Patient: Channels, receptors and enzymes as drug targets Flashcards Preview

Pharmacy Year 2 Semester 1 > Patient: Channels, receptors and enzymes as drug targets > Flashcards

Flashcards in Patient: Channels, receptors and enzymes as drug targets Deck (39):
1

Define pharmacokinetics

What the body does to a drug

2

Define pharmacotherapeutics

The use of drugs to prevent and treat disease

3

Define pharmacodynamics

What the drugs does to the body

4

How does a drug produce an effect?

A drug interacts with (binds to) its target usually in/on a cell. Targets forms tight bonds with the drug dependent on the size, shape and stereo-specificity.

5

When a drug produces a response, what is it dependent on?

The type of target and what the target is linked to
Affinity - degree of attraction
Efficacy (intrinsic activity) ability to change target in a way that produces an effect

6

Target interaction is due to what 3 types of charge distribution?

ions
dipoles
van der Waals forces

7

What are ionic bonds dependent on?

Related to drugs being weak acids or bases
pH and pKa influence the degree of ionisation

8

What are dipoles due to?

Uneven distribution of electrons between atoms in molecules

9

What are van der Waals forces due to?

flexible movement of charge (electrons) through chemical groups

10

What are the 3 types of agonist?

Full, partial and inverse

11

What do agonists do?

They have affinity and they have efficacy
All bind to the binding site/active site

12

Name the 3 types of allosteric modulators

Positive, negative and neutral

13

What do allosteric modulators do and how do they do it?

Indirectly influence the binding of an agonist
Alter affinity and efficacy
Binds to a different site on receptor compared to the agonist

14

What do antagonists do?

They prevent agonist binding

15

Name the 4 types of binding of anatagonists

competitive
non-competitive
reversible (always competitive)
irreversible (competitive or non-competitive)

16

Reversible antagonists have what kind of bonds?

Short lived bonds - dissociates easily

17

Irreversible anatagonists have what kind of bonds?

Strong (covalent) bonds - does not dissociate

18

Name 4 types of target receptor

Ion channels
G-proteins
Protein kinases
Cytoplasmic/nuclear receptor

19

Opening of Na+ or Ca2+ ion channel causes...

the opening of Na+/Ca2+ channels cause further depolarisation
Ca2+ channels open
Increase in Ca2+
Hence increase in cellular activity

20

Opening of K+ channels causes...

hyperpolarisation
Ca2+ channels close
Decrease in Ca2+
Hence decrease in cellular activity

21

What does GTP stand for?

Guanosine triphosphate

22

How many lipophilic membrane domains does a GTP receptor have?

7

23

Describe how GTP coupled receptors work

Ligand binds to exterior section of the receptor
Interior section linked to G-protein
ligand binding changes conformation activates G-protein
G-protein linked to enzyme systems or ion channels

24

Describe how GTP coupled receptors work in terms of alpha, beta and gamma subunits

Receptor occupied by agonist
GTP hydrolysed to GDP
causes alpha and beta-gamma subunits to dissociate
alpha one binds to target 1
beta-gamma one binds to target 2
effect repeats if presence of drug still there

25

Describe how adenylyl cyclase works with G proteins

ATP becomes cAMP (catalysed by adenylyl cyclase)
cAMP can become 5'AMP via a phosphodiesterase
OR
cAMP can activate protein kinase A
this then leads to protein phosphorlyation and a change in Ca2+ concentration
Which then leads to biological response
OR the phosphorylated protein can be dephosphorylated by phosphatase enzyme

26

Give an example of a G-protein receptor
Gs-GTP

beta-adrenoreceptors

27

Differentiate Gs-GTP and Gi-GTP

Gs-GTP = stimulatory (activates adenylyl cyclase)
Gi-GTP = inhibitory (inhibits adenylyl cyclase)

28

Give an example of a G-protein receptor
Gi-GTP

opiod receptors

29

What about Gq-GTP?

Different enzyme - activates phospholipase C (PLC)
PLC-->inositol triphosphate (IP3)-->change in Ca2+ conc
then biological response
OR
PLC-->diacylgylcerol (DAG)-->activates protein kinase C-->protein phosphorylation-->biological response

30

Give an example of a Gq-GTP receptors

muscarnic receptors and alpha-adrenoceptors

31

Describe the Na+/K+ ATPase (Na+ pump)

3Na+ out of cell
2K+ into cell
Powered by ATP hydrolysis
Contributes to resting membrane potential

32

What kind of drug is digoxin?

cardiotonic
used in heart failure

33

How does digoxin work?

Blocks Na+/K+ ATPase
Increase in intracellular Na
Na+/Ca2+ exchanger stimulated
Increase in Ca2+
Increase in force of contractions

34

Give an example of a tyrosine kinase receptor

Insulin receptor

35

How does a tyrosine kinase receptor work?

Signal molecule binds
Dimerisation of receptor
Activate of tyrosine-kinase regions and phosphorlyation of the dimer.
Dimer goes on to phosphorlyate tyrosine molecules and activate inactive relay proteins via this mechanism

36

Give examples of nuclear receptor drugs

steroids and thyroid hormones (lipophilic drugs)

37

Name some illnesses associated with malfunctioning nuclear receptors

inflammartion, cancer, diabetes, cardiovascular disease, obestiy and reproductive disorders

38

describe speed of:
ligand gated ion channels
g protein coupled receptors
kinase-linked receptors
Nuclear receptors

Milliseconds
seconds
hours
hours-days

39

Look at dose response curves!

Okay