Pharm 2 Lecture

Question 1

Bioavailability

Answer 1

the fraction of an administered drug that reaches the systemic circulation

Question 2

What bioavailability do IV drugs have?

Answer 2

100%

Question 3

What factors affect bioavailability?

Answer 3

First pass (hepatic) elimination
Solubility characteristics of the drug
Chemical Stability in the GI tract
Drug formulation (ex. extended release)

Question 4

First pass (hepatic) elimination

Answer 4

Via the portal circulation
The liver can metabolize or excrete (via bile) drugs such as nitro and thus limiting their bioavailability

Drugs with high first-pass metabolism must be given in higher doses (orally) or parentally

Question 5

Solubility characteristics of the drug

Answer 5

Too lipophilic and the drugs may be poorly absorbed; too hydrophilic and the drugs have difficulty passing through lipid cell membranes
(this is why commonly administered drugs are either weakly alkaline or weakly acidic)

Question 6

What drug is unstable in stomach acid?

Answer 6

Penicillin-G

Question 7

Biggest determinant of sieving coefficient

Answer 7

Degree of protein binding (NOT well correlated with molecular weight)

Question 8

Volume of Distribution

Answer 8

volume of fluid that is required to contain an entire drug in the critter’s body at the same concentration measured in a given “compartment” such as plasma, for example.

Vd = Drug in body (dose)/ Concentration at time zero in given compartment

Question 9

Drugs confined to the intravascular space have a ________ volume of distribution.

Answer 9

smaller

Question 10

Drugs that have extensive distribution outside the plasma appear to have a ______volume of distribution.

Answer 10

large

Question 11

What drugs have a large volume of distribution?

Answer 11

Ex. Digoxin, diltiazem, labetalol, meperidine, or nortriptyline

Question 12

Main ways to eliminate drugs

Answer 12

urine, bile, hepatic metabolism, lung/oxygenator expiration, artificial filtration (hemoconcentrator)

Question 13

Half-Life

Answer 13

time required for the concentration or amount of drug in a critter’s body to be reduced by 1/2; goes in both directions
(Assumes first order kinetics)

Question 14

First-Order Kinetics

Answer 14

The rate of drug metabolism and elimination is directly proportional to the concentration of free drug; proportion of the drug is metabolized per unit time

Question 15

Formula for 1/2 Life

Answer 15

F = A(1/2) ^ (t/h)

Question 16

90% of the steady-state drug concentration is achieved in how many 1/2 lives

Answer 16

3.3 half lives

Question 17

Clearance Equation

Answer 17

Cl = (0.693 x Vd) / (Half-life)

Question 18

Zestil (Lisinopril)

Answer 18

commonly used angiotension-converting enzyme inhibitor; first-order elimination
Half-life: 12 hours
Distribution appears to be limited to the intravascular space

Question 19

Zero-Order Kinetics

Answer 19

they are eliminated by a constant amount over time because they’ve overwhelmed clearance mechanisms

Question 20

Target Concentration

Answer 20

The drug concentration that will produce the desired therapeutic effect

Question 21

Loading Doses

Answer 21

particularly important with drugs that have long half-lives

Loading dose = Vd x Target plasma concentration/ Bioavailability %

Question 22

Maintenance dose equation

Answer 22

Maintenance dose = dosing rate x dosing interval

Question 23

Maintenance dosing rate Equation

Answer 23

(CI x Target Plasma Concentration)/ Bioavailability %

Question 24

What does Biotransformation accomplish?

Answer 24

Lipophilic drugs tightly protein-bound and thus unavailable for excretion by the kidneys

shorten drug’s 1/2 life
Convert into active form
Reduce activity

Question 25

What happens if you biotransform a drug into a more polar molecule?

Answer 25

Greatly decreases its activity
Less protein bound –> more readily filtered
Decreases half-life

Question 26

Where does biotransformation occur?

Answer 26

Liver, Intestine, Lungs, Skin

Question 27

Two Main Biotransformations

Answer 27

Phase I

Phase II

Question 28

Phase I Biotransformation

Answer 28

Metabolize the drug into a more polar form

Question 29

Phase II Biotransformation

Answer 29

Conjugates the drug with another chemical (such as acetylation)

Question 30

How does the liver (and GI) biotransform drugs?

Answer 30

Cytochrome P450 Complexes

Question 31

Cytochrome P450 Complex

Answer 31

A large family of heme-containing enzymes with enormous genetic variation

Question 32

Induction

Answer 32

Drugs/chemicals make the Cytochrome P450 systems more active by increasing rate of synthesis or decreasing rate of degradation

Question 33

Induced P450 Enzymes

Answer 33

Metabolize drugs faster

Question 34

Inhibited P450 Enzymes

Answer 34

Metabolize drugs slower

Question 35

How much of US health care dollars go toward drugs?

Answer 35

1/8

Question 36

How much did drug companies spend in lobbying dollars in 2013?

Answer 36

A quarter of a billion lobbying dollars

Question 37

What are the stages of drug development?

Answer 37

In vitro studies (2 years)
Animal testing (2 years)
Clinical testing (4-5 years)
marketing (11 years)

Question 38

After how many years does a patent expire after filing of application?

Answer 38

20 years

Question 39

After how many years of making a drug does the generic become available?

Answer 39

20 years

Question 40

Phase I Clinical Trials

Answer 40

20-100 Subjects

Is it safe? Pharmacokinetics?

Question 41

Phase 2 Clinical Trials

Answer 41

100-200 Subjects

Does it work in patients?

Question 42

Phase 3 Clinical Trials

Answer 42

1000-6000

Does it work? Double clind

Question 43

Phase 4 (Marketing)

Answer 43

Postmarketing surveillance

Question 44

After how many years of making a drug is the point of having an “investigational new drug”

Answer 44

4 years

Question 45

When is the NDA (new drug application)?

Answer 45

8-9 years

Question 46

Who oversees drug trials?

Answer 46

FDA