Consumption and costs of antihypertensive drugs in Mexico: are diuretic agents a standing technological trajectory?

BACKGROUND: Little is known about hypertension medication consumption and costs in Mexico. Hypertension control is a pharmacological challenge and a public health issue. OBJECTIVE: (a) To compare drug sales, number of written prescriptions, and monthly treatment costs among 5 classes of antihypertensive drugs and (b) to analyze diuretic drug sales and prescriptions to determine whether these antihypertensive agents represent an established technological trajectory. METHODS: A retrospective time series data study from 1999 to 2003. Data sources used were International Marketing Services of Mexico drug sales and the Mexico Prescription Audit databases. The 5 different classes of antihypertensive drugs were accommodated into 4 main technological trajectories according to their main biological mechanisms of action. Each technological trajectory was assessed using consumption and prescription data. Daily defined dose was used to calculate drug treatment costs. RESULTS: The market for cardiovascular agents is one of the largest, and in 2003 accounted for a value market share of 59 billion US dollar and a unit share of 40.7 million. Among cardiovascular agents, antihypertensive drugs made up a large percentage of market shares. Calcium channel blockers and angiotensin-converting enzyme inhibitors I had the biggest share value of the total cardiovascular market. Amlodipine had the highest share among calcium channel blockers, and enalapril and captopril had the largest share among angiotensin-converting enzyme inhibitors I. The top-selling diuretic drug was furosemide. The trend in number of prescriptions was parallel to that in sales. The diuretic spironolactone was the most expensive drug treatment (59 US dollar). Treatment with spironolactone might represent 47% of the income of a Mexican family if their household income was close to minimum wage (124 US dollar). CONCLUSIONS: The most effective and least expensive drugs-diuretics-had the smallest market share of all antihypertensive agents in Mexico. Nevertheless, diuretic agents are still in use and kept over time a steady market share both in value and in units.

Estrogenic effects of the synthetic aminoestrogen 17 beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol (pentolame).

In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in the castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the vehicle alone daily for 5 consecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased significantly (p < 0.05) the blood clotting time when compared with that obtained in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000 micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH levels (IC50 860 micrograms), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependent progestin binding sites at the anterior pituitary level. The affinity constants and the number of binding sites of pentolame-induced progestin receptors were similar to those obtained with estradiol at equipotent doses (860 micrograms vs. 1 microgram/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant increase in uterine weight (EC50 420 micrograms) and endometrial characteristics were indistinguishable from those observed in the group of rats treated with E2.

Estrogenic effects of p-hydroxybenzoic acid in CD1 mice.

Xenobiotic estrogens in the environment or diet have received much attention as a possible source of certain hormonal disease states in human and wildlife. Therefore, the detection of estrogenic activity of any substance, especially those related to the food industry, is important. The estrogenic activity of p-hydroxybenzoic acid (PHBA), a compound related to a commonly used group of preservatives in food, cosmetic, and pharmaceutical preparations, was evaluated with immature and adult ovariectomized female mice (CD1) using two well-known bioassays. Subcutaneous administrations (s.c.) of different doses of PHBA were compared with estradiol (E2), and their effects on vaginal cornification and uterotrophic activities were evaluated. Different groups of animals were treated s.c. daily for 3 days with vehicle (corn oil, 0.3 ml/100 g), E2 (1 microgram/100 g), and PHBA (0.5, 5, 50, and 500 micrograms/100 g). Four days after treatment, PHBA produced a dose-dependent response on vaginal cornification and uterotrophic activity in both immature and adult ovariectomized mice. The relative uterotrophic potency of PHBA (500 micrograms/100 g) to E2 (1 microgram/100 g) was 0.0011 in immature mice and 0.0018 in ovariectomized animals.

Anticoagulant and estrogenic effects of two new 17 beta-aminoestrogens, butolame [17 beta-(4-hydroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol] and pentolame [17 beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol].

The syntheses and characterizations of two new 17 beta-aminoestrogens, butolame [17 beta-(4-hydroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol] and pentolame [17 beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol], are presented. Both compounds, when administered in single subcutaneous injections to male mice and rats, produce dose-dependent increases in blood clotting times that may last several days. The estrogenic effects assessed by the vaginal cornification test are of relatively short duration.

The anticoagulant effect of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-6-hydroxyhexylamine, another amino-estrogen with prolonged anticoagulant effect.

The anticoagulant and estrogenic effects of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-6-hydroxyhexylamine, are described. A single subcutaneous injection of hexolame in adult and infant male mice produced dose-dependent increases in blood clotting time which could be observed even after 2 days. In ovariectomized mice, hexolame produced vaginal cornification (estrogenic response). The data suggested that if used in the treatment of prostatic cancer, hexolame, like prolame, would not induce cardiovascular accidents. It could also be useful in the prevention of thrombosis.

The anticoagulant effect of prolame, N-(3-hydroxy-1,3,5(10)estratrien-17 beta-yl)-3-hydroxypropylamine, a novel amino-estrogen.

The anticoagulant and estrogenic effects of prolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-3-hydroxypropylamine, are described. A single subcutaneous injection of prolame in male mice, ovariectomized mice, adult and infant male rats, produced dose-dependent increases of blood clotting time, which could be observed with the larger doses even after 4 days. In ovariectomized mice, prolame produced vaginal cornifications of shorter duration than those produced by estradiol-17 beta. The evidence suggests that, in contrast with currently used estrogens, prolame would not generate cardiovascular accidents if used for the treatment of prostatic carcinoma; it could also be exceptionally effective for the prevention of thrombosis.