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Medical Pharmacology Chapter 30: Thyroid and Antithyroid Drugs
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Active isomer is the levo form (L-form): thyroxine, triiodothyronine
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T4 -- well absorbed from the ileum and duodenum following oral administration-- about 80% absorbed on average
Modification of absorption:
Food
Drugs (e.g., sucralfate, iron, aluminum-containing antacids)
T3 -- almost completely absorbed (95%) following oral administration
T4 and T3 absorption may be impaired by myxedema (may require parenteral administration {IV}, as a result)
Factors that alter T4 and T3 clearance:
Hyperthyroidism: increases
Hypothyroidism: decreases
Drugs (hepatic microsomal enzymes inducers): Clearance is enhanced; Euthyroid state may be maintained because of thyroid hyperfunction.
Phenobarbital
Carbamazepine (Tegretol)
Phenytoin (Dilantin)
Rifampin
Increases in the number of TBG binding sites (due to pregnancy, estrogen use, oral contraceptive use)
More thyroid hormone is bound; elimination rate declines (only free hormone can be eliminated); normal hormone concentration would be eventually restored
Unbound T4 and T3 diffuse into the cell (passive diffusion, possibly active transport)
Inside cell:
T4 converted to T3
T3 is transported to the cell nucleus where T3 binds to a specific T3 nuclear receptor
Thyroid hormones: metabolic actions
Nuclear receptor activation results in increased RNA and protein synthesis: examples --
Increased Na+/K+ ATPase causes increased ATP turnover, increased oxygen consumption associated with the calorigenic effect.
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Physiological system |
Hyperthyroidism (thyrotoxicosis) |
Hypothyroidism |
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Skin, appendages |
Warm, moist skin; sweating; fine, thin hair; Plumber's nails; pretibial dermopathy (Graves' disease) |
Pale, cool, puffy skin; brittle hair and nails |
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Eyes, face |
Upper lid retraction (wide stare); periorbital edema; exophthalmos, diplopia (Graves' disease) |
Eyelid drooping; periorbital edema; puffy, nonpitting facies; large tongue |
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Cardiovascular |
Decreased peripheral resistance, increased cardiac output, stroke volume, heart rate, pulse pressure; congestive heart failure (high-output); increased contractility, arrhythmogenic; angina |
Increased peripheral resistance, decreased cardiac output, stroke volume, heart rate, pulse pressure; congestive heart failure (low output); bradycardia (low voltage ECG with prolonged PR interval, flat T wave); pericardial effusion |
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Respiratory |
Dyspnea; reduced vital capacity |
Hypoventilation (CO2 retention) pleural effusions |
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Gastrointestinal |
Increased appetite; increased bowel movement frequency; hypoproteinemia |
Decreased appetite, decreased bowel movement frequency; ascites |
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CNS |
Nervousness, hyperkinesia, variable emotional states |
Lethargy, neuropathy |
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Musculoskeletal |
Weakness; fatigue; hypercalcemia, osteoporosis, increased deep tendon reflex |
Muscle fatigue, reduced deep tendon reflex, increased alkaline phosphatase, LDH, AST |
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Renal |
Increased renal blood flow; increased GFR; mild polyuria |
Decreased renal blood flow; decreased GFR; reduced water excretion |
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Hematopoietic |
Anemia (increased RBC turnover); increased erythropoiesis |
Anemia (decrease production rate, decreased iron absorption, decreased folate acid absorption, autoimmune pernicious anemia),decreased erythropoiesis |
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Reproductive |
decreased fertility; menstrual irregularity; enhanced gonadal steroid metabolism |
Infertility;hypermenorrhea, decreased libido; impotence, decreased gonadal steroid metabolism |
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Metabolic |
Increased basal rate; negative nitrogen balance, hyperglycemia; increased free fatty acids, decreased cholesterol and triglycerides; increased hormone degradation; increased requirement for fat-and water-soluble vitamins; enhanced drug detoxification |
Decreased basal rate; delayed insulin degradation, with increased sensitivity; enhanced cholesterol and triglyceride levels; decreased hormone degradation; decreased requirements for fat-and water-soluble vitamins; decreased drug detoxification. |
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* Adapted from Table 38-4, Greenspan, F.S., and Dong, B. J.. Histamine, Thyroid and Antithyroid Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 625.
Greenspan, F.S., and Dong, B. J.. Histamine, Thyroid and Antithyroid Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 619-633.
Wartofsky, L., Diseases of the Thyroid, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2012-2034
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