NSAIDS, Gout tx Flashcards
Describe cellular and molecular events that contribute to Inflammatory soup
antigen/stim, local vasodilation, inc capillary perm, activation of many molecular inflammatory mediators (Kinins, neuropeptides, vasoactive amines, AA metabolites, cytokines, free radicals), Inc stim of mast cells, infiltration of leukocytes, phagocytosis, tissue degeneration
Describe properies and functions of arachidonic acid metabolites, COX1 and COX2 and their roles in the inflammatory process, pain and fever/temp reg.
COX1 - always active, housekeeping, Protective function
COX2 - Inducible, prod inflammatory molecules, Inflammatory function
Acetylasalicilic Acid (aspirin)
Characteristic
Uses
Non Selective NSAID
Irreversible acetylates COX
significant amount is hydrolyzed to salicylic acid in blood - which is excreted in urine
80% potential for drug interactions
Effects: Analgesic, Anti-Inflammatory, Anti-Pyretic (blocks PG in CNS to reset temp, plus dilation of superficial blood vessels), Anti coagulant (prolonged bleeding time)
Use: Anti Pyresis, Acute RA, Analgesia
describe the dose dependent pharmakokinetics of aspirin.
Low dose: 80mg - antiplatelet aggregation
Moderate: 600mg - analgesia/antiparesis
- half life: 3-5h First order kinetics
HIgh: >4000mg/day - Anti-inflammatory
- Half life 12h - Zero order kinetics
Describe Uses and AEs of aspirin - pay attention to GI and platelet side effects. Remember these are driven by COX1 not COX2
Effects: Analgesic, anti-inflammatory, Anty pyretic, Anti coagulant,
AE: Gi Upset, GI irritation, Platelet inhibition, Hepatic and Renal toxicity, Hypersensitivity, Tinnitus, Reye’s Syndrome
Why were COX2 inhibitors developed?
what are their advantages?
What is the major downfall?
When would you prescribe COX2 selective NSAIDS?
They are better
anti inflam, anti pyretic, analgesic still
Less GI AE
No impact on platelet aggregation
Cardiovascular thrombotic events associated with Cox2 inhibitors
Prescribe when you dont want GI effects.
How does acetaminophen differ from NSAIDs in effect? what is the major acetaminophen safety concern?
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Acetaminophen has no anti inflammatory effect!
- not useful for treating pnts with inflamm dz
-Inhibits COX in CNS not in periphery
Safety concern is Hepatotoxicity at high doses. \
Antidote: N acetylcysteine - replenishes GSH
Narrow TI
Describe the pathophysiology of gout
Hyperuricemia - leads to uric acid crystal formation - inflammation results in phagocytosis of crystals - low pH leads to increased uric acid crystalization
What are agents used to treat acute gouty attack?
NSAIDs are first line for inflammation (indomethacin)
- not aspirin - renal retention of uric acid
- Colchicine used to be first line
Corticosteroids - second line
Intra articular steroid injection
Treatment strategy for gout prophylaxis
Xanthine Oxidase Inhibitors
- Allopurinol: blocks xanthine to Uric acid
- Febuxostat: well tolerated if allopurinol sensitive
Uricosuric drugs
- Probenecid and Sulfinpyrazone: Increase renal excretion of uric acid by inhibiting reabsorption - couild cause kidney stones/dont use if renal damage/acute attack
Treatemtn strategy for RA
Which drugs treat symptoms?
Which drugs slow progression?
Nsaids treat symptoms
Glucocorticoids reduce inflam.
Then slow progression with DMARDs
Advantages/Disadvantages of DMARDS
What is first line DMARD for RA?
WHich DMARD was first agent indicated for symptomatic AND retardation of jt damage in RA?
What are biologic DMARDS?
DMARDs are more long term tx Synthetic #1 - MTX: inhibits AICAR Leflunomide was first DMARD indicated for both symptomatic improvement and retardation Biologic DMARDs has a double meaning: - Organic compound made by living cells - Modify biologic processes
What is the current hypothesis and pathophysiology of migraine?
Headache: 4-72 hrs
Headache is: Pulsing, unilateral, mod-sev pain, avoidance
During headache: N/V, Photophobia
at least 5 attacks with these criteria
Migraine starts from deep in brain, spreads out, causes visual disturbances/numbness/tingling, chemicals cause blood vessel dilation, which irritates the trigeminal nerve causing throbbing
What strategies and drug classes are used for preventive therapy of migraine?
Avoid triggers, regular sleep, meals, exercise
Beta blockers - Propanolol Metoprolol - Red energy
Amitriptyline - TCA - drowsy
Anticonvulsants - Divalproex, Topiramate-drowsy, terat
Ca chan block - FLunarizine-Tiredness
What strategies and drug classes are used for treatment of acute migraine attacks?
1)Aspirin - 900mg Naproxen, Ibuprofen (NSAID) Acetaminophen - poorly effective Take with ANTI EMETIC for better absorption-prev N/V- -Metoclopramide - Chlorpromazine - Prochlorperazine
Do NOT overuse - 2-3 days max or it will transform
2) Opiate analagesics
for severe migraine, risk of transforming, dependence
