Christopher S. Conner

Marijuana and Alcohol Use in Pregnancy

The literature is sparse on the adverse effects of moderate alcohol consumption and marijuana use during pregnancy. Recent studies have evaluated the association of these drugs of abuse with pregnancy outcome, each using interview and medical record data of over 12000 women. Children of marijuana users were more likely to have one or more major malformations, lower birthweight, and shorter gestation than children of nonusers. However, when logistic regression was used to control for other variables, these relationships were not statistically significant. The odds ratio for major malformations does, however, remain suggestive for marijuana. The use of similar logistic regression techniques revealed that the only statistical association between alcohol intake of 14 or more drinks per week was placenta abruptio. With the exception of placenta abruptio, alcohol intake of fewer than 14 drinks weekly was not associated with an increased risk of any adverse outcome. There was no association between alcohol use at any level and the rate of congenital malformations. Recommendations based on these data are presented.

Asymptomatic Theophylline Overdose

A case of severe theophylline overdose is described in which clinical signs of toxicity initially were minimal despite extremely high serum drug levels. Hemodialysis was performed because of the risk of seizures and cardiac arrhythmias. The predialysis, dialysis, and postdialysis half-lives were 13.1, 4.3, and 6.7 hours, respectively. Corresponding total body clearance values were 23.8, 72.5, and 46.3 ml/kg/h. The patient showed apparent saturation kinetics of theophylline clearance at high serum levels. Hemodialysis is effective for enhancing the removal of theophylline.

Acute poisoning from over-the-counter sleep preparations

All cases received by the Rocky Mountain Poison Center involving over-the-counter (OTC) sleep preparations were studied during an 18-month period to elucidate 1) the range of toxicity; 2) characteristic symptoms, and 3) the time of onset of symptoms. In 155 cases reviewed retrospectively, the three most commonly ingested agents were Sominex, Nytol and Sleepeze. Multiple ingestions were also involved. Symptomatology was equally divided among no symptoms, mild symptoms and possible life-threatening symptoms. The least amount taken to produce possible life-threatening symptoms was 16 Sominex, 18 Nytol and 15 Sleepeze, although the average amount producing the same symptoms was approximately twice that. These symptoms were seen within six hours in all but three of the 39 cases presenting with these symptoms. There were no deaths.

Isotretinoin: A Reappraisal

Isotretinoin is remarkably effective in the treatment of severe cystic acne, however, many complications have been observed during treatment and new toxic effects have been reported. Hypertriglyceridemia associated with decreases in high density lipoprotein (HDL) cholesterol has occurred in 25 percent of patients and requires monitoring during treatment. Painful erosions with granulation tissue recently have been reported in patients with severe acne. Other complications have included corneal opacities, pseudotumor cerebri, hypercalcemia, photosensitivity reactions, abnormal liver function tests, and skeletal hyperostosis. Isotretinoin is teratogenic and should be avoided during pregnancy. With the increasing acceptance and use of isotretinoin for cystic acne, as well as related disorders (inflammatory papulopustular acne with scarring, gram-negative folliculitis, and acne rosacea), a reevaluation of isotretinoin aimed at reducing complications is in order. Patient selection criteria and guidelines directed at reducing these complications are presented.

Mitoxantrone: A Replacement for Doxorubicin?

Doxorubicin (Adriamycin) is an unquestionably effective anticancer agent for many types of tumors, including advanced breast cancer. However, cardiotoxic effects of the drug have limited its use. Methods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone (Novantrone). Mitoxantrone was developed to reduce the cardiotoxicity associated with doxorubicin while maintaining effective antitumoral effects. Initial reports suggested that mitoxantrone might lack cardiotoxic potential; however, recent studies indicate that the drug can produce adverse cardiac effects (congestive heart failure), perhaps with similar frequency to that observed with doxorubicin. It is doubtful that mitoxantrone will be a significant advance over doxorubicin if direct comparative studies reveal a similar incidence of cardiomyopathy.

Oral Gold in Arthritis

There are few drugs available with purported disease-modifying or healing effects in rheumatoid arthritis. The two agents that have gathered the most support in favor of these effects are parenteral gold and cyclophosphamide; however, both can produce intolerable toxicity. A new oral gold compound (auranofin; Ridaura) is being investigated in rheumatoid arthritis. Available studies suggest that auranofin may be slightly less effective than parenteral gold, but is significantly less toxic, the main side effect being diarrhea. There is evidence to suggest auranofin slows radiologic progression of the disease, but further studies are indicated. If further studies demonstrate a healing effect of the drug, comparable with data suggesting this effect for parenteral gold, auranofin may become a first-line agent in rheumatoid arthritis.

Transdermal Nitroglycerin: A Reevaluation

A case report of impramine-induced syndrome of inappropriate antidiuretic hormone (SIADH) secretion in a 54-year-old woman is presented along with a review of the literature on antidepressant-induced SIADH. The clinical and laboratory presentation, diagnosis, treatment, and monitoring of antidepressant-induced SIADH also are discussed. Drug Intell Clin Pharm 1984;/8:890-4.

Therapy of Syndrome Malin

Syndrome malin refers to neuroleptic malignant syndrome (NMS), a combination of extrapyramidal symptoms, hyperthermia, autonomic dysfunction, hypertension, and coma, which has been reported primarily with haloperidol administration, but also with fluphenazine, thiothixene, and thioridazine. NMS is much more severe than typical extrapyramidal reactions to neuroleptic agents and can result in fatality. The syndrome is not dose related and can begin within hours of initiation of therapy or after months of treatment. Treatment of NMS has been mainly supportive in the past. Recent reports have suggested benefits from the use of bromocriptine and amantadine (dopaminergic agonists), based on a possible etiology of neuroleptic-induced dopaminergic blockade. Dantrolene also has been utilized successfully in NMS on the hypothesis that the syndrome is similar to anesthetic-induced malignant hyperthermia. These agents provide a more specific treatment for this potentially lethal syndrome.

Treatment of bulimia.

Bulimia (bulimia nervosa; binge eating) is characterized by episodic eating of large amounts of food, followed by self-induced vomiting or laxative abuse. Psychotherapy has been the mainstay of treatment and often has been unsuccessful. The similarity of bulimia to major depression has led to evaluation of antidepressant drugs for treatment of the disease. Imipramine has proven effective in reducing binging episodes, and further evaluation of antidepressants seems warranted. Phenytoin also has been effective in some cases, suggesting that bulimia may be a neurologic disorder analogous to epilepsy. Optimal treatment may be antidepressants combined with a nutrition/psychotherapy program.

Drug Information — The Problems and Some Solutions:

Several problems evident in the drug information delivery process and some solutions are presented. Major problems with current sources of drug information are accessibility of data, completeness of data, validity of information, appropriateness in the clinical setting, and currency. Better drug information sources are needed to provide rapid answers to patient-related questions routinely occurring in the clinical setting. Currently available mechanisms described to solve existing drug information problems are clinical pharmacologists and specialists, clinical pharmacists, drug information centers, and a computer-output microfiche drug information system (DRUGDEX®).