Page 706 - Basic _ Clinical Pharmacology ( PDFDrive )

692 SECTION VII Endocrine Drugs

TABLE 38–3 Drug effects and thyroid function.

Drug Effect Drugs
Change in thyroid hormone synthesis
Inhibition of TRH or TSH secretion without induction of Bexarotene, dopamine, bromocriptine, cabergoline, levodopa, corticosteroids,
hypothyroidism or hyperthyroidism somatostatin, octreotide, metformin, interleukin-6, heroin
Inhibition of thyroid hormone synthesis or release Iodides (including amiodarone), lithium, aminoglutethimide, thioamides, ethionamide,
with the induction of hypothyroidism (or occasionally tyrosine kinase inhibitors (eg, sunitinib, sorafenib, imatinib), HIV protease inhibitors
hyperthyroidism)
Alteration of thyroid hormone transport and serum total T 3 and T 4 levels, but usually no modification of FT 4 or TSH
Increased TBG Estrogens, tamoxifen, raloxifene, heroin, methadone, mitotane, 5-fluorouracil,
perphenazine
Decreased TBG Androgens, anabolic steroids, glucocorticoids, danazol, l-asparaginase, nicotinic acid
Displacement of T 3 and T 4 from TBG with transient Salicylates, fenclofenac, mefenamic acid, intravenous furosemide, heparin
hyperthyroxinemia
Alteration of T 4 and T 3 metabolism with modified serum T 3 and T 4 levels but not TSH levels (unless receiving thyroxine replacement therapy)
Increased hepatic metabolism, enhanced degradation Nicardipine, phenytoin, carbamazepine, primidone, phenobarbital, rifampin, rifabutin,
of thyroid hormone tyrosine kinase inhibitors (eg, sunitinib, sorafenib, imatinib), sertraline, quetiapine
Inhibition of 5′-deiodinase with decreased T 3 , Iopanoic acid, ipodate, amiodarone, β blockers, corticosteroids, propylthiouracil,
increased rT 3 flavonoids, interleukin-6
Other interactions
Interference with T 4 absorption from the gut Oral bisphosphonates, cholestyramine, colesevelam, colestipol, chromium picolinate,
charcoal, ciprofloxacin, proton pump inhibitors, sucralfate, Kayexalate, raloxifene,
sevelamer hydrochloride, aluminum hydroxide, ferrous sulfate, calcium carbonate,
bran/fiber, soy, coffee, orlistat
Induction of autoimmune thyroid disease with Interferon-α, interleukin-2, interferon-β, lithium, amiodarone, tyrosine kinase inhibitors
hypothyroidism or hyperthyroidism (eg, sunitinib, sorafenib, imatinib)
Effect of thyroid function on drug effects
Anticoagulation Lower doses of warfarin required in hyperthyroidism, higher doses in hypothyroidism
Glucose control Increased hepatic glucose production and glucose intolerance in hyperthyroidism;
impaired insulin action and glucose disposal in hypothyroidism
Cardiac drugs Higher doses of digoxin required in hyperthyroidism; lower doses in hypothyroidism
Sedatives; analgesics Increased sedative and respiratory depressant effects from sedatives and opioids in
hypothyroidism; converse in hyperthyroidism

replacement by conventional laboratory tests. T should also be liothyronine has been reported. Any dosage conversions should be
3
avoided in patients with cardiac disease due to significant eleva- re-titrated based on laboratory and clinical response.
tions in peak levels and a greater risk of cardiotoxicity. Using the The shelf life of synthetic hormone preparations is about
more expensive thyroxine and liothyronine fixed-dose combina- 2 years, particularly if they are stored in dark bottles to minimize
tion (liotrix) and desiccated thyroid has not been shown to be spontaneous deiodination. The shelf life of desiccated thyroid is
more effective than T administration alone. T is best reserved not known with certainty, but its potency is better preserved if it
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for short-term TSH suppression. Research is ongoing to clarify is kept dry.
whether T might be more appropriate in patients with a poly-
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morphism in the D2 gene or in those who continue to report ANTITHYROID AGENTS
fatigue, weight gain, and mental impairment while on T alone.
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The use of desiccated thyroid rather than synthetic prepara- Reduction of thyroid activity and hormone effects can be
tions is never justified, since the disadvantages of protein antige- accomplished by agents that interfere with the production of
nicity, product instability, variable hormone concentrations, and thyroid hormones, by agents that modify the tissue response to
difficulty in laboratory monitoring far outweigh the advantage thyroid hormones, or by glandular destruction with radiation
of lower cost. Significant amounts of T found in some thyroid or surgery. Goitrogens are agents that suppress secretion of T
3
3
extracts may produce significant elevations in T levels and and T to subnormal levels and thereby increase TSH, which in
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toxicity. Exact equi-effective doses have not been determined. turn produces glandular enlargement (goiter). The antithyroid
Approximate equivalence of desiccated thyroid 60 mg (1 gr) to compounds used clinically include the thioamides, iodides, and
80 to 100 mcg of levothyroxine, and approximately 37.5 mcg of radioactive iodine.