HOW DO DRUGS WORK?

Question 1

What is a drug?

Answer 1

A drug is a chemical that produces a biological effect when given to a living organism. It’s structure must be known.

Question 2

What needs to happen for a drug to exert a pharmacological effect?

Answer 2

They have to be bound to macromolecular components of a cell. The binding is highly specific,

Question 3

What are the main regulatory proteins that are targets for drugs?

Answer 3

Enzymes
Carrier (transporter) proteins
Ion channels
Recceptors

Question 4

Where are the targets for drugs found?

Answer 4

Outside cells - in extracellular space

Anchored in the cell membrane

Inside cells - inside the cytoplasm, in intracellular membranes or in the nucleus

Question 5

What causes unwanted drug action or side effects?

Answer 5

If the drug binds to regulatory proteins that are non specific targets or interacts with more than one target protein.

Question 6

What is a receptor?

Answer 6

A cellular sensor for chemical messengers within the body. They allow coordinated function of different cells/tissues.

Question 7

What is an agonist?

Answer 7

An agonist activates the receptor and has a direct effect

Question 8

What is an antagonist?

Answer 8

An antagonist binds but does not activate the receptor. It blocks the action of endogenous ligands.

Question 9

What is an allosteric modulator?

Answer 9

It alters the action of an agonist by binding to the accessory site on a receptor. There is no effect in the absence of an agonist.

Question 10

What is a ligand?

Answer 10

Any drug that binds with specificity to a molecular (protein) target.

Question 11

What is affinity?

Answer 11

Describes the ability of a drug to bind to its target. Determines receptor occupancy. Agonists and antagonists/ blockers/ inhibitors all have affinity

Question 12

What is efficacy?

Answer 12

Describes ability of a drug to activate a receptor once bound i.e. the ability to elicit an effect. Only agonists have efficacy.

Question 13

What is potency?

Answer 13

Usually an indication of dose of drug needed to achieve desired effect. For an agonist potency is a combination of affinity and efficacy. For an antagonist, potency may depend solely on affinity.

Question 14

What is bioavaliabilty?

Answer 14

The fraction of an orally administered dose reaching the systematic circulation (plasma)

Question 15

What factors govern the concentration of drug that reaches its desired target when administered to the body?

Answer 15

Absorption
Distribution
Metabolism
Elimination

Question 16

What is absorption?

Answer 16

Defined as the passage of a drug from site of administration to the
plasma (blood).
Absorption is intimately related to route of drug administration

Question 17

What is enteral administration?

Answer 17

Drug placed directly into gastrointestinal (GI) tract:

• oral
• sublingual
• rectal

Question 18

What is parenteral administration?

Answer 18

Delivery through route other than GI tract

• epithelial surfaces (topical)
• inhalation
• injection

Question 19

What factors affect the absorption of a drug after oral administration?

Answer 19

• Ionisation and lipid solubility-strongly ionised drugs are poorly absorbed
• Metabolism in the gut wall and liver – “first-pass metabolism”
• Gastrointestinal motility – both stasis and increased motility can affect
  absorption
• Splanchnic blood flow – absorption can be increased by increased blood
  flow after a meal
• Particle size and formulation of drug can affect absorption - slow and fast release formulations
• Physicochemical factors e.g. calcium binding can prevent absorption

Question 20

How are drugs carried to compartments?

Answer 20

By circulation

Question 21

What does distribution depend on?

Answer 21

• Barrier permeability e.g. Blood-Brain Barrier
• Binding in compartments
• pH partition
• Water-fat partition

Question 22

What is the blood brain barrier?

Answer 22

A continuous layer of epithelial cells joined by tight junctions forming a
barrier to drug entry.

Question 23

What needs to happen to lipid soluble drugs before they can be eliminated?

Answer 23

They must be made water soluble

Question 24

What is phase 1 metabolism?

Answer 24

alterations to molecule by oxidation, reduction,

hydrolysis

Question 25

What is phase 2 metabolism?

Answer 25

conjugation usually in the liver with glucuronide or

sulphate prior to elimination

Question 26

What are possible routes of elimination?

Answer 26

kidneys
liver / bile
lungs - respiratory
(anaesthetics)

Question 27

What quantifies the lifetime of a drug in the body?

Answer 27

Its half-life – the time taken to reduce the concentration of drug to half its original
concentration

Question 28

What are the advantages of oral administration?

Answer 28

• convenient, self administration
• no pain
• absorption area large
• cheap

Question 29

What are the disadvantages of oral administration?

Answer 29

• often only partial absorption
• mucosa irritation
• gastric acid/enzymic
  breakdown
• slow onset
• taste unpleasant
• cannot be used when
  unconscious
• first pass metabolism

Question 30

What are the advantages of intravenous administration?

Answer 30

- allows accurate control of
amount of drug delivered to
target
- pharmacological effects
produced very quickly
- bypasses major sites of
drug metabolism – GI tract
and liver

Question 31

What are the disadvantages of intravenous administration?

Answer 31

• difficult to reverse if too much drug delivered
• can lead to harmful effects
  caused by blood clotting or the introduction of air or microbes into the vessel.