Osteoarthritis/Rheumatoid Arthritis Drugs Flashcards
Acetaminophen (Tylenol)
- Non-specific COX inhibitor
- No anti-inflammatory effect like other NSAIDs (does relieve pain/fever)
- NOT USED TO TREAT ARTHRITIS
- Crosses BBB; can cause hyperventilation through direct brain stimulation (respiratory alkalosis)
- May cause acute hepatic failure
- Acute hepatic failure from CYP450 production of NAPQI (N-acetylcysteine is the antidote)
Acetyl-Salicylic Acid (Aspirin)
- Non-specific COX inhibitor (OA)
- Significant GI toxicity because of the acetylation of this drug
- In high doses, it’s as effective as any other NSAID
- Irreversible COX inhibition via acetylation (unlike all other NSAIDs)
- Worry of Reye’s Syndrome if given to children or high dose (liver and neural toxicity)
Diclofenac
- Non-specific COX inhibitor (OA)
* Big worry of cardiotoxicity
Ibuprofen
- Non-specific COX inhibitor (OA)
* Big worry of cardiotoxicity
Indomethacin
• Non-specific COX inhibitor (OA)
Ketoprofen
• Non-specific COX inhibitor (OA)
Ketorolac
- Non-specific COX inhibitor (OA)
* Largely unchanged by liver metabolism (58% parental drug excreted)
Naproxen
- Non-specific COX inhibitor (OA)
* Thought to be the most cardio-friendly
Piroxicam
• Non-specific COX inhibitor (OA)
Sulindac
- Non-specific COX inhibitor (OA)
* Moderate risk of hepatotoxicity due to hypersensitivity reactions
Celecoxib
- COX-2 specific inhibitor (OA)
- The only COX-2 specific drug on the market
- Works well, but worry of CV toxicity has limited this class
Methotrexate
• Non-steroidal DMARD
• Enters the cell and is polyagglutinated to retain it’s place within the cell (good concentrations)
• Inhibits:
o DHFR directly – stops folate (Vit. B9; cofactor for DNA synth.) production so cell can’t grow
o AMP deaminase/Adenosine deaminase indirectly – stops adenosine signaling in the cell
• Suppresses bone marrow, lymphocyte production, and ultimately IL-1 to decrease inflammation
• Increased IL-4 results in decreased histamine/neutrophil chemotaxis
• Side Effects
o Fatal interstitial pneumonitis (dry cough/shorness of breath) may occur (PFTs are recommended; always CXR/listen to the lung)
o Category X teratogen (don’t take if you may become pregnant or if breastfeeding)
o Myelosuppression
• Vaccinations are discouraged because lead to inadequate immune response formation against the bug to vaccinate against
• Increased risk of oppostunistic infections
• Increased risk of tumor deveopment
o Toxicity from high dose can be fixed with Leucovorin (THF analogue)
Hydroxychloroquine
• Non-steroidal DMARD
• Alkalinizes (increased pH) intracellular vacuoles to upset the typical acidic environment needed to digest proteins for antigen presentation
• Reduced antigen presentation from inability to form peptide-MHC protein complexes = little CD4+ stimulation and down-regulated immune response
• Side effects
o Hepatic damage from metabolism may occur
o Eye problems with vision loss is a rare, but testable side effect (ophthalmologic exams are recommended if you’re on this drug). Dose dependent.
Lefunomide
• Non-steroidal DMARD
• Converted to A771726 (active metabolite) that inhibits dihydroorotic acid dehydrogenase
• Stop pyramidine nucleic acid production and arrests B/T-cell proliferation (thus immunoglobulin production)
• Also slows production of uric acid so it can be used to treat gout
• Side Effects
o Will add to immunosuppressive drugs, so don’t use them together
o Liver damage from metabolic products (LFTs recommended)
o Category X teratogen (don’t take if you may become pregnant or if breastfeeding)
Sulfasalazine
- Non-steroidal DMARD
- Converted to sufapyridine and mesalamine by colon bacteria
- Mesalamine is the active metabolite; inhibits leukotriene/prostaglandin production (anti-inflam.)
- Sulfa drug so be aware of allergies!
Betamethasone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Cortisone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Dexamethasone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Hydrocortisone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Methylprednisolone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Prednisolone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Prednisone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Triamcinolone
• Corticosteroid DMARD
o Decreases NfKß/NF-AT signaling resulting in 1decreased IL-1 (fever/inflammation), 2IL-6 (acute phase reactants/inflammation), and 3TNF-a (inflammation)
Side Effects
o Glucocorticoid induced osteoporosis – increases RANKL/MCF expression in osteoblasts
o Cushingoid syndrome
o Rheumatoid Arthritis + Corticosteroids = 2x risk for cardiovascular events
o Can be avoided via intra-articular injection when possible
• Drug must have limited solubility so it stays within the joint capsule
• Worry of septic joints; if there’s signs of infection you must check before injection
Abatacept
- Biologic DMARD
- Binds CD-80/86 (CTLA4) to prevent T-cell co-stimulation with CD-28 (immunosuppressive)
- Contains maltose, which may complicate blood glucose testing
Adalimumab
• Biologic DMARD
Binds TNF-a action on p55/p75 cell surface receptors (anti-inflammation)
Anakinra
• Biologic DMARD
IL-1 receptor antagonist; inhibits IL-1a and IL-1b binding to receptors (anti-inflammation)
Certolizumab
• Biologic DMARD
antibody that neutralizes TNF-a through binding and sequestration (anti-inflammation)
Etanercept
• Biologic DMARD
false p75 receptor bound to IgG; binds TNF-a to neutralize it but doesn’t affect TNF production/serum levels (anti-inflammation)
Golimumab
• Biologic DMARD
antibody that neutralizes TNF-a through binding and sequestration (anti-inflammation)
Infliximab
- Biologic DMARD
- antibody that neutralizes TNF-a through binding and sequestration (anti-inflammation)
- Contraindicated in patients with previous cardiac problem
Rituximab
- Biologic DMARD
- IgG type antibody against CD-20 (B-cell marker); mediates B-cell lysis (immunosuppressive)
- Women MUST be on reliable birth control because B-cell depletion of the fetus will occur (IgG drug crosses the placenta)
- Must be off the drug for 4-6 months after therapy
Tocilizumab
• Biologic DMARD
false IL-6 receptor to neutralize/sequester IL-6 (anti-inflammatory)
Apremilast
• Biologic DMARD
• orally active phosphodiesterase inhibitor (PDE4); produces pro-inflammatory mediators
• Weight loss is a major side effects (10-15% loss is typical)
o Bodyweight requirement to take this drug
• BBW of suicidal ideation (rare, but necessary to look out for)
