Steroids and NSAIDs Flashcards
What are the effects of NSAIDS?
Anti inflammatory - NSAIDS reduce the production of COX-2 products.
Analgesic effects - NSAIDS reduce prostoglandin synthesis which in turn decreases the amount of pain felt in response to inflammation and tissue damage
Antipyretic effects - PGE2 acts on pre optic area to increase thermostatic set point. NSAIDS inhibit cox-2 therefore reduce the amount of PGE2 produced which in turn lowers the thermostatic set point and allows heat loss mechanisms to occur. (sweating + vasodilation).
What is the target of aspirin?
COX-1
What are some additional effects of aspirin?
Reduces platelet aggregation.
Analgesic
antipyretic.
Reduces risk of stroke + thromboembolism
How is Aspirin absorbed?
It is a weak acid - it is absorbed from stomach which is facilitated by the low pH.
It is hydrolysed to salycylic acid in plasma and at low theraputic doese most is bound to serum albumin.
How is Aspirin metabolized and excreted?
25% excreted unchanged
25% is oxidised
Some is conjugated with glucuronide or sulphate.
What are some of the adverse effects of aspirin?
Gastric bleeding due to the inhibition of COX-1 which is responsible for gastric mucosa protection - inhibition of platelets contributes to this effect.
Overdose (salicylism).
Due to viral infecton which causes liver/cns disturbances.
Also caused by chronic toxicity with repeated ingestion of high doses.
Causes altered acid base balance in the body which in turn uncoupled oxidative phosphrylation.
This leads to respiratory and metabolic acidosis
- causes tittinus, dizziness, hearing loss and nausea
What is the effects of paracetamol?
Weak antipyretic
Mild analgesic
Weak to no anti inflammatory properties.
How does paracetamol work?
Appears to inhibit Cox-1 and Cox-2 through metabolism by the perioxidase function.
Selectively inhibits synthesis of PGs when arachidonic acid and peroxides levels are low. However has little activity when levels of AA and PG are high.
- Does not suppress the severe inflammation for rheumatoid arthritis but will have some help in reducing inflammation following tooth extraction.
What are some of the adverse effects of paracetamol?
Overdose
- Can cause fatal liver toxicity due to saturation of normal liver enzymes.
- This causes paracetamol to be broken down by other enzymes which produces NAPQI.
- NAPQI is toxic if it isnt conjugated by glutathione.
What is the effects of ibuprofen?
Anti inflammatory
Anti-pyretic
Analgesic
Mild antiplatelet + vasodilation
What ways can ibuprofen be administered?
Orally, topically as is stable in solution.
What is one of the benefits of using topical ibuprofen compared to oral?
Less risk of gastric problems
What is the target of ibuprofen?
Cox- 1 and Cox- 2.
What are some adverse effects of ibuprofen?
Nausea dyspepsia, GI ulceration, Raised liver enzymes.
Exacerbate asthma sometime fatal
How can COX-1 inhibition cause gastric ulceration?
PGG2 and PGE2 usually protect gastric mucosa. - inhibition of COX decreases PG production.
Some drugs (aspirin) cause damage to mucosal cells directly.
COX-1 inhibitors inhibit platelet aggregation.
GI damage can be increased by concurrent glucocorticoid administration and dehydration and hypovolaemia.
What is the risks associated with using Cox-2 selective inhibitors?
Increases the risk of heart attacks and strokes
What is the inflammatory effects of Leukotrienes?
Bronchostriction
Vasodilation and oedema
Increased mucus secretion in airway and gut
Recruitment of leukocytes to site of inflammation.
What are some common CysLT receptor antagonists?
Zafirlukast
Montelukast.
Where are corticosteroids produces?
outer layer or cortex - mineralcorticoids
middle layer - glucocorticoids (hydrocortisone, corticosterone)
What is the result of low cortisol levels?
Muscle weakness
Hypotension
Hypoglycaemia
Weight loss
What is addisons disease?
Autoimmune destruction of the adrenal cortex .
Causes a decreased levels of glucocorticoids.
Treated by extrinsic hydrocortisone supplementation.
What are the anti-inflammatory effects of glucocorticoids?
Stimulate the production of Annexin 1 which inhibits Phospholipase A2- reduced concentration of AA.
When Glucocorticoids bind to their receptor they -
- up regulate the expression of nuclear anti inflammatory proteins.
- Repress the expression of cytosolic pro inflammatory proteins. Such as complement, NO, Histamine, IgG.
What are some of the clinical uses of glucocorticoids?
Asthma
Eczma
Rhinits
Hypersensitivty states (severe allergic response).
Misellaneous disease with autoimmune/anti inflammatory components.
Immunosuppression for graft rejection etc.
How are glucocorticoids administered?
oral, topical , parenteral (IV IM).
Once administered how do glucocorticoids get into cells?
Once in the blood they bind to the corticosteroid binding globulin then enter cells by diffusion.
How are glucocorticoids metabolized?
By the liver and secreted in urine.
What are some adverse effects of the use of glucocorticoids?
Increased risk of infection
Suppress endogenous cortisol production. - hypocortism.
Cushings disease due to excessive administration.
In what case would we not give a patient corticosteroids based upon their patient history?
Renal insufficiency / congestive heart failure.
Drug interactions may increase risk of bleeding and complications during dental surgery.
