Naisbitt

Question 1

How do developments in medchem impact drug discovery?

Answer 1

With greater knowledge, drugs can be developed to have higher affinities and hence be more selective - therefore a lower dose can be given with less adverse effects

Question 2

What’s significant about sulphonamides?

Answer 2

1st synthetic antibacterial agents

Effective against a wide range of infections - bar Salmonella

Highly toxic in some patients

Question 3

What is the MOA of sulphonamides?

Answer 3

They inhibit Dihydropteroate synthase - blocking para-aminobenzoic acid - which is responsible for synthesising folic acid.

Folic acid is critical for replication of bacteria - ONLY PATHWAY

Humans can get it through diet

Question 4

What’s an issue with using sulphonamides clinically?

Answer 4

They can form toxic metabolites - resulting in allergic reactions and haematoxicity in some patients.

The hydroxylamine metabolites responsible bind to endogenous proteins - the protein is then attacked by immune system

Question 5

What is the function of noradrenaline wrt asthma?

Answer 5

NA binds to the ß2 receptors and increases bronchodilation

However, NA is not selective, binding to ß1 adrenoreceptors - increasing heart rate.

NA also interacts with alpha receptors in blood vessels

Question 6

What’s the difference in structure between noradrenaline and salbutamol?

Answer 6

Salbutamol has a t-But group stuck on the terminal amine

Also has extra carbon on upper OH group of catechol group

Question 7

What does enteral and parenteral routes of administration describe?

Answer 7

Enteral = GI tract - sublingual, oral & rectal

Parenteral = non- GI tract - injections and inhalers

Question 8

What factors must be considered when deciding the route of administration of drug?

Answer 8

Extent of transport across membranes - adsorption

Transit to site of action - distribution

Compliance - age, physical/mental ability

Question 9

What is the definition of bioavailability?

Answer 9

The proportion of drug that passes into the systemic circulation following the first-pass metabolism

Question 10

What is meant by first pass metabolism?

Answer 10

It is the metabolism of a drug after administration but before reaching the systemic circulation

Question 11

What can be done if therapeutic failure is observed in a patient?

Answer 11

Increase dosage, increase doses per day, alter site of administration, change formulation

Question 12

What factors affect the distribution of a drug?

Answer 12

Bulk flow in blood
Diffusion rate
Partitioning - into fat deposits
Binding to plasma proteins - no pharma effect, non-covalent forces

Question 13

What’s the benefit of the small intestine with oral administration?

Answer 13

V. Large surface area ~ 200m^2

High blood flow ~ 1L/min
- maintains diffusion gradient

Question 14

What does good absorption require a drug to be?

Answer 14

Drug must be water soluble
-so molecules in solution can be absorbed

And lipid soluble
-to pass through cell membranes

Question 15

Rank the types of formulations in order of best—> worst

Answer 15

Solution
Emulsion
Suspension
Capsule
Tablet

Question 16

What protein is bound to by acidic drugs?

Answer 16

Albumin

Question 17

What protein is bound to by basic drugs?

Answer 17

Beta globin

Acid glycoprotein

Question 18

What’s the issue with drugs binding to plasma proteins or partitioning into fat?

Answer 18

These drugs have no pharmacological effect

Toxic build up could also occur in fat deposits - low blood supply so drugs become trapped

Question 19

Most drugs are weak acids and bases and so are often in ionised and unionised forms. Can ionised drugs cross cell membranes?

Answer 19

NO, only unionised molecules can cross cell membranes

The degree of ionisation - pH - determines the extent of transfer across cell membranes

Question 20

What is the Henderson-Hasselbach equation?

Answer 20

pH = pKa + log [A-]/[HA]

Question 21

What does a large [A-]/[HA] mean in the Henderson-Hasselbach equation?

Answer 21

A large value for [A-]/[HA] means that there are many ionised molecules for 1 unionised one.

A [A-]/[HA] of 0.01 means there are 100 unionised molecules for every ionised one

Question 22

What’s the point of metabolising drugs?

Answer 22

Since most drugs are lipophilic they cannot be excreted efficiently

Such drugs must be metabolised to more polar products to aid excretion

Question 23

Where is the main site of metabolism in the body? What’s the significance of pro-drugs?

Answer 23

In liver cells - usually abolishes a drugs pharmacological action

Pro-drugs are metabolised in the body to BECOME pharmacologically active.

Question 24

What does cytochrome p450 require?

Answer 24

NADPH

Question 25

Where does Phase 1 CYP450 metabolism occur?

Answer 25

On smooth endoplasmic reticulum of hepatocytes

Question 26

What class of enzymes are responsible for Phase 2 metabolism?

Answer 26

Transferase enzymes - transferring a polar group from a conjugating agent to the Phase 1 metabolite

Mainly occurs in the liver

Question 27

What compounds are excreted through the kidney?

Answer 27

Polar compounds - particularly phase 2 conjugates

Question 28

How does the liver excrete drug metabolites?

Answer 28

Process is called biliary excretion - active secretion of drug molecules or their metabolites from hepatocytes into the bile.

Favours high MW polar compounds

Question 29

What are the other routes of excretion other than the liver and kidneys?

Answer 29

Lungs - volatile compounds
Saliva
Sweat
Breast milk - think morphine overdose in baby

Question 30

If the drug does not reach its target, what happens?

Answer 30

Nothing, no pharmacological effect is exerted/observed