anti-inflammatories

Question 1

DEFINE: analgesic

Answer 1

reduces pain

Question 2

DEFINE: antipyretic

Answer 2

lower raised body temperature

Question 3

what are headaches associated with?

Answer 3

vasodilation of blood vessels in the brain

Question 4

describe the general structure of COX

Answer 4

homodimer
enzyme anchored into ER
2 active sites
channel through which arachidonic acid enters

Question 5

COX-1

Answer 5

constitutively expressed in epithelial cells lining stomach, kidneys and platelets

Question 6

COX-3

Answer 6

spliced variant of COX-1

largely expressed in CNS

Question 7

what is the structural difference between COX-1 and COX-2 and what implications does this have for the development of NSAIDs?

Answer 7

COX-2 has valine instead of isoleucine
Side chain of valine is larger than isoleucine so channel is bigger
drugs can be developed which can enter cox-2 but are too big to enter cox-1 –> selectivity for COX-2

Question 8

which drug shows selectivity for COX-3

Answer 8

paracetamol

Question 9

Misoprostol

Answer 9

prostaglandin analogue administered alongside COX-1 inhibitors to preserve stomach function

Question 10

what is the mechanism of action for aspirin?

Answer 10

aspirin converts back to salicylic acid in the body

salicylic acid binds serine residue on COX-1 and blocks arachidonic acid from reaching the cyclooxygenase site

Question 11

Methatrexate

Answer 11

DMARD

folic acid antagonist (so patients must supplement diet with extra folic acid)

Question 12

Sulfasalazine

Answer 12

DMARD
sulfa drug
bacteria in the colon break down sulfasalazine into 5-Aza = free radical scavenger decreasing damage produced by inflammatory reactions mediated by neutrophils

Question 13

Ciclosporin

Answer 13

immunosuppressant used to treat rheumatoid arthritis

blocks activation of calsinorin

Question 14

How are glucocorticoids used to treat rheumatoid arthritis?

Answer 14

enter cell and bind to glucocorticoid receptor. ligand bound receptor translocates into nucleus and inhibits transcription of pro-inflammatory genes

Question 15

what are some classes of drugs that specifically target cytokines

Answer 15

1. biopharmaceuticals = peptides targeting cytokines
2. therapeutic monoclonal antibodies - antibodies binding to cytokines to inhibit them
3. soluble receptor proteins = proteins binding to cytokines to prevent them from binding to their receptors

Question 16

Salbutamol

Answer 16

asthma treatment
β₂ adrenergic receptor agonist
vasoconstriction of airways

Question 17

Prednisolone

Answer 17

glucocorticoid
anti-inflammatory - inhibit transcription of cytokines
asthma treatment

Question 18

Histamine

Answer 18

released by mast cells

vasodilator of airways

Question 19

IgE mediated hypersensitivity seen in asthma

Answer 19

1. allergen encountered by patient
2. TH2 cells are overactive and release cytokines which activate cells producing IgE antibodies
3. patient produces IgE antibodies in response
4. IgE antibodies bind to IgE receptors on mast cells, eosinophils and basophils
5. EARLY PHASE REACTION - Mast cells release histamines and prostaglandins - causes airway constriction + some inflammation
6. LATE PHASE REACTION: Mast cells release cytokines - recruits leukocytes and causes inflammation

Question 20

what is Zolaire?

Answer 20

monoclonal antibody that binds to IgE when it is free in the plasma