Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The withdrawal from the market of the oral contraceptives Volidan 21 and Serial 28 was based on work in beagle dogs treated for 7 years with high doses of megestrol acetate. The treated animals developed significantly more tumors than untreated controls. Chlormadinone acetate was withdrawn from clinical use in 1970 on the basis of similar reports. All other progestogens in use in Britain had no effect on the incidence of tumors. The only neoplasm linked with oral contraceptives by clinical evidence is hepatic adenoma. In menopausal and postmenopausal patients estrogen therapy may increase the risk of endometrial uterine cancer. For most young women oral contraception is a compromise between safety and reliability. Serious thromboembolic complications increase with age, cigarette smoking, and hypertension. Patients should be screened for the presence of risk factors and the effects of treatment regularly assessed. In menopausal women, regular monitoring for endometrial cancer is advised. Medical supervision of hormone therapy is needed.
 ...
PMID:Editorial: Cancer risks from hormone treatment. 120 97

The history of the development of oral contraceptives (OCs) has been a progressive reduction in dosage to what is now probably the lowest does that is compatible with the desired therapeutic effect -- to inhibit ovluation. Yet, controversy and argument continue. A table lists the OCs that are available in Australia. Many of these preparations, although having different trade names, have an identical composition. Since the withdrawal of sequential OCs from the Australian market, there are only 2 generic types. These are the progestogen only (mini) OCs, which consist of either 30 mcg of levonorgestrel or 350 mcg of norethisterone given at the same time every day; and the combined OCs, which contain an estrogen and a progestogen. In the last 12 months, some of the older high-dose OCs have been withdrawn, and it seems likely that further withdrawals will follow. Only 2 estrogens are used in the formulation of the OC, but there is a greater variety of progestogens. Ethinyl estradiol is used in most preparations. A small minority of OCs contain mestranol, the 3-methyl ether of ethinyl estradiol. Currently, there are only 4 OC agents that are available in Australia that contain mestranol and 2 of these contain the high doses of 100 mcg. Fundamentally, there are 2 types of progestogens -- those that contain, or are metabolized to, norethisterone and those that contain norgestrel or its close relative, desogestrel. With the exception of the norgestrel group and desogestrel, all other progestins, including norethisterone itself, are effective in vivo after they have been metablized to norethisterone. Mestranol is effective in humans after demethylation to ethinyl estradiol. In the norgesterel group, since d-norgestrel is inert endocrinologically, 250 mcg of levonorgestrel and 500 mcg of dl-norgestrel are equivalent. Levonorgestrel and desogestrel are of approximately equal potency. With the combined OC agents, the overwhelming mechanism of action is by the inhibition of the midcycle peak of luteinizing hormone (LH) secretion and, hence, the inhibition of ovulation. Progestogen-only OCs have additional actions such as effects on cervical and fallopian tube mucin. Minor side-effects include disturbance of the menstrual cycle, changes in weight, and changes in mood. Major side-effects relate to 4 areas -- subsequent reproduction, the cardiovascular system, other metabolic effects, and the risk of malignancy. A table presents the absolute contraindication contraindications. There is not the slightest doubt that a woman who is over 35, who smokes, and who, in addition, may be obese and has hypertension should not use OCs. Progestogen (mini) OCs have a slightly higher failure rate and a greater incidence of irregular bleeding than have combined OCs. The mini OC has little place in women who need effective hormonal contraception and good cycle control. The mini OC may have a place in a patient who finds other contraception unacceptable and in whom estrogens are contraindicated specifically.
 ...
PMID:Oral contraceptive agents. 394 19

Low dose estrogen tablets, containing less than 50 mcg of ethinyl estradiol, were formulated because of the recognized dose response relationship with the steroid content of the tablet and side effects. These new oral contraceptives (OCs) are as effective as the older high-dose OCs, and available evidence reports fewer side effects. This discussion reviews pharmacology of these new OCs, the mechanism of action, contraindications, side effects, and problems with the low-dose estrogen OC. Ethinyl estradiol is the only estrogen used in the low-dose combination OC. There are several synthetic progestins: norethindrone, norethindrone acetate, norgestrel, levonorgestrel, and ethynodiol diacetate. These progestins have different potencies so the pharmacologic activity cannot be accurately predicted based on the amount present in the tablet. The synthetic steroids in OCs are absorbed in the small intestine, metabolized in the liver, excreted in the bile and feces with a half-life of 24 hours. The low-dose estrogen combination preparation is taken 3 out of every 4 weeks. Its contraceptive effect is primarily a result of hypothalamic mediated gonadotropin suppression with subsequent inhibition of ovulation. Contraindications to taking the low-dose OC are the same as for the higher dose OC: thromboembolic or cardiovascular disease, estrogen dependent neoplasia, markedly impaired liver function, undiagnosed genital bleeding, congenital hyperlipidemia, pregnancy, and women over age 30 who smoke. Relative contraindications include hypertension, diabetes mellitus, migraine headaches, uterine myomas, and epilepsy. The often quoted 2-5-fold increased incidence of thromboembolic disease, myocardial infarction, and stroke is based on large epidemiologic studies involving patients taking the older higher dose OCs. Current data from patients taking the newer low-dose medication demonstrate minimal if any increased incidence of these problems in young women who do not smoke. The low-dose estrogen OCs have minimal effect on lipid levels. Early reports of patients using the low-dose OC have shown little if any increased incidence of hypertension. The low-dose contraceptives have little effect on glucose tolerance, and there is no evidence to show an increased incidence of overt diabetes in OC users. There is no evidence that use of the combination OC causes an increase in cancer of the cervix, uterus, or ovaries. Clinical complaints of nausea, breast discomfort, chloasma, weight changes, and depression are reduced with the low-dose estrogen preparation. Hypomenorrhea while taking the OC occasionally occurs because the lower dose of estrogen is insufficient to stimulate the endometrial growth in face of the predominant progestin-atrophy effect.
 ...
PMID:Oral contraceptives in 1984. 649 Mar 38

Ethinyl estradiol is the only estrogen form used in low-dose oral contraceptive (OC) pills. Progestogenic compounds used in OCs include norethindrone, norethindrone acetate, ethynodiol diacetate, norgestrel, levonorgestrel, and norethynodrel. The newest third generation progestins are desogestrel and norgestimate. The most important benefits associated with OC use are a decrease in benign breast disease, less incidence of ovarian and endometrial cancers, and a decrease in the incidence of pelvic inflammatory disease. The most serious risks to OC users who are over age 35 and smoke are deep vein thrombosis, pulmonary embolus, retinal thrombosis, or cardiovascular disease. Other risk factors for cardiovascular disease include obesity, diabetes, hypertension, increased serum cholesterol, and a family history of premature myocardial infarction. All users should have blood pressure checks 3 and 6 months after commencing pill use. OC preparations cause an increase in total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and a decrease in high density lipoprotein (HDL), but norgestimate may actually increase HDL levels. Preparations with levonorgestrel may produce the greatest decrease in glucose tolerance, while those with 35 mcg of ethinyl estradiol and 0.5 mg of norethindrone have the least effect. OCs do not increase the risk of developing breast cancer, but can stimulate the growth of breast cancer once it has occurred. The incidence of gallbladder disease is increased slightly in OC using women who are predisposed. Hepatocellular adenomas are associated with combined OC use. Underweight women are more prone to side effects and need a very low potency preparation. A common problem encountered by patients on OCs is amenorrhea. This usually resolves after 3 cycles. Breakthrough bleeding is also very common. Post-pill amenorrhea is frequently found after stopping OCs. Combined oral contraceptives are a safe and effective contraceptive method for most women throughout their reproductive years.
 ...
PMID:Combined oral contraceptive pills: a brief review. 783 35

Although combined oral contraceptives (OCs) do not create a true cardiovascular risk, they may increase the impact of existing vascular risk factors. Pill use disturbs metabolism of lipids and carbohydrates as well as the balance of water and sodium. New combinations with lower doses of steroids have significantly reduced these risks, and the development of new and less androgenic progestins for low dose pills is expected to reduce them further. The diabetogenic effect of OCs has been noted since 1963. Among normal women, the observed modifications in carbohydrate metabolism are minor and temporary, with increases in levels of blood sugar maximal at the beginning of use and normalizing after 12 months. Among women with family histories of diabetes or who have had gestational diabetes, use of combined OCs can entail irreversible deterioration of glucose tolerance or diabetes. The number of women with poor glucose tolerance increases with the duration of pill use. Reversibility of the condition decreases with duration of use. The proportion of women with poor glucose tolerance who develop diabetes is higher than among normal subjects. Women with poor glucose tolerance must be considered at risk of diabetes. Ethinyl estradiol is responsible for the early modification of glucose tolerance, which regresses after about 6 months of use. Hyperinsulinemia is caused by the direct stimulation of progestins on insulin secretion by the pancreas as well as by the development of peripheral resistence to glucose utilization resulting from a decrease of insulin receptors. The effect on insulin resistence is among the most androgenic progestins. Chronic hyperinsulinism represents a classic risk factor for atherosclerosis because of the effects on the arterial wall: proliferation of smooth muscle fibers, inhibition of lipolysis, and development of lesions of the intima analogous to those of atheroma. Estrogen is primarily responsible for the increased blood pressure of pill users, but the development of hypertension is also correlated with the progestin content. Progestins have an antidiuretic effect which contributes to increases in blood pressure when added to the estrogen stimulation of the renin-aldosterone-angiotensin system. Gestodene, a new progestin in the gonane series, is the most powerful synthetic progesterone yet known. Its uniqueness derives from the dissociation between its very powerful antigonadotropic activity even at small doses and its androgenic effects which only appear at considerably higher doses. Most of the metabolic effects of progestins are linked to their degree of androgenicity. Different studies of gestodene tolerance in a triphasic formulation have concluded that it is innocuous. The use of gestodene in a low-dose triphasic formulation may result in a combined OC that does not increase the individual atheromatous risk of the user.
 ...
PMID:[Combined estrogen-progestagen contraception and glucid and water-sodium metabolism]. 1234 1

The objective of our work was to study the intrahypothalamic actions of irbesartan, an angiotensin receptor antagonist, on blood pressure and dopaminergic and serotoninergic neurotransmission in sham operated (SO) and aortic coarctated (ACo) rats by using the microdialysis perfusion technique. We also studied a possible enhanced pressor response to angiotensin II in aortic coarctated rats in the anterior and posterior hypothalamic area. Wistar urethane-chloralose anaesthetised rats were used. A cannula was inserted in the carotid artery. A concentric microdialysis probe was implanted into the anterior hypothalamus or posterior hypothalamus and irbesartan (6 microg ml(-1)) was perfused through the probe. Changes of mean arterial pressure (MAP) were measured. 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in dialysate samples by HPLC-EC. A greater response to irbesartan perfusion in the anterior hypothalamic area of aortic coarctated rats was observed (SO rats, DMAP: -4.3+/-2.3 mm Hg; ACo rats, DMAP: -11.4+/-1.5 mm Hg, P<0.05). The pressor response to angiotensin II in the anterior hypothalamic area (SO rats, DMAP: 4.2+/-1.2 mm Hg; ACo rats, DMAP: 21.7+/-3.7 mm Hg, P<0.05) but not in the posterior hypothalamic area was enhanced in aortic coarctated rats. The perfusion of irbesartan in the anterior hypothalamic area did not modify the extracellular levels of 5-HIAA in both experimental groups, but induced a slightly reduction of DOPAC levels in sham operated rats. The results suggest that the angiotensin system in the anterior hypothalamic area is involved in the maintenance of hypertension in ACo rats and it appears that the increased pressor reactivity to angiotensin II is related to this enhanced function. On the other hand, the effect of irbesartan on DOPAC dialysate levels suggests that the drug produces an alteration of the dopaminergic neurotransmission in the SO rats.
 ...
PMID:Study of the hypothalamic angiotensin system in aortic coarctated rats using the reverse microdialysis technique. 1286 Apr 51

Calcilytics, antagonists of calcium receptor, decrease sensitivity of this receptor to plasma calcium concentration and increase parathyroid hormone (PTH) secretion. Moreover, it was recently indicated that calcilytic NPS 2143 induces hypertension in rats. This study tested whether the increase of mean arterial blood pressure (MAP) induced by NPS 2143 administration is mediated by calcium channel and angiotensin II type 1 (AT1) receptor activity. Wistar rats were anaesthesized with Thiopental i.p. and infused i.v. with saline supplemented with the anaesthetic. Blood pressure was monitored continuously in the carotid artery. Effects of NPS 2143 administered i.v. as bolus on MAP in the presence and absence of felodypine and losartan were investigated. Both, felodipine and losartan pretreatment provoked a persistent DMAP decrease by 18+/-3 and 14+/-3 mmHg, respectively. Infusion of NPS 2143 at 1 mg/kg b.w. confirmed hypertensive activity of calcilytic and increased blood pressure for 21+/-4 mmHg. In contrast, administration of NPS 2143 in felodipine as well as in losartan pretreated rats did not change DMAP as compared to felodipine/control and losartan/control groups, respectively. Our study indicated that both the blockade of calcium channels and the AT1 receptor activity prevented the hypertensive effect of calcilytic NPS 2143. This finding might be particularly important in understanding the mechanisms that mediated blood pressure changes related to the activity of calcium receptor.
 ...
PMID:Blockade of calcium channels and AT1 receptor prevents the hypertensive effect of calcilytic NPS 2143 in rats. 2043 16