Term
Which non-opioid analgesic is used to treat OA? |
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Definition
Tylenol/Acetaminophen Site of action: CNS. Inhibits COX only there |
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Term
Why doesn't Tylenol work at the site of inflammation? |
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Definition
Tylenol is inhibited by peroxides, no peroxides in the CNS. Inhibits fever due to CNS action |
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Term
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Definition
The amount it takes to inhibit to 50%. A lower number is more potent. |
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Term
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Definition
The highly reactive intermediate of tylenol found in the liver. Tied up by glutathione. If glutathione cannot process all of the NAPQI --> Liver toxicity |
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Term
What drug can be used to treat APAP toxicity? |
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Definition
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Term
What are the classifications of COX inhibitors? |
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Definition
- COX1 selective - Cox1 inhibitor with no activity on Cox2 - COX nonselective - Can inhibit both by fitting into both enzymes - COX 2 Preferential - Affects COX2 more than Cox1, but will inhibit Cox1 in higher doses - Cox-2 selective - Only inhibits Cox2 at maximum doses. |
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Term
Why were Cox2 inhibitors developed? |
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Definition
- Anti-inflammator effect - No effect on platelets, GI, renal function |
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Term
How is cox activity compared with IC50? |
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Definition
If you are looking at Cox1/Cox2 - a low ratio tells you the drug is more effective on Cox1 If you are looking at cox2/cox1 - a high number indicates more selective for cox1 Remember - lower IC50 = less required to take effect. |
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Term
What effect will different NSAIDs have on platelet aggregation? |
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Definition
ASA>Diclofenac>Celebrex/control ASA - irreversible platelet aggregation Motrin - reversible |
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Term
Which NSAID has uricosuric properties? |
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Definition
ASA in high doses, but can't use due to gastric side effects. |
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Term
How do drugs move to sites of inflammation? |
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Definition
The drug is unionized, moves to the site of inflammation and becomes ionized at a basic pH (weak acid) |
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Term
Which NSAID produces the highest maximum benefits? Are COX2 inhibitors better than non-selective? |
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Definition
None of them. They just take different doses to get there. No, best anti-inflammatory effect achieved if you inhibit COX1 and 2 |
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Term
How are ASA and sodium salicylate related? |
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Definition
Both act on neutrophils, but sodium salicylate has no effect on COX/platelets |
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Term
How does ASA affect NFkB? What other mechanisms are prostaglandin independent? |
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Definition
Blocks phosphorylation of IkB by IKK --> no transcription ASA also produces lipoxins when inhibiting COX2 |
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Term
What is the main mechanisms of NSAIDs? |
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Definition
Inhibits prostaglandins by inhibiting COX enzymes --> less pain from BK, less inflammation Inhibiting prostaglandins also inhibits IL-1 --> fever reduction. |
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Term
Are selective COX2 inhibitors better analgesics than non-selective? |
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Definition
No, but they last longer. |
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Term
What are the main side effects of NSAIDs? |
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Definition
Increased acid due to PG inhibition - PGs produce bicarb and protect mucous. Renal function - increase in blood pressure, decreased renal perfusion Reye's syndrome w/ ASA in children under 18 |
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Term
What are potential drug interactions w/ NSAIDs? |
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Definition
- Decrease in RBF interferes w/ loop diuretic activity, which increase PGs. - AceI - builds up BK while NSAIDs reduce BK - Hyperkalemia |
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Term
Which drugs are COX non-specific? |
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Definition
ASA Salsalate Diflunisal/Dolobid - weak Choline Salsalate/Trilisate |
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Term
Which drugs are Propionic Acids? Non-specific COX inhibitors |
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Definition
IBU/advil Fenoprofen/Nalfon Flurbiprofen/Ansaid - S isomer Ketoprofen/Orudis Fenoprofen/Nalfon Oxaprozin/Daypro Naproxen/Aleve |
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Term
Which drugs are Acetic acids? Non-specific COX inhibitors |
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Definition
Indomethacin/Indocin - potent Sulindac/Clinoril - prodrug Tolmetic/Tolectin Nabumetone/Relafen - metabolite Diclofenac/Voltaren Diclofenac + Misoprostil/Arthrotec Ketorolac/Toradol - analgesic only |
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Term
What drug is a Fenamate? Non-specific COX inhibitor? |
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Definition
Meclofenamic acid/Meclomen For dysmenorrhea |
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Term
What drugs are Pyranocarboxylic acids? Non-specific COX inhibitor |
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Definition
Etodolac/Lodine - may be more selective than mobic Oxicam Piroxicam/Feldene |
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Term
What drug is a Preferential COX2 inhibitor? |
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Definition
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Term
What drug is a Cox2 Specific inhibitor? |
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Definition
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Term
What drug depletes neuropeptides and how does it work? |
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Definition
Zostrix/Capsaicin - works on TRPV-1 receptors. Substance P. Depolarize nerve ending --> release of neuropeptide and eventual depletion --> some pain but then desensitization |
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Term
What are neutraceuticals? |
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Definition
OTCs that are chondroprotective: - Glucosamine - increased GAGs and hyaluronic acid, aggrecan. Inhibits MMPs, IL-1, iNOS - Chondroitin - inhibits NFkB, decreases cartilage loss Can be equivalent to IBU |
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Term
Which 3 class of drugs can reduce symptoms in RA? |
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Definition
- NSAIDs - DMARDs - Steroids |
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Term
How does NSAID use treat RA? |
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Definition
Less PGs, less neutrophils, may have a TNF and IL-1 effect. |
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Term
What is an example of a glucocorticoid? |
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Definition
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Term
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Definition
Hypothalamus --> anterior pituitary, ACTH released --> adrenal gland, cortisol released. Cortisol is a negative feedback, controls itself |
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Term
What is the MOA of steroids? |
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Definition
- Genomic theory - enters cytoplasm to produce proteins - Non-genomic theory - binds to cell membranes Anti-inflammatory activity tied to glucocorticoid activity EITHER NFkB blocked from going into nucleus or block NFkB binding to DNA |
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Term
What are the physiological effects of steroids? |
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Definition
tissue thinning, muscle wasting, diabetes, moon face and buffalo hump. Elevated mood, suppressed immune system Cushing's syndrome |
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Term
What are sites of action for steroids? |
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Definition
- Vascular permeability - Vasodilation - Adhesion - Chemotaxis - Leukocytes - Elimination of mediators |
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Term
How are steroids beneficial? |
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Definition
OA - reduce mediators, iNOS, MMPs RA - prevents migration of macrophages and neutrophils into synovial fluid SLE - blocks cytokines, reduces antibody complexes |
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Term
How do you compare steroid potency? |
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Definition
Everything is relative to cortisol, so divide mg equivalent by AIF potency = equivalent dose. |
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Term
What are the adverse effects of steroid drops? |
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Definition
Increase ocular pressure Ocular infections |
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Term
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Definition
Disease modifying anti-rheumatic drugs - Gold/Myochrysine or Solganol - Penicillamine/Depen or Cuprimine - Hydroxychloroquine/Plaquenil - Methotrexate/Rheumatrex - Sulfasalazine/Azulfidine - Cyclosporine/Sandimmune - Minocyline/Minocin - Azathoprine/Imuran - Leflonomide/Arava |
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Term
What drugs are in the class of biological agents? |
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Definition
- Etanercept/Enbrel - TNF, not antibody - Infliximab/Remicade - TNF - Adalimumab/Humira - TNF - Anakinra/Kineret - IL-1 - Rituximab/Rituxan - CD20 on B cells - Abatacept/Orencia - B7 on APCs - Golimumab/Simponi - TNF - Certolizumab pegol/Cimzia - TNF, not an antibody - Tocilzumab/Actemra - IL-6 |
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Term
What is the MOA of hydroxychloroquine? |
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Definition
Immunomodulator, interferes with antigen processing and the ability to produce antibodies. Concentrates in neutrophils Used in RA and SLE. Takes 2-4 months to work. |
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Term
What is the MOA of sulfasalazine? |
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Definition
Sulfa + salacylic acid Decreases antibodies and inhibits T/B cells. Increased formation of adenosine works in 1-2 months, not teratogenic |
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Term
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Definition
Decreases T cell activation and RF. Very toxic, takes 6 months to work |
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Term
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Definition
Inhibits DHFR - give folic acid to prevent this. Increased formation of adenosine --> anti-inflammatory. Low dose affects AICAR, inhibits adenosine deaminase, adenosine buildup. Decreased secretion of TNF, IL-1, IL-2, IL-6. Weekly dose, can cause severe fatigue. |
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Term
What is the MOA of Leflonamide? |
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Definition
Inhibits DHO dehydrogenase, reduces proliferation of T and B cells. Less toxic, still teratogenic. Alternative to MTX. |
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Term
What is the MOA of cyclophosphamide? |
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Definition
Inhibits mostly B cell activation, some T cells. Immunosuppressive, causes bladder inflammation and pulmonary fibrosis. Last resort. |
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Term
What is the MOA of azathioprine? |
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Definition
Decreases T and B cell activation - immunosuppressive. A purine antagonist. Bad in gout, some liver toxicity. |
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Term
What is the MOA of Mycophenolate? |
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Definition
Inhibits the enzyme that makes guanylic acid. Will still have some due to salvage, but lymphocytes have no feedback loop. Overall inhibition of purine synthesis. Similar to AZA in supressing B and T cells |
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Term
What is the MOA of cyclosporine? |
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Definition
Calcineurin must bind to calmodulin for IL-2 to be produced. Prevents that binding. Don't get the 3rd signal to activate T cells. Gingival hyperplasia |
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Term
Which drugs MOA are TNF antagonists? |
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Definition
- Etanercept/Enbrel - soluble TNF receptor. Can't use in crohn's. - Infliximab/Remicade - humanized, used IV. - Adalimumab/Humira - Golimumab/Simponi - Certolizumab pegol/Cimzia - pegylated. Decr immunogenicity, longer T1/2. No Fc = no phagocytosis |
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Term
What is the MoA of Anakinra/Kineret? |
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Definition
IL-1 receptor antagonist Should not use in combo with a TNF antagonist due to side effects |
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Term
What is the MoA of Abatacept/Orencia? |
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Definition
CTLA4 + Fc --> competes with CD28 for B7, blocking the 2nd signal in T cell activation |
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Term
What is the MoA of Rituxan/Rituximab? |
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Definition
Complement mediated cell lysis. Affinity for CD20, activation of complement. MAJOR reactions, can lead to death |
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Term
What is the MoA of Tocilzumab/Actemra? |
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Definition
IL-6 receptor antagonist. Can be used with MTX |
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Term
What is Benlysta/Belimumab? |
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Definition
A new drug that targets circulating Blys from B cells, avoiding ADCC. Decreases B cell activation, decreased side effects |
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