OA and Gout Medications Flashcards
What is first line pain relief in OA
Acetaminophen is considered first line therapy for pain relief in osteoarthritis (OA) and has less toxicity in comparison to NSAIDs.
Acetaminophen mechanism of actions
Acetaminophen has some prostaglandin changes, but the mechanism of action is not fully elucidated. Acetaminophen reversibly inhibits cyclooxygenase, mostly in the CNS.
Adverse affects of acetaminophen
it is metabolized in liver and high doses overwhelm conjugation mechanism and acetaminophen is converted to toxic NAPQI (N-acetyl-p-benzoquinone imine) which depletes glutathione. N-acetylcysteine is the antidote and regenerates glutathione.
Liver failure is main cause of morbidity/mortality.
No GI toxicities like other NSAIDS
Why are NSAIDS not first line for OA treatment
Chronic NSAIDs have significant side effects and proven aggregate efficacy for any drug is poor. Additionally, older patients have more NSAID risks, and some NSAIDs seem to have increased cardiovascular risk.
What are the 4 main lines of treatment for acute Gout
- NSAIDS
- Colchicine
- Steroids
- Rest, analgesia, ice, time
Mechanism for NSAIDs
NSAIDS are COX-1 and COX-2 inhibitors, but essentially provide equivalent relief of pain and inflammation.
The primary effect of NSAIDs is to reversibly inhibit COX-cyclooxygenase (prostaglandin synthase), impairing the transformation of arachidonic acid to prostaglandins, prostacyclin, and thromboxanes (TXA2)
What is COX-1
COX-1 is expressed in most tissues but variably and is the “housekeeping” enzyme, regulating cellular processes (such as gastric cytoprotection, vascular homeostasis, platelet aggregation, kidney function).
What is COX-2
COX-2 is usually undetectable in most tissues but COX-2 expression is increased during states of inflammation, constitutively expressed in brain, kidney, bone, some others.
NSAIDs side effects
Non-selective NSAIDS have more GI effects, including gastric bleeding and peptic ulcers, and anti-platelet effect than selective COX2 inhibitors. Because of the effects of NSAIDS on the kidney and CV system, stroke, MI, hypertension and acute kidney injury can occur. More selective COX-2 inhibitors spare COX-1 which helps maintain gastric mucosa and have less corrosive effects of other NSAIDs on GI lining. COX-2 inhibitors also spare platelet function as TXA2 production is dependent on COX-1.
Only selective COX-2 inhibitor in the US
Celecoxib
Aspirin uses in low, medium, and high doses
Low dose aspirin (<300mg/day) decreases platelet aggregation.
Intermediate doses of 300-2400 mg/day are used for its antipyretic and analgesic effects.
High doses of aspirin in excess of 2400 mg/day are used for its anti-inflammatory effect.
Mechanism of aspirin
Aspirin irreversibly inhibits cyclooxygenase, both COX-1 (mostly) and COX-2 (somewhat). Most other NSAIDs are reversible inhibitors. Briefly, aspirin decreases the synthesis of TXA2 (low doses) and prostaglandins (intermediate and high doses). Because of its affects on TXA2, aspirin increases bleeding time.
Side effects of aspirin
Since aspirin inhibits both COX-1 and COX-2, it can causes GI issues including ulcers and GI bleeding. It also can cause acute kidney injury and interstitial nephritis with chronic use.
Tinnitus and hearing loss
Reye syndrome in children
Colchicine use
used for centuries for the treatment of gout. It acts as an anti-inflammatory agent, but has no analgesic properties.
Colchicine mechanism
Colchicine decreases leukocyte mobility by binding to tublin and inhibiting microtubule formation, arresting neutrophil motility. It decreases phagocytosis in joints and decreases lactic acid production. Overall effect-Interruption of inflammatory process
Xanthine oxidase inhibitors mechanism
Allopurinol prevents the formation of uric acid from hypoxanthine xanthine.
Mechanism of uricosuric drugs
Prevent reuptake of uric acid
