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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence, pathogenesis and management of hypertension in 1600 pregnant women admitted to El-Hussein University Hospital, Cairo, in 1980 was studied. A total of 100 women had pregnancy related hypertension, e.g.: 67 or 4.18% had pre-eclampsia, 7 or .44% had eclampsia, 25 or 1.56% had essential hypertension, and 1 or .06% had chronic nephritis. Total fetal mortality was 18%. Maternal mortality was 2% in all cases. Maternal complications or morbidity was 14: 10 in pre-eclampsia; 1 in eclampsia; and 3 in essential hypertension. From all pathological states 54 patients ended with spontaneous vaginal delivery. Termination of pregnancy occurred only in 2 patients, one with severe pre-eclampsia and the other with severe essential hypertension. Induction of labor was done in different weeks of gestation according to the severity or complications discovered. Caesarean section was done in 12 patients, 7 of them for hypertension and in the remaining 5 for other reasons. Management of hypertension at the hospital consisted of 3 approaches: 1) rest in bed and sedation such as pethidine, valium or Algafan; 2) a combination of sedatives and hypotensives such as Brinerdin, Serpasil and Aldomet; and 3) a combination of sedatives, hypotensives and diuretics.
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PMID:Al-Azar experience in pregnancy associated hypertension. 1226 17

Hypertension is the most common medical complication of pregnancy in South Africa and a major cause of maternal and perinatal morbidity and mortality worldwide. At King Edward VIII Hospital in Durban, 18% of all admissions to the obstetric unit have some degree of high blood pressure. Hypertension in its most severe form produces convulsions, proteinuria, and edema and may lead to fetal and maternal death. High-risk groups for preeclampsia are teenage mothers, primigravidas, and women with a history of elevated blood pressure, previous preeclampsia, molar pregnancies, multiple pregnancies, or hydrops fetalis. Methods used to prevent preeclampsia include a low-salt diet supplemented with calcium, magnesium, zinc, fish, and pharmacological manipulation. In developing countries, prevention and detection of preeclampsia is difficult since women seek antenatal care late in their pregnancies. In Durban, the average gestational age at first antenatal attendance is 28 weeks, and 80% of patients presenting with eclampsia have defaulted antenatal care. Treatment includes admission to hospital to establish the etiology of the hypertension and maternal renal function tests . Fetal condition is a sensitive index of hypertension and is judged by 1) clinical evidence of fetal growth, 2) weekly antepartum cardiotocography, and 3) ultrasonographic screening. Patients are managed according to three clinical groups: 1) those identified before 36 weeks, 2) those identified after 36 weeks, and 3) patients in hypertensive crisis. Dihydralazine is the drug of choice for imminent eclampsia. If the patients has a ripe cervix, delivery is induced with 6-8 hours. Steroid contraception use in the older hypertensive patient should be avoided because of possible development of atherosclerosis and stroke. Puerperal tubal ligations in the hypertensive patient ought to be avoided because of the risks of thromboembolic phenomena and pulmonary embolism. Methyldopa is the treatment of choice in cases of moderate to severe hypertension. Intravenous dihydralazine is relatively safe for the rapid reduction of high blood pressure.
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PMID:Coping with hypertension in pregnancy. 1234 38

a-Methyldopa sesquihydrate is used in the treatment of hypertension; over 20 million prescriptions are written annually for a -methyldopa or a-methyldopa sesquihydrate in the United States. a-Methyldopa sesquihydrate (USP grade, greater than 99% pure) was selected for study because of widespread human exposure and the lack of carcinogenicity studies on this compound. Fourteen-day, 13-week, and 2-year studies were conducted in F344/N rats and B6C3F1 mice. The chemical was administered in feed because human exposure is primarily by the oral route. Short-term studies were performed in bacteria and mammalian cells to evaluate the potential for genetic damage. Fourteen-Day and Thirteen-Week Studies: In the 14-day studies, the chemical was administered at dietary concentrations of 0 and 6,250-100,000 ppm. All rats receiving 100,000 ppm and 2/5 female rats receiving 50,000 ppm died. All mice lived until the end of the studies. Final mean body weights of dosed male rats were 14%-43% lower than that of controls, and those of dosed female rats were 9%-24% lower. Feed consumption by dosed male and female rats was reduced. Final mean body weights of dosed mice were generally within 10% of those of controls; feed consumption by dosed groups was lower than that by controls during the first week of the studies. In the 13-week studies, the chemical was administered at dietary concentrations of 0 and 3,100-50,000 ppm. Deaths occurred in 4/10 male rats, 7/10 female rats, and 2/10 female mice at 50,000 ppm and in 1/10 female rats at 25,000 ppm. Final mean body weights of dosed rats were 6%-46% lower than those of controls. Feed consumption by dosed rat groups was lower than that by controls. Final mean body weights of male mice at 25,000 and 50,000 ppm and female mice at 50,000 ppm were reduced 12%-19%. Feed consumption by dosed and control mice was comparable. Rats and mice receiving 25,000 and 50,000 ppm exhibited clinical signs of toxicity including lethargy, hyperexcitability, ocular discharge, and rough hair coats. Clinical signs of toxicity were judged to be more severe in dosed male mice than in female mice. Minimal to moderate kidney tubular cell regeneration was seen in male and female rats at 12,500, 25,000, and 50,000 ppm. Bone marrow hypoplasia occurred in male rats at 25,000 and 50,000 ppm and in female rats at 6,300 ppm and higher. Nuclear enlargement (karyomegaly) of the renal corticaltubular epithelium was observed in male and female mice administered 12,500-50,000 ppm; these kidney lesions were judged to be more severe and occurred more frequently at concentrations of 25,000 ppm and higher. Because of kidney lesions, bone marrow responses, and body weight effects at 12,500 ppm and higher and increased deaths and clinical signs at 25,000 and 50,000 ppm, dietary concentrations selected for male and female rats in the 2-year studies were 0, 3,100, and 6,300 ppm. Based on clinical signs, kidney effects, and body weight decreases at 25,000 and 50,000 ppm, dietary concentrations selected for male and female mice in the 2-year studies were 0, 6,300, and 12,500 ppm. Diets containing the chemical at these concentrations were fed to groups of 50 male and 50 female rats and 50 male and 50 female mice for 103 weeks. Body Weight and Survival in the Two-Year Studies: Mean body weights of dosed rats were generally 8%-17% lower than those of controls, and mean body weights of dosed mice were generally 5%-22% lower than those of controls throughout the studies. The average amount of a-methyldopa sesquihydrate consumed per day was approximately 110-120 or 230-240 mg/kg per day by low and high dose rats and 830-890 or 1,760-1,800 mg/kg by low and high dose mice. Survival was comparable among dosed and control groups (male rats: control, 28/50; low dose, 26/50; high dose, 27/50; female rats: 35/50; 34/50; 29/50; male mice: 44/50; 42/50; 39/50; female mice: 42/50; 40/50; 38/50). Clinical signs considered to be dose-related included fighting in male rats, irritability in male mice, and rough hair coats in female mice. Nonneoplastic and Neoplasle rats, irritability in male mice, and rough hair coats in female mice. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Several lesions of the forestomach, including edema, chronic inflammation, epithelial hyperplasia, and ulcers, were seen at low incidences in high dose rats. No forestomach neoplasms occurred. No neoplastic lesions were observed in either male or female rats which were considered related to a-methyldopa sesquihydrate exposure. Nephropathy (control, 3/50; low dose, 21/50; high dose, 32/50), karyomegaly (nuclear enlargement) of cells of the tubular epithelium (0/50; 46/50; 44/50, and cysts (2/50; 10/50; 10/50) were observed in the kidney of dosed female mice. Low incidences of tubular cell hyperplasia (0/50; 1/50; 1/50), tubular cell adenomas (0/50; 2/50; 0/50), and tubular cell adenocarcinomas (0/50; 0/50; 1/50) were observed in male mice. Tubular cell adenomas (3/2,029, 0.15%) and tubular cell adenocarcinomas (3/2,029, 0.15%)are uncommon in untreated control male B6C3F1 mice. No neoplastic lesions in female mice were considered related to a-methyldopa sesquihydrate exposure. Decreased incidences of several site-specific neoplasms were observed in dosed rats and mice; these decreases might have been due in part to decreased weight gain in dosed groups. The decreases occurred in the adrenal medulla of male rats (pheochromocytomas or malignant pheochromocytomas, combined: 21/49; 3/49; 10/50), uterus of female rats (endometrial stromal polyps: 15/50; 5/49; 1/50), liver of male and female mice (hepatocellular adenomas or carcinomas, combined-- male: 15/50; 5/50; 6/50; female: 4/50; 1/50; 0/50), and anterior pituitary gland of female mice (adenoma: 9/49; 4/40; 2/50). The incidences of malignant tumors (male: 19/50; 9/50; 8/50; female: 21/50; 16/50; 12/50) and benign or malignant tumors (combined) (male: 32/50; 15/50; 17/50; female: 33/50; 22/50; 21/50) were reduced in dosed mice. Reproductive Studies: a-Methyldopa sesquihydrate was administered to male F344/N rats in corn oil by gavage 5 days per week for 65 days at doses of 0, 50, 100, 200, or 400 mg/kg. Decreased body weight was seen in dosed animals. Male rats were mated to untreated female F344/N rats on days 57-61, necropsies were performed on days 65-67, and reproductive toxicity was measured by sperm count, sperm motility, organ weights, hormone levels, and histologic evaluation of the testis. Decreased fertility was observed in males dosed with a-methyldopa sesquihydrate at 200 and 400 mg/kg. Decreases were also seen in sperm count, sperm motility, apparent number of late spermatids, and plasma testosterone levels in males in the 200 and 400 mg/kg groups. This alteration of reproductive function in male rats was found to be reversible after a 13-week recovery period (without dosing). The decreased fertility observed after a-methyldopa sesquihydrate administration was probably due in part to the decreases in plasma testosterone levels. Genetic Toxicity: a-Methyldopa sesquihydrate was not mutagenic when tested with or without exogenous metabolic activation with a preincubation protocol in four strains of Salmonella typhimurium (TA97, TA98, TA100, or TA1535). No increase in chromosomal aberrations or sister chromatid exchanges was observed in Chinese hamsterovary (CHO) cells exposed to a-methyldopa sesquihydrate with or without S9. Audit: The data, documents, and pathology materials from the 2-year studies of a-methyldopa sesquihydrate have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of a-methyldopa sesquihydrate for male or female F344/N rats fed diets containing 3,100 or 6,300 ppm. There was equivocal evidence of carcinogenic activity of a-methyldopa sesquihydrate for male B6C3F1 mice, as shown by three dosed mice having uncommon tubular cell tumors of the kidney. There was no evidence of carcinogenic activity of a -methyldopa sesquihydrate for female B6C3F1 mice fed diets containing 6,300 or 12,500 ppm. Nonneoplastic lesions of the kidney including karyomegaly were observed in dosed female mice. Decreased incidences of several tumor types (in the adrenal gland in male rats, uterus in female rats, liver in male and female mice, and anterior pituitary gland in female mice) were considered related to a-methyldopa sesquihydrate exposure. Synonyms for a-Methyldopa or a-Methyldopa sesquihydrate: 3-hydroxy-a-methyl-L-tyrosine sesquihydrate; L-(a-MD); a-methyl-L-3,4-dihydroxyphenylalanine; L(-)-b-(3,4-dihydroxyphenyl)-a -methylalanine; L-(-)-3-(3,4-dihydroxyphenyl)-2-methylalanine; L-a-methyl-3,4-dihydroxyphenylalanine; a-methyl-b-(3,4-dihydroxyphenyl)-L-alanine; L-(-)-a-methyl-b-(3,4-dihydroxyphenyl)alanine; (-)-methyldopa; L-methyldopa; L-a-methyldopa; a-methyl-L-dopa Trade Names for a-Methyldopa or a-Methyldopa sesquihydrate: Aldomet; Aldometil; Aldomin; a-Medopa; AMD; Bayer 1440 L; Baypresol; Dopamet; Dopatec; Dopegyt; Hyperpax; Medomet; Medopren; Methoplain; MK. B51; MK-351; Presinol; Presolisin; Sedometil; Sembrina
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PMID:NTP Toxicology and Carcinogenesis Studies of alpha-Methyldopa Sesquihydrate (CAS No. 41372-08-1) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1270 36

The current prescription patterns for essential hypertension and the efficacy, safety, tolerability and cost-effectiveness of the newer antihypertensive drugs were evaluated in Nigerian patients. The findings were compared with that of a previous study conducted in the same tertiary hospital 10 years earlier. A cross-sectional evaluation of blood pressure (BP) control in a hypertension clinic was undertaken among 150 Nigerian patients aged 61 +/- 12 years (55% females), with a duration of treatment on a particular drug class or combination of 9 +/- 3 months. The initial blood pressure was 176 +/- 20/108 +/- 11 mmHg and 22% of the patient had concurrent diabetes mellitus. Thiazide diuretics (D) alone or in combination remained the most commonly prescribed drugs in 56% of all patients. There were significant increases in the prescriptions of calcium channel blockers (CCBs) (51%), P < 0.0001, and ACE-inhibitors (ACEIs) (24%), P < 0.0001, but a slight reduction in the use of methyldopa, and fixed drug combinations (P < 0.01) compared to the previous study. The fall in systolic blood pressure on D (r = 0.65, P < 0.001) or CCB (r = 0.48, P < 0.02) was significantly correlated with the initial systolic blood pressure, but not age. More patients achieved normotension BP < 140/90 mmHg on CCB monotherapy (71%), than D monotherapy (56%). Combination therapy with ACEIs + D or methyldopa+thiazides normalized BP in 63 and 68%, respectively. Pulse pressure, a surrogate marker for cardiovascular complications and mortality in essential hypertension, was significantly reduced (P < 0.01) equally by all treatments, with 95% confidence intervals ranging from -28 to -1 mmHg. However, hypertensive-diabetic (HT-DM) patients (n = 33) exhibited no significant change in pulse pressure in response to treatment. Adverse drug reactions that occurred in 11% were impotence or postural dizziness with D, headache and pitting oedema with CCB, and dry cough with ACEI. Pharmaco-economic comparison of the drug classes revealed that for every US dollar (dollar) spent per month, the percentage of treated patients attaining normotension was 18.6 for D, 4.73 for CCB, 3.5 for ACEI + D and 13.6 for methyldopa + thiazides. A combination of ACEI + CCB or D was the preferred treatment for hypertensive-diabetic Nigerians, but only 24% attained a BP < 130/85 mmHg. These results demonstrate a shift in trend to a more rational and efficacious treatment of hypertension over a 10 year period. This may be associated, at least in part, with the intensive and continuous education of the prescribers in rational drug use and the introduction of a hospital formulary. Methyldopa is still a highly efficacious and cost-effective drug in this population. Black HT-DM Africans still constitute a subgroup who not only require more and costlier antihypertensive drugs, but whose BP control is suboptimal, and exhibit a poor therapeutic response to other risk factors (pulse pressure) that constitute a continuing risk for cardiovascular mortality.
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PMID:Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs. 1271 73

Both chronic hypertensive disorders in pregnancy and pregnancy-induced hypertension are the main causes of morbidity and mortality of mothers and fetuses. The great significance in the prevention of serious complications of them has properly pharmacology treatment. One of the most early and the most often used drug is Methyldopa--a drug from the group acting via central nervous system, causing the depression in the cardio-vascular system.
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PMID:[Methyldopa in therapy of hypertension in pregnant women]. 1510 91

This review reflects both the variable presentation and the systemic nature of preeclampsia. Recommendations for the comprehensive evaluation and management of organ dysfunction associated with pre-eclampsia are included. The main points in the review are that: (1) Preeclampsia is a systemic disorder that may affect many organ systems. (2) For preeclampsia remote from term (<34 weeks), expectant management improves perinatal outcomes, but requires obsessive surveillance to mitigate maternal risks and is a "package." (3) Initial assessment and ongoing surveillance of women with preeclampsia should include assessment of all vulnerable maternal organs as well as of the fetus. (4) Initiate antihypertensive drug treatment immediately if sBP >160 mmHg or dBP more than 110 mmHg, or if sBP 140-159 mmHg and/or dBP 85-109 mmHg (prepregnancy renal disease or diabetes). (5) The treatment of nonsevere pregnancy hypertension should include a treatment goal of dBP 80-105 mmHg (depending on practitioner preference), with one of the following agents, Methyldopa, Labetalol, Nifedipine, or, with special indications (renal or cardiac diseases), diuretics. (6) Drugs to avoid: angiotensin-converting enzyme inhibitors; angiotensin II receptor antagonists; and atenolol. (7) For the acute management of severe hypertension, initially reduce dBP by 10 mmHg and maintain the blood pressure at or below that level with either Nifedipine or Labetalol. (8) For both prophylaxis against and treatment of eclampsia, MgSO4 (4 g IV stat, then 1 g/hr). (9) For recurrent seizures, MgSO4 (2g IV stat, then increase to 1.5 g/hr). (10) Total fluid intake should not exceed 80 ml/hr; tolerate urine outputs as low as 10 ml/hr. (11) Early-onset and/or severe preeclampsia predict later cardiovascular morbidity and mortality; it would seem prudent to offer such women screening and lipid lowering interventions.
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PMID:Evidence-based management for preeclampsia. 1748 66

The decision to treat elevated arterial pressure in pregnancy depends on the risk and benefits imposed on the mother and the fetus. Treatment for mild-to-moderate hypertension during pregnancy may not reduce maternal or fetal risk. Severe hypertension, on the other hand, should be treated to decrease maternal risk. Methyldopa and beta-adrenoceptor antagonists have been used most extensively. In acute severe hypertension, intravenous labetalol or oral nifedipine are reasonable choices.
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PMID:Use of antihypertensive drugs during pregnancy and lactation. 1846 19

An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250 mg, theophylline SR 200 mg, indapamide 2.5 mg and paracetamol 500 mg). He had prolonged, severe hypotension, necessitating the use of 3000 ml of Gelofusine and almost 2 days of intravenous norepinephrine infusion. He had marked diuresis for 4.5 days, requiring continuous and bolus infusions of intravenous fluids. He had marked renal potassium loss, requiring vigorous potassium replacement therapy. Multiple-dose activated charcoal was used to enhance theophylline elimination. The plasma paracetamol level was below the treatment line. Methyldopa via its metabolite stimulates postsynaptic alpha-adrenergic receptors in cardiovascular control centres in the brain, causing a reduction in peripheral sympathetic tone and a fall in arterial blood pressure and heart rate. In overdose, it causes hypotension, bradycardia and drowsiness. The natriuretic, kaliuretic and vasodilatory effects of indapamide are exaggerated in overdose, resulting in diuresis, hypokalaemia and hypotension. Theophylline markedly increases the level of circulating catecholamines, which stimulate the vascular beta(2)-adrenergic receptors with decreased peripheral vascular resistance. Peripheral vasodilation and hypotension occur in significant theophylline poisoning. Intracellular shift of potassium results in hypokalaemia. The prescribing physicians should recognise elderly patients at a high risk of self-poisoning and avoid using drugs with a high toxicity in overdose (e.g. theophylline and methyldopa). Restricting access to hazardous drugs (in overdose) would be of paramount importance to reduce the number of severe acute poisoning cases and case-fatalities.
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PMID:Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient. 1962 66

Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy. Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice since decades. The reactive hepatitis is not frequent, but known serious side effect of alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity is 2.5-10%. In our case, gestation hypertension developed at the 21st gestation week of a 35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker therapy was introduced. On the 23rd gestation week acute hepatitis developed. During differential diagnosis of hepatitis, the etiology of methyldopa was taken into account. Viral and autoimmune origin was rolled out. No fetal aberration was found during ultrasound examination. The function of drug metabolizing function from blood was measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4 gene expression. With the reduced nifedipine therapy (30 mg daily), blood pressure was successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was based on anamnesis, clinical picture and the results of chemical and radiological examination and confirmed by the level of drug-metabolizing capacity. The gestation hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in pregnancy in their case report. Our case report confirms that monitoring of serum aminotransferase level is still valuable when treating a pregnant woman with alpha-methyldopa.
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PMID:[Methyldopa-induced acute reactive hepatitis in pregnancy, drug-metabolizing capacity of the liver]. 2021 8

Family physicians should carefully follow their patients receiving methyldopa for liver toxicity. Methyldopa is commonly used in treating hypertension and its hepatotoxic potential is frequently overlooked. This point is illustrated in the following case report involving a 45-year-old black female. The patient had been receiving oral methyldopa for 7.5 months prior to hospitalization for control of severe hypertension. Methyldopa was discontinued on her second hospital day when her liver tests were found to be abnormal. She developed progressive liver failure and lapsed into hepatic coma. Subsequently, her liver biopsy showed severe hepatic necrosis. She slowly improved with medical management. Her liver tests returned to normal; she resumed work and at 14 months follow up her liver biopsy showed no evidence of chronic active liver disease. Monitoring for methyldopa toxicity as outlined in this article could have prevented this costly and near lethal side effect.
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PMID:Severe hepatic necrosis associated with methyldopa. 2128 17


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