Anti Inflammatories Flashcards
Why are NSAIDs used in Rheumatoid Conditions?
- reduce associated pain
- improve mobility
- slow or arrest tissue-damage, not curative though
**aspirin is no longer the initial drug of choice in treating articular and musculoskeletal disorders
What is the adverse result of reduction in PGE2 levels caused by NSAIDs?
-decreased gastric mucosal acid secretion
What is the adverse result of reduction in PGI2 levels caused by NSAIDs?
-decreased vasodilatory actions reducing cytoprotective properties
What is the beneficial result of reduciton in PGE2 levels caused by NSAIDs?
-decreased erythema, edema, pain, local heat, and systemic fever
What is the beneficial result of reduction in PGI2 levels caused by NSAIDs?
-Decreased erythema, pain, local heat, and systemic fever
What is erythema?
-redness of the skin or mucosa
Why is inhibition of COX-1 bad?
- it results in most of the unwanted side effects of NSAIDs
- particularly gastric ulcers
Why is inhibition of COX-2 good?
Inhibition of COX-2 is thought to mediate,at least in part, the antipyretic (antifever), analgesic and anti-inflammatory actions of NSAIDs
What are the most common GI side effects of NSAIDs? Mechanism?
- Gastric or intestinal ulceration
- Caused by inhibition of PGI2 and PGE2
What are the most common Hemostatic effects of NSAIDs? Mechanism?
- disturbances in platelet function
- Inhibition of Thromboxane A2
What kind of patient is more susceptible to Stevens-Johnson Syndrome caused by NSAIDS?
-patients with Lupus or HIV
What is Stevens-Johnson syndrome?
-A diffuse, severe, mucocutaneous eruption involving 2 or more mucosal surfaces
+/- visceral involvement
What is the most common use of Aspirin?
-inhibition of platelet aggregation
How does aspirin affect warfarin levels? Why?
- Increases plasma warfarin levels
- displaces warfarin from plasma protein binding sites
How do we manage aspirin overdose?
- Patient will be acidemic
- cardiovascular and respiratory support followed by administration of sodium bicarbonate to correct acid-base abnormalities
Is acetaminophen a NSAID?
- maybe
- it is an effective alternative to aspirin, used as an analgesic-antipyretic, but lacks the anti-inflammatory and anti platelet effects
- It is a weak inhibitor of peripheral COX
What is the antidote for acetaminophen overdose?
- activated charcoal
- N-acetyl-cysteine (Mucomyst), a replacement for glutathione
- consider liver transplant for pts with fulminant hepatic failure
What is Indomethacin used for?
- NSAID
- Anti-inflammatory in treatment of gouty arthritis and ankylosing spondylitis
- Also promotes closure of patent ductus arteriosus in newborns
**not for simple analgesia
Ketorolac is a potent analgesic, when is it used?
- One of the few NSAIDs approved for parenteral administration
- Use for post-op pain when pt cannot swallow, and you don’t want to give a narcotic
What are COXIBs?
-NSAIDs that have been designed to selectively target COX-2 over COX-1 to minimize stomach ulcer risk
Do NSAIDS affect leukotriene synthesis?
-no
Why don’t we give aspirin to children? What can we give instead?
- there is an epidemiological association of Reye’s Syndrome in children (ages 2 to 16) with administration of aspirin for the treatment of febrile viral illnessess (influenza B > A) -> FUO
- can give acetaminophen
What does Reye’s syndrome involve?
-swelling of the liver and edema of the brain
What should Grammy do if she decides to take aspirin/NSAIDs while taking warfarin?
-Have her prothrombin time checked
What are the higher strength fluorinated glucocorticoids?
- dexamethasone
- triamcinolone
Glucocorticoids bind to Hormone Responsive Elements (HREs) which cause induction of ________.
Lipocortins
What do lipocortins do?
- suppress phospholipase A2
- decrease release of arachidonic acid & production of proinflammatory eicosanoids
What are the adverse effects of long term corticosteroids?
- perforations
- ulcerations
- bleeds
- immunodeficiency
- hyperglycemia/diabetes
- osteoporosis/osteonecrosis
- cateracts
- adrenal atrophy
How do corticosteroids work on the cellular level?
block cellular recruitment to a site of inflammation by inhibiting chemotactic factors
How do corticosteroids function on connective tissue?
- promote tissue repair
- synthesis of new tissue & repair damaged tissue
What does 11B-HSD II do?
- degrades glucocorticoids
* chemists want to decrease affinity of synthetic steroids for this enzyme, so they last longer
Addison’s disease
- don’t make enough cortisol
- treat with hydrocortisone with a mineralocorticoid
Are steroids a good treatment for meningitis?
-yeh
Cushing’s Syndrome
- too much ACTH
- caused by pituitary or ectopic ACTH overproduction
What are the adverse effects of withdrawal from glucocorticoid therapy?
- Most frequent: flare up of the disease
- Most severe: acute adrenal insufficiency
**if changing route of administration, keep in mind the systemic effects, might need to taper dose
