Hormone Replacement Therapy.

In the United States, approximately one third of perimenopausal and postmenopausal women use hormone replacement therapy (HRT), either estrogen in combination with a progestin or a

natural estrogen alone. There has been recent controversy about the risks and benefits of HRT. Short-term benefits include reduction in symptoms that accompany menopause, including

hot flashes, vaginal dryness, and sleep disturbances. Long-term benefits include maintenance of bone mineral density and prevention of osteoporotic fractures. The major controversies

surrounding HRT are the potential increased risk of cancer versus the potential benefits associated with prevention of ischemic heart disease and dementia. Recent results from the

Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study have provided new information about the risks and benefits of HRT:[31]

• Cancer. Unopposed estrogen therapy greatly increases the risk of endometrial hyperplasia and cancer; therefore, most postmenopausal women now use estrogen in combination

with a progestin. This combination drastically reduces or eliminates the risk of endometrial cancer. The risk of colon cancer was reduced in women who used HRT in some studies,

but not in the Heart and Estrogen/Progestin Replacement Study. Recent results from the Women's Health Initiative indicate an increased risk of breast cancer in women who used

HRT combined therapy for 5 years.

• Venous thrombosis and pulmonary embolism. The risk of thromboembolic events, including deep vein thrombosis,

pulmonary embolism, stroke, and retinal thrombosis, is elevated approximated twofold in HRT users, especially within the first 2 years.

• Cardiovascular disease. The recent Women's Health Initiative reported an approximate 29% increased risk of myocardial infarction, especially during the first year of combined

HRT use. This is in contrast to earlier studies in which either no effect or slight protection against cardiovascular diseases was reported. Methodologic differences probably

underlie these divergent results. [32]

• Cholecystitis. There is an increased risk of gallbladder disease in HRT users that increases with time.

• Dementia. The current studies are not adequate to evaluate whether HRT use prevents dementia.

Overall, the risks and benefits associated with the use of oral contraceptives and HRT must be evaluated for each individual patient in the context of her overall health, individual risk

factors, and family history.

Acetaminophen

When taken in large doses, this widely used nonprescription analgesic and antipyretic causes hepatic necrosis. The window between the usual therapeutic dose (0.5 gm) and the toxic dose

(15 to 25 gm) is large, however, and the drug is ordinarily safe in adults. Doses should be reduced for infants and children, especially in the setting of fever, reduced food intake, or

dehydration, since these conditions may predispose to liver injury.[33] Toxicity begins with nausea, vomiting, diarrhea, and sometimes shock, followed in a few days by evidence of

jaundice; with serious overdosage, liver failure ensues, with centrilobular necrosis that may extend to the entire lobule. Some patients show evidence of concurrent renal and myocardial

damage.

Aspirin (Acetylsalicylic Acid)

Overdose may result from accidental ingestion by young children; in adults, overdose is frequently suicidal. The major untoward consequences are metabolic with few morphologic

changes. At first respiratory alkalosis develops, followed by metabolic acidosis that often proves fatal before anatomic changes can appear. Ingestion of as little as 2 to 4 gm by children or

10 to 30 gm by adults may be fatal, but survival has been reported after doses five times larger.

TABLE 9-9-- National Ambient Air Quality Standards: Sources and Number of People at Risk

Pollutant Primary Standard Tons Emitted (Millions) People at Risk (Millions)

Ozone 0.08 ppm 8 hr average Not applicable 143••

Nitrogen oxides 0.053 ppm annual arithmetic mean 25 Not available

Sulfur dioxide 0.03 ppm annual arithmetic mean 19 0.3

Particulates (PM10 ) 50 μg/μL annual arithmetic mean 24 8.7

Carbon monoxide 9 ppm 8 hr average 97 31••

Lead 1.5 μg/μL quarterly average 30 2.5

Data from U.S. Environmental Protection Agency: epa.gov/oar/oaqps, www.scorecard.org/env-releases, the American Lung Association: www.lungusa.org/air, and Goldman LR:

Environmental health and its relationship to occupational health. In Levy BS, et al. (eds): Occupational Health. Recognizing and Preventing Work-Related Disease and Injury, fourth ed.

Philadelphia, Lippincott Williams & Wilkins, 2000, p. 51.

Chronic aspirin toxicity (salicylism) may develop in persons who take 3 gm or more daily, the dose required to treat chronic inflammatory conditions. Chronic salicylism is manifested by

headache, dizziness, ringing in the ears (tinnitus), difficulty in hearing, mental confusion, drowsiness, nausea, vomiting, and diarrhea. The central nervous system changes may progress to

convulsions and coma. The morphologic consequences of chronic salicylism are varied. Most often there is an acute erosive gastritis ( Chapter 17 ), which may produce overt or covert

gastrointestinal bleeding and lead to gastric ulceration. A bleeding tendency may appear concurrently with chronic toxicity, because aspirin acetylates platelet cyclooxygenase and blocks

the ability to make thromboxane A2 , an activator of platelet aggregation. Petechial hemorrhages may appear in the skin and internal viscera, and bleeding from gastric ulcerations may be

exaggerated.

Proprietary analgesic mixtures of aspirin and phenacetin or its active metabolite, acetaminophen, when taken for a span of years, have caused renal papillary necrosis, referred to as

analgesic nephropathy ( Chapter 20 ).

Date: 2016-04-22; view: 584