drug receptor interactions

Question 1

define pharmacokinetics and pharmacodynamics

Answer 1

PK=what the body does to the drug
PD=what the drug does to the body

Question 2

what is ADME

Answer 2

absorption, distribution, metabolism, elimination

Question 3

By what medium are most drugs excreted

Answer 3

urine=ary

Question 4

drugs with a large Vd (volume of distribution) are mostly

Answer 4

in the tissue

Question 5

if a drug is mostly in the plasma, what Vd does it have?

Answer 5

small

Question 6

what is a “large” Vd?

Answer 6

compared to a given body weight (volume - 70kg=70l), a few times bigger eg 500 l

Question 7

what’s the formula for Vd> volume of distribution

Answer 7

amount of drug in the body/drug plasma concentration

Question 8

what is a small Vd?

Answer 8

<10l

Question 9

why would a drug stay in the plasma?

Answer 9

binds to albumin or molecule is too big

Question 10

name some other proteins in teh plasma that drugs can bind to

Answer 10

lipoproteins globulin alpha1-acid glycoproteins

Question 11

how would you find out how much drug is in left in the body

Answer 11

Vd is known constant, take away how much drug is in the plasma and Bob is your uncle

Question 12

name 2 drugs with excessive protein binding

Answer 12

diclofenac 99.5% and mefloquine >98%

Question 13

what drugs bind to albumin

Answer 13

acidic salicylates, frusemide, warfarin, basic drugs

Question 14

what binds to alpha 1-acid glycoproteins

Answer 14

basic drugs - psychoactive drugs and propranolol

Question 15

explain why cessation of one drug such as warfarin could have an effect on the efficacy of another drug

Answer 15

polypharmacy - both drugs are extensively bound to a protein. When warfarin is ceased, the other drug suddenly binds to all the receptors, meaning there will be a lot less in the system

Question 16

what happens to bound drugs

Answer 16

not much. they stay hanging about in the person. not metabolised or excreted

Question 17

what are the 4 main classes of receptors

Answer 17

GPCR, ligand-gated, kinase-linked and nuclear receptors

Question 18

what’s the fastest type of receptor

Answer 18

ligand0 gated ion channels

Question 19

what ligands can bind to ligand-gated ion channels

Answer 19

GABA, aCh, glutamate, 5-HT(seratonin release), ATP

Question 20

where are there no slit junctions and what’s the implication

Answer 20

BBB, hydrophilic drugs and large molecules can’t get across

Question 21

how do you get a drug into the brain that can’t cross the BBB. what is this called

Answer 21

inject it into the CSF - intrathecal

Question 22

how many alpha helices in a ligand gated ion channel and which one opens when the ligand binds

Answer 22

4
2

Question 23

what happens to a GPCR when a ligand binds

Answer 23

G protein is activated - GDP->GTP. Alpha part dissociates and activates downstream signals such as ion channel mediation

Question 24

Which receptors are most associated with phosphorylation

Answer 24

protein kinases

Question 25

what sort of things does phosphorylation do

Answer 25

Opens ion channels
Activates enzymes
Regulates transporters
Controls gene transcription

Question 26

what is important about a phosphorylation cascade

Answer 26

the signal is amplified exponentially

Question 27

what are the majority of tyrosine kinase receptors activated by

Answer 27

growth factors
and cytokines, but less so

Question 28

name 2 tyrosine kinase pathways

Answer 28

MAPK and IP3/DAG

Question 29

what is a nuclear receptor

Answer 29

receptor in the nucleus. activated by small tiny molecules like steroids and estrogen. Drug is transported to the DNA and affects transcription

Question 30

what are cortisol thyroid and retinoid

Answer 30

intracellular ligands. bind directly to DNA ADJACENT to the area where the target genes are

Question 31

how does the transcription increase once eg thyroid has bound

Answer 31

coactivator proteins bind to the receptor’s transcription activating domain.

Question 32

what is it called when a person becomes acutely tolerant to a drug

Answer 32

tachyphylaxis

Question 33

name some desensitisation mechanisms

Answer 33

Beta-adrenoreceptors are internalised so they are no longer on the cell membrane
Depletion of signalling molecules
increased rate of drug metabolism

Question 34

Which sort of receptor is the most common drug target

Answer 34

GPCR