Anti-inflammatory drugs Flashcards
Where is asparin derived from naturally?
Willow tree
Who isolated the parent compound for asparin?
Henry La Roux
What is the parent compound for asparin?
Salicylic acid
Asparin is acetlysalicylic acid
How many types of NSAIDs are there?
50
NSAIDs work to reduce the production of what?
prostaglandins and thromboxane
What is PG12?
Prostacyclin which causes endothelial vasodilation
What is TxA2?
Causes endothelial vosoconstriction
What is PGE2?
Causes inflammation, bronchorestriction and vasodilation
What is PGF2?
Causes uterus contraction
What is the action of NSAIDs?
Normally prostaglandin production is caused by the following pathway: Phospholipase A causes lipids to breakdown in the membrane, Arachadonic is produced which is acted on by COX to cause the production of prostaglandins
NSAIDs inhibit COX enzmes
What is the role of prostaglandins E?
It is a vasodilator and hypoallgesic
How does prostaglandins E cause heightened pain?
Nococeptors have receptors for prostaglandins E - these nococeptors are G protein coupled receptors
This binding causes an increase in excitability of nococeptors in response to other sources of pain eg touching the area
What is the role of prostaglandins D2?
Platelet aggregation
Asparin can reduce the risk of stroke by reducing aggregation
What does Thromboxane A favour?
Blood clotting
How do NSAIDs modify the inflammatory reaction?
They decrease vasodilation and therefore decrease oedema
They are ineffective against mediators that contribute to tissue damage associated with chronic inflammatory conditions
They work on COX enzymes outside of the CNS
Why is paracetomol a poor anti-inflammatory drug?
It exerts its effect mostly in the CNS
What is an analgesic?
A drug which reduces pain
How do NSAIDs reduce pain?
They decrease the production of prostaglandins which sensitises nociceptors to inflammatory mediators
What is an antipyretic?
A drug which lowers a raised temperature
What are the three types of cyclooxygenases and where are they found?
COX1 - all cell types
COX2 - only produced under inflamed conditions ie they are induced
COX3 - spliced variant of COX1 which is limited to the CNS and kidneys
Which type of COX is paracetamol a good inhibitor of?
COX3
Which types of COX is asparin a good inhibitor of?
COX1 and 2
Where are COX enzymes found inside the cell?
They are docked into the endoplasmic reticulum membrane
What is meant by ‘asparin is a suicide inhibitor’?
It makes the COX enzyme permanently inactived as it forms makes a covalent bond in the enzyme ( forms an ester bond with serine from asparin’s acetyl group)
How long does it take for asparin to be cleared and why?
It takes 4 hours as this is how long it takes for COX enzymes to be resynthesised
How quickly is asparin absorbed?
10 to 20 minutes
What are the differences in structure between COX1 and COX2?
COX1 has an isoleucine lining the channel
COX2 has valine lining the channel which is a smalle amino acid
The channel of COX1 is narrower than COX2
Drugs that treat back pain work better if they are selective for which COX enzyme?
COX2
What are the side effects of NSAIDs in the gut?
dyspespsia, diarrhoea, nausea, vomitting, gastric bleeding and ulceration
This is because prostaglandins work to inhibit acid secretion and protect mucosa
What are the side effects of NSAIDs in the kidney?
May cause renal failure
Prostaglandins maintain renal blood flow
What are the side effects of NSAIDs in the liver?
Usually side effects are more of a result to use of paracetomol. This is because in its first phase metabolism it produces a toxic intermediate compound which can cause death in very large amounts eg overdose
Why can NSAIDs cause asthma attacks?
Prostaglandins are bronchodilators so if they are inhibited they could cause astha attacks
What is rofecoxib?
It is a very potent COX2 inhibitor which is toxic
Using asparin is associated with reducing the risk of what?
Colonic and rectal cancer, alzheimer’s
What is the hepatoxic compound formed from paracetomol called?
N-acetly-p-benzoquinone
How are headaches caused and how does NSAIDs treat the pain caused?
Headaches are caused by the vasodilation of vessels in the brain which press on pain sensory fibres and nociceptors in the skull
Use of NSAIDs reduces vasodilation so reduces activation of pain fibres
What is rheumatoid arthritis?
Where the synovium of the joint becomes inflamed causing pain, stiffness and poor sleep
It is an example of an autoimmune disease
What is the onset of rheumatoid arthritis?
40 to 60 years of age usually but can also be juvenile
What is mehotrexate and what does it do?
Helps suppress immune activity and interacts with folic acid
It is used in the induction stage of RA
It inhibits the action of T helper cells so they dont form Th1 cells
It also inhibits the proliferatio if Th1 which limits the production of cytokines (IL-1 and TNF- alpha)
What is sulfasalazine?
A drug used for chronic inflammatory bowel disease and RA
Bacteria in the colon can produce 5-aminosalicylic acis which may act as a free radical scavenger to decrease damage produced by neutrophils
What are glucocorticoids?
Steroidal drugs
They act at the level of transcription to inhibit the production of pro-inflammatory cytokines
What are DMARDs?
Disease modifying anti rheumatic drugs
Work to reduce symptoms by a diverse mechanism of action
Different targets used
Not well understood
What is cyclosporine?
Used to control the rejection of implants
Works to supress the action of cytokines
Large complicated molecule
Inhibits the induction phase of RA
What happens inside a T cell once it has been activated?
Intracellular calcium rises
Enzyme called calcaneum is activates which is a phosphatase
This enzyme targets NFKappaB which is a transcription factor which enters the nucleus to control transcription
What two categories of drugs have been developed to treat arthritis?
Antibodies
Mimic Small Molecule Receptors
How do mimic small molecule receptors work?
They mop up free cytokines so it can’t interact with the receptors on cells
List some anti-asthmatic drugs
Bronchodilators eg salbutamol
Anti-inflammatory agents eg prednisolone and omalizumab
Glucocortoids eg zolaire
How can different materials cause allergies?
They can be: Inhaled Injected Ingested Contacted
What is the emergency treatment for allergies?
Epinephrine (adrenaline)
Where can allergies occur and what are the effects of the allergy?
Cardiovascular system - Causes cardiovascular collapse
Respiratory system - Bronchospasm, Laryngeal Oedema
Skin - Erythma (redness), Angiodema (swelling), Urticaria (rash/hives)
GI tract - vomitting, diarrhoea
Where are mast cells found?
Everywhere in the body where there is an opening to the body
Where are basophils found?
In the blood
