Page 708 - Basic _ Clinical Pharmacology ( PDFDrive )

694 SECTION VII Endocrine Drugs

TABLE 38–4 Manifestations of thyrotoxicosis and hypothyroidism.

System Thyrotoxicosis Hypothyroidism
Skin and appendages Warm, moist skin; sweating; heat intolerance; fine, Pale, cool, puffy, yellowish skin, face, and hands; dry and
thin hair; Plummer’s nails; pretibial dermopathy brittle hair; brittle nails
(Graves’ disease)
Eyes, face Retraction of upper lid with wide stare; periorbital Drooping of eyelids; periorbital edema; loss of temporal
edema; exophthalmos; diplopia (Graves’ disease) aspects of eyebrows; puffy, nonpitting facies; large tongue,
hoarseness
Cardiovascular system Decreased peripheral vascular resistance; increased Increased peripheral vascular resistance; decreased heart
heart rate, stroke volume, cardiac output, pulse pres- rate, stroke volume, cardiac output, pulse pressure; low-
sure; high-output heart failure; increased inotropic output heart failure; ECG: bradycardia, prolonged PR interval,
and chronotropic effects; arrhythmias; angina flat T wave, low voltage; pericardial effusion
Respiratory system Dyspnea; hypoventilation; decreased vital capacity Pleural effusions; hypoventilation and CO 2 retention; sleep
apnea
Gastrointestinal system Increased appetite; increased frequency of bowel Decreased appetite; decreased frequency of bowel
movements; hypoproteinemia movements, constipation; ascites
Central nervous system Nervousness; hyperkinesia; emotional lability, Lethargy/fatigue; general slowing of mental processes;
agitation neuropathies; weakness and muscle cramps
Musculoskeletal system Weakness and muscle fatigue; increased deep tendon Stiffness and muscle fatigue; carpal tunnel syndrome;
reflexes; tremors; hypercalcemia; osteoporosis decreased deep tendon reflexes; increased alkaline
phosphatase, LDH, AST
Renal system Mild polyuria; increased renal blood flow; increased Impaired water excretion; decreased renal blood flow;
glomerular filtration rate decreased glomerular filtration rate
Hematopoietic system Increased erythropoiesis; anemia 1 Decreased erythropoiesis; anemia 1
Reproductive system Menstrual irregularities; amenorrhea; infertility; Menorrhagia; infertility; decreased libido; impotence;
increased gonadal steroid metabolism oligospermia; decreased gonadal steroid metabolism
Metabolic system Increased basal metabolic rate; negative nitrogen Decreased basal metabolic rate; slight positive nitrogen
balance; hyperglycemia; increased free fatty acids; balance; delayed degradation of insulin with increased
decreased total cholesterol and triglycerides; sensitivity; increased total cholesterol and triglycerides;
increased hormone degradation; increased require- hyponatremia; decreased hormone degradation; decreased
ments for fat- and water-soluble vitamins; increased requirements for fat- and water-soluble vitamins; decreased
drug metabolism; decreased warfarin requirement drug metabolism; increased warfarin requirement
1
The anemia of hyperthyroidism is usually normochromic and caused by increased red blood cell turnover. The anemia of hypothyroidism may be normochromic, hyperchromic,
or hypochromic and may be due to decreased production rate, decreased iron absorption, decreased folic acid absorption, or to autoimmune pernicious anemia. LDH, lactic
dehydrogenase; AST, aspartate aminotransferase.
In contrast, propylthiouracil is rapidly absorbed, reaching peak
serum levels after 1 hour. The bioavailability of 50–80% may be
H O H due to incomplete absorption or a large first-pass effect in the liver.
N N
The volume of distribution approximates total body water with
S S accumulation in the thyroid gland. Most of an ingested dose of
propylthiouracil is excreted by the kidney as the inactive glucuro-
N N
H C H nide within 24 hours.
3 7
The short plasma half-life of these agents (1.5 hours for pro-
CH 3
Propylthiouracil Methimazole pylthiouracil and 6 hours for methimazole) has little influence
O on the duration of the antithyroid action or the dosing interval
because both agents are accumulated by the thyroid gland. For
C O C H
2 5
propylthiouracil, giving the drug every 6–8 hours is reasonable
N since a single 100 mg dose can inhibit iodine organification by
S 60% for 7 hours. Since a single 30 mg dose of methimazole exerts
an antithyroid effect for longer than 24 hours, a single daily dose
N is effective in the management of mild to severe hyperthyroidism.
Both thioamides cross the placental barrier and are concen-
CH 3
Carbimazole trated by the fetal thyroid, so that caution must be employed
when using these drugs in pregnancy. Because of the risk of fetal
FIGURE 38–5 Structure of thioamides. The thiocarbamide hypothyroidism, both thioamides are classified as FDA pregnancy
moiety is shaded in color. category D (evidence of human fetal risk based on adverse reaction