General Principles

Question 1

What is pharmacodynamics?

What is pharmacokinetics?

Answer 1

Pharmacodynamics = what the drug does to the body

Pharmacokinetics = what the body does to the drug

Question 2

What are the general categories of how drugs work?

Answer 2

1. Physical interactions - e.g. antacids, activated charcoal
2. Enzyme interactions - binding/changing active sites (competitive/non-competitive)
3. Receptor interactions -

Question 3

What’s a binding site?

Answer 3

A specific area on a receptor where a ligand Binds

Question 4

What are the categories of receptor defined by mechanism of action?

Answer 4

Altered ion permeability
Regulation of gene transcription
Production of intermediate messenger (AKA G-protein)

Question 5

What is the nicotinic acetylcholine receptor?

Answer 5

A ligand gated sodium channel found on the post-synaptic membrane of the neuromuscular junction.

The site of action of muscle relaxants.

Question 6

Can you give some examples of G-protein coupled receptors?

Answer 6

Opioid receptors
Adrenoceptors
Muscatinic acetylcholine receptors

Question 7

Can you give some examples of intermediate messengers used by receptors?

Answer 7

Adenyl cyclase
Phospholipase c
Membrane guanyl cyclase

Question 8

What are the two properties of a drug that affects its pharmacological effect?

Answer 8

1. Affinity - how well the drug binds to the receptor (stickiness for the receptor)
2. Efficacy - (intrinsic activity) the magnitude of effect the drug has once bound

I.e. a drug with no efficacy but good affinity will act like an antagonist

Question 9

What is an agonist?

Answer 9

Agonist:
Affinity for receptor and intrinsic activity

Binds and makes something happen

Question 10

What is an antagonist?

Answer 10

Antagonist:
Affinity for a receptor but no intrinsic activity

• Binds but doesn’t make anything happen

Question 11

What is a full agonist?

Answer 11

A drug that generates the maximal response from the receptor (maximum affinity and efficacy)

Question 12

What is a partial agonist?

Answer 12

Can have good affinity but less than maximum efficacy, therefore can never make the maximal effect like a full agonist can.

Question 13

How can you tell a competitive and a non-competitive antagonist? (Both are reversible antagonists)

Answer 13

A competitive antagonist can be crowded out - the effects can be reversed by increasing the concentration of agonist.
This is because they both bind in the same place.

A non-competitive antagonist’s effect can’t be overcome by increasing the concentration of agonist, just like an irreversible antagonist.

Question 14

What is tachyphylaxis?

Answer 14

Rapid decrease in response to repeated doses of a drug over a short period of time (rapid, short term tolerance).

MOA: most commonly due to depletion of neurotransmitter stores

Question 15

What is desensitisation?

Answer 15

Chronic loss of response to a drug over a long time period - the basis of tolerance.

MOA: structural change in receptor morphology and/or a decrease in receptor numbers.

Question 16

How do things pass through the cell membrane phospholipid bilayer?

Answer 16

Passive diffusion - Graham’s law, smaller molecules move faster than large ones/ Fick’s law, higher conc means more diffuses across

Facilitated diffusion - only way for polar molecules like glucose to pass through (moving with the gradient, so not active)

Active transport

Pinocytosis - invagination of the cell membrane around the entering object (large molecules)

Depends on:
Molecule size
pH/ionisation
Concentration
Protein binding
Lipid solubility

Question 17

The same drug given by different routes can have a different effect that lasts for different times, why is this?

Answer 17

Variability within:
Absorption - bioavailability (depends on route of administration)
First pass metabolism
Coating of tablets
Food/drink eaten at the same time 
Malabsorption syndromes

e.g. Morphine oral bioavailability is 30-50%
Morphine IV same dose is 100%

Not the same effect!

Question 18

What are the three main types of distribution between drugs in the body?

Answer 18

Confined to plasma

Limited distribution - e.g. only in muscles

Extensive distribution - everywhere

Question 19

Which areas of the body do drugs reach first?

Answer 19

This depends on where there are areas of high blood flow.

High blood flow: Brain, lungs, kidneys, thyroid and adrenal glands

Moderate blood flow: Muscles

Low blood flow: Fat

Question 20

What is the volume of distribution? (Vd)

Answer 20

The distribution of a drug throughout the body, the intrinsic solubility of the drug which makes its distribution wide or narrow.

The apparent volume into which a drug disperses.

This depends on how soluble the drug is and where it will distribute itself if given the chance.

e.g. warfarin is confined to blood, so it’s Vd is 9L

Digoxin goes in to all the blood, muscles, organs etc so it Vd is 500L

Question 21

What are the phases of metabolism?

Answer 21

Phase 1 = Oxidation, reduction and hydrolysis

• cytochrome p450 system in ER
• monoamine oxidase in the mitochondria

Phase 2 = Conjugation
- glucoronide, sulphate, glutamate, acetate and metal groups (increases polarity, increasing water solubility)

Metabolism occurs in: liver, kidneys, lungs and blood

Question 22

Which substances cause enzyme induction?

Answer 22

MOA: Enzyme induction is increased transcription of genes for metabolism enzymes

Rifampicin - antibiotic

Alcohol - chronic alcohol abuse

Phenytoin and carbamazepine - anticonvulsants

All cause increase in enzyme effects, therefore reduce the level of other drugs.

Question 23

Where is excretion most often carried out?

Answer 23

The kidneys

Either as:
Filtration in glomerulus
Secretion in the proximal tubule
Diffusion in the distal tubules

Question 24

What is enterohepatic recycling?

Answer 24

Drugs conjugated in the liver and secreted in to bile, then unconjugated by gut bacteria and reabsorbed by the bowel.

This causes the concentration of the drug after one dose to peak, trough, peak trough etc since not all of it is excreted, some is reabsorbed by this mechanism.

The OCP is recycled like this.

Question 25

What is clearance?

Answer 25

Clearance is the rate of elimination divided by the plasma concentration.

Systemic clearance = clearance of (liver+kidney+other)