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Superoxide Dismutase

Class: antioxidant.

Mechanism of action: superoxide dismutase catalyzes the conversion of superoxide to oxygen and hydrogen peroxide, reducing damage from radical oxygen species.

  • Use: osteoarthritis, rheumatoid arthritis.
  • Dosing:

° Osteoarthritis: 16 mg as an intra-articular injection every two weeks.54

=> Rheumatoid arthritis: 4 mg intra-articular injection once weekly for up to 6 weeks.55

  • Adverse effects: pain or allergic reaction at the injection site.56
  • Contraindications: hypersensitivity to superoxide dismutase or any of its components.
  • Drug interactions: none known.
  • Cautions: insufficient reliable information available regarding pregnancy and lactation; avoid using.

Vitamin C

  • Class: water-soluble vitamin, antioxidant.
  • Mechanism of action: mechanism of action related to pain is unknown and further research is needed to understand how vitamin C helps to alleviate pain in osteoarthritis and postoperative pain.
  • Use: osteoarthritis, post-operative pain.
  • Dosing:

° Osteoarthritis: vitamin C in the form of calcium ascorbate 1 gram daily for 2 weeks has been used.57

° Postoperative pain: a single prophylactic dose of 2 grams of vitamin C by mouth, 1 hour prior to anesthesia has been used in patients (tested in patients receiving cholecystectomy).58

Adverse effects: dose-related adverse effects, most common including nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, fatigue, flushing, headache, insomnia, sleepiness, and diarrhea.59

° Doses greater than the tolerable upper limit of 2 g per day can increase the risk of severe adverse effects such as osmotic diarrhea.

  • Contraindications: hypersensitivity to vitamin C and any of its components.
  • Drug interactions:

° Acetaminophen: high doses of vitamin C (3 grams) competitively inhibit the sulfate conjugation of acetaminophen, resulting in an increase in the fractions of the dose of acetaminophen excreted as acetaminophen glucuronide and a decrease in the fraction excreted as acetaminophen sulfate. May not be clinically significant.60

° Alkylating agents: use of vitamin C during chemotherapy may reduce the activity of chemotherapy and generate free radicals.61

=> Aluminum: vitamin C can increase the amount of aluminum absorbed from aluminum compounds.62

=> Aspirin/salicylates: acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules and increase plasma salicylate levels.63

=> Estrogen: vitamin C may increase plasma estrogen levels up to 47% when vitamin C is taken with oral contraceptives or hormone replacement therapy, including topical products.64

° Fluphenazine: vitamin C may decrease fluphenazine levels when used concurrently with vitamin C 500 mg twice daily.65

=> Protease inhibitors: taking vitamin C orally along with indinavir may modestly reduce indinavir levels.66 Vitamin C may modestly reduce levels of other protease inhibitors as well.

=> Dihydropyridine calcium channel blockers: these medications (e.g., nicardipine) inhibit uptake of vitamin C by intestinal cells. It is unknown if this is clinically significant.67

=> Warfarin: high doses of vitamin C may reduce the response to warfarin, possibly causing diarrhea and reduced w'arfarin absorption, and it was concluded that it was not clinically significant.68

Cautions: do not exceed tolerable upper limit of 2g per day.

Vitamin E

Class: antioxidant.

Mechanism of action: mechanism in relation to pain reduction is not known and further research is needed.

  • Use: osteoarthritis, rheumatoid arthritis.
  • Dosing:

<= Rheumatoid arthritis/osteoarthritis: 600 mg orally twice daily.69

  • Adverse effects: nausea, diarrhea, intestinal cramps, weakness, headache, blurred vision, rash, gonadal dysfunction, and creatinuria.70
  • Contraindications: none knowm.
  • Drug interactions:

<= Alkylating agents: the use of antioxidants such as vitamin E during chemotherapy can interfere with chemotherapy activity and may generate free radicals.61

<= Anticoagulant/antiplatelet drugs: concomitant use of vitamin E and anticoagulant or antiplatelet drugs might increase the risk of bleeding by inhibition of platelet aggregation and antagonization of the effects of vitamin К-dependent clotting factors.71

<> Cytochrome P450 3A4 substrates: vitamin E may increase the metabolism of drugs metabolized by CYP3A4. Vitamin E appears to bind with the nuclear receptor (pregnane X receptor [PXR]), which may result in increased expression of CYP4A4.72

  • Warfarin: greater than 400IU of vitamin E per day may prolong prothrombin time, INR, and increase the risk of bleeding due to interference with vitamin К-dependent clotting factors.73
  • Cautions: none reported.

Chondroitin Sulfate

  • Class: structure-modifying agent.
  • Mechanism of action: in chondrocytes, chondroitin sulfate has been suggested to reduce the interleukin-1 (IL-1) beta-induced increase in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase V2 (Erkl/2) phosphorylation, resulting in a decrease in the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the reduction of proinflammatory cytokine and enzyme production.74
  • Use: osteoarthritis, exercise-induced muscle soreness.
  • Dosing: 800 to 2000 mg daily as a single dose or in two or three divided doses for up to 3 years.75
  • Adverse effects: well-tolerated.
  • Contraindications: allergy to shark and bovine.
  • Drug interactions:

° Warfarin: taking chondroitin in combination with glucosamine might increase the anticoagulation effects of warfarin and increase risk of bruising and bleeding. May increase INR.76

Cautions: allergy to shark and bovine.

 
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