Immunotherapeutics

Question 1

Describe the process of drug development?

Answer 1

• Long, costly, risky
• First pre clinical phase involving chemistry and pharmacology (usually takes a few years)
• Clinical trials then (4 phases), phase 3 the largest scale and very expensive
• After phase 3 there is NDA (new drug application) which is an authorisation process

Question 2

What are some examples of NSAIDs?

Answer 2

• Aspirin

- Ibuprofen

Question 3

Do NSAIDs reuire prescription?

Answer 3

-No

Question 4

What actions do NSAIDs have?

Answer 4

• Anti pyretic (reduce body temp)
• Analgesic (pain killing)
• Anti inflammatory (at high doses)

Question 5

How do NSAIDs impact inflammation?

Answer 5

• They act on cyclooxygenases, usually cell membrane phospholipids produce arachidonic acid through action with phospholipases.
• The arachidonic acid would then produce COX and lipoxygenase.
• The COX would produce prostaglandins and thromboxane
• NSAIDS block the COX action so there is no production of mediators such as prostaglandins (by COX 2) which are key in inflammations usual key signs.

Question 6

What is a potential problem with NSAIDs?

Answer 6

• They are non-selective so block COX 1 and 2.
• Block on COX 2 will act on inflammation
• Block on COX 1 will reduce thromboxanes which have role in normal body house keeping functions of body

Question 7

What are groups of people more likely to have side effects as result of NSAIDs and what may these side effects be?

Answer 7

• Present in continous use with people with chronic inflammation
• Eg. Platelet dysfunction
• Eg. gastritis and peptic ulceration with bleeding

Question 8

Describe how the side effect of gastritis and peptic ulceration with bleeding could come about?

Answer 8

• GI mucosa usually protected by mucous and bicarbonate layer, prostaglandins aid production of this protection.
• By taking aspirin you block prostagalndin production so less protection and gastric acid may cause damage
• Can lead to bleeding of stomach
• Or can lead to perforation of wall causing leakage of stomach contents which may lead to septisaemia

Question 9

Describe the effects of paracetamol?

Answer 9

• Mild analgesic effect
• Good antipiretic
• No significant anti inflammatory effect
• At high doses can be hepatotoxic

Question 10

Describe the anti piretic action of paracetamol?

Answer 10

• Fever leads to pyrogen (eg.IL-1) being released from leukocytes which act directly on hypothalamus, increasing body temp.
• This is associated with increase in brain prostaglandins, allowing paracetamol to act as an antipiretic.

Question 11

What are glucocorticids?

Answer 11

Drugs mimicking endogenous hormones usually made by adrenal gland.

Question 12

What are the normal role of the hormones produced by adrenal gland (glucocorticoids and mineralcorticoids) and what are the differences in chemistry?

Answer 12

• Glucocorticoids = immunosupressants
• Mineralcorticoids = regulate Na and water metabolism
• Both very similar in chemistry

Question 13

What do glucocorticoids act on and why is this significant?

Answer 13

• Endogenous recptors

- So are very specific (receptor in cytoplasm)

Question 14

What will happen once a glucocorticoid drug has bound to receptor?

Answer 14

-Complex will migrate to nucleus and have 1 of 3 effects:
increase protein expression (eg. annexin 1)
decrease protein expression
decrease activation of nuclear kappa factor B (master regulation of inflammation)

Question 15

Why is the increasing of protein expression significant with the example of annexin 1?

Answer 15

-Can block phospholipases so block production of arachidonic acid, so block production of arachidonic acid, so block release of all inflammatory mediators.

Question 16

When may glucocorticoids be used?

Answer 16

• In all chronic inflammatory pathologies

eg. rheumatoid, asthma, addisons disease

Question 17

What are some possible side effects of glucocorticoids?

Answer 17

• Euphoria
• Poor wound healing
• Messes metabolism up
• Cataracts
• Change in % muscle and body fat

Question 18

Describe use of glucocorticoids in asthma?

Answer 18

• In asthma is it safe as not being given systemically

- It goes where it needs to and is modded in such a way that once it reaches the liver it is destroyed.

Question 19

What are biologics?

Answer 19

• More specific drugs

- Monoclonal antibodies targeting specific antigens eg. TNF alpha

Question 20

What is an issue with biologics?

Answer 20

-Specificity as it makes them less effective for the majority of a population

Question 21

Describe cancer therapy/immunotherapy?

Answer 21

• Want to increase strength of T cells
• We stimulate action by blocking checkpoint proteins
• We use inhibitor drugs to counter these checkpoint effects eg. CTLA-4, PD-1 checkpoints

Question 22

When can immunotherapy have issues?

Answer 22

-Very effective against cancers but in people with chronic inflammatory diseases can cause side effects.