anti-inflammatories Flashcards
DEFINE: analgesic
reduces pain
DEFINE: antipyretic
lower raised body temperature
what are headaches associated with?
vasodilation of blood vessels in the brain
describe the general structure of COX
homodimer
enzyme anchored into ER
2 active sites
channel through which arachidonic acid enters
COX-1
constitutively expressed in epithelial cells lining stomach, kidneys and platelets
COX-3
spliced variant of COX-1
largely expressed in CNS
what is the structural difference between COX-1 and COX-2 and what implications does this have for the development of NSAIDs?
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
which drug shows selectivity for COX-3
paracetamol
Misoprostol
prostaglandin analogue administered alongside COX-1 inhibitors to preserve stomach function
what is the mechanism of action for aspirin?
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
Methatrexate
DMARD
folic acid antagonist (so patients must supplement diet with extra folic acid)
Sulfasalazine
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
Ciclosporin
immunosuppressant used to treat rheumatoid arthritis
blocks activation of calsinorin
How are glucocorticoids used to treat rheumatoid arthritis?
enter cell and bind to glucocorticoid receptor. ligand bound receptor translocates into nucleus and inhibits transcription of pro-inflammatory genes
what are some classes of drugs that specifically target cytokines
- biopharmaceuticals = peptides targeting cytokines
- therapeutic monoclonal antibodies - antibodies binding to cytokines to inhibit them
- soluble receptor proteins = proteins binding to cytokines to prevent them from binding to their receptors
Salbutamol
asthma treatment
β₂ adrenergic receptor agonist
vasoconstriction of airways
Prednisolone
glucocorticoid
anti-inflammatory - inhibit transcription of cytokines
asthma treatment
Histamine
released by mast cells
vasodilator of airways
IgE mediated hypersensitivity seen in asthma
- allergen encountered by patient
- TH2 cells are overactive and release cytokines which activate cells producing IgE antibodies
- patient produces IgE antibodies in response
- IgE antibodies bind to IgE receptors on mast cells, eosinophils and basophils
- EARLY PHASE REACTION - Mast cells release histamines and prostaglandins - causes airway constriction + some inflammation
- LATE PHASE REACTION: Mast cells release cytokines - recruits leukocytes and causes inflammation
what is Zolaire?
monoclonal antibody that binds to IgE when it is free in the plasma
