NSAIDs and Steroids

NSAIDs

most common drugs; nonsteroidal

stop COX-1 and COX-2 enzyme activity(if non selective)

primary: anti-inflammatory

analgesic

antipyretic

anticoagulant

ex: aspirin, ibuprofen, naproxen

Prostaglandins

lipid-like compounds

produced by virtually every type of cell in our bodies

hormones act locally to regulate cell function

increase sensitivity of pain receptors, elevate body temp, cramps in endometrium, platelet aggregation

GI and cardiovascular protective functions

what are prostaglandins synthesized from

arachidonic acid(lipid like compound pulled from phospholipid bilayer)

what are arachidonic acid metabolized by

cyclooxygenase(COX) enzyme

changes arachidonic acid into prostaglandins

what happens with tissue damage

injury → phospholipids → arachidonic acid →

COX -2 enzyme = changes it into inflammatory prostaglandins to heal the tissue

COX-1 keeps creating cytoprotective prostaglandins

cytoprotective prostaglandins

always going on through COX-1 enzyme

protects gastric mucosa

aid platelet aggregation

aspirin

gold standard NSAIDs

non-aspirin NSAIDs

nonselective COX inhibitors

• aspirin, ibuprofen, naproxen

preferential COX-2 inhibitors(mostly cox-2, but some cox-1 may be affected)

• meloxicam

selective COX-2 inhibitors

• celebrex

acetaminophen/tylenol

NOT an NSAID

its an analgesic, antipyretic

NOT anti-inflammatory, NOT anticoagulant, NO GI irritation

liver toxicity in high dosis

generally safe(TI = 27)

Aspirin & nonselective NSAID MOA

potent inhibitors of cyclooxygenase enzyme(1st step in prostaglandin synthesis

gastric irritation/risk(no cox-1 activity which protects the mucosa)

cardiac risk

selective NSAIDs(cox-2 inhibitors) MOA

selective inhibition of COX-2 enzyme, which is produced primarily in injured or diseased cells

COX-1 enzymes produce prostaglandins that are beneficial to tissues such as stomach lining and kidneys

little gastric irritation and no anticoagulation

increased cardiac risk

COX-2 inhibitor(-coxib)

increased risk of heart attack and stroke

impair production of prostacyclin, which promotes vasodilation in coronary arteries

DO NOT inhibit thromboxone(COX-1 anticoagulant product)

increased risk of clots in susceptible patients

cardiac screening for cardiac risk

not more effective, but good alternative

how do NSAIDs impact cardiovascular health

impeach prostaglandins that dilate vasculature

NSAIDs to know

Aspirin

Ibuprofen - less than aspirin’s half-life

Naproxen - more than aspirin’s half-life

Meloxicam(mobic) - preferential cox-2 inhibitor; longer half-life

Celecoxib(celebrex) - 11hr half-life, cox-2 specific

diclofenac(voltaren) - more effective in acute situations; shorter half-life

ketorolac(toradol) - most potent and effective; intravenous; good for those who can’t use opioids or need to wean off

NSAIDs PT implication

mainstay in treatment of mild-moderate pain

most common treatment of acute and chronic musculoskeletal disorders

increased risk of bleeding/bruising, GI risk

patient education

caution with chronic use

potential gastric and cardiac side effects

Corticosteroid - Glucocorticoids

endogenous - released by adrenal gland as cortisol/coricosteron

Glucocorticoid MOA

alter protein synthesis in the cell via RNA transcription by turning off inflammatory and immune response and suppressing products of inflammation

clinical uses of glucocorticoids

anti-inflammation: reduce heat, redness, swelling and tenderness of inflammation regardless of the cause

immunosuppression: inhibit transcription of factors that signal and direct cells in an immune response

allergic reactions, nonrheumatic inflammation, neoplastic disease, neurological disease, neurotrauma, renal disease, organ transplant

dermatologic, endocrine, GI, hematologic, rheumatic, ophthalmic, respiratory disorders

glucocorticoids adverse effects

adrenocortical suppression

cushing syndrome

tissue breakdown

peptic ulcer

immunosuppression

hypertension

hyperglycemia

need to give time for adrenals to kick back in when weaning off of glucocorticoids

steroid PT implication

catabolic breakdown of muscle and bone(higher chance of strain, sprain or fracture) - need strategic exercise and educate why its necessary

caution with local injection sites(worse before better) and rheumatic disorders

guard against infection

focus on strength and ambulation

gradual increase in intensity

steroids

Prednisone - middle time effect; intermediate; becomes prednisolone when activated

cortisone - shorter acting

dexamethasone - longer acting

prednisolone - active metabolite; for those with liver issues

-sone - not active

-olone - step closer to active

cortisol pathway

cortisol - stress hormone adrenals form and metabolized into prednisone which becomes prednisolone then methylprednisolone