Pharmacology Introduction

Question 1

pharmacokinetics

Answer 1

effects of body on the drug (1. absorption 2. distribution 3. metabolism 4. elimination)

Question 2

pharmacodynamics

Answer 2

effects of drug on body (1. receptor binding 2. signal transduction 3. physiological effect)

Question 3

where do drugs come from?

Answer 3

natural: plant derived like digoxin, quinine, morphine or biologics like insulin or cytokines
semisynthetic: hydromorphone
synthetic: fentanyl

Question 4

Phase 1

Answer 4

i have a drug, it looks like it works in animals, im going to give it to 20-100 normals. Is it safe? What are its kinetics

Question 5

Phase 2

Answer 5

does the drug work? Im going to give it to 20-100 patients

Question 6

Phase 3

Answer 6

how well does it work? randomized trial with 100+ patients comparing it to something thats out there or to placebo

Question 7

phase 4

Answer 7

postmarket surveillance

Question 8

Overall process

Answer 8

you do some pre-clinical research and you develop a drug and test it in animals (average of about 18 months)
then you submit the IND
then you begin clinical trials and development (phase 1,2,3) and that takes an average of about 5 years
then you submit the NDA- takes an average of 2 years
then you can go to post-market surveillance

Question 9

Drug names

Answer 9

chemical (we don’t use)
non-proprietary (generic) (adopted)
trade/ proprietary name

Question 10

There are some naming conventions that we have like:

Answer 10

-olol = beta blocker
-mab = monoclonal antibody
but for the rest it can get confusing and a mistake can be made if medications sound or look the same SO use the adopted name AND the proprietary name AND write what the med is indicated for AND use tall-man letter to prevent confusion

Question 11

bioavailability

Answer 11

the amount of drug that reaches the blood

Question 12

bioavailability with IV

Answer 12

Given by IV- bioavailability = 100% because im squirting it right into your blood

Question 13

why do they say to put NTG under your tongue if you are having chest pain?

Answer 13

Because you have veins under your tongue that drain right into the systemic circulation (instead of going to the liver through first pass metabolism)

Question 14

factors that affect bioavailability

Answer 14

gastric emptying/ food
properties of the drug like dissolution and disintegration
dosage form (enteric coated formulations)
chemical formulation
first pass metabolism

Question 15

you take a pill and the first things that happens…

Answer 15

disintegration and this can be slowed by product formulation like sustained release with enteric coating

Question 16

then as it is doing this process, the second thing that happens is

Answer 16

it dissolves. and all the things that can affect solubility can affect it here:acidic pH for weak acids, water solubility, large particle size

Question 17

after the drug dissolves it can be…

Answer 17

absorbed

Question 18

and once the drug is absorbed it goes through…

Answer 18

first pass metabolism in the liver before it can reach your systemic circulation

Question 19

absorption can be slowed by

Answer 19

decreased gastric emptying,
increased ionized drug pyloroplasm
fast small intestine transit time
decreased mesenteric blood flow

Question 20

distribution

Answer 20

where in the body does the drug reside and what factors change that

Question 21

1 compartment model of apparent volume of distribution

Answer 21

put a pill in a bucket (the body), measure the concentration, and you can find the size of the bucket; we call it apparent because we arent buckets and in reality it is just theoretical

Question 22

how does vd work with regard to amount found in blood

Answer 22

large vd means that the drug doesnt reside in the blood (maybe it is in the ECM or the total body water/ fat). but the smaller the Vd the more you will find of that drug in the blood

Question 23

[drug mg/L] = s x f x dose (mg) / Vd

Answer 23

S = % of the drug that is not in salt form so if only 20% of the drug is actually drug because the rest is salt then that is .2
F = bioavailability- if we know things arent well absorbed we can correct for that; for IV f is always 1

useful for risk assessment

Question 24

1 compartment

Answer 24

immediate distribution

Question 25

2 compartment

Answer 25

slow distribution into a particular region

Question 26

half life is talking about what phase

Answer 26

the terminal elimination phase with the slope B because in the beginning we have absorption and distribution going on

Question 27

whats the difference between asking about half life and duration of effect

Answer 27

half life is asking a mathematical question. the clinical correlate is the duration of the effect

Question 28

what decides where a drug goes?

Answer 28

lipophilicity
protein binding
pH (development of charge)

Question 29

total body water =

Answer 29

.6 L/kg (4 in plasma, 10 in interstitial fluid, 28 in intracellular fluid)

Question 30

Sites of distribution

Answer 30

total body water (.6L/kg) (4 L in plasma, 10 in interstitial fluid, 28 in intracellular fluid), fat, soft tissue, bone

Question 31

Lipophilicity

Answer 31

some drugs live in fat, some drugs live in water

Question 32

octanol/water partition coeffecient

Answer 32

log P

Question 33

log d

Answer 33

log P at physiological pH

Question 34

Protein binding

Answer 34

some drugs are bound to proteins in the blood and when they are they cannot leave- they stay there in the blood
some drugs (acidic ones) like albumin; other basic drugs like alpha1-acid glycoprotein
change in protein concentration for drugs bound to protein can result in a dramatic change in biological effect by altering distribution

Question 35

pH and charge

Answer 35

charged molecules dont cross membranes well because membranes are fatty spaces and charges increase water solubility

Question 36

weak acids and bases can be affected by

Answer 36

pH, which can affect their movement through biological membranes