Pharmacokinetics

Question 1

What does ADME stand for?

Answer 1

Absorption -> gets the drugs into the blood
Distribution -> where it goes in the body
Metabolism -> what happens to it
Excretion -> how it gets out

Question 2

Where does absorption take place?

Answer 2

stomach, blood, and small intestine

Question 3

How does absorption happen?

Answer 3

movement of drug from site of administration into the blood (passive diffusion)

Question 4

What factors influence absorption?

Answer 4

• concentration gradient
• size of the drug (smaller is better, so it can pass the lipid membrane)
• lipid solubility (to pass hydrophobic tail)

Question 5

How does charge effect lipid solubility and permeability?

Answer 5

Only uncharged molecules can passively diffuse across the lipid bilayer. This is because uncharged particles are hydrophobic, whereas charged particles are hydrophilic.

Question 6

What is the pH of the stomach and urine?

Answer 6

Stomach: 2
Urine:6

Question 7

Where does the drug know where to go?

Answer 7

It does not, it circulates through the blood and binds to the receptors that they have affinity for.

Question 8

What is distribution?

Answer 8

The process by which the drug reversibly leaves the bloodstream.

Question 9

What are the influencing factors?

Answer 9

• concentration gradient
• size
• lipid solubility
• blood flow
• protein binding

Question 10

How does blood flow influence distribution?

Answer 10

Blood circulates to drugs to the highest areas first. These are the heart, brain and other vital organs.
2nd = muscles, skin
3rd = fat

Question 11

How does protein binding influence distribution?

Answer 11

Plasma proteins like albumin attach to the drug at different degrees. This can decrease the therapeutic effect by trapping the drug. Additionally, since the plasma proteins are large, they make the small drug particle large too. This renders the drug pharmacologically inactive.

Question 12

What is an important consideration when formulating a drug?

Answer 12

Checking how much of the drug could potentially be trapped.

Question 13

What is metabolism? Where does it occur?

Answer 13

Irreversible biotransformation of the drug. It occurs primarily in the liver, but on rare occasions the lung or gut.

Question 14

How does metabolism transform the drug?

Answer 14

It makes the drug more polar to make excretion easier through the urine. (urine is mostly water, which is polar)

Question 15

What is Phase 1 metabolism?

Answer 15

Oxidization, reduction and hydrolysis occurs.

CYP 450 enzymes add or uncover chemical groups to increase solubility (-NH2, -OH, -SH).

Question 16

Inducers and inhibitors

Answer 16

inducers -> decrease therapeutic effect (alcohol and St. Johns Wart)
inhibitors -> decrease the rate of metabolic activity hence increasing the toxicity of the drug (grapefruit, or antibiotics)

Question 17

What is Phase 2 metabolism?

Answer 17

Various non-CYP 450 liver enzymes covalently add large, polar, endogenous molecules to the drug.

Question 18

After metabolism why cant the drug re-absorb?

Answer 18

It is large, polar, charged and has a changed shape.

Question 19

What is excretion?

Answer 19

Irreversible loss of drug or metabolite from the body

Question 20

Where does excretion occur?

Answer 20

through the urine, but sometimes in bile, feces and breastmilk.

Question 21

How does the metabolite move?

Answer 21

Active transport

Question 22

How do diseases affect ADME process?

Answer 22

GI tract -> vomiting, chrons diastase (decrease absorption)
Circulatory -> heart failure (decreases distribution)
Liver ->hepatitis, liver failure (decreases metabolism)
Kidney -> renal failure (decreases excretion)

Question 23

How are drug overdoses treated?

Answer 23

If the drug has not been absorbed you can induce vomiting or get the stomach pumped.
If the drug has already been absorbed, it can be forced out by the urine.

Question 24

If you have a weak acidic drug, how do you promote excretion?

Answer 24

Increase pH. This shifts the eq’m so there is more water soluble form. Sodium bicarbonate raises pH.

Question 25

If you have a weak basic drug, how do you promote excretion?

Answer 25

Decrease pH. This increases the amount go H+ available to form the ionized drug. Ammonium chloride drops pH.

Question 26

Designing a dose regimin curve

Answer 26

• Magnitude of therapeutic and toxic effect depends on drug dose
• Method of absorption and rate of metabolism affects how often the drug should be taken
• Cost, side effects and toxicity affect how long the drug should be taken for

Question 27

What does MEC stand for?

Answer 27

minimum effective concentration (minimum # of receptors needed to be effective)

Question 28

What does MTC stand for?

Answer 28

minimum toxic effect

Question 29

What is therapeutic range?

Answer 29

in between minimum toxic concentration in the body and min. effective concentration

Question 30

What is the difference between TR and TI?

Answer 30

therapeutic range is for drug concentration whereas therapeutic index is w/ respect to effect

Question 31

What are the non-dosing factors that impact response?

Answer 31

• Patient compliance
• drug interactions
• disease
• age
• genetics

Question 32

What is patient compliance?

Answer 32

3/4 of individuals are non-compliant with their medications

Question 33

What is primary compliance?

Answer 33

People are compliant in filling out their prescription

Question 34

What is secondary compliance?

Answer 34

If the drug is actually taken

Question 35

What factors prevent people from taking medication?

Answer 35

Side effect, cost, inability to open package, physical appearance of drug

Question 36

How does age affect ADME?

Answer 36

• as a child, pH of stomach is 4 and not 2. This means, drugs may not break down as readily and may accumulate to a toxic point.
• children have thinner skin -> ointments may absorb too much and become systemic
  METABOLISM: fully functional after 1.5 years of age
  EXCRETION: kidney function is only at 20% as a kid, and it works less efficiently in the elderly