Anti-Inflammatory agents Flashcards
What is an NSAID?
Non-Steroidal Anti-Inflammatory Drug
How are membrane phospholipids converted into leukotrienes?
Membrane phospholipids get converted into arachidonic acid by phospholipase A2
Arachidonic acid is then broken down into leukotrienes by Lipoxygenase
How are membrane phospholipids converted into prostaglandins?
Membrane phospholipids get converted into arachidonic acid by phospholipase A2
Arachidonic acid is then broken down into different prostaglandin classes by Cyclo-oxygenase (COX) enzyme
Which enzyme is targeted by corticosteroids?
Phospholipase A2 preventing the formation of arachidonic acid
What are some examples of glucocorticosteroids?
Hydrocortisone
Betamethasone
Prednisolone
Which enzyme is targeted by NSAIDs?
The Cyclo-oxygenase enzyme (COX)
What are some examples of NSAIDs?
Aspirin, Ibuprofen, Naproxen and celecoxib
Where are steroid hormones produced?
In the adrenal gland that sit on the kidneys
What are the 2 types of corticosteroid receptors?
Glucocorticoid receptors
Mineralocorticoid receptors
How do steroid drugs affect the cell?
Drugs pass through the plasma membrane
Here, they bind to glucocorticoid receptors
These allow passage into the nucleus where they bind to GRE (Glucocorticoid Response Elements) on DNA
What are the main therapeutic effects of glucocorticoid drugs?
Pain relief
Anti-allergy
Immunosupression
Anti-inflammatory
Decreased blood vessel permeability
What side effects can glucocorticoid drugs have on muscles?
Increased risk of myopathies causing muscle weakness
What side effects can glucocorticoid drugs have on bone?
Can cause osteoporosis
Can cause aseptic necrosis of the femur
What side effects can glucocorticoid drugs have on the skin?
Causes skin thinning
What side effects can glucocorticoid drugs have on metabolism?
Hyperglycaemia
Weight gain
Fluid retention
Cushingoid appearance - fat build up on the sides of the face
What side effects can glucocorticoid drugs have on the CNS and adrenal system?
HPA insufficiency
Neuropsychiatric disorders
What side effects can glucocorticoid drugs have on the eyes?
Cataracts
Glaucoma
What side effects can glucocorticoid drugs have on the cardiovascular system?
Hypertension
What side effects can glucocorticoid drugs have on the gastrointestinal system?
Increased stomach acid production
What do inhaled steroids increase the risk of thrush?
Steroids can be deposited in the oropharynx causing local immunosuppression, allowing the growth of Candida albicans
What is CRH?
Corticotrophin Releasing Hormone
What causes the release of CRH and where is it released from?
The hypothalamus, stimulated by stress or the Circadian rhythm
What does CRH do?
It stimulates the anterior pituitary gland to release ACTH
What is ACTH?
AdrenoCorticoTrophic Hormone
What does ACTH do?
It stimulates the release of glucocorticoids from the adrenal glands
What is the HPA axis?
Stress/circadian rhythm
Stimulates hypothalamus
Releases CRH
Stimulates anterior pituitary gland
Releases ACTH
Stimulates adrenal glands
Releases glucocorticoid steroids
Stimulates hypothalamus to reduce CRH production
Regulates steroid hormone levels
How do glucocorticoid drugs cause HPA insufficiency?
Addition of glucocorticoid steroids into the blood stream stimulates the hypothalamus to reduce CRH levels
After prolonged use (3 weeks) the adrenal glands no longer produce glucocorticoids on their own, leading to adrenal insufficiency
What would happen if steroids were stopped instantly, instead of slowly decreased?
The adrenal glands would no longer produce endogenous glucocorticoids, so the person would fall into a coma
What are the 2 types of COX enzyme?
COX-1 and COX-2
What is the function of COX-1?
COX-1 is always present in low levels , within the body and involved in platelet regulation, kidney function and regulation of stomach acid
What is the function of COX-2?
COX-2 is an inducible enzyme that, when activated, causes inflammation, leading to pain, heat and swelling
What are some common side effects of NSAIDs?
Adverse GI effects (Abdominal bleeding)
Reduced renal function in predisposed patients)
Hypertension
What is misoprostol and why is it combined with NSAIDs?
Misoprostol is a synthetic prostaglandin medication
When bound to an NSAID, it can prevent gastric bleeding and discomfort by regulating the stomach lining which can be prevented by the NSAID alone
What is a DMARD?
Disease Modifying Anti-Rheumatic Drug
What are some examples of DMARDs?
Methotrexate
Sulfasalazine
What are the advantages of DMARDs over NSAIDs?
They can be used for longer periods of time
What are some examples of immunosuppressant drugs?
Ciclosporin
Azathioprine
Tacrolimus
Mycophenolate mofetil
What are some examples of biological immunosuppressant?
Infliximab
Rituximab
What are the 2 types of antihistamines and what are some examples of each?
1st generation (Sedating) - Promethazine, Cyclizine, Chlorphenamine
2nd generation (Non-sedating) - Fexofenadine, loratadine
