Exam I: Pharmacokinetics Flashcards Preview

Pharmacology > Exam I: Pharmacokinetics > Flashcards

Flashcards in Exam I: Pharmacokinetics Deck (50):
1

Why is pharmacokinetics important?

PROPER DRUG THERAPY!

1. Proper drug to be used
2. Route of administration (IV v. oral v. solution)
3. Dosing schedules

2

What are the 4 processes of pharmacokinetics?

ADME

Absorption (bioavailability)
Distribution
Metabolism (Biotransformation)
Excretion/Elimination

3

What is the difference between pharmacokinetic interaction and pharmacodynamic interactions?

Pharmacokinetic:
- The relationship between the DOSE and CONCENTRATION changes the outcome
- Pharmacologic effect has changed as a result in a change in DRUG CONCENTRATIONS

Pharmacodynamic:
- The relationship between the DRUG CONCENTRATION and EFFECT changes the outcome
- Pharmacologic effect has changed despite a lack of change in drug concentration

4

How is bioavailability determined?

Area Under Curve (AUC)

--> expressed as a percentage

5

What affects movement across cell membranes?

1. Lipid solubility
2. Passive/Active Transport
3. Ionization

6

If a drug is lipid soluble does it move freely though cell membranes or not freely though membranes?

Lipid soluble substance can move freely though cell membranes

Referred to as "non polar" substances

7

Passive Transport

Diffusion from higher to lower concentration

8

Active Transport

Going against the concentration gradient

Requires energy

9

Ionization: Non-ionized v. ionized

Ionized: poor solubility
--> because it is polar

Non-Ionized: can move across membranes
--> because it is non polar

10

What is the only administration method that bypasses absorption?

Intravenous (IV)

11

AUC

serum concentration v. time

12

Factors that effect the extent to which an orally administered drug reaches systemic circulation?

1. Absorption characteristics of drug and dose form

2. Amount of metabolism that occurs prior to drug reaching systemic circulation

3. Presence of interaction substances (drugs, food, type of food)

13

Hepatic First Pass Metabolism

Metabolism in the liver that occurs prior to drug reaching systemic circulation

14

Absolute Absorption

Comparing the AUC of a drug form to that in which there is "absolute" (100%) absorption

So you can compare it to IV dose form because it bypasses absorption

15

Relative Absorption

Comparing the AUC of two different drug forms of same compound

Ex: Tablet v. capsule

If comparing to a product with 100% (IV dose) then this would still be referred to as relative absorption

Can also use relative absorption to figure out bioavailability w/ and w/o food: AUC fasting/AUC food

16

How is Volume Distribution (Vd) determined?

After drug is administered, maximum concentration is measured and using the calculation:

Cp max = (Dose) / (Vd)

to get Volume Distribution

17

If a drug's Vd is small (<0.25) where is it likely to distribute?

Extracellular fluid (interstitial fluid + plasma/blood)

Stays in systemic system...not peripheral

18

If a drug's Vd is medium (0.55-0.7) where is it likely to distribute?

Extracellular fluid and intracellular fluid (both central and peripheral tissues)

Move freely in and out of central compartment

19

If a drug's Vd is large ( >0.7) where is it likely to distribute?

Distributed throughout body (peripheral tissues) and is NOT allowed to reenter central component

20

What is the relationship between Vd and drug's lipid solubility?

The higher the lipid solubility, the higher the Vd

21

What is the relationship between Vd and drug's protein binding?

WHY?

The higher the Vd, the lower protein binding a drug has

WHY?
When drug binds to blood proteins, they don't distribute as freely. They stay in central compartment

22

What is the relationship between Vd and drug's tissue binding ability?

The higher the Vd, the higher tissue binding occurs

23

Is second distribution phase faster or slower than the first?

Slower

24

Where is drug usually delivered in second distribution phase?

Muscle, skin, fat

25

What happens when a drug is highly lipid soluble and binds to adipose tissue?

Since there is low blood flow in adipose tissue, it acts as a drug reservoir and prolongs effects of drugs

Examples:
- Benzodiazepines
- Barbiturates
- Phenothiazines

26

What is a metabolite?

byproduct of the reaction in which enzymes modify the chemical structure of drugs.

Usually has less/no pharmacologic activity

27

What is the typical location of biotransformation (metabolism)?

The Liver

28

What is a prodrug?

a parent drug that has no activity but its metabolite does

29

Hepatic Biotransformation: Phase I Reaction

Introduction of functional groups to prepare for phase II reaction

-OH
-COOH
-SH
-O-
-NH

30

Name the 3 reactions of Phase I (hepatic biotransformation)

1. Oxidation (Most Common)

2. Reduction

3. Hydrolysis

31

Oxidation

Oxygen is added or removed

32

What are the enzymes that mediate oxidation?

Cytochrome P450 enzymes

33

CYP450 enzymes are sensitive to...

...substrates (drugs, alcohol, smoking)

...hepatic disease

...againg

34

Drugs, alcohol, smoking can act as _______, _______, or ________ of CYP metabolism.

Substrates

Inhibition

Induction

35

Enzyme Inhibition:

Decreases rate of metabolism of object drug by obstructing metabolizing enzymes

This leads to an INCREASE in drug concentration

INCREASED half-life, accumulation, and side effects/toxicities

Ex: Grapefruit juice, Tagamet

36

Enzyme Induction:

Stimulates the increase in CYP450 enzyme activity

INCREASE clearance of drug

DECREASE drug concentration

Ex: cigarette smoking, phenytoin

37

Prototype for enzyme inducers?

Phenobarbital

38

Define reduction

oxygen is removed or hydrogen is added

39

What occurs during phase II reactions?

Parent drug or metabolite is conjugated with:

- Glucuronic acid
- A methyl group
- An acetyl group
- Sulfate group

40

What type of enzymes conjugate metabolites during phase II reactions?

Transferases

41

What happens to metabolites after conjugated during phase II reactions?

Hint: polar, or non polar and what that means

Metabolite produced is more polar (less lipophilic)

This is likely to stay in blood stream (central compartment) and be available for excretion via kidneys

42

Location of excretion?

Kidneys

43

Describe the 4 steps (or processes) of excretion

1. Filtration
At glomerulus

2. Reabsorption
Less polar substances reabsorbed from tubule
Reenter systemic circulation

3. Secretion
Into tubules via active transport

4. Excretion
Drugs may be unchanged
After biotransformation in liver

44

Enterohepatic Recirculation

When small intestine takes off conjugation from phase II so that drug is reabsorbed and re-enters systemic circulation

Systemic circulation --> Liver --> Gallbladder --> Bile --> Small Intestine --> Systemic circulation
(repeat circle)

45

Besides the kidney, what are other ways a drug can be excreted?

1. Feces

2. Lungs

3. Skin

4. Breast Milk

46

Substrates excreted in feces are :

- unabsorbed orally ingested drugs

- drug metabolites excreted either in bile or secreted directly into intestinal tract and not reabsorbed

47

Substrates excreted in lungs are primarily:

anesthetic gases

48

List factors that affect the pharmacokinetic principles (ADME):

1. Age

2. Sex

3. Weight

4. Disease States (COPD for example)

5. Genetic factors (race for example)

49

Bound Drug v. Unbound (free) drug

Bound: drug is bound and inactive

Unbound (free): active drug

50

Factors that can affect absorption?

GI
pH
Chelatin bidning
Increase or decrease in motility
Changes in GI flora