Pharm Lec 1

Front 1

What is determined in pre-clinical phase of drug development?

Back 1

250 compounds tested in animals- how boes body handle drug (kinetics)? what is best route delivery?

Front 2

Phase I drug trial

Back 2

20-100 healthy volunteers-

Front 3

Phase II drug trial

Back 3

100-500 volunteers w/ disease of interest

Front 4

Phase III drug trial

Back 4

1000-5000 volunteers- to prove clinical significance

Front 5

How many years in Phase I, II, III?

Back 5

6 yrs

Front 6

Total process of drug discovery to approval takes how long?

Back 6

15 yrs

Front 7

1st pass metabolism means what?

Back 7

If drug has high first pass effect, then 1st place it reaches is where most elimination occurs

Front 8

Pre-systemic extraction means?

Back 8

metabolized by liver

Front 9

all drugs go via what pathway?

Back 9

oral med---intestinal tract---portal vein---liver---hepatic vein---systemic circulation---hepatic artery

Front 10

Define half-life?

Back 10

amt of time required for a therapeutic concentration of a drug to decr by 50% after discontinuation of drug

Front 11

Kinetics most impt for what type of drug?

Back 11

Antibiotics

Front 12

Does drug route affect t 1/2?

Back 12

No, drug owns its t 1/2 not the route

Front 13

Time to steady state requires how many half-lives?

Back 13

3-5

Front 14

TSS affects what?

Back 14

times that blood levels are drawn AND whether or not a loading dose is needed

Front 15

In continuous infusion model, which concentration will reach steady state first- 5mg/hr or 10g/hr?

Back 15

both concentrations reach steady state at same time

Front 16

Pharmacokinetics?

Back 16

What body does to drug!
Absorption/Metabolism/Distribution/Exretion

Front 17

Therapeutic drug monitoring examples?

Back 17

Digoxon, Procainamide
Aminoglycosides
tegretol, phenytoin
Amitryptylline, Imipramine
Heparin, Warfarin

Front 18

Factors influencing drug distribution?

Back 18

membrane permeability- ex BBB
plasma protein binding
depot storage- ex lipophilic drugs

Front 19

Carbidopa Levodopa example?

Back 19

Carbidopa does not cross BBB- but Levodopa does- so Levodopa crossed and broken down by decarboxylse into DA!

Front 20

Phase I drug metabolism?

Back 20

Oxidation to reduction to more polar forms- ex cytochrome P450

Front 21

Phase II drug metabolism?

Back 21

conjugation to a stable adduct

Front 22

Renal route of excretion 3 ways?

Back 22

glomerular filtration via diffusion; tubular secretion via transporter; tubular reabsorption via diffusion

Front 23

3 routes of drug excretion?

Back 23

Renal, Biliary, Exhaled

Front 24

Pharmacodynamics?

Back 24

What drug does to body- drug effect and mechanism of action

Front 25

Explain Beta-agonist pathway?

Back 25

B receptor stimulated via G-protein signal transduction--which activates adenylate cyclase--which utilizes ATP to generate incr CAMP which produces bronchodilation, vasoconstriction--incr HR, incr BP

Front 26

What is Cockroft and Gault equation to estimate GFR?

Back 26

140-age(IBW)
___________ X 0.85 (female)
72 x serum Cr

Front 27

How do you adjust dose for renal function?

Back 27

by dose or frequency!

Front 28

Good GFR is :

Back 28

>50-90 100% dosing, q6hr

Front 29

CrCl 10-50 dosing guide

Back 29

50-75% dose/ q8-12hr

Front 30

CrCl < 10 dosing guide?

Back 30

50% dose/q24hr

Front 31

Category risk A

Back 31

no risk to fetus in 1st trimester

Front 32

Category risk D

Back 32

+ human fetal risk exists
benefit MAY outweigh risks in certain situations

Front 33

Importance of pharmacogenetics?

Back 33

to predict rapid metabolizers

Front 34

Pharmacokinetic is to ______ as Pharmacodynamic is to ______?

Back 34

kinetic-- absorption
dynamic--- metabolism

Front 35

Example of drug distribution interaction?

Back 35

Protein binding- Ex Phenytoin and Sulfonamice

Front 36

Example of drug excretion interaction

Back 36

competition for renal tubular secretion- Ex probenecid + penicillin

Front 37

Inhibition of 3A4 will_____
rapid onset, slow duration

Back 37

inhibit breakdown of drug therefore increasing drug concentration

Front 38

Additive

Back 38

A + B = AB
Ex ace inhibitor and beta blocker for decr BP

Front 39

Synergistic

Back 39

A + B = incr A + incr B
Ex gent and PCN for streptococcal endocarditis

Front 40

Digoxin and antibiotic reactions?

Back 40

digoxin is metabolized by bacteria in gut that Biaxin decreased === dig toxicity

Front 41

Name the major metabolizing enzymes and their location

Back 41

cytochrome P450: 1A2, 2C9, 2D6, 3A4
Liver, GI tract

Front 42

Most common enzyme involved in drug interactions?

Back 42

3A4

Front 43

Which interactions take longer? enzyme induction or inhibition?

Back 43

Enzyme induction take awhile to decr therapeutic effect of drug Ex 1-2 weeks

Front 44

Inducer leads to what side of therapeutic window?

Back 44

Not effective

Front 45

Inhibitor leads to what side of therapeutic window?

Back 45

Toxic

Front 46

name some common CYP450 inducers?

Back 46

Rifamycins (Rifampin)
NNRTIs (Efavirenz)
Anticonvulsants (tegretol, dilantin)

Front 47

name some common CYP450 inhibitors?

Back 47

protease inhibitors (Ritonavir)
azole antifungals (ketoconazole)
macrolide anx
grapefruit

Front 48

Grapefruit is _____ of what enzyme?

Back 48

Inhibitor of 3A4

Front 49

Common CYP450 substrates

Back 49

Statins (HMG-CoA reductase)
Sidenafil (Viagra)
Cisapride (arrythmias)
Terfenadine, Astemizole (antihistamines)