is steady state?

Answer 39

steady state is reached when the rate of drug elimination is equal to the rate of drug administration such that plasma and tissue levels remain relatively constant

Question 40

How many half lives does it take to reach steady state?

Answer 40

4 to 5

Question 41

What can be done in order to reach steady state faster?

Answer 41

Give a loading lose (ex.: Z-pack - 500mg on day 1 and then 250mg on days 2-5)