Drug Topics - December 10, 2007 - (Page 33)

33 petite, sleepiness, nausea, vomiting, abdominal cramps, tinnitus in the ear, and dizziness. Renal insufficiency may occur if calcium phosphate precipitates in the renal tubules. Symptoms of renal insufficiency may include increased thirst, inability to concentrate urine, nighttime awakening to urinate, and urinary frequency. It is important for the calcium supplement to be administered in daily divided doses. Calcium absorption is by active transport mechanisms, which limit the amount of calcium absorbed by the GI tract at one time. Another administration concern focuses on the absorption of commercially available calcium products. There are two main formulations of calcium supplementation. Calcium carbonate provides 40% of elemental calcium, while calcium citrate provides 21%. For patients older than 50 years, calcium citrate is the best alternative because it does not require acid in the stomach to be activated and can be taken without regard to meals. The citrate salt is also the salt form of choice with the use of a proton pump inhibitor because proton pump inhibitors diminish gastric acid. Other medications such as thiazide diuretics, calcium-channel blockers, and bisphosphonates increase calcium concentrations. It also appears thyroid replacement agents, tetracycline, quinolone antibiotics, and sotalol may all decrease calcium absorption if taken along with calcium because of the formation of insoluble complexes. These medications should be separated from calcium consumption by at least two hours. Vitamin D: Vitamin D is a fat-soluble vitamin. It is found pri- marily in two forms in the body: cholecalciferol (D3) and ergocalciferol (D2). Cholecalciferol is synthesized in the skin by a cholesterol precursor, 7-dehydrocholesterol, because of exposure to ultraviolet light. Skin exposure to ultraviolet radiation provides the body with its most significant amount of daily vitamin D. Brief sun exposure produces 25% of recommended daily vitamin D, and full sun exposure produces 80% to 90% of daily required vitamin D. These percentages have been shown to be decreased for patients where ultraviolet intensity is weak, based on the latitude, seasons, altitude, cloud cover, and ozone levels of the region. Adequate dietary intake can be obtained from fish and fortified milk or cereals. Ergocalciferol is the form of vitamin D that comes from plant sterols and has one-third the potency of cholecalciferol. Through a process of hydroxylation, both forms are converted to the active metabolite, calcitriol. Activated vitamin D is believed to decrease bone loss, increase bone mineral density, reduce the risk of fracture, and reduce the risks of falls in elderly patients diagnosed with osteoporosis. In the body, vitamin D works more like a hormone than a vitamin, based on its control of target cells. It is primarily responsible for the regulation of intracellular and extracellular levels of calcium and phosphate in the body. Calcitriol, the active form of vitamin D inhibits the release of parathyroid hormone. Parathyroid hormone is normally responsible for the increase in serum blood calcium levels. Inhibiting parathyroid hormone in the body brings about an increase in calcium and phosphate resorption from the kidneys and a decrease in release of calcium from the bone matrix. Vitamin D controls the levels of calcium and phosphate in the body primarily by promoting absorption from food into the jejunum and ileum of the small intestine. Vitamin D also appears to have a mobilization effect on stem cells in the body, leading to an increase of osteoblasts being synthesized. A normal therapeutic dose of vitamin D for the prevention of fractures and osteoporosis in elderly patients is 800 to 1,000 IU per day. It also appears that an intake of vitamin D along with 1,200 mg of calcium per day may be necessary for it to reach the maximum effect as well as for it to be used in the prevention of falls for elderly patients. Vitamin D has a daily upper limit of 2,000 IU. A meta-analysis of randomized controlled trials published in 2005 found 700 to 800 IU of oral vitamin D3 alone reduced both institutionalized and ambulatory bone fracture risk. Subsequent reports stated the addition of calcium to the medication regimen was warranted to significantly reduce fracture risk. However, a large-scale study by Jackson in 2006 found a different outcome. This study focused on postmenopausal women aged 50 to 79. Patients were treated with 1,000 mg of calcium along with 400 IU daily of vitamin D3 for seven years. The study concluded there were only modest improvements in bone mineral density and no reduction in risk factors. The regimen most likely to be effective is a combination of vitamin D with calcium. A unique benefit vitamin D appears to offer is the ability to reduce the number of falls by 22%. It has been shown that vitamin D can increase muscle strength and neuromuscular activity by increasing the synthesis of muscle protein through a process of phosphorylation and the addition of secondary messengers. An important consideration for this natural product is the dose administered. One study by Broe et al. found lower doses were not effective, but doses of 800 IU daily did significantly reduce the risk of falls when compared with the placebo group. Vitamin D is considered to be well tolerated by patients when taken orally. When excessive doses are ingested, symptoms of hypercalcemia and renal failure may occur. These signs and symptoms are the same as those previously discussed with calcium. Renal impairment is usually reversed upon discontinuation of vitamin D. Because vitamin D is a fat-soluble vitamin, medications such as mineral oil, cholestyramine, and orlistat may lead to a decrease in the absorption of fat from the diet as well as fatsoluble vitamins. Other possible drug interactions may be seen with hydrochlorothiazide, verapamil, and diltiazem. These medications can lead to additional increases in calcium blood levels, as previously reported with calcium. Contraindications with this medication include patients with hypercalcemia and renal insufficiency because of the increased risk of toxicity and renal failure. Ipriflavone: Ipriflavone (7-isopropoxyisoflavone) is synthe- sized from soy isoflavone. Isoflavones act as antioxidants and

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Drug Topics - December 10, 2007

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