Immunotherapeutics Flashcards
Describe the process of drug development?
- 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
What are some examples of NSAIDs?
- Aspirin
- Ibuprofen
Do NSAIDs reuire prescription?
-No
What actions do NSAIDs have?
- Anti pyretic (reduce body temp)
- Analgesic (pain killing)
- Anti inflammatory (at high doses)
How do NSAIDs impact inflammation?
- 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.
What is a potential problem with NSAIDs?
- 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
What are groups of people more likely to have side effects as result of NSAIDs and what may these side effects be?
- Present in continous use with people with chronic inflammation
- Eg. Platelet dysfunction
- Eg. gastritis and peptic ulceration with bleeding
Describe how the side effect of gastritis and peptic ulceration with bleeding could come about?
- 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
Describe the effects of paracetamol?
- Mild analgesic effect
- Good antipiretic
- No significant anti inflammatory effect
- At high doses can be hepatotoxic
Describe the anti piretic action of paracetamol?
- 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.
What are glucocorticids?
Drugs mimicking endogenous hormones usually made by adrenal gland.
What are the normal role of the hormones produced by adrenal gland (glucocorticoids and mineralcorticoids) and what are the differences in chemistry?
- Glucocorticoids = immunosupressants
- Mineralcorticoids = regulate Na and water metabolism
- Both very similar in chemistry
What do glucocorticoids act on and why is this significant?
- Endogenous recptors
- So are very specific (receptor in cytoplasm)
What will happen once a glucocorticoid drug has bound to receptor?
-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)
Why is the increasing of protein expression significant with the example of annexin 1?
-Can block phospholipases so block production of arachidonic acid, so block production of arachidonic acid, so block release of all inflammatory mediators.
