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Biomedical subjects

R W Derlet

Publications and source records attributed to R W Derlet.

At least 55 records · Page 3Linked to original sources
PubMed1991

Lidocaine potentiation of cocaine toxicity.

STUDY HYPOTHESIS: The toxic effects of cocaine are enhanced in the presence of lidocaine. STUDY POPULATION: Male Sprague-Dawley rats weighing 200 to 300 g. METHODS: Animals received intraperitoneal injections of cocaine (10, 20, 35, or 50 mg/kg), lidocaine (30 or 40 mg/kg), or a combination of all doses of cocaine given simultaneously with 30 or 40 mg/kg lidocaine. The incidence and time to seizure and death were recorded in these groups and compared by chi 2 and analysis of variance analyses, respectively. RESULTS: At doses of 30 or 40 mg/kg, lidocaine does not induce seizures or death. The effect of simultaneous injection of both cocaine and lidocaine was to dramatically increase the incidence of both seizures and death over that of cocaine alone. The incidence of seizures in animals receiving 35 mg/kg cocaine alone was 10%; this increased to 50% and 80% with the addition of 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .05; P less than or equal to .01). Death did not occur in animals receiving 35 mg/kg cocaine alone; the addition of 30 and 40 mg/kg lidocaine resulted in death in 30% and 60% of animals, respectively (P less than or equal to .01 each group). Similarly, in rats receiving 50 mg/kg cocaine, the incidence of death increased from 0% to 60% and 80% with 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .01). CONCLUSION: In the rat, overall toxicity of cocaine is significantly increased with simultaneous exposure to lidocaine.

Animals↗
PubMed1990

Modification of amygdaloid kindling by diazepam in juvenile rats.

The amygdaloid kindling phenomenon has been widely used to evaluate and screen potential anticonvulsant compounds in adult rats. In the current study, weanling rats (ages 23-25 days) were implanted chronically with amygdaloid electrodes. They were treated with dimethylsulfoxide (DMSO), 0.5 mg/kg diazepam or 1.0 mg/kg diazepam before twice daily kindling stimulations to determine the effect of diazepam on the acquisition of the kindled seizure. Additional juvenile rats implanted as weanlings and simulated twice daily without drug pretreatment until fully kindled were used to test for the acute anticonvulsant effects of diazepam (0.25-4.0 mg/kg). Diazepam was demonstrated to have anticonvulsant properties in juvenile rats by both prolonging the time to develop the fully kindled response during acquisition and by reducing the elicited seizure severity and the length of the afterdischarge in the fully kindled juvenile rats. Together, these data point to the extension of the anticonvulsant profile of diazepam to now include juvenile amygdaloid kindling in rats. They further point to the potential ability of screening proposed anticonvulsant drugs for their efficacy against amygdaloid kindling in immature rats.

Amygdala↗
PubMed1990

The effect of SCH 23390 against toxic doses of cocaine, d-amphetamine and methamphetamine.

The effect of SCH 23390, a dopamine-one (D1) antagonist, in preventing acute toxicity induced by lethal doses of cocaine, d-amphetamine, and methamphetamine was studied in the rat. Animals were first pretreated with SCH 23390 (0.0, 0.5, 1.0, and 2.5 mg/kg, i.p.) and then were challenged with cocaine (70 mg/kg, i.p., an LD85), d-amphetamine (75 mg/kg, i.p., an LD95), and methamphetamine (100 mg/kg, i.p., an LD90). SCH 23390 did not alter the incidence of stimulant-induced seizures compared to the vehicle controls. Significant protection against cocaine-induced death was afforded only by the lowest dose of SCH 23390 tested. Significant protection against d-amphetamine-induced death was provided by all doses, with a dose dependent effect noted so that the incidence decreased from 95% for vehicle to 30% (p less than or equal to 0.01) with 2.5 mg/kg SCH 23390 pretreatment. No statistically significant reduction in the incidence of methamphetamine-induced death was seen with SCH 23390 pretreatment. The ability of SCH 23390 to protect against d-amphetamine, but apparently not against methamphetamine-induced death, suggests that different mechanisms of toxicity may exist between these drugs at high doses.

Animals↗
PubMed1990

Anticonvulsant modification of cocaine-induced toxicity in the rat.

A number of anticonvulsant drugs were studied for their efficacy in preventing seizures and death from intoxication with cocaine. Rats were first pretreated with the test drug then subjected to large doses of intraperitoneally administered cocaine. In this model, control animals developed seizures in approximately 6 min, followed by death in approximately 10 min. Statistically significant protection against seizures and death was afforded by pretreatment with diazepam, phenobarbitol and the blocker of the uptake of gamma-aminobutyric acid (GABA), SKF 100330A. Only partial protection was afforded by the N-methyl-d-aspartate (NMDA) antagonist MK 801, the benzodiazepine antagonist, flumazenil and the novel aminobenzamide, LY 201116. Valproic acid and phenytoin demonstrated limited efficacy against cocaine-induced seizures, without consistently reducing death. Carbamazepine and ethosuximide did not significantly reduce seizures or death. In this model of acute cocaine toxicity, the anticonvulsants diazepam, phenobarbital and the blocker of the uptake of GABA, SKF 100330A were the most effective in protecting rats from cocaine-induced seizures and death. These data offer insight into future approaches for the treatment of patients with the acute toxic effects of cocaine.

Animals↗
PubMed1990

Antagonism of cocaine, amphetamine, and methamphetamine toxicity.

The effect of diazepam, haloperidol, MK-801, and propranolol in antagonizing behavioral symptoms induced by lethal doses of cocaine, amphetamine, and methamphetamine were studied in a rat model. Animals were first pretreated IP with potential antagonists, diazepam (2, 5, and 10 mg/kg), haloperidol (5, 10, and 20 mg/kg), propranolol (5, 10, and 20 mg/kg), MK-801 (0.5, 1.0, and 2.5 mg/kg), and then were challenged IP with cocaine (70 mg/kg) (LD85), d-amphetamine (75 mg/kg) (LD100), and methamphetamine (100 mg/kg) (LD90). Diazepam, at all doses, provided significant protection against cocaine- (p less than or equal to 0.01) and methamphetamine- (p less than or equal to 0.05) induced seizures and produced a dose-dependent effect against amphetamine-induced seizures. MK-801, at all doses, reduced seizures in all groups (p less than or equal to 0.01). Propranolol altered the incidence of methamphetamine-induced seizures. Significant protection against cocaine-induced death was afforded by diazepam (p less than or equal to 0.01) and propranolol (p less than or equal to 0.05). Significant protection against amphetamine-induced death was provided by haloperidol (all doses, p less than or equal to 0.1), MK-801 (all doses, p less than or equal to 0.1), and propranolol (10 and 20 mg/kg, p less than or equal to 0.1). No agent reduced the incidence of methamphetamine- (50 or 100 mg/kg) induced death. The failure of d-amphetamine antagonists to protect against methamphetamine-induced toxicity and death suggest that different mechanisms of toxicity may exist between these drugs.

Amphetamine↗
PubMed1990

Acute cocaine toxicity: antagonism by agents interacting with adrenoceptors.

Agents which interact with alpha- or beta-adrenoceptors were evaluated for efficacy in preventing seizures and death from a lethal dose of cocaine. Rats were first pretreated with the test drug(s), then subjected to an intraperitoneal LD86 of cocaine (70 mg/kg). In this model, control vehicle-pretreated animals developed seizures within six minutes, followed by death within 10 minutes. Significant protection against death was afforded by pretreatment with clonidine (0.25 mg/kg), prazocin (5.0 to 20 mg/kg), propranolol (8.0 to 32 mg/kg), or labetalol (40 mg/kg). Surviving animals still experienced seizures as judged through behavior and EEG recordings. Phentolamine did not affect the incidence of seizures or death. Two nonadrenoceptor agents were also studied: hydralazine reduced the incidence of death and seizures at 5.0 and 10 mg/kg, but reserpine did not alter the incidence of death or seizures. A combination of prazocin and propranolol did not provide additional protection compared to single agents. We conclude that the pathogenesis of acute cocaine death is complex, and that this toxicity can be antagonized by agents having either central or peripheral effects.

Animals↗
PubMed1990

Protection against d-amphetamine toxicity.

The efficacy of diazepam, haloperidol, propranolol, and yohimbine in antagonizing the toxic manifestations of d-amphetamine were studied in rats. In the control group of animals given 75 mg/kg intraperitoneal (ip) d-amphetamine, 95% developed seizures, and 100% died in mean times of 12.6 +/- 1.0 and 50.1 +/- 5.9 minutes, respectively. Significant protection against d-amphetamine-induced death was afforded by pretreatment with haloperidol (1.0 to 20.0 mg/kg) or propranolol (20.0 to 30.0 mg/kg). Diazepam (5.0 to 10.0 mg/kg) significantly reduced the incidence of clinically overt seizures but offered no protection against death. Yohimbine (2.5 to 10.0 mg/kg) was ineffective in preventing either seizures or death. When haloperidol (1.0 mg/kg) was administered in combination with diazepam (2.0 mg/kg), the incidence of death was no different than if haloperidol were given alone. In combination, haloperidol (1.0 mg/kg) and propranolol (10.0 mg/kg) reduced death more than either agent alone. These data support a protective role of haloperidol or propranolol in the treatment of d-amphetamine intoxication and show no protection with diazepam or yohimbine.

Animals↗
PubMed1990

Refusing care to patients who present to an emergency department.

In July 1988, our emergency department adopted a policy of refusing to treat patients in the ED if they failed to have what was considered an emergency condition. Screening examinations were performed by triage nurses to determine whether patients were eligible to be seen in the ED. Patients whose vital signs fell within specific categories and who had one of 50 minor chief complaints were refused care in the ED and referred to off-site clinics. The referral of these patients out of the ED after a screening examination falls within the scope of legislation governing ED care and transfer (federal COBRA, Cal SB-12, and Title 22) as determined by the University of California legal counsel. In the first six months of this new triage system, 4,186 patients were referred from the ED; this represented 19% of total ambulatory patients who presented to the triage area. Of the 4,186 patients refused care, 84% were referred to off-site nonuniversity clinics, and 15% were referred to a university-affiliated faculty-staffed clinic. Follow-up letters and telephone calls to their clinics identified no patients who needed retriage to an ED, and only 54 patients (1.3%) complained about their referral out of the ED. Only 42 patients returned to the ED within 48 hours of initial triage, and none had a deterioration of their condition. In conclusion, a selective triage system may be used to effectively decompress an ED, although further study is needed to identify potential rare adverse outcomes.

Adult↗
PubMed1990

Methamphetamine. Stimulant of the 1990s?

During the past several years, the use of a smokable form of methamphetamine hydrochloride called "ice" has increased rapidly. The heaviest use has occurred on the West Coast and in Hawaii. Many regional emergency departments treat more methamphetamine users than cocaine-intoxicated patients. The ease of synthesis from inexpensive and readily available chemicals makes possible the rampant abuse of a dangerous drug that can produce a euphoria similar to that induced by cocaine. Clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity.

Central Nervous System Diseases↗
PubMed1989

Rapid venous access using saphenous vein cutdown at the ankle.

Injured adults can usually be treated adequately with peripheral intravenous lines. However, in hypotensive patients, alternative techniques such as venous cutdown may be necessary. There are no adult studies that document the success rate or time required to complete this procedure in the emergent situation. During a 1-year period, 73 cutdowns were attempted on 56 patients. Sixty-two of these attempts resulted in venous cannulation with a free flow of fluid (84.9%). The average time required for placement was 4.9 minutes. First-year residents had a significantly lower success rate (70%) than emergency department staff (89%) or second- through fifth-year surgical residents (94%). One patient who lived developed a local cellulitis. There were no other complications. In the hands of an experienced operator, saphenous vein cutdown at the ankle is a reliable method of rapidly gaining venous access in the adult patient. There are few immediate or late complications if the catheter is removed within 24 hours.

Adult↗
PubMed1989

Potentiation of cocaine toxicity with calcium channel blockers.

Three calcium channel blockers were studied for efficacy in preventing seizures and death from cocaine intoxication. Rats were first pretreated with a test drug then subjected to high dose intraperitoneal cocaine. In this model, control animals developed seizures within six minutes, followed by death within ten minutes. Animals that were pretreated with diltiazem, nifedipine, or verapamil developed seizures significantly faster than controls, and at specific doses the death rate was higher than in controls for all three drugs. The potentiation of seizures and death by 2 mg/kg nifedipine pretreatment was further shown by challenge with three different doses of cocaine. This study fails to demonstrate a protective effect and suggests augmentation of cocaine toxicity by pretreatment with the three currently available calcium channel blockers. Several mechanisms by which calcium channel blockers may augment cocaine-induced toxicity are discussed.

Animals↗
PubMed1989

Emergency department presentation of cocaine intoxication.

All patients who presented to the emergency department as a result of cocaine intoxication during a one-year period were reviewed retrospectively. One hundred thirty-seven cases were reviewed. Patients presented with a wide variety of chief complaints including altered mental status (40%), chest pain (21%), syncope (19%), suicide attempt (13%), palpitations (12%), and seizures (12%), as well as numerous other complaints. There was only one death. Few patients required treatment within the ED; sixteen required hospitalization.

Adult↗
PubMed1989

Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of acute toxic ingestions.

A prospective, randomized clinical trial compared the clinical effectiveness of syrup of ipecac and activated charcoal to that of activated charcoal alone in the treatment of acute toxic ingestions. Two hundred adult patients with mild to moderate oral overdoses were entered into the trial. Patients receiving only activated charcoal were discharged from the emergency department in significantly (P less than or equal to .05) less time than those receiving both syrup of ipecac and activated charcoal (6.0 +/- 0.3 vs 6.8 +/- 0.2 hours, respectively). The percentage of patients requiring nonpsychiatric hospitalizations was not significantly different between the two groups (11.2% vs 14.0%, respectively). For the hospitalized patients, the length of time spent in the ICU and in the hospital was not statistically different between the two groups. A complication rate of 5.4% was found with the ipecac and activated charcoal treatment compared with a 0.9% complication rate in the activated charcoal group (P less than or equal to .05). Three episodes of aspiration pneumonitis occurred after administration of ipecac and activated charcoal, while no episodes of aspiration were noted after treatment with only activated charcoal. Together, these data are consistent with the recommendation that ED treatment with activated charcoal alone be the gastrointestinal decontamination procedure of choice for the routine mildly-to-moderately orally poisoned adult patient.

Adult↗
PubMed1989

Diazepam in the prevention of seizures and death in cocaine-intoxicated rats.

Rats were exposed to high-dose intraperitoneal cocaine. Pretreatment with diazepam was found to be highly effective in reducing observed seizures from 90% to 0% and reducing the incidence of death from 85% to 10%. Furthermore, diazepam treatment after cocaine exposure was also effective in decreasing deaths, from 80% to 21%, even when given after the onset of seizures. Although diazepam pretreatment was shown to prevent clinically overt seizures, cortical EEGs in these rats demonstrated a continuum of convulsantlike electrical activity. Our study points to the protective effects of diazepam when given before or after cocaine exposure. Together, these data suggest that diazepam has significant efficacy against cocaine intoxication even though it does not totally suppress cocaine-induced cortical EEG seizure activity.

Animals↗
PubMed1989

Cocaine intoxication.

Cocaine intoxication can be manifested by a multitude of chief presenting complaints. Although cardiovascular and central nervous system stimulation is common, patients may present with a broad array of symptoms. Thus, whenever the underlying cause of a set of symptoms is unexplained, the primary care physician needs to consider the possibility of cocaine abuse.

Cocaine↗
PubMed1987

3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients.

Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringer's solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field.

Adult↗
PubMed1986

Activated charcoal--past, present and future.

Poisoned patients were first treated with charcoal more than 150 years ago. Despite its almost universal acceptance today, activated charcoal's role has been overshadowed by the emphasis on treating poisoned patients first with gastric emptying. We review the current use of activated charcoal and recent studies that suggest that activated charcoal may be the single most effective treatment in many types of poisoning. New explanations for the mechanisms of action include "back diffusion" and disruption of enterohepatic loops. Clinical data endorse a new and aggressive role for activated charcoal in the management of poisoned and overdosed patients.

Adsorption↗