pharmacology II

Question 1

what is a drug?

Answer 1

any substance that brings about a change in biologic functions through its chemical actions

Question 2

what is a medicine

Answer 2

a subset of drugs used for selective, therapeutic effects

Question 3

what is a xenobiotic

Answer 3

chemicals not synthesized in the body

Question 4

absorption if affected by what four things

Answer 4

route of administration
blood flow
drug characteristics
cell membrane characteristics(diffusion or active transport)

Question 5

what are some drug characterisitcs

Answer 5

lipid or water soluble
size of molecule
formulation
concentration
acidity

Question 6

passive transfer methods

filtration

Answer 6

water soluble molecules small enough to pass through membrane channels

Question 7

passive transfer methods

simple diffusion

Answer 7

lipid-soluble drugs across lipoprotein membranes

***only non-ionized drugs are soluble in lipid

Question 8

specialized transport methods

Answer 8

active transport

facilitate diffusion

Question 9

what is bioavailability

Answer 9

the fraction of unchanged drug reaching the systemic circulation following administration by any route

Question 10

what affects bioavailability?

Answer 10

dissolving of drug in the GI tract

destruction of drug by the liver

Question 11

how much of a drug is bioavailable if delivered intravenously?

Answer 11

100%

Question 12

what two things are important determinants for determining dose to be administered to a patient?

Answer 12

distribution and clearance

Question 13

what is volume of distribution?

Answer 13

the measure of the apparent space in the body available to contain a drug
V=amount of drug in body/concentation

Question 14

volume of plasma

Answer 14

3L

Question 15

volume of extracellular space

Answer 15

14L

Question 16

volume of total body water

Answer 16

42L

Question 17

as the volume of distribution gets bigger the drug is more or less restricted?

Answer 17

more restricted because less of it is found through out the body thus a small concentation

Question 18

drugs with very high volumes of distribution have much higher concentrations in extra vascular tissue than where?

Answer 18

in the vasculature compartment

Question 19

drugs that are completely retained within the vasculature compartment would have a minimum possible volume of distribution equal to the blood component in which they are distributed. T/F

Answer 19

true

eg. 3.0L for a drug that is restricted to the plasma compartment

Question 20

if the volume of distribution is much greater than 40-50L, the drug is probably being concentrated where?

Answer 20

in tissues outside the plasma and interstitial fluid

Question 21

what is clearance

Answer 21

• the process of drug elimination form the body or from a single organ without identifying the individual processes involved
• clearance=rate of elimination/concentration of drug
• mL/min or L/hr

Question 22

t1/2 is =?

Answer 22

0.693 Volume of distribution/clearance

Question 23

how are drugs cleared?

Answer 23

urine (mostly)
feces(some)
lungs
salivary glands, sweat and hair (small amount)

Question 24

drug transporters

Answer 24

solute carrier (SLC) transporters ie OCTs and OATs
ATP binding cassestte (ABC) transport ie p-glycoproteins

Question 25

what do p-glycoprotiens do?

Answer 25

transports drug molecule from cells back into the intestinal lumen for excretion

Question 26

half life
time it take to eliminate 50% of drug
after 4.5 half-lives, how much remains assuming 1st order kinetics?

Answer 26

95%

t1/2-0.693 Vd/Cl

Question 27

zero order

Answer 27

a constant amount of drug is eliminated per unit time. The process that takes place at a constant rate INDEPENDENT of drug concentration involved in process
eg 100%->80%->60%->40%

Question 28

first order

Answer 28

the process that is DIRECTLY proportional to the drug concentration involved in process
eg. 100%->90%->81%->72%->64% or 5->2.5->1.25

Question 29

metabolism of drugs does what?

Answer 29

inactivates
makes it more hydrophilic
makes it less toxic
phase II can come before phase I

Question 30

what is phase I

Answer 30

oxidation, reduction and hydrolysis

phase I metabolites that are hydrophilic are excreted all others go to phase II

Question 31

what is phase II

Answer 31

Includes glucuronidation and glutathione conjugation thus making drug more hydrophilic

Question 32

cytochrome p450

Answer 32

heme containing enzyme primarily found in liver hepatocytes and small intestine enterocytes
-key for drug oxidation, biotransformation, and detox

Question 33

substrate

Answer 33

a drug that is the target of a particular enzyme

Question 34

inducer

Answer 34

increases the activity of a particular p450 enzyme and thus increases metabolism and clearance of a drug

Question 35

inhibitor

Answer 35

inhibits the activity of a particular p450 enzyme and thus decreases metabolism and clearance of a drug
-grapefruit juice

Question 36

types of conjugation of phase II

there are 7

Answer 36

glucuronidation
acetylation
glutathione
glycine 
sulfation
methylation
water conjugation

Question 37

factors that affect hepatic drug metabolism

Answer 37

microsomal enzyme inhibition of CYP450
microsomal enzyme induction
plasma binding protein(if bound won’t enter liver)
liver disease

Question 38

microsomes

Answer 38

purified liver endoplasmic reticulum
rough microsomes contain ribosome
smooth microsomes contain mixed function oxidases

Question 39

smooth microsomes

Answer 39

NADPH-cyp450-oxidoreductase

Cyp450