Week 3

Question 1

What are the different types of drug receptors

Answer 1

Enzymes:
-cyclooxygenase; the aspirin receptor
Ion channels:
-Ca2+ channels blocked by nifedipine used to manage hypertension, angina, raynauds phenomenon
Transporters (pumps, transport proteins):
-noradrenaline transporter blocked by cocaine
‘Physiological’ receptors- receptors for hormones, neurotransmitters etc :
-acetylcholine, histamine, insulin etc

Question 2

Nomenclature around drugs

Answer 2

In pharmacology distinct words used for drugs depending on the effect they have on a certain receptor
E.g. -100% efficacy= full inverse agonist

Question 3

Ways of regulating cell function

Answer 3

Altered membrane potential
Altered enzyme activity
Altered gene expression
Most drugs affect cell function via physiological receptors

Question 4

What is agonism

Answer 4

How drugs produce effects by binding to receptors- various ways in which effects are produced

Question 5

What is antagonism and desensitization

Answer 5

How drugs block effects by binding to receptors- ways in which effects blocked or reduced

Question 6

Why are partial agonists worse

Answer 6

Reduced frequency of open channels

Question 7

What is a partial agonist

Answer 7

An agonist which is unable to induce maximal activation of a receptor population regardless of amount of drug applied
Lower efficacy than a full agonist

Question 8

What is a inverse agonist

Answer 8

Is a ligand that binds to the same receptor-binding site as an agonist and not only antagonises the effects of an agonist but also exerts the opposite effect by suppressing spontaneous receptor signalling
Have negative efficacy

Question 9

What is meant by allosteric effects on receptors

Answer 9

The allosteric modulation may result in slowing or inhibition of binding of ligands to the orthosteric binding site causing weakening of a signal or decreased activity

Question 10

Super-agonists

Answer 10

Highly efficacious agonists
Can produce a maximal response from the cell without binding to all of the available receptors
Emax for these then >100%

Question 11

Example of super-agonist

Answer 11

Goserelin (Zoladex) is a super agonist of the gonadotropin-releasing hormone receptor (GnRH-R).
It suppresses production of the sex hormones (testosterone and oestrogen) particularly in the treatment of breast and prostrate cancer

Question 12

Example of partial agonist

Answer 12

Buprenorphine is an opioid used to treat opioid addiction, moderate acute pain and moderate chronic pain

Question 13

What are competitive antagonists

Answer 13

Bind reversibly at the same site as the (natural) agonist doesn’t activate it, blocks action
Produce a parallel shift to the right of agonist dose/response curves
Need a higher concentration of agonists to get same effect

Question 14

What are irreversible antagonists

Answer 14

Bind irreversibly at the same site as the agonist, forming a covalent bond or binding incredibly tight
Decrease maximal response to agonists
May produce an initial shift to the right of the dose/response curve with no decrease in max
Evidence for spare receptors

Question 15

What are allosteric antagonists

Answer 15

Rare
Bind reversibly at a distinct site from agonist and decrease agonist affinity
Reduce likelihood of agonist binding

Question 16

What are channel blockers

Answer 16

Bind inside the channel and prevent passage of ions
Binding of channel blockers tends to be enhanced by receptor activation
Use dependence

Question 17

What are physiological antagonists

Answer 17

They antagonise the physiological effect of some agonists but via different mechanism. Opposite effect of agonist, will indirectly oppose action of agonist
Several substances that have anti-histaminergic action despite not being ligands for the histamine receptor are physiological antagonists to histamine

Question 18

What are the classes of antagonists

Answer 18

Competitive antagonists
Irreversible antagonists
Allosteric antagonists
Channel blockers
“Physiological antagonists”

Question 19

How are receptors classified

Answer 19

On the basis of the selective action of drugs
They’re named according to the transmitter or hormone with which they interact

Question 20

What are the receptor super families

Answer 20

Integral ion channels e.g. Nicotinic receptor glycine receptor
Integral tyrosine kinases e.g. insulin receptor
Steroid receptors =nuclear receptors e.g. oestrogen receptor, androgen receptor
G protein coupled receptors e.g. muscarinic receptors, adrenoreceptors
Cytokine receptors e.g. prolactin receptor

Question 21

Nuclear receptors

Answer 21

Act in the nucleus but most often located in the cytoplasm
Their ligand binding domain functions like a folding sensor. Without steroid ligand its unfolded and with steroid its folded
The DNA binding domain mediates binding of nuclear receptors to thousands of sites within genome

Question 22

What can be a drug receptor

Answer 22

Anything that a drug binds to, to produce its pharmalogical effect

Question 23

How does asparaginase act

Answer 23

As a medication, L-asparaginase is used to treat acute lymphoblastic leukaemia, acute myeloid leukaemia, and non-Hodgkin’s lymphoma. It’s given by injection into a vein, muscle or under skin

Question 24

What is toxicology

Answer 24

The study of the unwanted or deleterious effects of drugs or chemicals on the body

Question 25

What does the distribution of drugs into CNS usually depend on

Answer 25

Lipid diffusion

Question 26

What can competition between two drugs for binding to plasma proteins result in

Answer 26

Change in concentration of free drug and potential drug toxicity

Question 27

When considering absorption of drugs weakly basic drugs have a higher solubility at

Answer 27

Lower pH

Question 28

At which stage of drug development can it first be proved that a drug is effective

Answer 28

Phase II trials