Basic Principles

Question 1

What is pharmacology?

Answer 1

the study of the effects of drugs on the function of living systems

Question 2

What is a drug?

Answer 2

a substance of known chemical structure which when administered to a living organism produces a biological effect

Question 3

What is pharmacodynamics?

Answer 3

the study of how drugs work

Question 4

What is the general principle of a drug?

Answer 4

A drug will not work unless it is bound

Question 5

What can drugs target?

Answer 5

receptors, enzymes, ion channels, transporters and other miscellaneous targets i.e. DNA

Question 6

How might a drug target a receptor?

Answer 6

It may be an agonist - which initiates a biological response

It may be an antagonist - which has no effect but blocks the endogenous modulator

Question 7

How might an agonist work on a receptor?

Answer 7

Directly or Indirectly

Question 8

How might an agonist work directly on a receptor?

Answer 8

Ligand binding ion channels

Enzyme activation or inactivation

Question 9

How might an agonist work indirectly on a receptor?

Answer 9

Through transduction mechanisms
Through ion channel modulation
DNA transcription

Question 10

How might a drug target an ion channel?

Answer 10

Blockers- blocking the ion channel

Modulators - increasing or decreasing the permeability of an ion - i.e. NMDA receptor is blocked by MK-801

Question 11

How might a drug target enzymes?

Answer 11

Inhibition - inhibiting the normal reaction
False substrate - causing an abnormal metabolite to be produced
Pro-drug - drug is administered in an inactive form and the active form is produced by the enzyme

Question 12

Give an example of a drug which targets an enzyme

Answer 12

Monoamine Oxidase Inhibitor B - Selegine
MAOs metabolise monoamines such as dopamine, serotonin and noradrenaline
MAO-B Inhibitor is used in the treatment of Parkinson’s to prevent the metabolism of dopamine and phenylethylamine

Question 13

How might a drug target transporters?

Answer 13

Inhibitors can attack the same site or an allosteric site blocking transport

Question 14

Give an example how a transporter might be blocked and how it might be used

Answer 14

Uptake 1 inhibitors - the re-uptake of neurotransmitter is known as uptake 1 and may be blocked, such as in anti-depressants to maintain higher levels of neurotransmitter in the synapse

Question 15

What is a receptor?

Answer 15

Any cellular assembly (target molecule) that a drug molecule binds to in order to elicit a specific response

Question 16

What is the difference between affinity and efficacy?

Answer 16

Affinity is the ability of the drug to bind to a receptor

Efficacy is the ability of the drug to elicit a biological response once bound - agonists only

Question 17

What is a full agonist?

Answer 17

A full agonist has maximal effects and high efficacy

Question 18

What is a partial agonist?

Answer 18

A partial agonist has sub maximal effects and medium efficacy

Question 19

What is an antagonist?

Answer 19

Antagonists have no efficacy and do not exert an effect on the receptor other than to block it

Question 20

What is agonist potency?

Answer 20

How strongly an agonist can exert its effects can be used in comparison to other agonists when choosing drugs

Question 21

What kind of antagonists are there?

Answer 21

competitive - binds to same site as agonist
non-competitive - binds to an allosteric site
reversible - binds non-covalently
irreversible - binds covalently

Question 22

Give an example of a reversible competitive antagonist and its actions

Answer 22

Propanolol (decreases BP, B-blocker) is an antagonist of isoproterenol (increases HR and works on B-adrenoceptors)
The maximum response is not changed however there is a shift right in the dose-response curve as more agonist is needed.

Question 23

Give an example of an irreversible competitive antagonist and its actions

Answer 23

Naloxone is used in opioid overdose

The EC50 is not affected however the maximal effects are as an increase in agonist will not overcome this.

Question 24

Give an example of a reversible, non-competitive antagonist and its actions

Answer 24

Ketamine is an antagonist to NMDA by blocking the ion channel of the glutamate receptor
The maximum response is reduced but there is no change in the EC50

Question 25

Give an example of a irreversible non-competitive antagonist and its actions

Answer 25

Phenoxybenzamine blocks the effects of noradrenaline on a-adrenoceptors on vascular sm. muscle

Question 26

What are the other methods of antagonism?

Answer 26

Physiological - two drugs producing opposing effects i.e. NA and adrenaline Chemical - drug reduces concentration of an agonist by forming a chemical complex i.e. protamine sulphate(+ve) binder to heparin(an anticoagulant)(-ve) preventing heparin from working Pharmacokinetic - one drug affects the absorption, metabolism or elimination of another i.e. phenobarbital-induced enzyme induction increases the metabolism of the anticoagulant coumadin

Question 27

What kind of receptor families do you get?

Answer 27

Ion Channels GPCRs Tyrosine Kinase Nuclear Hormone Receptors

Question 28

How might drugs affect ion channels?

Answer 28

agonist binding results in a conformational change in the receptor and may cause the ion channel to open

Question 29

How might drugs affect GPCRs?

Answer 29

activation results in a stimulation of a second messenger signalling cascade

Question 30

How might drugs affect tyrosine kinase receptors?

Answer 30

these receptors mediate the first steps in transduction of signals by insulin and growth factors

Question 31

How might drugs affect Nuclear hormone receptors?

Answer 31

they may cause transcriptional changes in the DNA and hence change gene expression

Question 32

What is the pathway of drugs in the body?

Answer 32

absorption > distribution > metabolism > excretion

Question 33

How might the absorption of drugs be influenced?

Answer 33

Route of administration - how quickly it reaches the bloodstream and its bioavailability If to be absorbed in the GI tract it must be lipid soluble and able to cope with changes in pH - stomach is acidic and intestines are alkaline

Question 34

How might drug dissolution be affected?

Answer 34

The presence of food, the availability of HCl and the availablility of pancreatic/intestinal secretions

Question 35

What is the first-pass effect?

Answer 35

Where the liver is able to metabolise and inactivate drugs before they are distributed about the body i.e. heroin can be converted to morphine

Question 36

What may affect drug metabolism?

Answer 36

Liver metabolising enzymes may be induced or inhibited by other drugs - drug-drug interactions

Question 37

What are bioassays designed to do?

Answer 37

To see how one drug works against a standard on a dose response curve

Question 38

What are the parameters against which drugs are checked?

Answer 38

IC50 - antagonists - how well they can block agonists and enzymes at a 50% of max effect EC50 - 50% of the maximum effect of an agonist ED50 - the minimum dose required to show effect in 50% of the tested population LD50 - the dose required to kill 50% of the population after x time The therapeutic index - LD50/ED50

Question 39

How many phases of drug trials are there and what happens during them?

Answer 39

Phase I - hospital, v.controlled, safety checking Phase II - checking for efficacy and how well it works Phase III - confirm the findings in large populations Phase IV - testing the long term safety 2-3 years