Low bioavailability as a cause of apparent failure of dihydroergotamine in orthostatic hypotension.

Abstract

BRITISH MEDICAL JOURNAL 26 JULY 1980 275 properties at high blood concentrations. MacLeod and Lamberts3 have shown the dopamine agonist effects of high concentrations of haloperidol and pimozide on prolactin release. Seeman4 has shown that very high concentrations of some antipsychotic drugs may enhance presynaptic release of neurotransmitters, including dopamine. Altematively, at high concentrations of antipsychotic drugs maximal dopaminergic blockade may occur. Additional dosage increments would not produce further dopamine blockade, but other pharmacological effects, such as anticholinergic activity, might continue to increase and might be responsible for the presentations described. Toxic psychoses have been associated with high doses of anticholinergic drugs,5 usually combined with moderate doses of antipsychotic drugs. The episodes reported in these studies also appear to have been characterised by excitement and aggression, as in our cases.Requests for reprints to Dr Bridges. In the case of Pseudomonas aeruginosa this susceptibility has been associated with the administration of broad-spectrum antibiotics, pre-existing immunosuppression, and corticosteroids.1Gross-infection has often been by way of contaminated ventilator equipment. This may be due to inadequate disinfection of the apparatus after use.2 Dilution of topical anaesthetics with deionised tap water has produced an outbreak of Ps cepacia respiratory tract infection.3 Pseudomonas species are of a low order of pathogenicity and are rarely implicated as a cause of clinical infection. Nevertheless, they have been known to cause a granulomatous pneumonitis under certain circumstances.4 Patients and methodsDuring routine twice-weekly bacteriological monitoring of an intensive therapy unit Ps fluorescens was consistently isolated from the tracheal aspirates of those patients who had been ventilated for four days or more. Twenty-nine consecutive admissions for mechanical ventilation were finally analysed. Only seven of these patients were ventilated for four days or more, and from all these Ps fluorescens was isolated. Ps fluorescens was identified by means of both the analytical profile index (API Products Ltd) and fluorescein-pyocyanin production. All isolates had the same analytical profile index number, produced fluorescein only on King's medium, and had the same antibiogram.On more detailed bacteriological examination of the intensive therapy units, Ps fluorescens was isolated from the humidifier water of all the ventilators in use, from the inspiratory tubing, and from the pre-filter expiratory tubing. At this time it was also noted that the temperature of the humidifiers, which are connected between the ventilator and the patient, was between 38°C and 41°C. Bacteriological examination was then performed on the humidifiers, humidifier water, and ventilator tubing before use. Only the distilled water, used to fill the humidifiers, yielded Ps fluorescens (20 organisms/i). The distilled water was delivered from the pharmacy in 8-litre plastic co...

Management of Hypertension in the Setting of Autonomic Failure

“…toms, [33][34][35] but oral bioavailability is variable, 36,37 and there is concern about its long-term use. Octreotide is also very effective, even when other agents fail, in part because of its ability to constrict the splanchnic circulation, 38 where most of the orthostatic blood pooling occurs.…”

CLINICAL PERSPECTIVES: Management strategies for recurrent vasovagal syncope

“…It is probably a partial α‐agonist but is a more potent venous than arterial constrictor. The efficacy and dose regimen for DHE is highly variable as a result of low oral bioavailability 21 . Doses range from 2.5–15 mg orally three times daily.…”

“…The efficacy and dose regimen for DHE is highly variable as a result of low oral bioavailability. 21 Doses range from 2.5-15 mg orally three times daily. Absorption is dependent on gut blood flow and therefore it should be taken with food.…”

Treatment of chronic orthostatic hypotension with ergotamine.

“…However, the results of chronic oral treatment with the drug have been equivocal,8' 9 perhaps because of low bioavailability.9' 10 Hemodynamic studies indicate that the blood pressure-enhancing effect of dihydroergotamine in orthostatic hypotensives is associated with increases in total peripheral resistance. 8' 9 Changes in cardiac output have been variable.…”

“…Each series of measurements included at least five determi- All patients also were treated chronically with orally administered ergotamine tartrate in doses of 2-6 mg/ day. They were followed initially for at least 10 [ during recumbency,'6 and patients should be monitored closely for this potential complication.…”