Amiodarone-induced thyroid dysfunction.

Cases of hypothyroidism and hyperthyroidism associated with amiodarone therapy are described, and the mechanisms, clinical appearance, and management of amiodarone-induced thyroid dysfunction are discussed. A 72-year-old man with a history of recurrent ventricular tachycardia unresponsive to conventional antiarrhythmic drugs was started on amiodarone therapy. Initially he responded well, but after three months he began to have fatigue, dry skin, and intolerance of cold. His serum thyroid-stimulating hormone (TSH) concentration had risen from 4.4 microU/mL before amiodarone therapy began to 20 microU/mL, consistent with hypothyroidism. He was started on sodium levothyroxine for thyroid hormone replacement; the dosage was adjusted in accordance with subsequent TSH measurements. His hospital course was complicated by congestive heart failure. The second patient was a 43-year-old man with a history of atrial fibrillation who developed hyperthyroidism when placed on amiodarone therapy. He had persistent sweating, intolerance of heat, restlessness, and tachycardia. Thyroid function tests confirmed the presence of hyperthyroidism. The patient was treated with propylthiouracil and propranolol, and amiodarone was discontinued. He remained unresponsive to the propylthiouracil, which was discontinued, and was scheduled for radioactive iodine treatment. The mechanism of amiodarone-induced thyroid dysfunction may involve the large iodine content of the drug. Amiodarone-induced hypothyroidism may range in severity from mild symptoms to severe myxedema; the skin, hair, and nails are particularly affected. Persons with clinical hyperthyroidism secondary to amiodarone treatment show the signs and symptoms of a hypermetabolic state resulting from thyroid hormone excess. Amiodarone-induced hypothyroidism is treated with levothyroxine and hyperthyroidism with antithyroid drugs. Amiodarone can cause thyroid dysfunction, which can have serious consequences.

Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis.

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.

Use of retinoids in the treatment of psoriasis.

The limitations of conventional therapy for psoriasis are reviewed, and the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, dosing and therapeutic monitoring of etretinate and other retinoids are described. Traditional treatments for psoriasis include topical application of anthralin and coal tar ointments; systemic therapy with corticosteroids or methotrexate; and systemic or methotrexate; and systemic psoralens combined with exposure to ultraviolet light (PUVA). The topical therapies are beneficial but aesthetically displeasing to patients; the systemic treatments are associated with severe adverse reactions. Etretinate provides another option in the treatment of psoriasis. Etretinate and acitretin, an investigational retinoid, appear to be effective oral therapies for severe variants of psoriasis, especially pustular psoriasis. Retinoids generally do not offer substantial therapeutic advantages over other treatments for chronic-plaque psoriasis. The most common adverse effects of etretinate are cheilitis, alopecia, desquamation of the skin, drying of mucous membranes, and pruritus. Use of low-dose etretinae in combination with other forms of therapy, such as corticosteroids or PUVA, may minimize the frequency of adverse effects. Etretinate is a known teratogen. Its elimination half-life is prolonged to 100-120 days with long-term use. Acitretin, the carboxylic acid derivative of etretinate, has a much shorter elimination half-life than etretinate (50 hours after multiple doses). Its adverse-effect profile is similar to that of etretinate. Etretinate and acitretin appear to be clinically effective for therapy of severe variants of psoriasis. Etretinate should not be used to treat mild psoriasis because of the high incidence of serious adverse effects.

Albumin utilization in a university hospital.

The inappropriate use of high-priced agents such as human serum albumin significantly contributes to the rising cost of medical care. A utilization review was conducted at the University of Michigan Hospital in order to identify the appropriateness of use of this agent. Criteria were developed and prescribing was retrospectively evaluated for 81 patients. Of the 935 units administered to these patients, 692 (74 percent) were judged to be inappropriate. This inappropriate use accounted for a projected annual expenditure of nearly $281,000. Interventions have previously demonstrated success in improving prescribing.

Evaluation of N-acetylneuraminic acid, carcinoembryonic antigen, and alpha-fetoprotein as markers for advanced carcinoma.

Sialic acid (N-acetylneuraminic acid, NANA), carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were measured in a group of patients with advanced carcinoma (primarily colorectal). The percent change of NANA was less than that with CEA, and more reliably separated patients with stable disease from those with tumor regression or progression. AFP was a good predictor of clinical course in the few patients in which it was measured.

Use of midazolam hydrochloride in anesthesia.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage, and cost and availability of midazolam hydrochloride are reviewed. The anxiolytic, sedative, hypnotic, anticonvulsant, muscle-relaxant, and amnesic properties of midazolam are similar to those of other injectable benzodiazepines. Midazolam is approximately two to four times as potent as diazepam. Midazolam hydrochloride is water soluble (resulting in fewer local adverse reactions after injection), has a rapid onset and short duration of action, and causes relatively mild cardiovascular and respiratory effects. The drug generally is well tolerated. Midazolam is a good premedicant for general or regional anesthesia. Its greatest use will probably be for conscious sedation during surgical or diagnostic procedures performed under local or regional anesthesia. Induction of anesthesia with midazolam alone is somewhat unpredictable; opiate pretreatment makes induction more consistent. Midazolam is a less reliable induction agent than thiopental, but because it produces fewer adverse cardiovascular and respiratory effects than thiopental, midazolam appears to be a safer induction agent for elderly patients or patients with cardiovascular disease. The recommended dose of midazolam for preoperative sedation is 0.07-0.1 mg/kg given by intramuscular injection one hour before surgery. For conscious sedation, 0.1-0.15 mg/kg intravenously in divided doses is usually adequate. Lower doses of midazolam are recommended for elderly or debilitated patients and patients who have severe liver disease. The costs of equipotent doses of midazolam and injectable diazepam are similar. An oral dosage form is under investigation in the United States. Midazolam's pharmacologic and pharmacokinetic profile makes it an attractive alternative to other injectable benzodiazepines used in anesthesia.

Recent advances in antiviral therapy.

Virus replication is described, and the clinical trials and indications for amantadine, rimantadine, vidarabine, vidarabine phosphate, acyclovir, ribavirin, and other promising antiviral agents are reviewed. Amantadine and rimantadine are useful for the treatment and prophylaxis of viral influenza A infections. Vidarabine is a second-line agent and is effective for the treatment of herpes simplex encephalitis, neonatal herpes simplex types 1 and 2, and varicella-zoster infections. Vidarabine phosphate (also known as vidarabine monophosphate) has a similar spectrum of activity and can be administered in smaller volumes than vidarabine. Acyclovir has demonstrated clinical efficacy for chickenpox, shingles (herpes zoster), genital herpes, and other herpes simplex infections. Acyclovir is also useful for the suppression of herpes infections. Systemically administered ribavirin is indicated for the treatment of Lassa fever. Aerosol ribavirin is effective for the treatment of respiratory syncytial virus pneumonia in children and infants and influenza A infections in adults. Only acyclovir, amantadine, ribavirin, and vidarabine are used in clinical practice. Vidarabine phosphate and investigational agents such as rimantadine, ganciclovir (DHPG, BW B759U), phosphonoformate, and bromovinyl-deoxyuridine (BVDU) need further investigation.

The cost-effectiveness of clinical pharmacist intervention on tobramycin prescribing.

The cost-effectiveness of clinical pharmacist intervention in reducing the use of tobramycin and in the pharmacokinetic monitoring of aminoglycoside therapy to prevent serious nephrotoxicity were evaluated. Prescribing practices for tobramycin were compared between two similar medical teams, one with clinical pharmacist services, the other without. A statistically significant difference was observed between the number of patients who received tobramycin in the two teams, and a cost saving of $5,072.85 was achieved in 3 months. The potential for hospitalwide cost savings is substantial if gentamicin can be substituted for tobramycin in selected circumstances and followed with appropriate monitoring.

Recurrent dystonic reactions induced by thiethylperazine.

Three attacks of acute dystonia occurred in a 19-year-old male following the initiation and discontinuation of thiethylperazine administered rectally in therapeutic doses. The time course of onset of the attacks and the proposed mechanisms by which dystonia develops are discussed.

Acute intermittent porphyria: pathophysiology and treatment.

Acute intermittent porphyria is caused by an inherent error of porphyrin metabolism characterized by a deficiency of porphobilinogen deaminase and increased activity of delta-aminolevulinic acid synthase, key enzymes necessary for the biosynthesis of heme. During an attack patients may have abdominal pain, vomiting, muscle weakness, constipation and neuropsychiatric symptoms. In the majority of individuals the disease remains clinically latent throughout life. Various drugs and chemicals, hormones and nutritional factors predispose to clinical attacks, probably by inducing hepatic delta-aminolevulinic acid synthase. Avoidance of these substances is important in preventing attacks. Screening of family members to detect genetic carriers permits precautionary measures. Management of attacks includes symptomatic therapy, high carbohydrate intake and intravenous administration of hematin.

Serum sialic acid is a biologic marker for malignant disease.

Serial serum sialic acid (N-acetylneuraminic acid) was measured in 16 patients with advanced cancer of various histologic types. In the 15 evaluable patients serial changes in sialic acid correlated with the clinical course. Isolated sialic acid values were not predictive of clinical response. Serial determination of serum sialic acid appears to be a useful monitor of tumor burden.