Pharmacology principles

Question 1

Therapeutic Window

Answer 1

range of plasma concentrations needed to obtain optimal therapeutic effects =Toxicity-MEC

Question 2

MEC

Answer 2

minimum effective concentration

min plasma conc that produces the desired effect

Question 3

percutaneous administration

Answer 3

through the skin (abs limited by keratinous layers of skin)

slow, sustained absorption

patches, ointments

lipid soluble drugs penetrate better

Question 4

Sublingual (SL)

Answer 4

warm, moist, vascular area allows for more rapid absorption (Compared to PO)

bitterness of most drugs is limiting

Question 5

Oral (PO)

Answer 5

most common way
Most drugs absorbed in SI, must pass THRU cells
highly variable absorption and then have to deal with inactivation and first pass metabolism
can be recalled

slow absorption (esp for water solubles)

Question 6

Subcutaneous injection

Answer 6

Inject into low blood flow regions = slow absorption and sustained action

good for lipid soluble and depot injections

especially good for delivery of proteins (insulin and antibodies)

Question 7

Intramuscular injection

Answer 7

fenestrated capillaries allow for rapid absorption
water solubles are especially rapidly absorbed

good for depot (PCN G), allows for oily or particulate matter

Question 8

Plasma compartment

Answer 8

4L

drugs that are very large or protein bound

Question 9

Extracellular fluid compartment

Answer 9

14L

small drugs that can cross into the interstitium and hydrophilic enough to not diffuse into cells

Question 10

Total body water

Answer 10

42L

drug that is small and hydrophobic enough to cross into cells (approximates total body water)

Question 11

redistribution

Answer 11

after a single dose, drug has been completely absorbed, and on a second pass the plasma conc is lower than tissue conc, causing the drug to flow back down the CG into the plasma again

Often occurs in highly lipid soluble drugs destined for the CNS (d/t high blood flow)
=fast onset and fast offset (think thiopental)

Question 12

lipid/water partition coefficient

Answer 12

conc of drug absorbed in lipid phase/water phase
measure of solubility
>1=lipid soluble= ABSORBED RAPIDLY
<1= water soluble

Question 13

effect of a pH below the pKa of a weak acid

Answer 13

low pH= high H+= more associated drug (un-ionized form)= increased lipid/water=increases rate of absorption

Question 14

effect of a pH below the pKa of a weak base

Answer 14

low pH=high H+= more associated drug (ionized)= decreased lipid/water= decreases rate of absorption

Question 15

Efficacy

Answer 15

i.e. maximal effect or intrinsic activity of an agonist drug
Full agonist= produce maximal response
partial agonists have less intrinsic activity and therefore do not reach maximal effect

Question 16

potency

Answer 16

i.e. affinity
the amt of drug needed to obtain a particualr effect
higher affinity=more potent= lower ED50

Question 17

slope of LDR

Answer 17

drugs may work under different mechanisms

steeper= less biological variation, but may increase risk of adverse events

Question 18

Quantal response

Answer 18

catagorical data, yes or no

think sleep, or pain relief etc

large population trials, allows you to calculate LD50 and TD50

Question 19

TD50

Answer 19

specified effect produced in 50%of population at that dose (quantal doses only)
or dose that produces 50% of maximal response

Question 20

Therapeutic index

Answer 20

measures the relative safety of a drug
TD50/ED50
drugs with high TI are generally safer

Question 21

selectivity

Answer 21

drugs are NOT specific, but that can be selective for multiple receptor subtypes and have higher affinity for certain ones

i.e. B1 vs B2 receptors in bronchial smooth mm. and cardiac mm respectively

Question 22

antagonists

Answer 22

have effect but no action or efficacy bc they lack intrinsic activity

Question 23

competitive antagonism

Answer 23

“blockers”
prevent agonist binding
increases the conc of agonis needed to see effects (LDR and ED 50 shift right), but shape of curve (i.e. max effect are the same)

high conc of agonist can overcome blockade

can be used to treat OD of an agonist

Question 24

Noncompetitive antagonism

Answer 24

bind irreversibly
low doses shift the LDR right and decreases max effect

prolonged effects