Standard therapy for tuberculosis 1985.

PIP: Numerous clinical trials of chemotherapy for tuberculosis conducted throughout the world over the past 4 decades have established 2 basic principles of treatment: effective treatment requires the initial concomitant administration of at least 2 drugs to which the patient's organisms are susceptible; and cure of tuberculosis requires that treatment continue beyond the time of sputum conversion and amelioration of symptoms. The treatment of tuberculosis was revolutionized in the late 1960s with the introduction of rifampin. Shorter regimens of 6-9 months in duration became possible. Scores of trials of short-course chemotherapy have been conducted, and more are planned. The goals of the new treatment regimens are to achieve effective sterilization of the tuberculous lesion in the shortest time possible. A table lists drugs now in use in the US and Canada and gives the usual doses, common side effects, and important interactions among drugs. Chemotherapeutic regimens acceptable for use in the US and Canada are well-defined combinations of drugs which must be regularly administered in the recommended dosages and rhythm for a specific time period. Regimens should be highly effective, i.e., a relapse rate of less than 5%, and have a low risk of toxic effects. Regimens also should be acceptable to patients and applicable on a community-wide basis. The regimens recommended meet these criteria and are backed by well-conducted clinical trails. A 9-month regimen consisting of isoniazid and rifampin throughout, usually supplemented in the initial phase by ethambutol, streptomycin, or pyrazinamide, is a well-tolerated regimen which will cure virtually all patients with susceptible organisms. The initial daily phase may last 2-8 weeks; the continuation phase may be administered daily or twice weekly. These regimens have an overall bacteriologic relapse rate of between zero and 4%. When 4 drugs -- isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin -- are given under close during supervision during the initial 2 months of daily or "induction" therapy, followed by an additional 4 months of isoniazid and rifampin, the results have been excellent. Where primary resistance to isoniazid or streptomycin is suspected, the patient should be placed on 1 of the following 3 regimens: isoniazid, rifampin, and ethambutol; isoniazid, rifampin, pyrazinamide, and streptomycin; or isoniazid, rifampin, pyrazinamide, and ethambutol. Short-course chemotherapy for extrapulmonary tuberculosis and chemotherapy of tuberculosis in children are reviewed along with several conditions which affect therapy -- tuberculosis during pregnancy, renal and hepatic disease, cancer and other conditions associated with immunosuppression, and drug interaction.^ieng

Use of the Retinoid Pregnancy Prevention Program in Canada: patterns of contraception use in women treated with isotretinoin and etretinate.

We sought to describe demographic characteristics of and pattern of contraception use by Canadian women prescribed synthetic retinoids who voluntarily contacted the Motherisk Program in Toronto and to describe the degree of use of the Pregnancy Prevention Program (PPP) for retinoids. Prospectively gathered intake data from isotretinoin-exposed women was statistically compared to that from matched controls selected from our database. Intake data is qualitatively reported for etretinate-exposed women. We included women who voluntarily contacted the Motherisk Program from November 1, 1988, to January 30, 1991, for counseling about reproductive risks of isotretinoin or etretinate. Primary outcome parameters were maternal age, race, marital status, socioeconomic status; gravity, parity, previous miscarriages and elective abortions, maternal tobacco and ethanol exposure, contraception use, and use of PPP (educational components used, patient recollection of warnings). The 26 isotretinoin-exposed women were younger than controls (25.2 [SD 6.7] years vs 28.9 [SD 5.1] years, P = 0.03), tended to be adolescent (30.8% vs. 3.8%, P = 0.014) and sought counselling later in gestation (10.1 [SD 8] weeks vs. 6 [SD 4.2] weeks, P = 0.01). Twenty (77%) knew the drug was teratogenic, yet 10 (38.5%) used no contraception, 6 (23.1%) experienced method failure, and 2 (8%) stopped contraception during isotretinoin therapy. In conclusion, although cognizant of the teratogenicity of isotretinoin, more than one-third of the women in this study used no birth control or experienced contraception failure. In this same group, however, compliance with contraception use appeared to increase in those who saw more of the PPP.

[Drug interactions with oral contraceptive steroids]. / Vzaimodeistvie na medikamenti s oralni kontratseptivni steroidi.

PIP: Various drugs are capable of enhancing or inhibiting the effect of oral contraceptives (OCs). Drugs of the rifampicin group are active enzyme inductive agents which affect both the estrogenic and progestagenic components of OCs. This was demonstrated by the following pharmacokinetic study. 8 women received a single dose of Minovlar (50 mg of ethinyl estradiol and 1 mg of norethindrone acetate) during a rifampicin course, and another dose of the same OC was administered after the completion of the drug course. Rifampicin reduced the half-life of ethinyl estradiol from 6.2 to 3.2 hours and that of norethindrone acetate from 6.5 to 2.9 hours. Anticonvulsive drugs, e.g., phenytoin, phenobarbital, methylphenobarbital, and carbamazepine, often cause failures of contraceptive programs using OCs. A recent study followed the effect of phenobarbital in 4 women taking OCs. In two cases, the concentration of estrogen in blood plasma decreased significantly and hemorrhages occurred. In such cases, other methods of contraception should be recommended. Statistics show that, in 1982, 38 English women experienced unsuccessful contraception because they took various antibiotics simultaneously with OCs. This effect was reported for ampicillin, tetracycline, erythromycin, nitrofurantoin, and other antibiotics. On the other hand, ascorbic acid (Vitamin C) enhances the effect of OCs. The above studies prove that the interactions of rifampicin, anticonvulsive drugs, and antibiotics with OCs are pharmacodynamic, rather than pharmacokinetic, interactions. There is no clinical evidence to prove that OCs interfere with the metabolism of certain drugs. Future clinical and paraclinical studies are needed for a better understanding of these effects.^ieng

[Hormonal contraception and other drug treatments]. / Hormonaalinen ehkäisy ja muu lääkehoito.

PIP: In Finland, the combinations of ethinyl estradiol (EE) and levonorgestrel (LNG) or desogestrel are most used for oral contraception (OC) and LNG, linestrol or nethisterone are employed in the pills containing only progestogen. Their effect is reduced by antiepileptics primarily phenytoin, carbamazepine, barbiturates, and primidone, however, clonazepam and sodium valproate do not exert any influence. The cause is the effect of the drugs on the liver as they accelerate the metabolism of steroids by enzyme induction. Phenytoin induces sex hormones binding globulin (SHGB) synthesized by the liver. In addition to natural hormones also LNG and norethisterone are bound to SHGB. The decrease of the effect of progestogens has not been documented, in fact, some research data indicate that progesterone exerts a beneficial effect in the treatment of epilepsy. Thus, combination OC tablets that contain at least 50 mcg of EE can be used for hormonal contraception of epileptics. Rifampicin applied in chemotherapy of tuberculosis (TB) also exhibits an effect inducing liver enzymes, and that is the reason why rifampicin treatment resulted in undesired pregnancy and bleeding disorders during contraception by combination tablets. Therefore, the concomitant use of both agents is contraindicated. In Finland data are scarce on this effect, as TB is very rare there. In the case of other antibiotics the incompatibility with OCs is proven. It must be noted, however, that as a secondary effect, diarrhea and gastroenteritis treated by antibiotics can produce an unwanted pregnancy. The treatment of diabetes and hypertension can also be contraindication to the use of hormonal contraception, although it may be permitted under medical supervision and control of diabetes.^ieng

An American midwife in Moscow.

PIP: Having completed a 3-week visit to Soviet birth houses and abortion clinics, 2 American midwives report on the harmful treatment of women by the USSR's health care system. On November 1990, the midwives traveled to Moscow as envoys of the Soviet-American International Center for Better Health. They visited rodoms, Soviet birth houses, which are described as frightening, dirty places that lack supplies and medical reference books. A typical childbirth at a rodom (to which Soviet women are required to go, since home births are outlawed) was videotaped. The video shows a woman in labor, alone in a room while a group of midwives sits outside in the hall smoking cigarettes. She has been given a psychotropic drug. Later, the midwives begin to apply pressure to the woman's abdomen, then a doctor makes a cut in the woman's groin area to make it easier to push the baby through. These dangerous obstetric practices date back to the 1940s. At 26/1000, the USSR has the 3rd highest infant mortality rate in Europe (after Yugoslavia and Romania). Government figures indicate the 7000 women died in rodoms last year alone. The ill treatment of women can also extend to abortion clinics. Here, women receive no comfort; they are not even allowed to bring a support person. Because Soviets lack access to contraceptives, the country has the highest abortion rate in the world--8 abortions for every live birth. The American midwives have formed an organization called International Midwives Exchange (IME). IME hopes to lower the infant mortality rate in the USSR by educating doctors and midwives on the proper use of medication and birthing practices, stressing natural childbirth as the preferred method. IME will also attempt to lower the abortion rate by developing a pipeline of contraceptive supplies.^ieng