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P A R T 6  Drugs acting on the endocrine system

■■ TABLE 37.3 Signs and symptoms of calcium imbalance System Hypocalcaemia

Hypercalcaemia

Central nervous system Cardiovascular

Hyperactive reflexes, paraesthesias, positive Chvostek andTrousseau signs Hypotension, prolonged QT interval, oedema and signs of cardiac insufficiency Tetany, skeletal muscle cramps, carpopedal spasm, laryngeal spasm, tetany Abdominal spasms and cramps

Lethargy, personality and behaviour changes, polydipsia, stupor, coma

Hypertension, shortening of the QT interval, atrioventricular block Anorexia, nausea, vomiting, constipation Muscle weakness, muscle atrophy, ataxia, loss of muscle tone Polyuria, flank pain, kidney stones, acute and/or chronic renal insufficiency

Gastrointestinal

Muscular

Renal

Skeletal

Bone pain, osteomalacia, bone deformities, fractures Osteopenia, osteoporosis

■■ BOX 37.3  Treatments for secondary hyperparathyroidism

In 2004, a new drug in a new class of calcimimetic agents, cinacalcet hydrochloride ( Sensipar ), was approved for treatment of secondary hyperparathyroidism in people undergoing dialysis for chronic kidney disease and for treatment of hypercalcaemia in people with parathyroid carcinoma. Cinacalcet is a calcimimetic drug that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. In increasing the receptors’ sensitivity, cinacalcet lowers parathyroid hormone (PTH) levels, causing hyperparathyroidism are 30 mg/day PO, after which PTH, serum calcium and serum phosphorus levels are monitored to achieve the desired therapeutic effect. The usual dose range is 60 to 180 mg/day. The drug must be used in combination with vitamin D and/or phosphate binders. For parathyroid carcinoma, the initial dose is 30 mg PO twice a day titrated every 2 to 4 weeks to maintain serum calcium levels within a normal range; 30 to 90 mg twice a day up to 90 mg three to four times daily may be needed. Osteoporosis Osteoporosis is the most common bone disease found in adults. It results from a lack of bone-building cell (osteoclast) activity and a decrease in bone matrix and mass, with less calcium and phosphorus being deposited in the bone.This can occur with advancing age, when the endocrine system is slowing down and the stimulation to build bone is absent; with menopause, when the calcium-depositing effects of oestrogen are lost; with malnutrition states, when vitamin C and proteins essential for bone production are absent from the diet; and with a lack of physical stress on the bones from lack of activity, which promotes calcium removal and does not stimulate osteoclast activity.The inactive, elderly, postmenopausal woman with a poor diet is a prime candidate for osteoporosis. Fractured hips and wrists, shrinking size, and curvature of the spine are all evidence of osteoporosis in this age group. Besides the use of bisphosphonates to encourage calcium deposition in the bone, several other interventions can help prevent severe osteoporosis in this group or in any other people with similar risk factors. • Aerobic exercise—Walking, even 10 minutes a day, has been shown to help increase osteoclast activity. Gender considerations BOX 37.4 a concomitant decrease in serum calcium levels. The usual initial adult doses for secondary

Side effects that the person may experience include nausea, vomiting, diarrhoea and dizziness. Another treatment available for secondary hyperparathyroidism related to renal failure is paricalcitol ( Zemplar ). Paricalcitol is an analogue of vitamin D. Vitamin D levels are decreased in renal disease, leading to an increase in PTH levels and signs and symptoms of hyperparathyroidism. Zemplar is taken orally or can be injected during haemodialysis. The body recognises the vitamin D and subsequently decreases the synthesis and storage of PTH, allowing a control over calcium levels. The usual dose is 1 to 4 mcg PO from once a day to three times a week, based on the person’s calcium levels, or 0.04 to 0.1 mcg/kg injected during haemodialysis. The drug is rapidly absorbed with peak levels within 3 hours. The drug has a half-life of 12 to 20 hours. People will need regular serum calcium checks, and dose will be adjusted based on individual response. Adverse effects are usually mild, as long as the calcium levels are monitored. Diarrhoea, headache and mild hypertension have been reported. Encourage people to walk around the block or to park their car far from the door and walk. Exercise does not have to involve vigorous gym activity to be beneficial. • Proper diet—Calcium and proteins are essential for bone growth.The person who eats only pasta and avoids milk products could benefit from calcium supplements and encouragement to eat protein at least two or three times a week. Weight loss can also help to improve activity and decrease pressure on bones at rest. • Hormone replacement therapy (HRT)—For women, HRT has been very successful in decreasing the progression of osteoporosis. Results of theWomen’s Health Study showed an increase in cardiovascular events with long-term HRT, making it a less desirable treatment. Women who are at high risk for breast cancer or who do not elect to take HRT may be good candidates for bisphosphonates. The risk of osteoporosis should be taken into consideration as part of the healthcare regimen for all people as they age. Prevention can save a great deal of pain and debilitation in the long run.