Anti-inflammatories Flashcards
What do NSAIDS stand for
Non-steroidal anti-inflammatory drugs
What did Felix Hoffmann add to salicylic acid to improve its properties
An acetyl group
What was one of the first synthetic drugs created
Aspirin
Benefits of aspirin
Less gut effects
Examples of NSAIDS
Aspirin, Paracetamol, Ibuprofen
What do NSAIDS target
Prostaglandins and thromboxane’s
What do Phospholipase a2 generate
The precursors required for the synthesis of everything else (arachidonate)
What is arachidonate converted into
Other mediators by cyclo-oxygenase
What is PGF important for
Initiation of labour
What is PDG needed for
Platelet aggregation
What is PGE needed for
Blood vessel relaxation (Hyperalgesia)
What do prostaglandins attract
Immune cells known as chemo attractants
What are NSAIDS
Anti-inflammatory, analgesic anti-pyretic
What does analgesic mean
Decreases pain
What does anti-pyretic mean
Lowers raised temperature
What is the COX1 enzyme responsible for
Constant constitutive synthesis of prostaglandins, has many homeostatic functions for maintaining health
What is COX2 responsible for
It’s an inducible enzyme in response to inflammation
Where is COX3 found
In the brain and kidneys
What is COX made of
Two identical subunits
What’s the difference between COX1 and COX2
The structure of the little pore where the arachidonic acid has to go up is smaller in COX2
Which amino acid does COX1 have
Isoleucine
Which amino acid does COX2 have
Valine
Why does aspirin cause GI issues
Because prostaglandins maintain the mucus layer surrounding the stomach
What do prostaglandins maintain
Blood flow in the kidneys
What is a suicide inhibitor
A drug that covalently binds to its target to cause a permanent inactivation of its target
Side effects of NSAIDS
Gut issues, renal function issues, liver damage, bronchospasms and skin rashes
advantages of drugs to target COX1
Beneficial for people at risks of strokes - antithrombotic
What can inhibition of COX2 lead to
An increase in blood pressure and salt retention
What does arthritis involve
Swelling around the synovium of the joints
Symptoms of arthritis
pain, poor sleep, morning stiffness, swelling in affected joints
How is the inflammatory response activated in arthritis
t cells activate macrophages which release mediators
What are the two mediators involved in arthritis
Cytokines known as IL1 and TNF alpha
Which drugs limit the inflammatory response in arthritis
Methotrexate folic acid and DIMARDS
What does methotrexate do
Works as an antagonist for folic acid. It’s effective at low concentrations
What do DIMARDS stand for
Disease modifying anti- rheumatoid drugs
Examples of last resort drugs for arthritis
Cyclosporin’s and glucocorticoids
How do cyclosporins work
Binds to calcanewin and inhibits the function of NF Kabba B, limiting the production of cytokines
Example of glucocorticoid
Prednisolone
How do glucocorticoids work
Work directly on the level of transcription by binding to the DNA. They act as repressors, inhbiting the genes that make cytockines
Example of biopharmaceutical which treats arthritis
Adalmumab
What does Adalmumab do
It recognises and binds to TNF alpha so it can no longer bind to its receptors
Advantages and costs of Adalmumab
Its a single injection which lasts 3 months, has much lower side effects but is expensive
Issues with biological drugs
They are expensive and have a limited pattern time
Examples of inflammatory respiratory diseases
COPD and asthma
What is COPD
A progressive disease driven by macrophages
Symptoms of asthma
Shortness of breath, coughing and wheezing
What does asthma involve
Inflammation of the airways and involves bronchial-hyper reactivity
How to treat asthma
Avoid the allergen, give salbutamol, steroid drugs administered through an inhaler
How does salbutamol work
Its an agonist for the beta adreno receptors found in smooth muscle airways. These receptors relax once activated
Two phases of asthma
Early phase: mediated by mast cells secreting histamine
Late phase reactions: cytokines forcing an inappropriate inflammatory response to take place in the lungs
What is asthma driven by
T cells
What do steroid drugs do for asthma
Dampen down the production of cytokines and therefore control the response
What are the unwanted side effects of steroid use
Crushing’s syndrome
