Search

A 43-year-old man with a 19-year history of Crohn's disease experienced serum sickness with acute lobular panniculitis and vasculitis within 2 weeks of initiating 6-mercaptopurine therapy. He had no history of extraintestinal manifestations of Crohn's disease or drug allergy. Symptoms included disabling joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse drug reaction has not been described in association with 6-mercaptopurine.

Changes in alpha-2 adrenoreceptor density and affinity during antidepressant treatment were studied using 3H-yohimbine binding to human platelet membranes. Baseline measurements were conducted in 21 patients diagnosed as having major depressive disorder with melancholia, and an equal number of age and sex matched normal controls. No differences were observed in receptor density or binding between pre-treatment subject groups and normal matched controls. Subjects participated for 6 weeks in a trial of placebo, adinazolam, or amitriptyline. Alpha-2 adrenoreceptor binding was not significantly changed from baseline following antidepressant treatment.

The utility of a 30-drug, limited formulary in an adult internal medicine, ambulatory-care clinic was investigated. The formulary was developed using a mail survey of a random sample of members of the ASHP Ambulatory Care Pharmacy Practice Special Interest Group. The consensus formulary comprised the 30 most frequently recommended drugs; the utility of the formulary was then tested by chart review in a primary-care internal medicine clinic. Over a two-month period, the charts of alternating patients were reviewed daily; patient data collected included demographic information and prescribed drug therapy. A panel of two physicians and one pharmacist reviewed each patient's data and determined the appropriateness of drug treatment. If an agent was prescribed that was not on the consensus formulary, the panel determined whether an appropriate formulary agent could have been prescribed. Of the prescribed drug orders, 57.8% were for agents in the consensus formulary; by including patients who could have received formulary drugs appropriately, 73.7% of all prescription orders were or could have been for formulary drugs. Age, race, and sex of patients had no significant effect on utility of formulary agents. Had the 30 drugs most commonly prescribed in this clinic been in the formulary, 82.6% of all prescription orders would have been covered. This approach to establishing a new formulary and selecting drugs for inclusion is potentially useful.

Obstructive asphyxia, also known as cafe coronary, has been linked to both medicated and nonmedicated psychiatric patients. An 18-month prospective audit of choking patients was conducted in a psychiatric hospital. Based upon all medications received in the 5 days preceding the event, mean daily chlorpromazine and atropine equivalent dosages were also calculated for age, sex, and diagnosis matched controls based upon all medications received during their entire hospital stay. Paired t-tests showed no significant differences between choking patients and their matched controls except that greater mean daily chlorpromazine equivalents were present in the severe choking subgroup. Computation of log odds of choking risk increases with interaction of increased mean doses of each drug type and age, and also with interaction of increased chlorpromazine equivalents and increased atropine equivalents. Patients receiving high dosages of drug(s) with antidopaminergic or anticholinergic activity are at greater risk of choking and should be monitored closely.

These studies were done to characterize the rate of uptake of high (HDL) and low (LDL) density lipoprotein cholesterol by the adrenal gland of the rat under in vivo conditions. Animals were pretreated for 4 days with 4-aminopyrazolo[3,4-d]pyrimidine to essentially eliminate endogenous plasma lipoproteins and with aminoglutethimide for 1 h to block conversion of cholesterol to adrenal hormones. Such animals were then infused with varying amounts of HDL and LDL from both human and rat plasma, and this led to rapid accumulation of cholesterol, both free and esterified, in the adrenal glands over the subsequent 4-h period of observation. This uptake process was linear with respect to time and manifested saturation kinetics with respect to the steady state level of plasma lipoprotein cholesterol. When human lipoproteins were infused, the maximal rate of cholesterol uptake was approximately 0.45 mg/pair of adrenal glands/h for both HDL and LDL; however, the half-maximal rate of uptake (Km) was achieved at a plasma HDL cholesterol concentration of only 12 mg/dl while a concentration of 61 mg/dl was required to achieve the same velocity with LDL. When similar experiments were carried out with rat HDL, the Km equaled 7.2 mg/dl and a maximal rate of uptake of 0.32 mg/pair of adrenal glands/h was achieved. It was not possible to obtain complete kinetic curves using rat LDL, but at physiological plasma concentrations, there was no difference in the rate of cholesterol uptake from LDL of rat or human origin. When large amounts of both HDL (5.8 times Km) and LDL (3.1 times Km) were infused into the same animals, the rate of cholesterol uptake essentially equaled the sum of the maximal transport rates for the two lipoproteins. These data provide additional support for the concept that the adrenal gland (and ovary) of the rat can take up HDL and LDL cholesterol by separate mechanisms. However, from the quantitative data on the kinetics of these uptake processes, it is apparent that in this species HDL cholesterol must be the major substrate for the synthesis of adrenal hormones.

A case of protamine-associated hypertension in a 76-year-old Caucasian woman with chronic renal failure (CRF) undergoing hemodialysis is reported. Four dialysis runs during March 1977 are described in this report; all involved the i.v. administration of heparin sodium (2500-5000 units) during the five-hour procedures. Protamine sulfate (25-50 mg) was given i.v. at the end of each procedure to neutralize excess heparin. In three of the four dialyses, the patient became short of breath, hypertensive, and tachycardic, usually for less than 10 minutes. In the last of these runs, the patient first became hypotensive and then hypertensive, and was incontinent of urine and feces. Treatment in each case consisted of elevation of the head of the bed and oxygen administration. During the forth dialysis, no adverse reaction occurred. Possible explanations of this phenomenon are discussed, including hypersensitivity to protamine sulfate products and the action of protamine on platelets resulting in serotonin or histamine release. In dialyses where the patient became hypertensive, more protamine on platelets resulting in serotonin or histamine release. In dialyses where the patient became hypertensive, more protamine sulfate was given than was needed to neutralize the heparin. In the run where symptoms were most severe, the patient received only 2500 units of heparin but was given 50 mg protamine sulfate. It is concluded that this reaction occurred as a result of administering excess protamine sulfate, which then acted on platelets. The platelets released either histamine or serotonin, which mediated rapid changes in blood pressure, heart rate, and breathing pattern.