Pharmacodynamics

Question 1

PIP pathway

Answer 1

GTP-alpha turns on PLC which cleaves PIP2 into DAG and IP3. IP3 is water soluble and leads to increased Ca+2 release and contraction. DAG leads to PKC becoming active and phosphorylation which causes contraction and is the lipid soluble pathway

Question 2

P glycoprotein role

Answer 2

1. eliminate drugs from the brain
2. reduce GI absorption
3. excrete drugs in bile and urine

Question 3

constitutive activity

Answer 3

occurs when concentration of receptors becomes very high (artificial expression/tumors)

Question 4

cooperativity graph shape

Answer 4

dose-response curve has S shape

Question 5

tachyphylaxis

Answer 5

decline in response when drug is applied acutely in repeated fashion

Question 6

desensitization

Answer 6

receptor mediated, high doses of drugs applied continuously –> waning response

Question 7

what desensitizes GCPRS

Answer 7

GRKs phosphorylate cytoplasmic tail, binds beta arrestin –> desensitization and internalization

Question 8

3 determinants of drug movement across barriers

Answer 8

type of membrane, specialized transport mechanisms and physico-chemical property of drug

Question 9

sinusoidal v. non sinusoidal capillary

Answer 9

non sinusoidal are continuous and have basement membranes, sinusoidal = discontinuous

Question 10

2 active transport proteins

Answer 10

SLC (uptake, secondary) and ABC (efflux, primary)

Question 11

2 types of ABC transporters

Answer 11

p-glycoprotein (MDR1), MRP1, important for ADE by pumping drugs out of cells, leads to cancer resistance by pumping out chemotherapeutic drugs

Question 12

3 types of SLC transporters

Answer 12

SLC0, SLC22, SLC6

Question 13

SLC transporters

Answer 13

no ATP used, do coupled transport using preexisting gradient

Question 14

absorption efficiency relative to pKa

Answer 14

weak acids = high pKa, weak bases = low pKa

Question 15

what has pharmaceutical equivalence

Answer 15

same active ingredient, identical in strength/concentration, dosage form, RoA

Question 16

bioequivalent

Answer 16

same rates and extents of bioavailability of the active ingredient

Question 17

bioavailability

Answer 17

fraction of administered dose of unchanged drug that reaches the systemic circulation (IV = 100%)

Question 18

where are acidic and basic drugs best absorbed

Answer 18

both best absorbed in small intestine, acidic in stomach as well

Question 19

factors affecting oral absorption

Answer 19

1. direct interactions
2. drug metabolism in gut/liver (first pass)
3. inhibition of transport

Question 20

what is grapefruit’s role in absorption

Answer 20

inhibits organic anion transport polypeptides to reduce absorption

Question 21

what is subcutaneous injection good for

Answer 21

similar to IM, suitable for insoluble suspensions and implantation of solid pellets but NOT for large volumes or irritating substances (IM)

Question 22

initial rate of drug distribution depends on…

Answer 22

local blood flow (organs receiving high blood flow get rapid distribution)

Question 23

what binds weak acids

Answer 23

albumin

Question 24

what binds weak bases

Answer 24

alpha-acid glycoprotein

Question 25

apparent volume of distribution

Answer 25

Vd = total amount of drug administered/plasma conc.

Question 26

2 reasons for drug metabolism

Answer 26

xenobiotic depletion, cometabolism