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

This article reviews the potential of a number of drug classes to produce or aggravate hypertension, with particular emphasis on older patients. Although little information is available regarding the hypertensive effects of mineralocorticoids in the elderly, glucocorticoids usually induce an increase in blood pressure (BP) that is dosage-dependent. Nonsteroidal anti-inflammatory drugs occasionally increase BP, but this effect is not usually clinically relevant. The alleged hypertensive potential of oral antihyperglycaemic agents has not yet been substantiated. In contrast, some antidepressants may be particularly dangerous in terms of their hypertensive complications. Although hypertension may be induced by monoamine oxidase inhibitors (MAOIs) given as monotherapy, severe hypertension is more likely to occur when MAOIs are combined with other sympathomimetic drugs. Several other drugs may also increase the risk of hypertension in elderly patients, but reliable data are lacking for most of these agents. Elderly people who are being treated with drugs that may increase BP should be closely monitored. This is particularly true for drugs that act on the CNS.
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PMID:Drug-induced hypertension. Recognition and management in older patients. 930 78

Vladimir Zinovievich Gorkin's theory of the transformation of catalytic activity of amine oxidases and, therweby, selectivity of amine oxidases, carried over from my personal acquaintance with Vladimir Zinovievich, significantly influenced our studies into the mechanism of MAO-induced stimulation of pineal melatonin biosynthesis from serotonin. We found that this effect depended on the selective inhibition of MAO-A, but not MAO-B, which resulted in the increased formation of N-acetylserotonin (N-AS), the intermediate precursor of melatonin. The hypotensive effect of clorgyline was attenuated by pinealectomy, suggesting that increased N-AS and/or production might contribute to the hypotensive effect of selective MAO-A inhibition. Basal and isoproterenol-induced pineal levels of N-AS, but not melatonin, were lower in 12 week old (hypertensive) than in 4 week old (normotensive) spontaneously hypertensive (SHR) rats. N-AS decreased blood pressure in 12 week old SHR rats. The hypotensive effect of N-AS was augmented by pinealectome and by pretreatment with the S-adenosylhomocysteine, the inhibitor of N-AS conversion into melatonin. Our data demonstrate that hypotensive effect of N-AS is independent of its conversion to melatonin. We suggest that hypotensive effect of selective MAO-A inhibition might depend on the increased formation of N-AS, but not melatonin. The age-associated decrease in N-AS production may contribute to the developing of hypertension in SHR rats, and the age-associated increase of blood pressure in humans. Our data warrant the clinical trial of N-AS for the treatment of essential hypertension.
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PMID:[N-acetylserotonin and hypotensive effect of MAO-A inhibitors]. 950 69

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.
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PMID:Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. 967 55

The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associated with a low incidence of ED. Sympatholytic antihypertensives seldom cause importence but can cause retrograde ejaculation because of the relaxation of the smooth muscles in the prostatic urethra and bladder neck. The most commonly prescription drugs that can affect sexual function are briefly discussed and an integrated pharmacological approach to the patient with drug-induced ED is proposed.
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PMID:[Pharmacology of male sexual dysfunction]. 969 33

The psychopharmacology of depression is a field that has evolved rapidly in just under 5 decades. Early antidepressant medications--tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)--were discovered through astute clinical observations. These first-generation medications were effective because they enhanced serotonergic or noradrenergic mechanisms or both. Unfortunately, the TCAs also blocked histaminic, cholinergic, and alpha1-adrenergic receptor sites, and this action brought about unwanted side effects such as weight gain, dry mouth, constipation, drowsiness, and dizziness. MAOIs can interact with tyramine to cause potentially lethal hypertension and present potentially dangerous interactions with a number of medications and over-the-counter drugs. The newest generation of antidepressants, including the single-receptor selective serotonin reuptake inhibitors (SSRIs) and multiple-receptor antidepressants venlafaxine, mirtazapine, bupropion, trazodone, and nefazodone, target one or more specific brain receptor sites without, in most cases, activating unwanted sites such as histamine and acetylcholine. This paper discusses the new antidepressants, particularly with regard to mechanism of action, and looks at future developments in the treatment of depression.
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PMID:Mechanism of action of antidepressant medications. 1008 78

Blood pressure decrease, associated with postural hypotension, as well as spontaneous hypertension are considered to be typical side-effects of conventional, irreversible and nonselective MAO (A+B) inhibitors. The new generation of reversible MAO-A inhibitors is, however, expected to have negligible cardiovascular effects and low propensity to induce either blood pressure increases or decreases. But, the true incidence of such changes is largely unknown since observation studies, specifically assessing the frequency of blood pressure changes, in unselected population of patients treated in the practice, are lacking.
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PMID:Undesirable blood pressure changes under naturalistic treatment with moclobemide, a reversible MAO-A inhibitor--results of the drug utilization observation studies. 1033 64

Pharmacological interaction is identified among other aspects when the effects of a drug are significantly altered clinically by the presence of food. The most important clinical significance in the history of drug-food interactions occurred in the fifties, the vitamin B6 deficiency when administering the tuberculostatic isoniazide, but there is no doubt that the interaction in the sixties between drugs that were inhibitors of the enzyme mono-amine oxidase and the biogenic amines tyramine and histamine had an important clinical significance due to the increase in hypertension and deaths due to cerebro-vascular accidents. In the seventies the types of interactions were due to the chelation between tetracyclines and the calcium of milk products, influencing the bioavailability of the antibiotic, and from this point on, studies explore in depth the interaction of foods with the different steps in the pharmacokinetics of the drugs (absorption, distribution, metabolization, and excretion), and these have helped to explain the metabolization interactions of drugs like the clinical significance between grapefruit juice whose naringenine flavonoid is a powerful inhibitor of cytochrome 450, particularly the CYP3A4 family, and terfenadine (antihistamine), with an increase in the plasma levels of the drug and patient death due to ventricular arrhythmia. In the USA the Joint Commission on Accreditation of Health Care Organization (JCAHO) has recommended monitoring of the possible drug and food interactions since 1985, and recommends that patients be informed of this. Despite the recommendations of the JCAHO, few American hospitals have protocolized these interactions and even fewer comply with these, and according to some authors, this is due to the lack of motivation caused by the lack of clinical significance. In this chapter we will study the effect of foods on drugs in two aspects: at the pharamcokinetic level with the possible alterations in absorption, distribution, metabolization, and excretion, and at the pharamcodynamic level, by alterations in the action of the drug. Also, based on a study by Delgado, which we have changed somewhat, we will report how the drugs should be taken to avoid interactions with foods. As a conclusion, it is difficult to establish which are the relevant drug-food interactions, unless they have given clinical problems. The following are important: a) drugs with a narrow therapeutic margin in which an absorption problem or a metabolization problem may disrupt the plasma levels and the patient needs (digoxin, teophylline, cyclosporin, etc). And b) the drugs like some antibiotics that, because of their action mechanisms, need to maintain adequate plasma concentrations.
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PMID:[Drug-food interactions]. 1054 35

Previous reports suggest that neuronal norepinephrine (NE) reuptake may be impaired in essential hypertension, perhaps because of dysfunction of the NE transporter, although the evidence is inconclusive. To further test this proposition, we applied phenotypically relevant radiotracer methodology, infusion of tritiated NE and quantification of NE metabolites, to 34 healthy lean subjects (body mass index <27.0 kg/m(2)), 19 overweight (body mass index >28.0 kg/m(2)) but otherwise healthy normotensive subjects, 13 untreated lean patients with essential hypertension, and 14 obesity-related hypertensives. Spillover of NE from the heart was increased in lean hypertensives only (mean+/-SD 33.4+/-20.6 versus 16.1+/-11.7 ng/min in lean normotensives, P<0.05), but this could have resulted from high cardiac sympathetic nerve firing rates, faulty NE reuptake, or both. The arterial plasma concentration of 3-methoxy-4-hydroxylphenylglycol, an extraneuronal metabolite of NE, was elevated in lean hypertensives only (3942+/-1068 versus 3055+/-888 pg/mL in healthy subjects, P:<0.05). The fractional extraction of plasma tritiated NE in passage through the heart, determined on the basis of neuronal NE uptake, was reduced in lean essential hypertensives (0.65+/-0.19 versus 0.81+/-0.11 in healthy subjects, P<0.05). Cardiac release of the tritiated NE metabolite [(3)H]dihydroxylphenylglycol, produced intraneuronally by monoamine oxidase after uptake of [(3)H]NE by the transporter, was reduced in lean hypertensives only (992+/-1435 versus 4588+/-3189 dpm/min in healthy subjects, P<0.01) These findings suggest that neuronal reuptake of NE is impaired in essential hypertension. Through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension. In obesity-related hypertension, there was no phenotypic evidence of NE transporter dysfunction.
Hypertension 2000 Nov
PMID:Phenotypic evidence of faulty neuronal norepinephrine reuptake in essential hypertension. 1108 50

A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions.
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PMID:Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial. 1119 57

Linezolid is a novel oxazolidinone antibiotic with mild reversible monoamine oxidase inhibitor (MAOI) activity. The potential for interaction with over-the-counter (OTC) medications requires quantification. The authors present data evaluating the pharmacokinetic and pharmacodynamic responses to coadministration of oral linezolid with sympathomimetics (pseudoephedrine and phenylpropanolamine) and a serotonin reuptake inhibitor (dextromethorphan). Following coadministration with linezolid, minimal but statistically significant increases were observed in pseudoephedrine and phenylpropanolamine plasma concentrations; a minimal but statistically significant decrease was observed in dextrorphan (the primary metabolite of dextromethorphan) plasma concentrations. Increased blood pressure (BP) was observed following the coadministration of linezolid with either pseudoephedrine or phenylpropanolamine; no significant effects were observed with dextromethorphan. None of these coadministered drugs had a significant effect on linezolid pharmacokinetics. Minimal numbers of adverse events were reported. Potentiation of sympathomimetic activity by linezolid was judged not to be clinically significant, but patients sensitive to the effects of increased BP due to predisposing factors should be treated cautiously. No restrictions are indicated for the coadministration of dextromethorphan and linezolid.
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PMID:Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr. 1136 Oct 53


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