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Incomplete and delayed bioavailability of sublingual nitroglycerin
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ered during investigation. Approximately 50% of the patients had prominent gastrointestinal complaints; only 37 (46%) had normal renal function at admission. Decreased atrioventricular (AV) conduction, manifested by varying degrees of AV block, or by atria1 fibrillation with a ventricular response below 50, was seen in 68% of the patients. Evidence of enhanced automaticity such as premature atria1 or ventricular contractions, ventricular tachycardia, or new atria1 flutter or fibrillation was seen in 58%. [Thomas A. Reinecke, MD]
0 DEATH CAUSED BY RECREATIONAL COCAINE USE. Mittleman RE, Wetle CV. JAMA 1984; 252:1889-1893. The authors examined 60 cocaine-related overdose deaths occurring in Dade County, Florida, between 1978 and 1982. The mean age of persons dying from cocaine was 29 years. Of the victims, 58% were men; 30% were black. Of the 60 deaths, 36 were attributed to cocaine alone, and 24 were polydrug overdoses involving cocaine. Of the 19 persons who died from cocaine alone and in whom the route of administration could be determined, 11 (SSCro)had taken the cocaine intravenously, 7 (37%) nasally, and 1 (5%) vaginally. The mean blood concentration of victims dying from cocaine alone was 6.2 mg/L. Blood cocaine levels varied widely from 0.1 to 20.9 mg/L, however, necessitating careful interpretation of the relationship between toxicologic data and terminal events. Suicide was infrequent, and death was determined to be accidental in 92% of cases. Generalized seizure activity was witnessed in 13 of the cocaine-induced deaths and in I of the deaths due to polydrug overdose. Autopsy findings were generally nonspecific. Multiple needle-puncture marks with surrounding ecchymoses were found to be typical of intravenous cocaine abuse, but the scars (tracks) over peripheral veins generally seen with narcotic abuse were not common in persons using intravenous cocaine only. Nasal septal perforations were occasionally seen. Bite marks from preterminal seizures were found often. The authors postulate that because of the current popularity of cocaine and the increased purity of recent supplies of street cocaine, the incidence of cocaine-related deaths can be expected to rise in the future. [James E. Gruber, MD]
The Journal of Emergency Medicine
0 INCOMPLETE AND DELAYED BIOAVAILABILITY OF SUBLINGUAL NITROGLYCERIN. Noonan PK, Benet LZ. Am J Cardiol 1985; 55:184-187. The authors describe their study to evaluate the pharmacokinetics of sublingual nitroglycerin (NTG). Eight healthy male volunteers each received 0.4 mg NTG sublingually. After eight minutes after each subject rinsed out his mouth to halt the absorption process. Serum nitroglycerine concentrations were obtained serially for three hours following administration. Bioavailability was calculated by comparison with serum concentrations obtained when NTG was administered by continuous intravenous infusion at a rate of 40 pg/min. The mean bioavailability of sublingual NTG was 36.2 f 24.9% (range 2.6% to 113%). The amount of sublingual NTG not absorbed after eight minutes, as determined from analysis of mouth rinses, varied from 2.7% to 65.8%. NTG peak concentrations were obtained at a mean peak time of 5.3 *2.3 minutes. The authors conclude that the absorption of sublingual NTG is not instantaneous as previously assumed and may be relatively slow with peak times of as long as ten minutes. Bioavailability was found to be low and variable. [Eric Simrod, MD] Editor’s Note: Although the data presented here provide food for further thought and study, as with any bioavailability study, results can only be applied to the specific products tested, in this case, Nitrostat@ (Parke-Davis) and Tidil@ (American Critical Care).
0 MINIROLUS DIAZOXIDE IN THE MANAGEMENT OF SEVERE HYPERTENSION IN PREGNANCY. Dudley DKL. Am JObsret Gynecol 1985; 15 1: 196-200. Conventiona! therapy for the control of severe hypertension associated with preeclampsia involves the use of intravenous hydralazine. Although other drugs have been tried, side effects have limited their use. The standard 300-mg dose of diazoxide has been associated with severe maternal hypotension, fetal distress, renal failure, and myocardial infarction. To study the safety and efficacy of minibolus diazoxide, the author studied 34 preeclamptic patients with blood pressure > 160/l 15 mm Hg or mean arterial pressure of > 130 mm Hg. After receiving intravenous magnesium sulfate for seizure prophylaxis, each patient received intravenous di-
ered during investigation. Approximately 50% of the patients had prominent gastrointestinal complaints; only 37 (46%) had normal renal function at admission. Decreased atrioventricular (AV) conduction, manifested by varying degrees of AV block, or by atria1 fibrillation with a ventricular response below 50, was seen in 68% of the patients. Evidence of enhanced automaticity such as premature atria1 or ventricular contractions, ventricular tachycardia, or new atria1 flutter or fibrillation was seen in 58%. [Thomas A. Reinecke, MD]
0 DEATH CAUSED BY RECREATIONAL COCAINE USE. Mittleman RE, Wetle CV. JAMA 1984; 252:1889-1893. The authors examined 60 cocaine-related overdose deaths occurring in Dade County, Florida, between 1978 and 1982. The mean age of persons dying from cocaine was 29 years. Of the victims, 58% were men; 30% were black. Of the 60 deaths, 36 were attributed to cocaine alone, and 24 were polydrug overdoses involving cocaine. Of the 19 persons who died from cocaine alone and in whom the route of administration could be determined, 11 (SSCro)had taken the cocaine intravenously, 7 (37%) nasally, and 1 (5%) vaginally. The mean blood concentration of victims dying from cocaine alone was 6.2 mg/L. Blood cocaine levels varied widely from 0.1 to 20.9 mg/L, however, necessitating careful interpretation of the relationship between toxicologic data and terminal events. Suicide was infrequent, and death was determined to be accidental in 92% of cases. Generalized seizure activity was witnessed in 13 of the cocaine-induced deaths and in I of the deaths due to polydrug overdose. Autopsy findings were generally nonspecific. Multiple needle-puncture marks with surrounding ecchymoses were found to be typical of intravenous cocaine abuse, but the scars (tracks) over peripheral veins generally seen with narcotic abuse were not common in persons using intravenous cocaine only. Nasal septal perforations were occasionally seen. Bite marks from preterminal seizures were found often. The authors postulate that because of the current popularity of cocaine and the increased purity of recent supplies of street cocaine, the incidence of cocaine-related deaths can be expected to rise in the future. [James E. Gruber, MD]
The Journal of Emergency Medicine
0 INCOMPLETE AND DELAYED BIOAVAILABILITY OF SUBLINGUAL NITROGLYCERIN. Noonan PK, Benet LZ. Am J Cardiol 1985; 55:184-187. The authors describe their study to evaluate the pharmacokinetics of sublingual nitroglycerin (NTG). Eight healthy male volunteers each received 0.4 mg NTG sublingually. After eight minutes after each subject rinsed out his mouth to halt the absorption process. Serum nitroglycerine concentrations were obtained serially for three hours following administration. Bioavailability was calculated by comparison with serum concentrations obtained when NTG was administered by continuous intravenous infusion at a rate of 40 pg/min. The mean bioavailability of sublingual NTG was 36.2 f 24.9% (range 2.6% to 113%). The amount of sublingual NTG not absorbed after eight minutes, as determined from analysis of mouth rinses, varied from 2.7% to 65.8%. NTG peak concentrations were obtained at a mean peak time of 5.3 *2.3 minutes. The authors conclude that the absorption of sublingual NTG is not instantaneous as previously assumed and may be relatively slow with peak times of as long as ten minutes. Bioavailability was found to be low and variable. [Eric Simrod, MD] Editor’s Note: Although the data presented here provide food for further thought and study, as with any bioavailability study, results can only be applied to the specific products tested, in this case, Nitrostat@ (Parke-Davis) and Tidil@ (American Critical Care).
0 MINIROLUS DIAZOXIDE IN THE MANAGEMENT OF SEVERE HYPERTENSION IN PREGNANCY. Dudley DKL. Am JObsret Gynecol 1985; 15 1: 196-200. Conventiona! therapy for the control of severe hypertension associated with preeclampsia involves the use of intravenous hydralazine. Although other drugs have been tried, side effects have limited their use. The standard 300-mg dose of diazoxide has been associated with severe maternal hypotension, fetal distress, renal failure, and myocardial infarction. To study the safety and efficacy of minibolus diazoxide, the author studied 34 preeclamptic patients with blood pressure > 160/l 15 mm Hg or mean arterial pressure of > 130 mm Hg. After receiving intravenous magnesium sulfate for seizure prophylaxis, each patient received intravenous di-