High blood pressure. A side effect of drugs, poisons, and food

A variety of therapeutic agents or chemical substances can induce either a transient or a sustained increase in blood pressure. These agents increase arterial pressure by either causing sodium retention and extracellular volume expansion or directly or indirectly activating the sympathetic nervous system. Some agents act directly on arteriolar smooth muscle. For certain agents, the mechanism of pressure elevation is mixed or unknown. Paradoxically, some agents that are used to lower arterial pressure may acutely increase arterial pressure. Also, a rebound increase in pressure may be encountered after discontinuation of certain antihypertensive agents. In general, these chemically induced increases in arterial pressure are small and transient; however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure has been reported. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and prevent the need for evaluation and therapy. This study reviews the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action.     

Irreversible cataract as a possible side effect of isoretinoin

BACKGROUND: Isoretinoin, a drug used in the treatment of severe cystic acne, is known for its numerous adverse ocular side effects, among others. Generally these side effects are benign in nature and reversible on cessation of drug therapy, as for instance transient acute myopia. However, two cases of irreversible cataract possibly related to isotretinoin have been described up till now. PATIENT: We examined a 37-year-old woman with acute unilateral cataract that occurred after a treatment with isotretinoin for four months, terminated a few days previously. A clear etiological relation could not be established. CONCLUSION: The time relation, the acute onset and the absence of other factors nevertheless suggest an influence of isotretinoin therapy to the occurrence of the cataract.     

Hyponatremia as a side effect of serotonin uptake inhibitors

Hyponatraemia is a possible, potentially serious adverse reaction to treatment with selected serotonin re-uptake inhibitors (SSRIs). The article consists in a review of the 27 cases of such reactions that have been reported to the Swedish Medical Products Agency. The data from these reports suggest the risk of hyponatraemia to be particularly manifest during the first few weeks of treatment, and to be greater in women, the elderly, and patients concomitantly treated with diuretics. In the event of vague, non-specific symptoms occurring in conjunction with SSRI treatment, measurement of the serum sodium concentration is recommended.     

Nonsteroidal anti-inflammatory drugs and severe psychiatric side effects

In the systemic mucopolysaccharidoses (MPS) in animals, corneal clouding resulted from storage of glycosaminoglycans (GAG) in stromal keratocytes. The corneal epithelium was normal (MPS VI and VII) or minimally affected (MPS I), and stromal edema was not a feature even though the corneal endothelium demonstrated variable pathology. The MPS I (cat) cornea showed endothelial cells with large numbers of secondary lysosomal inclusions that were vacuolated or had a granular matrix. The endothelium was uniformly affected, but was not markedly hypertrophied. In contrast, the MPS VI (cat) cornea showed no endothelial cell disease. The MPS VII (dog) cornea had the most significant and dramatic endothelial pathology. The cells were massively hypertrophied and contained large numbers of vacuolated lysosomal inclusions. Regardless of the severity of the morphologic disease, the endothelial cells in these animal models functioned normally in maintaining the relative dehydration of the cornea. The corneal clouding was the result of storage in stromal keratocytes rather than corneal edema from endothelial dysfunction.     

Evaluation and treatment of gynecomastia

Gynecomastia is a proliferation of the glandular component of the male breast. Causes include altered estrogen-androgen levels, aging, puberty, chronic disease, tumors and drugs. The physician must determine whether the condition has a physiologic or pathologic cause. Pubertal gynecomastia is generally physiologic and regresses without treatment. The likelihood of pathology is increased in patients over 26 years of age who present with new-onset gynecomastia. A thorough history, a complete physical examination and an appropriate clinical evaluation facilitate the prompt diagnosis and treatment of this condition.     

Sexual side effects of antihypertensive drugs. Treatment strategies and strictures

Although not all sexual dysfunctions in patients receiving an antihypertensive medication are attributable to the drug, many are. The author advocates accepting a patient's report of such dysfunction without challenge, and assuming, at least initially, that the drug is at fault. He has found that systematic modification of the drug regimen eliminates the side effect or reduces its severity in most cases.     

Feminizing syndrome and gynecomastia in males

Gynecomastia is one of the common symptoms of feminizing syndrome in males. Causes of feminizing syndrome are considered the increase of serum level of estrogen, prolactin, LH and hCG and testosterone deficiency. The condition of gynecomastia was commonly silent. Gynecomastia is classified three groups those are physiological, pathological and ideopathic gynecomastia. Physiological gynecomastia was reported to break out healthy males. Ideopathic gynecomastia is the main cause in medicine. Characterization of pathological gynecomastia are known side effect of drugs, testosterone deficiency and increased estrogen production. Gynecomastia is making satisfactory progress by treatment of the causes, but long term of the history merely have need resection.     

Analgesic effect of antidepressant drugs

We have examined the association of 5-androsten-3beta-ol (androsterol) with saturated phosphatidylcholines (PCs), having symmetric acyl chains from 10 to 16 carbons in length, in both mono- and bilayer membranes. The emphasis of the study was to measure how hydrophobic mismatch (i.e. the difference in hydrophobic length of the interacting molecules) affected androsterol/PC interactions in model membranes. With monolayer membranes (33 mol% sterol, 20 mN/m, 25 degreesC), androsterol was found to be macroscopically miscible with all the tested PCs. Androsterol was observed to condense the lateral packing of di14 and di15 PCs (by 6 and 4.5 A2 per molecule, respectively), but failed to condense shorter (di10, di11, di12 and di13 PCs) or the longer chain di16PC. The rate of androsterol desorption from mixed monolayers to beta-cyclodextrin acceptors in the subphase was a clear function of the host PC acyl chain length. The slowest rate of androsterol desorption (i.e. best androsterol/PC interaction) was seen from a di14PC monolayer, whereas the desorption rate increased when the host PC had shorter or longer chains. When the cholesterol oxidase susceptibility of androsterol was determined in small unilamellar vesicles (SUV) containing PCs of different chain lengths (33 mol% androsterol), the slowest rate of oxidation was seen in di14PC vesicles, whereas higher rates were measured for shorter or longer chain PC vesicles, again suggesting that androsterol interacted more favorably with di14PC than with the other PCs. In conclusion, the hydrophobic mismatch between androsterol and different PCs appeared to greatly affect the intermolecular interactions, as determined from the condensation effect, from sterol desorption rates, and the oxidation susceptibility of androsterol. Although androsterol is not a physiological membrane component, the present model system clearly shows that hydrophobic mismatch has a great influence on how sterols and phosphatidylcholines interact in membranes.     

Bisphosphonates as anticancer drugs

During June 1996, water supplies of the city of San Pedro Sula, Honduras, were sampled to obtain an assessment of Cryptosporidium oocyst and Giardia cyst concentrations. Each sample was concentrated and stained with an indirect immunofluorescent antibody, and parasites were counted through microscopic analysis. In three surface water supplies, Cryptosporidium oocyst concentrations ranged from 58 to 260 oocysts per 100 L, and Giardia cysts were present in concentrations ranging from 380 to 2100 cysts per 100 L. Unlike the surface water samples, groundwater had a higher concentration of Cryptosporidium oocysts (26/100 L) than Giardia cysts (6/100 L), suggesting that the groundwater aquifer protects the water supply more effectively from larger Giardia cysts. Cryptosporidium oocyst concentrations are within the typical range for surface water supplies in North America whereas Giardia cyst concentrations are elevated. Efforts should be made to protect raw water from sources of contamination.     

Sebaceous gland hyperplasia as a side effect of cyclosporin A. Treatment with the CO2 laser

HISTORY AND CLINICAL FINDINGS: After renal transplantation 11 years previously followed by immunosuppression with cyclosporin A, a 59-year-old man developed, shortly after starting the medication, skin-coloured nodules in the region of both ears and the forehead. In the subsequent years the skin changes spread throughout the entire face. The nodes (up to 2 cm in diameter) and nodules were soft and yellowish-white in colour. In addition there were numerous distinct telangiectasias over the whole face. INVESTIGATIONS: Several skin biopsies were taken. They showed largely unremarkable epidermis but marked enlargement and multiplication of the sebaceous glands. DIAGNOSIS, TREATMENT AND COURSE: In view of the histological findings the diagnosis of sebaceous hyperplasia was established. After a trial with carbon dioxide laser, treatment over the entire surface of the two auricles was undertaken under full anaesthesia. The normal auricular contour was reconstituted by removal of the papules and nodes, without any scar formation. CONCLUSION: In the absence of an alternative medication and if the very marked skin changes show no sign of regression, "shaving off" by scalpel of the nodes and nodules or conventional surgery has been the available treatment. However, removal by carbon dioxide laser has the advantage of fewer side effect, is less stressful to the patient and provides a dry operative field.     

Dental and gingival pain as side effects of niacin therapy

Two 65-year-old white men with coronary heart disease, given niacin therapy for dyslipidemia for 5 months, developed intense dental and gingival pain that was associated with increases in dose and that was relieved with discontinuance of niacin treatment. One individual who took crystalline niacin had beneficial effects on lipid levels, while the other person who took a delayed release preparation had little lipid effect. The cause of these previously unreported side effects of niacin therapy is uncertain but may be related to prostaglandin-mediated vasodilatation, hyperalgesia of sensory nerve receptors, and potentiation of inflammation in the gingiva with referral of pain to the teeth.     

Vascular leak syndrome: a side effect of immunotherapy

The major dose-limiting toxicity of interleukin-2 (IL-2) and of immunotoxin (IT) therapies is vascular leak syndrome (VLS). VLS is characterized by an increase in vascular permeability accompanied by extravasation of fluids and proteins resulting in interstitial edema and organ failure. Manifestations of VLS include fluid retention, increase in body weight, peripheral edema, pleural and pericardial effusions, ascites, anasarca and, in severe form, signs of pulmonary and cardiovascular failure. Symptoms are highly variable among patients and the causes are poorly understood. The pathogenesis of endothelial cell (EC) damage is complex and can involve activation or damage to ECs and leukocytes, release of cytokines and of inflammatory mediators, alteration in cell-cell and cell-matrix adhesion and in cytoskeleton function. VLS restricts the doses of IL-2 and of ITs which can be administered to humans and, in some cases, necessitates the cessation of therapy. This review discusses the diversity of clinical manifestation, possible mechanisms and therapeutic modalities for VLS induced by IL-2 and ITs.     

Inhibitors of glutathione reductase as potential antimalarial drugs. Kinetic cooperativity and effect of dimethyl sulphoxide on inhibition kinetics

We have developed inhibitors of glutathione reductase that improve on the inhibition of literature lead compounds by up to three orders of magnitude. Thus, analogues of Safranine O and menadione were found to be strong, reversible inhibitors of yeast glutathione reductase. Safranine O exhibited partial, uncompetitive inhibition with Ki and alpha values of 0.5 mM and 0.15, respectively. Thionine O was a partial (hyperbolic) uncompetitive inhibitor with Ki and alpha values of 0.4 microM and 0.15, respectively. LY83583 and 2-anilino-1,4-naphthoquinone also showed (hyperbolic) partial, uncompetitive inhibition with micromolar Ki values. For Nile Blue A a model for two-site binding with (parabolic) uncompetitive inhibition fitted the data with a Ki value of 11 microM and a kinetic cooperativity between the sites of 0.12, increased to 0.46 by preincubation of the enzyme and Nile Blue A in the presence of glutathione disulphide. Analysis of the effects of preincubation on the kinetics and cooperativity indicated the possibility of a slow conformational change in the homodimeric enzyme, the first such indication of kinetic cooperativity in the native enzyme to our knowledge. Further evidence of conformational changes for this enzyme came from studies of the effects of dimethyl sulphoxide which indicated that this co-solvent, which at low concentrations has no apparent effect on initial velocities under normal assay conditions, induced a slow conformational change in the enzyme. Thionine O, Nile Blue A and LY83583 were redox-cycling substrates producing superoxide ion, detectable by means of cytochrome c reduction, but leading to no loss of glutathione reductase activity, under aerobic or anaerobic conditions. The water-soluble Safranine analogues Methylene Blue, Methylene Green, Nile Blue A and Thionine O (5 mg/kg i.p. x 5) were effective antimalarial agents in vivo against P. berghei, but their effect was small and a higher dose (50 mg/kg i.p. x 1) was toxic in mice. Comparison was made with human glutathione reductase and its literature-reported interactions with several tricyclic inhibitors as studied by X-ray diffraction. It is possible that the conformational changes detected in the present study from alterations in detailed kinetic inhibition mechanisms may shed light on information transfer through the glutathione reductase molecule from the dimer interface ligand pocket to the active-site.     

The effect of unilateral nasal patency on the contralateral side

This investigation was designed to verify the possible feed-back mechanism which works to compensate for changes in the nasal volume of one side by the other side. Acoustic rhinometry, with which nasal volume is easily evaluated, was used in this investigation. Acoustic rhinometry was performed at 4 points in time (immediately after, and three, six and nine minutes after, the setting of experimental conditions). This investigation was composed of two studies. In the first study, ten healthy subjects (nine males and one female, 26-49 years of age, mean age 30 years) were evaluated to estimate the effect of decreased unilateral nasal patency upon the other side. In this study, one nasal cavity was occluded with an acryle plug, and the nasal volume of the other side was evaluated by acoustic rhinometry before and after the occlusion. In the second study eight healthy subjects (five males and three females, 24-34 years of age, mean age 29 years) were evaluated to estimate the effect of increased unilateral nasal patency upon the other side. This study covered a period of three days. A small piece of cotton soaked in a vasoconstrictor solution (1/1000 adrenalin or 0.05% naphazolin nitrate) was put in one nasal cavity (the right on the first day, the left on the second day) and the other side was evaluated before and after administration of the solution. On the third day of the control study, a similar piece of cotton soaked in physiological saline solution was put in one nasal cavity, and the other side was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xanthone derivatives as potential anti-cancer drugs

When one is using nonhuman primates for studying the inhalation of infective or toxic agents, a respiratory minute volume (MV) range of +/- 50 ml is desirable to ensure the accurate delivery of calculated doses of the aerosolized agent. When one is working with highly infective or toxic agents, it is desirable to anesthetize the animals and to separate the plethysmograph, used to measure MV, from the aerosol chamber, used to administer agents, in order to minimize decontamination procedures and to maximize safety. In our laboratory the sequential completion of these procedures requires at least 20 min. Therefore it is necessary to find an anesthetic that achieves a +/- 50 ml steady-state MV for at least 20 min and that does not change when an animal is transported from one apparatus to another. Using 2.6- to 4.0-kg, 14- to 18-month-old rhesus macaques, we determined that tiletamine/zolazepam induced a steady-state MV of 48 +/- 17.8 min, beginning 21.5 +/- 4.7 min after injection of the anesthetic agent. This MV did not significantly change when animals were transported. The use of ketamine and ketamine/acepromazine resulted in a steady-state MV period of 11.5 +/- 4.5 and 22.0 +/- 7.9 min respectively. When we compared these findings with previously reported mathematical estimations of MV based on functions of weight or respiratory rate, we further determined that the accurate measurement of MV before each aerosol exposure was critical for calculating inhaled doses of the agent.     

Antioxidant effect of drugs used in cardiovascular therapy

With respect to clinical signs of the radiation syndromes, some remarkable species variations exist. For example the marked delayed reaction of the acute hematologic response in cows. An unusually high sensitivity of the central nervous system is found in burros, which is probably caused by acute vascular and/or metabolic changes in the brain. The species-specific number of intestinal crypt and hemopoietic stem cells may explain the early survival differences among species after high doses of irradiation. Mortality due to acute radiation syndromes is lowest in chickens. Regarding late effects, various neoplasms are typical in dogs, and cattle more commonly develop cataracts.