ABSTRACT
A fatality resulting from the self-administration of fentanyl is described. The decreased was a health care professional with a known history of drug abuse. At the scene, a syringe partly filled with red fluid was found. Pathological findings disclosed pulmonary congestion, hemorrhage, and aspiration of gastric contents and passive congestion in the liver and kidneys. Initial drug screening revealed the presence of fentanyl in the fluid from the syringe and diazepam/oxazepam in the urine. Fentanyl, diazepam, nordiazepam, and oxazepam in the submitted samples were simultaneously quantitated using a gas chromatograph equipped with a nitrogen-phosphorus detector. The fentanyl concentrations (micrograms/L or micrograms/kg) in serum, blood, urine, bile, liver, kidney, brain, lung, and stomach tissue were 17.7, 27.5, 92.7, 58.2, 77.5, 41.5, 30.2, 83.4, and 31.6, respectively. The tissue levels of diazepam and its metabolites were lower than the reported lethal concentrations. The fentanyl concentration in the syringe contents was 2,800 micrograms/L. The toxicological findings and circumstantial evidence of the case indicate that the death resulted primarily from fentanyl overdose.
Subject(s)
Fentanyl/poisoning , Adult , Brain/metabolism , Diazepam/metabolism , Diazepam/pharmacokinetics , Diazepam/urine , Fentanyl/metabolism , Fentanyl/pharmacokinetics , Fentanyl/urine , Gas Chromatography-Mass Spectrometry/methods , Gastric Mucosa/metabolism , Humans , Lung/metabolism , Male , Nordazepam/urine , Oxazepam/urine , Self Administration/psychology , Substance Abuse, IntravenousABSTRACT
Tioconazole is a new imidazole antifungal agent with broad-spectrum activity. Its in vitro activity against common dermal pathogens is generally better than miconazole by a factor of 2-8. This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. Pharmacokinetic studies in animals have demonstrated minimal systemic exposure following dermal application. Acute general pharmacology studies have shown that the compound is well tolerated in animals and unlikely to produce side-effects in man.
Subject(s)
Antifungal Agents/therapeutic use , Dermatomycoses/drug therapy , Imidazoles/therapeutic use , Animals , Antifungal Agents/metabolism , Chemical Phenomena , Chemistry , Disease Models, Animal , Guinea Pigs , Imidazoles/metabolism , Imidazoles/pharmacology , Kinetics , Miconazole/therapeutic use , Rabbits , RatsABSTRACT
The animal and human pharmacology of several new drugs (prazosin, trimazosin, pirbuterol, and carbazeran) useful in the treatment of congestive heart failure (CHF) is delineated in relation to the pharmacology of other agents employed for CHF management. Prazosin and trimazosin are selective alpha 1-blockers that cause a balanced increase in cardiac output (CO) and reduction in left ventricular filling pressure (LVFP); the reduction in diastolic blood pressure with these drugs is significantly related to increase in treadmill exercise, fall in LVFP, and increase in CO. Pirbuterol is a relatively selective beta 2-agonist with somewhat greater effects on CO than on LVFP. Early promise in CHF therapy is being shown by a novel series of cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitors with combined direct inotropic and vasodilator effects. Double-blind long-term studies demonstrate persistent efficacy of prazosin and trimazosin in CHF as measured by improvement in New York Heart Association functional class, treadmill exercise performance, and noninvasive measures of cardiac function; these data are supported by studies in which repeat cardiac catheterization has been performed after several months of therapy. Double-blind studies of other CHF drugs are in progress.
Subject(s)
Cardiovascular Agents/therapeutic use , Heart Failure/drug therapy , Animals , Asthma/drug therapy , Carbamates/therapeutic use , Cardiotonic Agents/therapeutic use , Clinical Trials as Topic , Drug Evaluation , Drug Evaluation, Preclinical , Ethanolamines/therapeutic use , Hemodynamics/drug effects , Humans , Hypertension/drug therapy , Piperazines/therapeutic use , Prazosin/therapeutic use , Quinazolines/therapeutic use , Vasodilator Agents/therapeutic useSubject(s)
Anti-Bacterial Agents/toxicity , Hearing Disorders/chemically induced , Hearing Tests/veterinary , Postural Balance/drug effects , Vestibule, Labyrinth/drug effects , Aminoglycosides/toxicity , Animals , Auditory Threshold/drug effects , Drug Evaluation, Preclinical , Guinea Pigs , Hearing Disorders/diagnosis , Labyrinth Diseases/chemically induced , Labyrinth Diseases/diagnosis , Time FactorsSubject(s)
Adrenergic beta-Antagonists , Heart/drug effects , Propanolamines/pharmacology , Adenylyl Cyclase Inhibitors , Animals , Benzamides/pharmacology , Binding, Competitive , Cresols/pharmacology , Dose-Response Relationship, Drug , Guinea Pigs , Heart Atria/drug effects , In Vitro Techniques , Isomerism , Isoproterenol/pharmacology , Lung/enzymology , Myocardium/enzymology , Organ Specificity , Practolol/pharmacology , Propranolol/pharmacology , Rats , Trachea/drug effectsSubject(s)
Adrenergic beta-Antagonists/pharmacology , Blood Glucose , Hypoglycemia/chemically induced , Insulin , Propanolamines/pharmacology , Propranolol/pharmacology , Administration, Oral , Animals , Benzamides/administration & dosage , Benzamides/pharmacology , Cresols/administration & dosage , Cresols/pharmacology , Drug Interactions , Injections, Intraperitoneal , Insulin Antagonists , Male , Practolol/pharmacology , Propanolamines/administration & dosage , Propranolol/administration & dosage , RatsSubject(s)
Adrenergic beta-Antagonists/pharmacology , Amino Alcohols/pharmacology , Heart/drug effects , Propranolol/pharmacology , Trachea/drug effects , Acetanilides/administration & dosage , Acetanilides/pharmacology , Adrenergic beta-Antagonists/administration & dosage , Amino Alcohols/administration & dosage , Anilides/administration & dosage , Anilides/pharmacology , Animals , Blood Pressure/drug effects , Guinea Pigs , Heart Atria/drug effects , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/pharmacology , Male , Muscle, Smooth/drug effects , Propranolol/administration & dosage , Propylamines/administration & dosage , Propylamines/pharmacologyABSTRACT
Triiodothyronine, diiodothyronine and diiodotyrosine have positive inotropic activity on normal guinea-pig left atria in vitro. The increases produced by triiodothyronine and diiodothyronine are small but their detection shows that the inotropic responses to these agents can be studied in vitro. Thyroxine, thyronine and monoiodotyrosine are inactive. Reserpine pre-treatment reduces the inotropic effect of diiodotyrosine but does not reduce those of triiodothyronine and diiodothyronine.
Subject(s)
Animals , Diiodotyrosine/antagonists & inhibitors , Diiodotyrosine/pharmacologyABSTRACT
1. The effects of atropine on the pithed rat blood pressure after (+/-)-amphetamine depend on the pattern of the cardiovascular responses to the latter.2. If the pressor response to amphetamine is followed by oscillations of blood pressure and a reduction in pulse pressure or by a fall in blood pressure terminating in circulatory failure, atropine increases blood pressure, but if it is not followed by these patterns, atropine decreases blood pressure.3. The fall in blood pressure produced by atropine after amphetamine might be due to weak alpha-adrenoceptor blockade.