Drug mechanisms and actions

Question 1

What is a magic bullet?

Answer 1

A drug that has an affinity only for the intended target (molecule/ receptor) and has no affinity for normal body constituents

Question 2

Give examples of drug targets and some drugs that work on them

Answer 2

• Enzymes: ACE inhibitors, aspririn
• Carrier molecules: digoxin
• Ion channels
• Receptors: benzodiazepine (GABA)
• Structural proteins (e.g. tubulin)
• DNA

Question 3

What are dose response curves?

Answer 3

A graph where you plot the concentration of a drug (log) against its response.
Useful to compare drugs acting at the same target to assess the affinity, efficacy and margins of safety.

Question 4

Why do we use the log dose in dose response curves as opposed to linear?

Answer 4

Because in log it is easier to see when saturation occurs

Question 5

Describe agonism

Answer 5

An agonist has AFFINITY and EFFICACY causing a biological response.
-Can have full or partial agonists

Question 6

What is the definition of efficacy?

Answer 6

The tendency of the drug to activate the receptor once it has bound

Question 7

What do EC50 and ED50 stand for?

Answer 7

• Effective concentration: concentration at which 50% of the maximal effect is achieved
• Effective dose: Dose for 50% of the population to obtain therapeutic effect

Question 8

How do you calculate the therapeutic index?

Answer 8

Divide the toxic dose by the effective dose

Question 9

What measures can used to evaluate a drugs strength and effectiveness?

Answer 9

• Potency and efficacy

Question 10

Define potency

Answer 10

Amount of drug needed to produce 50% of its maximal effects

Question 11

In terms of pharmacology what is the difference between specificity and selectivity?

Answer 11

• Selectivity relates to a drugs ability to target ONLY a selective population whereas….
• Specificity: capacity of a drug to cause an action WITHIN a population (target)

Question 12

Describe antagonism

Answer 12

-Binds to receptor but doesn’t activate it. i.e. they have affinity BUT 0 efficacy
-3 types:
Competitive
Non competitive
Irreversible

Question 13

What is competitive antagonism?

Answer 13

• Compete for the receptor binding site
• Structure= similar to the agonist
• Antagonist binds to receptor preventing agonist from binding
• It is SURMOUNTABLE: increasing conc of agonist can overcome it

Question 14

Which way does the dose response curve shift is you add a competitive antagonist?

Answer 14

To the right

Question 15

Describe non competitive antagonism

Answer 15

• They EITHER bind to a different receptor site which changes shape of the agonists binding site to it can’t bind
  OR
• blocks chain of events that occurs post binding(affects signalling pathways)

Question 16

What is irreversible antagonism?

Answer 16

• Antagonist dissociates from the receptor only very slowly or not at all.
• Antagonist forms covalent bonds with the receptor
• Irreversible antagonism = INSURMOUNTABLE

Question 17

Name some irreversible enzyme inhibitors

Answer 17

Aspirin

Omeprazole

Question 18

What is meant by an inverse agonist?

Answer 18

A drug that reduces the activation of a receptor- have a negative efficacy.

Question 19

What does IC50 mean? What is it used for?

Answer 19

• Concentration of antagonist to inhibit 50% of the agonists maximum effect
• Used to measure antagonist drug potency

Question 20

What is Tachyphylaxis?

Answer 20

Reduction in drug tolerance, develops after short period of repeated dosing (i.e. drug becomes less effective)

Question 21

List ways in which drug targets can become less sensitive

Answer 21

• Change in receptors: become resistant to drug stimulation
• Loss of receptors: endocytsosis
• Exhaustion of mediators
• Increased metabolic degredation ( high con of drug needed)

Question 22

What are the potential outcomes of drug-drug interactions?

Answer 22

• ENHANCEMENT of one or more drugs
• Development of NEW EFFECTS
• INHIBITORY effects on one or more drugs
• NO CHANGE

Question 23

What are the 3 mechanisms of drug interactions?

Answer 23

• Pharmaceutical (related to physiochemical poperties/ formulation)
• Pharmacokinetic (related to ADME)
• Pharmacodynamic (related to interactions within receptor signalling- antagonism, synergisms)

Question 24

What is meant by summation?

Answer 24

Two drugs administered together= the effect is equal to the sum of the individual effects of the drug (1+1=2)

Question 25

What is meant by potentiation?

Answer 25

Drug/ food increases effect of another drug BUT has no effect when given alone (1+0=2)

Question 26

What is meant by synergism?

Answer 26

2 drugs given together produce effects greater than would be seen if either drug given individually. (1+1=3)

Question 27

What affinity would a drug with low Km have?

Answer 27

High affinity