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

We present a case in which a patient took an overdose of captopril (Capoten) and alprazolam (Xanax) in a suicide attempt. The patient presented with hypotension (systolic blood pressure of 80 mm Hg) and drowsiness. The hypotension initially responded to administration of intravenous fluids and dopamine; however, it recurred twice at 18.5 and 24.5 hours after ingestion. These episodes again responded to administration of fluids and dopamine. A plasma captopril level of 27,391.1 nmol/L (5982 ng/mL) was documented, as well as a depressed level of angiotensin converting enzyme. Captopril is an angiotensin converting enzyme inhibitor used in the management of hypertension and ventricular failure; to our knowledge, this is the first case of an acute captopril overdose reported in the English-language literature. The role of captopril in inducing hypotension is discussed herein.
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PMID:Captopril overdose resulting in hypotension. 328 10

Clonidine is a centrally active antihypertensive agent effective in the treatment of mild, moderate and severe hypertension, alone or in combination with other drugs. Use of oral clonidine has often been limited by side effects which include dry mouth and drowsiness. Transdermal clonidine was therefore developed as an alternative to oral therapy. Ideally, a drug administered at a constant rate into the systemic circulation should attain steady-state concentrations with less peak-to-trough fluctuation than that associated with intermittent oral dosing. In theory, transdermal administration should thus minimise the adverse effects associated with peak plasma drug concentration, while avoiding the potential for decreased efficacy associated with trough levels. Clonidine has been incorporated into a small, pliable adhesive cutaneous delivery device designed to provide therapeutically effective doses of drug at a constant rate for at least 7 days. The transdermal therapeutic system is a laminate consisting of an external film impermeable to moisture and to the drug, a thin layer of active drug dispersed within a highly drug-permeable matrix, a membrane with a controlled intrinsic permeability regulating the rate of delivery of drug to the skin, and an adhesive coating that attaches the system to the skin surface. The permeation of drug through the skin occurs primarily by diffusion. Application of the clonidine transdermal system to both normotensive and hypertensive subjects has consistently reduced systolic and diastolic blood pressures. Maximum reduction in blood pressure occurs 2 to 3 days after initial application, and is maintained for at least 7 days or until the system is removed. The rate at which clonidine is presented to the skin surface is controlled by the microporous membrane: this rate is the same for all strengths of transdermal clonidine, the amount of clonidine released being proportional to its surface area. Thus, the daily dose is regulated by the area of skin covered. Typically, steady-state plasma concentrations are reached on the fourth day after initial transdermal system application. The lack of dose dependency in half-life and renal clearance estimates emphasise that the transdermal absorption of clonidine is linear. The plasma clonidine concentration produced by a particular transdermal dose varies considerably between individuals as a result of interindividual variation in renal clearance. For this reason, it is recommended that dosages be titrated up from the smallest system (3.5 cm2) until the desired pharmacological effect has been obtained.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of clonidine. 329 68

In an open, clinical trial comprising a total of 49 depressed in-patients, a new selective 5-HT uptake inhibitor citalopram was administered by intravenous infusion in doses of 20-60 mg once daily for per 3 weeks. The therapeutic effect was assessed globally and by means of the CPRS subscale for depression (MADRS). About 40 per cent of the patients showed a complete response whereas about 25 per cent showed a partial response. Side effects which were rated globally and recorded according to a check-list were generally mild and infrequent. The side-effects most frequently observed were tremor, drowsiness, and dizziness which occurred in about 15 per cent of the patients.' Three patients were withdrawn prematurely because of nausea and one because of a skin rash. Cardiovascular recordings were normal except for one patient, who developed a hypertension which may have been related to the test drug. No pathological laboratory values were detected during the trial period. The authors conclude that intravenously administered citalopram is well suited for the treatment of depressed patients.
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PMID:[Citalopram. An open study of a highly selective serotonin-uptake inhibitor administered by infusion to depressive patients]. 331 9

Snoring usually is trivial and unimportant, but it can turn into a social or medical problem. Obesity, hypertension and heart disease are more frequent among snorers than among nonsnorers, and especially snorers with hypersomnia during the day are at risk. Hypersomnia in association with snoring usually signifies obstructive sleep apnea. Increased resistance in the upper airways, together with negative inspiratory pharyngeal pressure and muscular hypotonia during deep non-REM and REM sleep, lead to collapse of the pharynx, hypoxia and hypercapnia. Only after arousal from sleep does muscle tone return, pharyngeal obstruction reopen and airflow resume. Since this process can occur 300 or 400 times a night, repetitive alveolar hypoventilation leads to pulmonary-arterial hypertension and cor pulmonale, and the repetitive sympathetic activations can cause systemic hypertension or serious cardiac arrhythmias. The countless arousals deprive the sufferer of deep non-REM and REM sleep and their consequence is sleep fragmentation. The symptoms are excessive daytime sleepiness, intellectual deterioration and personality and behavioral changes. Oronasomaxillofacial, endocrine and neuromuscular anomalies and diseases predispose to sleep apnea, and alcohol or CNS-depressant drugs can favour its occurrence. Diagnosis is made by nighttime oxymetry, and if this is abnormal, by polysomnography. After polysomnography it is possible to distinguish between obstructive and nonobstructive sleep apnea, and the decisions for an adequate treatment can be made.
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PMID:[Dangerous snoring. Sleep-apnea syndrome]. 331 92

Sleep apnoea syndromes are a frequent disease, with an incidence of more than 1% in the adult population, a strong male predominance, and a maximal frequency between 40 and 60 years. Their clinical manifestations are dominated by snoring and daytime sleepiness, at times associated with morning headaches, intellectual deficiency, sexual impotence. Obesity, hypertension and polycythemia are not uncommon. These patients are at risk for accidents due to sleepiness, sudden death due to sleep apnoea-related cardiac arrhythmias, ischemic attacks related to hypertension and polycythemia and right heart failure secondary to pulmonary hypertension and alveolar hypoventilation. The most frequent form of sleep apnoea syndromes include obstructive and mixed apnoeas. Their mechanism involves both anatomic factors (upper airway narrowing) and functional factors (defective activation of upper airways dilatory muscles) which lead to upper airway occlusion upon inspiration during sleep. Two therapeutic strategies are possible: a surgical one, uvulopalatopharyngoplasty, the efficacy of which is inconstant and unpredictable and nasal continuous positive airway pressure, which is constantly efficacious but constraining. Central sleep apnoea syndromes are rare, less clearly defined and more difficult to treat.
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PMID:[Sleep apnea syndromes in adults]. 332 Dec 51

15 patients aged between 24 and 66 years with 10 different malignant tumor diseases were treated with a recombinant human tumor necrosis factor preparation PAC-4D in a phase-I trial. The starting dose was 10(5) U PAC-4D as an intravenous short infusion. The maximally tolerable dose is around 18 X 10(5) U/m2. As the main clinical side effects were observed: fever, chills, hypertension with subsequent hypotension, lethargy, transient somnolence, headache, neurological deficiency symptoms, nausea and vomiting. Important laboratory-chemical parameters were the increase in transaminases and, in higher dose levels, leukocytosis with the left shift and lymphopenia in the differential blood picture. As dose-limiting toxicity are estimated hypotension, and neurological side effects and hepatotoxicity. In one female patient who received 27 X 10(5) U PAC-4D there appeared pronounced, histologically verified necroses in the metastases of a malignant fibrous histiocytoma.
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PMID:Human pharmacological investigation of a human recombinant tumor necrosis factor preparation (PAC-4D) a phase-I trial. 337 52

The clinical response and pharmacokinetics of intravenous urapidil were studied in patients with uncontrolled severe hypertension. Six of nine patients achieved a diastolic blood pressure (DBP) of 100 mm Hg after initial administration of serial bolus doses and were then placed on maintenance infusions. Three of these six patients maintained a DBP 100 mm Hg or lower at infusion rates of 10 to 20 mg/hr, whereas the remaining three patients experienced a loss of DBP control despite rates of 40 mg/hr. Mean DBP was significantly reduced from 126 +/- 6 mm Hg (N = 9) to 105 +/- 15 mm Hg after the bolus phase (N = 9, P less than .05) and 99 +/- 18 mm Hg after the infusion phase (N = 6, P less than .05). Significant reductions in systolic blood pressure were also achieved after bolus and infusion phases. Adverse reactions included drowsiness, tachycardia, nausea and vomiting but were considered mild. Estimated pharmacokinetic parameters included Vz (0.80 +/- 0.20 L/kg), CL (2.53 +/- 0.99 mL/min/kg) and t1/2 (4.0 +/- 1.5 hr). Urapidil safely reduces blood pressure in patients with severe hypertension. An alternative dosing regimen is suggested.
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PMID:Pharmacokinetics and pharmacodynamics of urapidil in severe hypertension. 339 39

Crisnatol is a novel lipophilic arylmethylaminopropanediol with significant antineoplastic activity in a variety of murine and human tumor models which functions as a DNA intercalator. In this Phase I trial, a 6-h infusion of the drug was administered i.v. in 700 to 1500 ml of 5% dextrose in water every 28 days. Eighty-five courses at doses of 7.5 to 516 mg/m2 were administered to 43 patients with refractory solid tumors. Reversible neurological toxicity was dose limiting at 516 mg/m2 and was manifested as somnolence, dizziness, blurred vision, unsteady gait, and alpha-slowing on electroencephalogram at the end of infusion. All neurological signs and symptoms were reversible. No hematological toxicity was observed. Other toxicities included phlebitis, mild to moderate nausea and vomiting, reversible sinus node arrest in one patient, and hypertension. Crisnatol plasma concentrations were determined by high-pressure liquid chromatography. After infusion, plasma concentrations declined biexponentially with a terminal t1/2 of 2.9 h. Using a two-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 58.8 liters/m2 and 18.3 liters/h/m2, respectively, indicative of extensive tissue distribution and rapid hepatic clearance. Peak plasma levels occurred at the end of infusion and correlated with the onset of neurological toxicity. The recommended Phase II dose for this schedule is 388 mg/m2.
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PMID:Phase I and clinical pharmacology trial of crisnatol (BWA770U mesylate) using a monthly single-dose schedule. 339 16

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8-1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.
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PMID:Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. 354 76

Synthetic progestins derived from nortestosterone provide a promising contraceptive alternative for women with contraindications for estrogens. Progesterone and synthetic progestins reduce vasodilatation and edema induced by estrogens and stop estrogen-dependent cellular multiplication in target tissue. Progestins have 2 kinds of contraceptive affect: antigonadotropic action at sufficient doses, and peripheral action at lower doses. The cervical mucus is modified in composition and volume, becoming hostile to sperm; the endometrial mucus atrophies; and tubal motility is slowed. High dose progestins are administered from the 5th or 10th to the 25th cycle day, with the earlier date preferred for women with shorter cycles. They are an ideal method for women with endometrial hyperplasia or benign breast disease or histories of breast or uterine cancer, as well as for women over 40 with dysovulatory cycles. Contraindications to high dose progestins include obesity, hypertension, lipid metabolic anomalies, and diabetes. Low dose progestin-only pills are administered at the exact same time each day including during menstruation. They are attractive for some women because they contain no estrogen, a reduced progestin dose causing fewer headaches and less somnolence, and fewer metabolic effects. Low dose progestins are indicated for lactating women, those with contraindications to estrogens such as obesity, hypertension, hyperlipidemia, and diabetes, and those with renal or cardiac insufficiency with valvulopathy. Low dose progestins are also indicated for nulliparas and other women for whom IUDS are contraindicated. Women using low dose progestins should never take drugs that act as enzymatic inductors, which speed hepatic degradation of steroids and reduce their efficiency. A resulting pregnancy is likely to be extrauterine because of slowed tubal transport. The failure rate of low dose progestins ranges from .9-3%, with higher failure rates among younger women. About 30% of users initially experience spotting, which despite its usual disappearance after 2-3 months of use is the most common reason for discontinuing the method. Low dose progestins have no metabolic or vascular effects, but they may cause a relative hyperestrogenism is some users. Other modes of administration of progestin contraception include continuous high doses, never justified solely for contraception. Trimonthly injections of medroxyprogesterone acetate of norethindrone enanthate provide contraception through a long lasting antigonadotropic effect. Metrorrhagia and amenorrhea are among possible side effects. The method is used primarily in developing countries where its ease of use is a major advantage. Subcutaneous implants releasing continuous doses of levonorgestrel provide contraceptive protection for over 5 years. The cumulative failure rate is 1.7 at 5 years. Metabolic tolerance is good. The major side effect is menstrual irregularity.
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PMID:[Progestational contraception]. 365 94


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