Pharmacology: Principles

Question 1

What is pharmacodynamics?

Answer 1

What the drug does to the body

Question 2

What is pharmacokinetics?

Answer 2

What the body does to the drug

Question 3

What can drugs target?

Answer 3

Enzymes (e.g. ACE inhibitors, aspirin, neostigmine)
Carrier Molecules (e.g. flavonoid – Pgp antagonist, digoxin)
Ion channels (e.g. verapamil - L-type calcium channel antagonist)
Receptors (e.g. benzodiazepine – GABA receptor agonist, adrenoceptor agonists and antagonists )
Structural proteins (e.g. Taxol – Tubulin “agonist”)
DNA (e.g. anti cancer agents like Doxorubicin)

Question 4

What are receptors?

Answer 4

Receptors are Protein molecules whose function is to recognise and respond to endogenous chemical signals.
Chemicals which mimic the endogenous signals (i.e. drugs) will also elicit an effect.

Question 5

What us an agonist?

Answer 5

molecule/drug that binds and activates the receptor

Question 6

What is affinity?

Answer 6

the tendency of a drug to bind to the receptor

Question 7

What is efficacy?

Answer 7

the tendency of a drug to activate the receptor once bound

Question 8

If the activation is 100%, namely each time a drug interacts with its target there is a response then the agonist is said to be a “full agonist”, If the activation is <100%, the agonist is said to be a ….

Answer 8

Partial agonists, which have lower efficacy than full agonists – even with maximal occupancy of receptors.

Question 9

What is EC50?

Answer 9

Effective concentration. The dose required for an individual to experience 50% of the maximal effect.

Question 10

What is ED50?

Answer 10

Effective dose. The dose for 50% of the population to obtain the therapeutic effect.

Question 11

What is the therapeutic index?

Answer 11

Therapeutic index = toxic dose (TD50)/ Effective dose (ED50)

Question 12

What therapeutic index does the ideal drug have?

Answer 12

A high one

Question 13

What is potency?

Answer 13

The amount of drug required to produce 50% of its maximal effects. Used to compare drugs within a chemical class (usually expressed in milligrams/kg).

Question 14

What is efficacy?

Answer 14

The maximum therapeutic response that a drug can produce (example: morphine vs buprenorphine)

Question 15

What is specificity?

Answer 15

Describes the capacity of a drug to cause a particular action in a population (for example, a drug of absolute specificity of action might decrease or increase, a specific function of a given gene or protein or cell type, but it must do either, not both).

Question 16

What is selectivity?

Answer 16

Relates to a drugs ability to target only a selective population i.e. a cell/tissue/ signalling pathway, protein etc in preference to others

Question 17

Do antagonists have efficacy and affinity?

Answer 17

Antagonist have affinity but zero efficacy (as they block the target activity)

Question 18

What are the two main types of antagonism?

Answer 18

Competitive, Non-competitive and Irreversible

Question 19

How does competitive antagonism work?

Answer 19

Competitive agonists compete with agonists for the receptor binding site.
The chemical structure of the agonist and competitive antagonist are often similar (lock and key hypothesis).
Antagonist binds to receptor in such a way as to prevent agonist binding
Competitive antagonism is surmountable – additional agonist can overcome the receptor blockade.

Question 20

How does non-competitive antagonism work?

Answer 20

Non-competitive antagonists either bind to a different receptor site OR block the chain of events “post” binding - acting “downstream” of the receptor.

Question 21

How does irreversible antagonism work?

Answer 21

Antagonist dissociates from the receptor only very slowly or not at all.
The antagonist forms covalent bonds with the receptor.
Irreversible antagonism is insurmountable – additional agonist cannot overcome the receptor blockade

Question 22

What is IC50?

Answer 22

Concentration of antagonist to inhibit 50% of the agonist maximal

Question 23

What is inverse agonism?

Answer 23

An agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist.

Question 24

What is tachyphylaxis?

Answer 24

(“rapid protection”): Reduction in drug tolerance which develops after a short period of repeated dosing (decrease in response). Not common. Often due to a lack of a co-factor.

Question 25

What is self-antagonism?

Answer 25

When a drug becomes antagonistic to its own effects

Question 26

What can cause loss of target sensitivity?

Answer 26

Change in receptors (become resistant to drug stimulation/conformational changes)
Loss of receptors (endocytosis)
Exhaustion of mediators (degradation/low re-expression level)
Increased metabolic degradation (higher concentration of drugs are needed)
Physiological adaptation (crosstalk between body systems, one takes over)
Drug transporters (drug removed from receptor sites)

Question 27

What is drug-drug interaction?

Answer 27

Altered pharmacologic response to one drug caused by the presence of a second drug

Question 28

What are the possible outcomes of drug-drug interaction?

Answer 28

Action of one or more drugs is enhanced
Development of totally new effects
Inhibitory effects on one drug on the other
No change

Question 29

What does pharmaceutical interaction mean?

Answer 29

Interaction prior to administration

Because of chemical or physical incompatibility/interaction
– Sodium bicarbonate and calcium
– Insulin is denatured by glucose
– Diazepam binds to plastics

Question 30

What does pharmacokinetic interaction mean?

Answer 30

Related to interactions within ADME (absorption, distribution, metabolism, and excretion)

Question 31

What are some possible mechanisms of pharmacokinetic interaction?

Answer 31

Absorption - one drug binding another
Decreased gastric emptying – metaclopramide
Chemical changes
– pH: Stability of drugs is often pH dependent: penicillin G is inactivated by sulphonamide (alkaline)
Oxidation/reduction
Loss of drug potency: e.g. tetracyclines are oxidised by riboflavin
Complex formation
Some drugs reduce circulation and may therefore reduce clearance and elimination E.g. alpha-2 agonists
Competition for binding sites on plasma proteins: Most are bound to albumin
Physical incompatibility: Insolubility

Question 32

What does pharmacodynamic interaction mean?

Answer 32

The action of one drug is altered by another due to interactions within receptor signalling

Question 33

What is summation interaction?

Answer 33

( 1 + 1 = 2)

When two drugs are administered together the effect seen is equal to the sum of the individual effects of each drug

Question 34

What is potentiation interaction?

Answer 34

(1 + 0 = 2)

When a drug or food increases the effect of another drug, but has no effect when administered alone

Question 35

What is synergism reaction?

Answer 35

(1 + 1 = 3)
When two drugs are administered together produce effects that are greater than would be produced if either drug were administered individually or would be seen with summative (additive) effects. This can be toxic or enhanced.