Drug-induced pulmonary edema and acute respiratory distress syndrome.

Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

The effects of amrinone and calcium chloride on pulmonary vasculature and biventricular function in ethchlorvynol-induced lung injury in sheep.

The effects of amrinone and CaCl2 on pulmonary vasculature and biventricular function in sheep with acute lung injury (ALI) were studied. Seven sheep were ventilated with a tidal volume of 10-12 ml.kg-1 with end-tidal CO2 of 40 +/- 5 mmHg (5.3 +/- 0.7 kPa) after acute lung injury was induced with up to 30 mg kg-1 of ethchlorvynol (ECV). Biventricular function and hemodynamic profiles were estimated with a rapid computerized thermodilution method and modified pulmonary artery catheters after acute lung injury, following a loading dose (1 mg kg-1) and maintenance dose (5 micrograms kg-1 min-1) of amrinone and after a bolus dose of CaCl2 (20 mg kg-1). ECV successfully induced acute lung damage in sheep, causing significant increases in pulmonary artery pressure (PAP) and pulmonary vascular resistance index (PVRI). Amrinone reversed the unfavorable changes induced by ECV, significantly reducing PAP, PVRI and left ventricular end-diastolic volume (LVEDV). CaCl2, however, reversed the effect of amrinone and increased PAP, PVRI, and LVEDV but decreased left ventricular ejection fraction.

Ethchlorvynol overdose.

Ethchlorvynol remains a drug that frequently surfaces in clinical emergency practice despite safer and more effective pharmaceutical agents on the market. Effects such as poisoning, dependence, ocular damage, and overdose continue to receive attention in the literature. Awareness of complications and treatment in ethchlorvynol exposure requires attention to a drug remaining clinically available without an appropriate clinical indication.

Swine model of early adult respiratory distress syndrome induced by intravenous ethchlorvynol.

Although ethchlorvynol (ECV) has been used to induce pulmonary damage in animals, changes after injection of this drug have not been studied, nor has the stability of the animal been assessed after injection. Continuously monitored hemodynamic and respiratory changes were followed during and after iv injection of 55 mg/kg ECV in ethanol into anesthetized, paralyzed, and ventilated swine (n = 5) and compared to changes in a control group given ethanol alone (n = 5). Arterial and mixed venous saturations were measured by fiberoptic vascular catheters and oxygen exchange by a gas monitor. Twelve direct and derived variables were monitored every 20 sec using a computer data acquisition system. Arterial oxygen saturation was kept at 90 +/- 2% by adjustment of FIO2. Ethanol produced only transitory changes during infusion. Significant elevations in pulmonary vascular resistance (PVR), shunt (Qsp/Qt) and deadspace (VD/VT) were observed during and after ECV. These were unaccompanied by changes in cardiac output or arterial pressure. PVR increased by 137%, Qsp/Qt by 67%, and VD/VT by 28% over 30 min. These changes were then sustained in the postinfusion period, producing a stable model of early adult respiratory distress syndrome for 3.5 h.

Ethchlorvynol pharmacokinetics during long-term administration in a patient with hyperlipidemia and hypothyroidism.

A 33-year-old obese, hypothyroid, white male with several medical problems was admitted to University Hospital in September 1984 for treatment of drug intoxication. Admitting medications included ethchlorvynol in addition to other central nervous system depressants. Initial serum concentrations were reported at 70 micrograms/ml in this somnolent yet totally conscious adult. Established therapeutic concentrations are 2-8 micrograms/ml, with toxic exceeding 20 micrograms/ml. A tolerance phenomenon seemed evident. Serum ethchlorvynol concentrations were monitored daily during early hospitalization and continued to be substantially greater than reported toxic concentrations. Kinetic values were as follows: total body clearance 9.92 ml/min, volume of distribution 68.0 liters, and half-life 78 hours. These values are unique in that they were calculated from a patient who had not suffered an acute overdose, thereby differing markedly from previously published values. The influence of hypothyroidism and hyperlipidemia on these markedly different values appears to be significant. Ethchlorvynol should probably be added to the list of drugs influenced by thyroid disease.

Chiasmal optic neuritis.

Two patients exhibiting bitemporal hemianopia due to chiasmal optic neuritis with pathological confirmation of noncompressive lesions are presented; the first due to a chronic, idiopathic demyelinating process, and the second a result of ethchlorvynol (Placidyl) toxicity. The literature regarding chiasmal optic neuritis is reviewed, and a discussion of other noncompressive causes of bitemporal hemianopia is presented.

Delirium and stereotypy from anticholinergic antiparkinson drugs.

1. This report describes two cases of psychotic syndrome from benztropine (Cogentin), which was used to treat haloperidol-induced extrapyramidal side effects. The patients' symptomatology meets DSM III criteria for delirium. Both patients displayed repetitive motor automatisms (stereotypy). 2. Symptomatology appeared one-to-two days after the start of benztropine 2 mg b.i.d. and subsided one-to-several days after benztropine was stopped. Treatment consisted of administration of sedative hypnotic drugs. 3. The literature on anticholinergic-induced psychotic syndromes is surveyed. Particular attention is drawn to the occurrence of stereotypy. 4. It is proposed, on the basis of a review of animal and clinical data, that stereotypies in delirious patients are related to muscarinic blockade in the central nervous system. This model is used to explain repetitive motor automatisms which are seen in Alzheimer's disease. 5. The paper concludes with brief guidelines for the management of anticholinergic delirium.

Ethchlorvynol: potential of metabolites for adverse effects in man.

Identification of low levels of a metabolite of unaltered skeletal structure, 1-chloro-3-ethynylpent-1-en-3,4-diol (VII), detected in biological specimens of both nonfatal and fatal poisonings with DL-1-chloro-3-ethylpent-1-en-4-yn-3-ol (ethchlorvynol, la), has been achieved by high-resolution GC/MS. Corroborative evidence for the assigned structure (VII) was provided by synthesis, the design of which included as a central objective, concurrent access to 1-chloro-3-ethynyl-3,4-epoxy-1-pentene (VI), the putative direct precursor of VII. The diastereomeric epoxide mixture (VI) is mutagenic toward Escherichia coli WP2 try-hcr-, a UV-deficient repair strain. By contrast, neither Ia, VI, nor VII proved to be mutagenic toward Salmonella typhimurium (TA98, TA100, TA1535, and TA1539) with or without a liver postmitochondrial fraction. However, the epoxides (VI) proved cytotoxic to, for example, TA100, which apparently overlies its potency as a mutagen. The cytotoxicity of VI was also apparent in an in vitro culture system.

Adult respiratory distress syndrome after Placidyl abuse.

A case of intravenous Placidyl injection is described which resulted in pulmonary pathophysiology consistent with adult respiratory distress syndrome (ARDS). Concise documentation of pulmonary and hemodynamic function demonstrated the dramatic response to PEEP therapy. Previously reported cases, mechanisms, and similarity to heroin-induced ARDS are discussed.

Comparative trial of a new hypnotic (Finorgal) with nitrazepam and triclofos sodium.

Thirty patients complaining of insomnia were studied in a double-blind trial with crossover of Finorgal, nitrazepam and triclofos sodium. Finorgal given as a hypnotic produced similar results to nitrazepam and triclofos sodium in terms of induction of sleep, duration and quality of sleep, dream recall and morning 'hangover'. Reported side-effects were not serious and occurred less frequently in association with Finorgal treatment than with nitrazepam or triclofos sodium. Laboratory investigations gave no indication of the development of any drug toxicity during the three-week period of the trial.

Comparison of a new hypnotic (Finorgal) with placebo in a double-blind trial.

The hypnotic effects of Finorgal (ethchlorvynol with diphenhydramine) were compared with those of placebo in a double-blind study with crossover of treatments in thirty-five hospital in-patients. During the four-week period of Finorgal treatment there was a significant reduction in the mean time elapsing between the administration of the hypnotic and the onset of sleep, and a significant increase in the duration of sleep, compared with the four weeks of placebo treatment. There was also a significant increase in the proportion of nights when the patients felt they had slept well, and in the incidence of morning 'hangover' and nocturnal confusion during the Finorgal treatment periods. Patients had to be actively woken in the morning significantly more often following Finorgal administration. In patients experiencing pain in the night there was a significant reduction in the occurrence of pain during the nights when Finorgal had been given.