drug action

Question 1

what is a receptor and what does it do?

Answer 1

receptor in pharmacology is the term used for a class of macromolecules (mostly proteins) that are concerned specifically and directly with chemical signalling (signalling cascade)

Question 2

are there limitless receptors and where are receptors found?

Answer 2

no, there is only a finite numbers and found in or on cells

Question 3

How does high drug concentrations effect receptors?

Answer 3

they are saturable (as finite numbers of them so likely to get saturated)

Question 4

what does it mean by receptors should display stereoselectivity ?

Answer 4

it means that the receptors should only recognise one of the naturally occuring isomers of a ligand (D or L)

Question 5

what are the 4 receptor super families?

Answer 5

1. ligand - gated ion- channel receptors
2. G-protein-coupled receptors
3. kinase-linked receptors
4. nuclear receptors

Question 6

what is a drug target & general examples?

Answer 6

term for class of cellular macromolecules that drugs bind to and mediate chemical signalling
examples - receptors, ion channels, enzymes & transport proteins

Question 7

what is affinity?

Answer 7

the tendency of a ligand to bind to its receptor. selectivity of drug of one over another

Question 8

what is an agonist?

Answer 8

A ligand that binds to a receptor and alters the receptor state resulting in a biological response. (cellular response - like opening up a door)

Question 9

what is an antagonist?

Answer 9

A drug that reduces the action of another drug, generally an agonist. Many antagonists act at the same receptor macromolecule as the agonist. (like key that sits in key whole to prevent opening of door)
- they don’t do anything, just sit there preventing other agonist from binding

Question 10

what is a partial agonist?

Answer 10

An agonist that cannot elicit as large an effect (even with 100% receptor occupancy) as can another agonist acting through the same receptors in the same tissue (ability to open door half way - less efficacy. example = beta blocker)

Question 11

what is efficacy?

Answer 11

the tendency for an agonist to activate the receptor state resulting in a biological response

Question 12

what is drug potency?

Answer 12

An expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect (e.g., EC50).

Question 13

what is drug potency dependant on?

Answer 13

Dependent upon receptor (affinity, efficacy) and tissue (receptor numbers, drug accessibility) parameters

Question 14

what is a dose and how do you decide what the dose is?

Answer 14

specified quantity of drug administered once or at stated intervals. Doses can be relative to body weight (e.g., mg/kg).

Question 15

what value can we determine from the dose-response curve?

Answer 15

we can estimate EC50
(does required to get 50% of Emax)

Question 16

when can you correctly apply dose-response curve?

Answer 16

only in vivo or human clinical scenarios (NOT in context of in vitro or cellular assay)

Question 17

how does structure link to affinity?

Answer 17

structurally related drugs will have greater affinity than structurally dissimilair

Question 18

what can lead to drugs binding to off targets and cause appearance of adverse drug reaction?

Answer 18

when higher dose (leading to higher blood plasma concentrations)
- this is also because no drug will be completely specific to particular receptor or in it’s physiological action

Question 19

what is Hill-Langmuir model?

Answer 19

equation that models relationship between ligand concentration & receptor occupancy

Question 20

what does logarithmic scale of Hill-Langmuir look like?

Answer 20

initially increases and the curve forms an elongated S shape

Question 21

what is relationship between Ka and affinity of ligand for receptor?

Answer 21

lower Ka = greater affinity of ligand for receptor

Question 22

what are competition experiments and what happens in them?

Answer 22

another experiment to estimate affinity
- competitively inhibit standard radio ligand , this gives us measure IC50 (tells you how much drug needed to inhibit biological process by half) and you can plug into equation which gives important value, Ki (inhibtion constant)

Question 23

what is an example of a tricycline antidepressant and what are it’s targets & symptoms?

Answer 23

amitriptyline = has 2 targets - noradrenaline transporter & serotinin transporter

main mechanism = block reuptake of serotonin

symptoms = sedation, constipation & dry mouth
- symptoms caused by drug effect on off targets (higher dose = more likely to effect)

Question 24

what is pKi and what is it’s relationship with affinity?

Answer 24

• log Ki
  higher pKi = greater affinity

Question 25

Roughly, how many receptors need to be occupied by agonists to give maximal response and why?

Answer 25

only a small % as 1 agonist molecule can set off signalling cascade that is progressively amplified within cell

so only small % of occupied receptors are required for tissue response

Question 26

what is used to determine potency of agonists?

Answer 26

EC50 and Hill equation

Question 27

what is drug potency?

Answer 27

an expression of activity of drug, in terms of concentration or amount needed to produce defined effect such as EC50 for agonists

Question 28

what is EC50?

Answer 28

‘half maximal effective concentration’.
In a pharmacological context, this can be the concentration of a drug that is necessary to cause half of the maximum possible effect

Question 29

what does drug potency depend on?

Answer 29

receptor - affinity & efficacy
tissue - receptor numbers, drug accessibility

Question 30

what are partial agonists?

Answer 30

An agonist that in a given tissue, under specified conditions, cannot elicit as large an effect (even when applied at high concentration with 100% receptor occupancy) as can another agonist acting through the same receptors in the same tissue

Question 31

what is reversible competitive antagonism?

Answer 31

• The most common and most important type of antagonist action.
• The antagonist ‘competes’ with the agonist for the same binding site on the receptor
• The interaction between the antagonist and the receptor is reversible.

Question 32

How can you overcome reversible competitive antagonism?

Answer 32

you can add a bunch of agonists as this type of antagonism is surmountable - meaning if add enough agonists then overpowered

Question 33

what effect does reversible competitive antagonist have on agonist concentration-response curve graph?

Answer 33

the curve is shifted to the right - without a change in maximal response or change in slope (i.e. shape remains same)

Question 34

what is irreversible competitive antagonist?

Answer 34

• no matter how much agonist you put in, blockage remains

example = aspirin (on core drugs list)

Question 35

what is non-competitive antagonist?

Answer 35

when acts on alternative active site on same enzyme - allosteric site

Question 36

what are other ways of antagonism - not involving receptor?

Answer 36

• chemical antagonism (combining in chemical solution)
• physiological antagonism (2 drugs with opposite actions - cancel each other out)
• pharmacokinetic antagonism (reduces concentration of the active site in specific location)

Question 37

what is chemical antagonism?

Answer 37

the antagonist combines in solution directly with the chemical being antagonised (e.g., chelating agents, used to treat lead poisoning, bind to heavy metals and form a less toxic chelate).

Question 38

what is physiological antagonism?

Answer 38

Two agonists that produce opposing physiological actions and cancel each other out. Each drug acts through its own receptors (e.g., adrenaline relaxes bronchial smooth muscle reducing the bronchoconstriction of histamine)

Question 39

what is pharmacokinetic antagonism?

Answer 39

= type of antagonism that’s about how body affects drug - like absoprtion, metabolism, excretion etc (affects of drug A & B could interfere with excretion of the other)
The ‘antagonist’ reduces the concentration of the active drug at its site of action (e.g., phenobarbitone increases hepatic metabolism of the anticoagulant drug warfarin)

• drug basically jumps up action in liver, lowers blood plasma conc. messes around with other drugs, good examples are alcohol and epilepsy drugs (drug list for next year but not this year)
• makes it less efficacious

Question 40

what is example of non selective competitive antagonist?

Answer 40

propranolol

Question 41

what is non-selective partial agonist example?

Answer 41

pindolol