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? |
|
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
|
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? |
|
Definition
Increase ocular pressure
Ocular infections |
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Term
|
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? |
|
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? |
|
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
|
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? |
|
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? |
|
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? |
|
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? |
|
Definition
| IL-6 receptor antagonist. Can be used with MTX |
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Term
| What is Benlysta/Belimumab? |
|
Definition
| A new drug that targets circulating Blys from B cells, avoiding ADCC. Decreases B cell activation, decreased side effects |
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