Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy.

Lactate infusions are anxiogenic in patients with panic disorder or agoraphobia with panic attacks, but few neuroendocrine profiles of this effect have appeared. The authors measured the number and intensity of panic symptoms and blood hormone levels during double-blind lactate infusions in 25 patients and 10 normal subjects and during placebo infusions in another five patients. Each patient was rechallenged with an identical infusate after chronic double-blind outpatient treatment with alprazolam or placebo. The results confirm the effectiveness of lactate infusions in evoking anxiety, extend previous hormone profiles of this maneuver, and indicate that chronic alprazolam treatment minimizes the neuroendocrine response to lactate challenges in patients with panic disorder or agoraphobia with panic attacks.

Elevated serum bromide in patients taking lithium carbonate.

Serum bromide levels were determined for 20 patients receiving lithium carbonate for manic depressive illness. Bromides averaged 17.06 +/- 8.15 mg/dl, which exceeded the control average of 3.22 +/- 3.2 mg/dl. Elevated serum bromide in patients taking lithium may reflect altered renal function.

Protocols for the use of psychoactive drugs--Part IV: Protocol for the treatment of anxiety disorders.

In Part IV of a series on the use of psychoactive drugs, the appropriate use of antianxiety agents is discussed. A step-wise approach which focuses on practical methods of managing anxiety is formulated. A framework is presented as a guide to clinicians treating anxiety symptoms in a variety of conditions.

Protocols for the use of psychoactive drugs: Part III. Protocol for the treatment of bipolar affective disorder with lithium.

A step-wise protocol is described for the treatment of bipolar affective disorder, with emphasis on the use of lithium. The objective of this protocol is to delineate the steps clinicians must consider in monitoring a patient who is receiving treatment for bipolar affective illness. While not covering every aspect of treatment, the protocol does provide the basic steps necessary for care; it is intended for use in conjunction with the clinician's personal expertise. The protocol has also been found useful in the training of residents and students.

Stimulants and narcotic drugs.

This article focuses on the use of stimulant and narcotic drugs, as well as lookalike preparations that are subject to abuse. There is a brief discussion of the pharmacology of these agents, demographic use patterns, and treatment modalities.

Rational use of psychoactive drugs in the geriatric patient.

It is impossible in an article such as this to present every aspect of psychopharmacology for the geriatric patient. Pharmacists occupy a unique position in the health care system that enables them to monitor and provide input into the pharmacotherapy of the elderly. The reader is encouraged to maintain competency in this important area of practice. Only by diligent attention to the problems experienced by the geriatric patient can we produce a framework of knowledge upon which to make rational therapeutic decisions.

DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum(II).

The DNA unwinding produced by specific adducts of the antitumor drug cis-diamminedichloroplatinum(II) has been quantitatively determined. Synthetic DNA duplex oligonucleotides of varying lengths with two base pair cohesive ends were synthesized and characterized that contained site-specific intrastrand N7-purine/N7-purine cross-links. Included are cis-[Pt(NH3)2[d(GpG)]], cis-[Pt(NH3)2(d(ApG)]], and cis-[Pt(NH3)2[d(GpTpG)]] adducts, respectively referred to as cis-GG, cis-AG, and cis-GTG. Local DNA distortions at the site of platination were amplified by polymerization of these monomers and quantitatively evaluated by using polyacrylamide gel electrophoresis. The extent of DNA unwinding was determined by systematically varying the interplatinum distance, or phasing, in polymers containing the adducts. The multimer that migrates most slowly gives the optimal phasing for cooperative bending, from which the degree of unwinding can be obtained. We find that the cis-GG and cis-AG adducts both unwind DNA by 13 degrees, while the cis-GTG adduct unwinds DNA by 23 degrees. In addition, experiments are presented that support previous studies revealing that a hinge joint forms at the sites of platination in DNA molecules containing trans-GTG adducts. On the basis of an analysis of the present and other published studies of site-specifically modified DNA, we propose that local duplex unwinding is a major determinant in the recognition of DNA damage by the Escherichia coli (A)BC excinuclease. In addition, local duplex unwinding of 13 degrees and bending by 35 degrees are shown to correlate well with the recognition of platinated DNA by a previously identified damage recognition protein (DRP) in human cells.

Some biochemical correlates of panic attacks with agoraphobia and their response to a new treatment.

Thirty-two patients with chronic debilitating agoraphobia and panic attacks participated in a comparative study of the triazolobenzodiazepine alprazolam and the anti-inflammatory agent ibuprofen. After a 2-week placebo washout period, patients were randomly assigned to 8 weeks of treatment with alprazolam (2 to 6 mg/day) or ibuprofen (0.8 to 2.4 g/day). Medication was identically packaged and patients were blind to the treatment condition, but investigators were aware of which medication was dispensed. Alprazolam recipients (mean daily dose: 5.4 mg) improved markedly with respect to physician and patient global rating of disease severity, frequency and severity of panic attacks, and phobic anxiety target symptoms on the 90-Item Hopkins Symptom Check List. Ibuprofen recipients (mean daily dose: 2.13 g) experienced significantly less clinical improvement than patients on alprazolam. After 8 weeks of treatment, ibuprofen patients were crossed over to alprazolam, while the original alprazolam group continued on that drug. The daily dosage ceiling was increased to 10 mg. In the ensuing 4 weeks (mean daily alprazolam dose: 6.3 mg), all patients achieved comparably marked clinical improvement relative to baseline. Pretreatment plasma concentrations of platelet factor 4 and beta-thromboglobulin--two measures of platelet turnover and release--were significantly elevated in patients relative to normal controls. The elevated platelet factor 4 and beta-thromboglobulin normalized during treatment with both drugs. Alprazolam appears to produce rapid and specific clinical improvement in patients with severe agoraphobia and panic attacks and deserves further evaluation under double-blind conditions.