Page 750 - Basic _ Clinical Pharmacology ( PDFDrive )

736 SECTION VII Endocrine Drugs

a whole does not seem to be affected by oral contraceptive use. 14 weeks. Almost all users experience episodes of unpredictable
Some studies have shown an increased risk in younger women, spotting and bleeding, particularly during the first year of use.
and it is possible that tumors that develop in younger women Spotting and bleeding decrease with time, and amenorrhea is
become clinically apparent sooner. The relation of risk of cervical common. This preparation is not desirable for women planning
cancer to oral contraceptive use is still controversial. It should be a pregnancy soon after cessation of therapy because ovulation
noted that a number of recent studies associate the use of oral suppression can sometimes persist for as long as 18 months after
contraceptives by women who are infected with human papillo- the last injection. Long-term DMPA use reduces menstrual blood
mavirus with an increased risk of cervical cancer. loss and is associated with a decreased risk of endometrial cancer.
Suppression of endogenous estrogen secretion may be associated
5. Other—In addition to the above effects, a number of other with a reversible reduction in bone density, and changes in plasma
adverse reactions have been reported for which a causal relation lipids are associated with an increased risk of atherosclerosis.
has not been established. These include alopecia, erythema multi- The progestin implant method utilizes the subcutaneous implan-
forme, erythema nodosum, and other skin disorders. tation of capsules containing etonogestrel. These capsules release
one-fifth to one-third as much steroid as oral agents, are extremely
Contraindications & Cautions effective, and last for 2–4 years. The low levels of hormone have
little effect on lipoprotein and carbohydrate metabolism or blood
These drugs are contraindicated in patients with thrombophlebitis,
thromboembolic phenomena, and cardiovascular and cerebrovas- pressure. The disadvantages include the need for surgical insertion
cular disorders or a past history of these conditions. They should and removal of capsules and some irregular bleeding rather than
not be used to treat vaginal bleeding when the cause is unknown. predictable menses. An association of intracranial hypertension
They should be avoided in patients with known or suspected with an earlier type of implant utilizing norgestrel was observed in
tumors of the breast or other estrogen-dependent neoplasms. Since a small number of women. Patients experiencing headache or visual
these preparations have caused aggravation of preexisting disorders, disturbances should be checked for papilledema.
they should be avoided or used with caution in patients with liver Contraception with progestins is useful in patients with
disease, asthma, eczema, migraine, diabetes, hypertension, optic hepatic disease, hypertension, psychosis or mental retardation,
neuritis, retrobulbar neuritis, or convulsive disorders. or prior thromboembolism. The side effects include headache,
The oral contraceptives may produce edema, and for that dizziness, bloating and weight gain of 1–2 kg, and a reversible
reason they should be used with great caution in patients in heart reduction of glucose tolerance.
failure or in whom edema is otherwise undesirable or dangerous.
Estrogens may increase the rate of growth of fibroids. There- A. Postcoital Contraceptives
fore, for women with these tumors, agents with the smallest Pregnancy can be prevented following coitus by the adminis-
amounts of estrogen and the most androgenic progestins should tration of estrogens alone, progestin alone, or in combination
be selected. The use of progestational agents alone for contracep- (“morning after” contraception). When treatment is begun
tion might be especially useful in such patients (see below). within 72 hours, it is effective 99% of the time. Some effective
These agents are contraindicated in adolescents in whom schedules are shown in Table 40–4. The hormones are often
epiphyseal closure has not yet been completed. administered with antiemetics, since 40% of patients have nausea
Women using oral contraceptives must be made aware of or vomiting. Other adverse effects include headache, dizziness,
an important interaction that occurs with antimicrobial drugs. breast tenderness, and abdominal and leg cramps. Considerable
Because the normal gastrointestinal flora increase the entero- controversy has accompanied the proposal to make these agents
hepatic cycling (and bioavailability) of estrogens, antimicrobial available without a prescription in the United States.
drugs that interfere with these organisms may reduce the efficacy Mifepristone, an antagonist at progesterone and glucocorticoid
of oral contraceptives. Additionally, coadministration with potent receptors, has a luteolytic effect and is effective as a postcoital
inducers of the hepatic microsomal metabolizing enzymes, such as
rifampin, may increase liver catabolism of estrogens or progestins TABLE 40–4 Schedules for use of postcoital
and diminish the efficacy of oral contraceptives. contraceptives.

Contraception with Progestins Alone Conjugated estrogens: 10 mg three times daily for 5 days
Ethinyl estradiol: 2.5 mg twice daily for 5 days
Small doses of progestins administered orally or by implantation Diethylstilbestrol: 50 mg daily for 5 days
under the skin can be used for contraception. They are particu- 1
larly suited for use in patients for whom estrogen administration Mifepristone: 600 mg once with misoprostol, 400 mcg once
2
is undesirable. They are about as effective as intrauterine devices l-Norgestrel: 1.5 mg once (Plan B One-Step )
2
or combination pills containing 20–30 mcg of ethinyl estradiol. l-Norgestrel: 0.75 mg twice daily for 1 day (eg, Plan B )
There is a high incidence of abnormal bleeding. Norgestrel, 0.5 mg, with ethinyl estradiol, 0.05 mg (eg, Ovral, Preven ):
2
Effective contraception can also be achieved by injecting Two tablets and then two in 12 hours
150 mg of depot medroxyprogesterone acetate (DMPA) every 1 Mifepristone given on day 1, misoprostol on day 3.
3 months. After a 150-mg dose, ovulation is inhibited for at least 2 Sold as emergency contraceptive kits.