Page 711 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 38 Thyroid & Antithyroid Drugs 697

Since interactions with certain foods (eg, bran, soy, coffee) and It is important to give all preparations intravenously, because
drugs (Table 38–3) can impair its absorption, thyroxine should be patients with myxedema coma absorb drugs poorly from other
administered on an empty stomach (eg, 60 minutes before meals, routes. Intravenous fluids should be administered with caution
4 hours after meals, or at bedtime) to maintain TSH within an to avoid excessive water intake. These patients have large pools of
optimal range of 0.5–2.5 mIU/L. Its long half-life of 7 days per- empty T and T binding sites that must be filled before there is
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mits once-daily dosing. Children should be monitored for normal adequate free thyroxine to affect tissue metabolism. Accordingly,
growth and development. Serum TSH and free thyroxine should the treatment of choice in myxedema coma is to give a loading
always be measured before a change in dosage to avoid transient dose of levothyroxine intravenously—usually 300–400 mcg ini-
serum alterations. It takes 6–8 weeks after starting a given dose of tially, followed by 50–100 mcg daily. Intravenous T 5–20 mcg
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thyroxine to reach steady-state levels in the bloodstream. Thus, initially, followed by 2.5–10 mcg every 8 hours also can be added
dosage changes should be made slowly. but may be more cardiotoxic and more difficult to monitor. Lower
In younger patients or those with very mild disease, full T and T doses should be considered for smaller or older patients,
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replacement therapy may be started immediately. In older patients or those with concomitant cardiac disease or arrhythmias. Intra-
(>50 years) without cardiac disease, levothyroxine can be started venous hydrocortisone is indicated if the patient has associated
at a dosage of 50 mcg/d. In long-standing hypothyroidism and in adrenal or pituitary insufficiency but is probably not necessary
older patients with underlying cardiac disease, it is imperative to in most patients with primary myxedema. Opioids and sedatives
start with reduced dosages of levothyroxine, 12.5–25 mcg/d for must be used with extreme caution.
2 weeks, before increasing by 12.5–25 mcg/d every 2 weeks until
euthyroidism or drug toxicity is observed. In cardiac patients, the C. Hypothyroidism and Pregnancy
heart is very sensitive to the level of circulating thyroxine, and if Hypothyroid women frequently have anovulatory cycles and are
angina pectoris or cardiac arrhythmia develops, it is essential to therefore relatively infertile until restoration of the euthyroid state.
stop or reduce the thyroxine dosage immediately. This has led to the widespread use of thyroid hormone for infer-
Thyroxine toxicity is directly related to the hormone level. In tility, although there is no evidence for its usefulness in infertile
children, restlessness, insomnia, and accelerated bone maturation euthyroid patients. In a pregnant hypothyroid patient receiving
and growth may be signs of thyroxine toxicity. In adults, increased thyroxine, it is extremely important that the daily dose of thy-
nervousness, heat intolerance, episodes of palpitation and tachycar- roxine be adequate because early development of the fetal brain
dia, or unexplained weight loss may be the presenting symptoms. depends on maternal thyroxine. In many hypothyroid patients,
If these symptoms are present, it is important to monitor serum an increase in the thyroxine dose (about 25–30%) is required to
TSH and FT levels (Table 38–2), which will determine whether normalize the serum TSH level during pregnancy. It is reason-
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the symptoms are due to excess thyroxine blood levels. Chronic able to counsel women to take one extra dose of their current
overtreatment with T , particularly in elderly patients, can increase thyroxine tablet twice a week separated by several days as soon as
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the risk of atrial fibrillation and accelerated osteoporosis. they are pregnant. Thyroxine should also be administered apart
from prenatal vitamins and calcium by at least 4 hours. Because
Special Problems in Management of of the elevated maternal TBG levels and, therefore, elevated total
Hypothyroidism T levels, adequate maternal thyroxine dosages warrant mainte-
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A. Myxedema and Coronary Artery Disease nance of TSH between 0.1 and 3.0 mIU/L (eg, first trimester,
0.1–2.5 mIU/L; second trimester, 0.2–3.0 mIU/L; third trimester,
Since myxedema frequently occurs in older persons, it is often 0.3–3.0 mIU/L) and the total T at or above the upper range of
associated with underlying coronary artery disease. In this situa- normal. 4
tion, the low levels of circulating thyroid hormone actually protect
the heart against increasing demands that could result in angina
pectoris, atrial fibrillation, or myocardial infarction. Correction D. Subclinical Hypothyroidism
of myxedema must be done cautiously to avoid provoking these Subclinical hypothyroidism, defined as an elevated TSH level and
cardiac events. If coronary artery surgery is indicated, it should normal thyroid hormone levels, occurs in 4–10% of the general
be done first, prior to correction of the myxedema by thyroxine population and increases to 20% in women older than age 50.
administration. Levothyroxine should be individualized based on the risks and
benefits of treatment. The consensus of expert thyroid organiza-
B. Myxedema Coma tions concluded that thyroid hormone therapy should be consid-
Myxedema coma is an end state of untreated hypothyroidism. ered for patients with TSH levels greater than 10 mIU/L while
It is associated with progressive weakness, stupor, hypothermia, close TSH monitoring is appropriate for those with lower TSH
hypoventilation, hypoglycemia, hyponatremia, water intoxication, elevations.
shock, and death.
Myxedema coma is a medical emergency. The patient should E. Drug-Induced Hypothyroidism
be treated in the intensive care unit, since tracheal intubation and Drug-induced hypothyroidism (Table 38–3) can be satisfactorily
mechanical ventilation may be required. Associated illnesses such managed with levothyroxine therapy if the offending agent cannot
as infection or heart failure must be treated by appropriate therapy. be stopped. In the case of amiodarone-induced hypothyroidism,