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P A R T 6
Drugs acting on the endocrine system
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TABLE 37.3 Signs and symptoms of calcium imbalance
System
Hypocalcaemia
Hypercalcaemia
Central nervous
system
Hyperactive reflexes, paraesthesias, positive
Chvostek andTrousseau signs
Lethargy, personality and behaviour
changes, polydipsia, stupor, coma
Cardiovascular
Hypotension, prolonged QT interval, oedema and
signs of cardiac insufficiency
Hypertension, shortening of the QT interval,
atrioventricular block
Gastrointestinal
Abdominal spasms and cramps
Anorexia, nausea, vomiting, constipation
Muscular
Tetany, skeletal muscle cramps, carpopedal spasm,
laryngeal spasm, tetany
Muscle weakness, muscle atrophy, ataxia,
loss of muscle tone
Renal
Polyuria, flank pain, kidney stones, acute
and/or chronic renal insufficiency
Skeletal
Bone pain, osteomalacia, bone deformities, fractures Osteopenia, osteoporosis
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
a concomitant decrease in serum calcium levels.
The usual initial adult doses for secondary
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.
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.
■■
BOX 37.3
Treatments for secondary hyperparathyroidism
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.
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.
Gender considerations
BOX 37.4
