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Biomedical subjects

N L Benowitz

Publications and source records attributed to N L Benowitz.

At least 253 records · Page 14Linked to original sources
PubMed1980

Disposition kinetics and effects of intravenous nicotine.

Nicotine was given intravenously to subjects during acid and alkaline urine conditions in doses and a dosing schedule to simulate cigarette smoking. Total clearances were greater, terminal half-lifes shorter, but volumes of distribution much the same in acid (pH < 5) and alkaline (pH > 7) urine conditions. The effect of urinary pH on total clearance was due entirely to changes in renal clearance, which accounted for 23% and 2% of total clearance in acid and alkaline urine conditions. Nicotine injections induced a sensation of arousal and increased heart rate and blood pressure over the short term, but with repeated injections tolerance to these effects developed rapidly. No differences in subjective or physiologic responses to intravenous nicotine were observed and we consider it unlikely that the effects of smoking a cigarette differ as a function of urinary pH.

Adult↗
PubMed1980

Enhanced bioavailability of pethidine and pentazocine in patients with cirrhosis of the liver.

We studied the bioavailability and disposition kinetics of pethidine and pentazocine in patients with alcoholic cirrhosis and age-matched healthy subjects. In the presence of liver disease, the bioavailability of pethidine was 31% and pentazocine 233% greater than in normals. Systemic clearance was approximately half and terminal half-life double normal for both drugs, whereas volumes of distribution were unchanged. Because of greater bioavailability, oral doses of pethidine and pentazocine should be reduced substantially in patients with cirrhosis. When multiple oral or parenteral doses are required, dosing interval should be lengthened or repeated doses reduced below initial doses because of lower systemic clearance.

Administration, Oral↗
PubMed1979

Dissociation of autonomic and cognitive effects of THC in man.

Intravenous THC, 30--44.8 microgram/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.

Adult↗
PubMed1979

Cardiovascular effects of intravenous delta-9-tetrahydrocannabinol: autonomic nervous mechanisms.

The contribution of autonomic nervous system activity to the cardiovascular effects of delta-9-tetrahydrocannabinol (THC) was evaluated in 4 normal subjects. The peak heart rate rise after THC was attenuated by atropine and by propranolol, and nearly abolished by atropine-propranolol pretreatment. Blocking drugs also attenuated THC-induced changes in forearm blood flow and vascular resistance but did not affect changes in fingertip temperature. The data suggest that THC acts to induce sympathetic stimulation and parasympathetic inhibition of cardiovascular control pathways. Cardiovascular responses in an additional subject who developed hypertension after either intravenous or smoked marijuana are described.

Adult↗
PubMed1979

Diazepam kinetics in acute alcohol withdrawal.

We performed a within-subject comparison of the kinetics of diazepam given to 7 alcoholic subjects during acute alcohol withdrawal and again after detoxification. The initial rapid exponential decline of plasma diazepam concentrations (t1/2 alpha) was more rapid during (0.21 +/- 0.03 hr) than after withdrawal (0.44 +/- 0.14 hr, p less than 0.05). Terminal t1/2, clearance, and volumes of distribution changed in individual patients, but mean values did not change. Protein binding was less in patients (93.4 +/- 2.4%) than in healthy controls (97.0 +/- 1.0, p less than 0.05). The effects of alcohol withdrawal on diazepam disposition do not explain the high doses of diazepam commonly required to treat the withdrawal.

Adult↗
PubMed1979

Hypertensive emergencies.

The clinical syndrome of accelerated hypertension is a relatively rare complication of hypertensive disease. The syndrome is recognized by high blood pressures, progressive neurologic and visual symptoms, acute renal damage, cardiac failure, and microangiopathic hemolytic anemia. When diagnosed, it must be recognized as an acute medical emergency. The patient should be admitted to an intensive care unit, arterial lines should be placed, and the blood pressure lowered as soon as possible. Once blood pressure has been controlled, oral medications should be begun. Long-term results in the treatment of hypertensive emergencies are gratifying. It is anticipated that with more experience gained in the use of medications in this situation, an even better prognosis will be achieved.

Adrenal Gland Neoplasms↗
PubMed1979

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Adult↗
PubMed1977

Prolonged delta-9-tetrahydrocannabinol ingestion. Effects of sympathomimetic amines and autonomic blockades.

In order to evaluate the possible effects of delta-9-tetrahydrocannabinol (THC) on autonomic nervous system function, cardiovascular responses to intravenous isoproterenol, phenylephrine, atropine, and propranolol were compared in hospitalized volunteers before and after 14 days of THC ingestion. There was no significant alteration in responses to isoproterenol or phenylephrine, although in one subject the pressor effect of phenylephrine was considerably augmented by THC. Heart rates after parasympathetic (atropine) blockade and after combined parasympathetic and sympathetic (propranolol) blockade were significantly greater during THC ingestion. These and other data presented are consistent with the picture of reduced sympathetic and enhanced parasympathetic activity described in animals on THC. During THC ingestion, atropine had a pronounced pressor effect, which might represent a clinically significant drug interaction.

Adult↗
PubMed1977

Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol.

Delta-9-tetrahydrocannabinol (THC) has been reported to inhibit drug metabolism in animals. Twenty-two hospitalized healthy volunteer subjects received THC, 60 to 180 mg/day in divided doses for 14 days. Body weight increased and plasma proteins decreased in all subjects, which is consistent with previously reported plasma volume expansion. Total bilirubin was significantly lower, while other liver function tests remained normal. A within-subject comparison of the pharmacokinetics of antipyrine, pentobarbital, or ethanol given before, during, and after THC was performed. Antipyrine plasma half-life increased during THC in 5 of 6 subjects--mean, 7.9 hr +/- 3.3 (SD) to 9.6 +/- 3.8. Pentobarbital half-life increased in 7 of 8 subjects--mean, 16.9 hr +/- 2.0 to 20.8 +/- 4.2. Blood ethanol disappearance rate decreased in 7 of 8 subjects from a mean of 0.26 mg/100 ml/min +/- 0.05 to 0.23 +/- 0.07. The effect of THC on disappearance rate of these drugs appeared to be due to a combination of: (1) increased distribution volume, due in part to expansion of extracellular fluid volume noted during THC ingestion, and (2) diminished metabolic clearance. THC also delayed absorption of pentobarbital and ethanol in several subjects. This is consistent with THC effects of slowing intestinal motility in animals. The effects of THC on absorption and drug elimination must be considered in evaluating interactions with other drugs.

Absorption↗
PubMed1976

Depression of growth hormone and cortisol response to insulin-induced hypoglycemia after prolonged oral delta-9-tetrahydrocannabinol administration in man.

Six hospitalized volunteer male subjects were given insulin, 0.15 U/kg, before and after 14 days of administration of delta-9-tetrahydrocannabinol (THC) at a dose of 210 mg/day. A diminished maximal serum human growth hormone (GH) increase followed the prolonged THC ingestion. The mean maximal GH response was: 52.6 ng/ml +/- 8.7 (+/-SE) before THC and 18.8 ng/ml +/- 6.7 (+/-SE) during THC, P less than 0.01; corresponding cortisol responses were 20.1 mug/dl +/- 3.0 before THC and 10.0 mug/dl +/- 1.1 during THC, P less than 0.05. The data suggest suppression of the hypothalamic-pituitary axis after prolonged high dose THC use. This is consistent with other reported endocrine effects of marijuana in man.

Administration, Oral↗
PubMed1975

Phencyclidine poisoning.

Phencyclidine hydrochloride abuse has become increasingly common and should be considered in patients with unexplained acute psychosis, dystonic reactions, status epilepticus, or coma. Two phencyclidine-intoxicated patients had bizarre combinations or disorientation, hallucination, agitation, and dyskinetic motor activity. Supportive care and reduction of sensory stimulation are the basis for management of the symptoms.

Acute Disease↗
PubMed1975

Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion.

In contrast to the tachycardia and unchanged or increased blood pressure seen after single doses, prolonged delta-9-tetrahydrocannabinol (THC) ingestion produced significant heart rate slowing and blood pressure lowering in hospitalized volunteers. Impaired circulatory responses to standing, exercise, Valsalva maneuver, and cold pressor testing suggest a state of sympathetic insufficiency. Marked weight gain was observed in all subjects, which has been shown to be related to fluid retention and plasma volume expansion. Tolerance developed to orthostatic hypotension, possibly related to plasma volume expansion, but did not develop to the supine hypotensive effects. Nearly complete tolerance developed to the tachycardia and psychological effects produced by smoked marijuana while ingesting THC. Electrocardiographic changes were minimal despite the large cumulative dose of THC. The hypothesis that THC has a biphasic effect on the sympathetic nervous system in man, producing excitation with single doses and inhibition with prolonged administration, is discussed.

Administration, Oral↗