Drug therapy reviews: clinical use of hemostatic agents.

Systemic hemostatic agents are reviewed. Among the agents discussed are vitamin K preparations (phytonadione, menadione, menadione sodium bisulfite, menadiol sodium diphosphate); and blood products (whole blood, plasma, cryoprecipitate, factor VIII concentrates, factor IX concentrates and fibrinogen concentrates). Normal and abnormal hemostasis and fibrinolysis are discussed, as is the general management of systemic hemostatic defects. Specific disorders covered are clotting factor deficiencies, hemophilia A, factor VIII inhibitors, von Willebrand disease, hemophilia B (Christmas disease), other congenital coagulation disorders, acquired deficiency of factors II, VII, IX and X, and defibrination syndrome.     

Drug therapy reviews: nitrofurantoin.

Mechanism of action, antimicrobial spectrum, pharmacology, adverse reactions and therapeutic uses of nitrofurantoin, a broad-spectrum antimicrobial agent, are discussed. The frequency and potential severity of reactions attributed to nitrofurantoin, plus its inability to achieve therapeutic blood concentrations, relegate this drug to a position of secondary importance. Nitrofurantoin compares favorably with other standard agents for the therapy of acute and recurrent urinary tract infections in women which may be caused by susceptible organisms, and it is an effective chemoprophylactic agent for patients with recurrent urinary tract infections. The compound has no apparent adverse effects on the developing fetus and can be used in pregnant women. This is not sanctioned by the package insert, however. Nitrofurantoin should not be administered when the possibility of bacteremia exists, as the drug does not achieve therapeutic serum levels when administered orally. Nitrofurantoin is contraindicated for patients with renal insufficiency. The value of this compound for men with acute urinary tract infection, recurrent urinary tract infection, acute bacterial prostatitis or chronic bacterial prostatitis has not been established. There are no indications for prescribing parenteral nitrofurantoin.     

Drug therapy reviews: trimethoprim-sulfamethoxazole.

The mechanism of action, antimicrobial spectrum, pharmacokinetic properties, drug interactions, adverse reactions and therapeutic uses of trimethoprim-sulfamethoxazole, a combination enzyme-specific inhibitor of bacterial folate synthesis, are reviewed. Trimethoprim-sulfamethoxazole currently is approved by the FDA for the therapy of established recurrent bacterial urinary tract infections, pneumocystosis, otitis media in children and shigellosis. Claimed advantages of the drug are synergistic activity, bactericidal activity and ability to decrease the rate of emergence of resistance to the individual components. Trimethoprim-sulfamethoxazole is the drug of choice for treatment of pneumocystosis and an acceptable oral therapy for recurrent urinary tract infections caused by susceptible bacteria. In children with otitis media, it is used as an alternative to ampicillin and amoxicillin and is preferred when these patients are penicillin-sensitive or when the infection is caused by beta-lactamase-producing Haemophilus influenzae. Hematologic reactions (anemia, thrombocytopenia, granulocytopenia, agranulocytosis) to trimethoprim-sulfamethoxazole occur rarely. Gastrointestinal intolerance and skin eruptions are the most prevalent adverse reactions. Most untoward reactions to trimethoprim-sulfamethoxazole develop within two weeks of onset of therapy, and their incidence compares favorably with that of standard agents administered for the same indications.     

Drug therapy reviews: chronic hepatitis.

The classification, clinical course, etiology and treatment of chronic hepatitis are discussed. The clinical manifestations of chronic hepatitis are of limited diagnostic use. Diagnosis must be made by liver biopsy. The disease is classified as chronic persistent or chronic active hepatitis. The prognosis for chronic persistent hepatitis is excellent, and no treatment is required. Chronic active hepatitis may progress to cirrhosis and is associated with a poor prognosis if untreated. Recognized causes of chronic active hepatitis are hepatitis-B virus infection, post-transfusion hepatitis not associated with hepatitis-B virus, and certain drugs. For drug-induced hepatitis, discontinuation of the medication is indicated. For other types of chronic active hepatitis the recommended treatment is prednisone 10 mg and azathioprine 50 mg daily.     

Drug therapy reviews: treatment of sarcoidosis.

Sarcoidosis, the possibility of its spontaneous remission, and its responsiveness to corticosteroid and other drug therapies are discussed. Sarcoidosis is a disease of unknown etiology characterized histologicaly by a granulomatous process with cellular infiltration. The granulomatous changes may remit spontaneously or may develop into fibrosis that, at times, is severe; factors that influence these progressions of the disease are not known. Cellular and humoral immunological abnormalities may be associated with this disease. Any organ can be affected although there is a high frequency of pulmonary involvement. Sarcoidosis may be benign and remit spontaneously in as many as 70% to 80% of cases, but the overall case fatality rate can be as high as 10%. Corticosteroids, the most effective therapy, cause temporary remission of the granulomatous changes but do not influence established fibrosis. Corticosteroids only temporarily influence the natural progression of sarcoidosis; however, corticosteroid therapy can preserve the function of vital organs. Other forms of treatment, such as chloroquine, methotrexate, oxyphenbutazone, allopurinol and levamisole hydrochloride, also produce remissions of the granulomatous infiltrate of sarcoidosis but offer no therapeutic advantages over corticosteroids. The decision to treat is often a difficult one, since corticosteroids and these other therapies have potentially hazardous side effects.     

Drug therapy reviews: management of hypothyroidism.

The therapeutic management of hypothyroidism caused by deficient thyroid hormone production is discussed. The therapeutic use of the following thyroid agents is reviewed: levothyroxine sodium, Thyroid USP, thyroglobulin, liotrix, and liothyronine sodium. Myxedema coma, neonatal hypothyroidism, primary hypothyroidism, and secondary and tertiary hypothyroidism are specific hypothyroid states for which drug therapy is discussed. Levothyroxine sodium is the preferred agent because of consistent potency, restoration of normal, constant serum levels of thyroxine (T4) and triiodothyronine (T3) and ease of interpretation of thyroid hormone levels. Other agents, because they contain T3, result in postabsorptive elevated T3 serum concentrations that may cause thyrotoxic symptoms and reduction of T4 levels. This, in turn, may give rise to misleading estimates of thyroid dosage. Patients with the sick euthyroid or low T3 syndromes are not candidates for thyroid hormone therapy.     

Drug therapy reviews: pharmacotherapy of diarrhea.

Gastrointestinal physiology, and the pathophysiology, diagnosis, symptoms and treatment of acute and chronic diarrhea are reviewed. Drugs used in the treatment of diarrhea include opiates (morphine, codeine), synthetic anti-diarrheals (diphenoxylate, loperamide), anticholinergics (atropine, propantheline), adsorbents (kaolin, pectin, cholestyramine resin) and Lactobacillus acidophilus. Chronic diarrhea and acute diarrhea caused by microorgansims, drugs and viruses are described. The management of diarrhea can be divided into three categories: (1) supportive therapy (fluid and electrolyte replacement); (2) symptomatic therapy which improves the consistency of the stool and reduces the frequency of bowel movements; and (3) specific therapy aimed at treating the cause (e.g., antibiotics for bacteria-induced diarrhea) or blocking the cellular mechanisms of fluid and electrolyte loss. Most acute diarrheal conditions can be managed successfully by avoiding oral solids and ingesting carbohydrate-electrolyte solutions. Synthetic antidiarrheals may increase the toxicity associated with bacterial diahhrea.     

Drug therapy reviews: drug therapy of status epilepticus.

Drug treatment of status epilepticus is reviewed. Tonic-clonic, focal motor, complex partial and absence status epilepticus are discussed. In managing tonic-clonic status epilepticus one should: (1) maintain vital functions at all times, (2) identify and treat precipitating factors and (3) administer an intravenous loading dose of phenytoin sodium or phenobarbital sodium. Careful use of i.v. diazepam sometimes helps to achieve these objectives. Intravenous phenytoin sodium and phenobarbital sodium provide definitive, long-term control of tonic-clonic seizures but must be administered slowly and require time to reach peak brain concentrations. Intravenous diazepam appears to enter and exit from the brain rapidly and may control seizures while therapeutic brain concentrations of long-acting drugs are being achieved. Phenytoin, phenobarbital and diazepam should not be administered intramuscularly in treating status epilepticus. Treatment of focal motor and complex partial status epilepticus is similar to that of tonic-clonic status epilepticus, but i.v. diazepam is required less frequently and loading doses of phenytoin and phenobarbital sometimes can be given more slowly. Status epilepticus of the absence type is managed with i.v. acetazolamide sodium or diazepam. Paraldehyde, muscle relaxants, general anesthesia and lidocaine may be tried when conventional therapies fail.     

Drug therapy reviews: intravenous fluid therapy

The indications for use of large-volume parenteral solutions are reviewed, and the types of fluids administered and their potential hazards are described. The indications discussed are replacement therapy, maintenance therapy and emergency venous access. Hazards presented include thrombophlebitis, infection, volume overload, air embolism, particulate matter and chemical contamination. The indications for specific parenteral fluids, such as saline solutions, dextrose solution, fructose and alkaline solutions are discussed. Also reviewed are agents used to treat alkalosis, intravenous potassium therapy, calcium salts, magnesium salts and mixed solutions. Most clinical situations can be managed with judicious use of 0.9% saline and 5% dextrose with the addition of other electrolytes as determined by the needs of the individual patient.     

Drug therapy reviews: evaluation of butorphanol tartrate.

The chemistry, pharmacology, uses, side effects, pharmacokinetics and dosage of butorphanol tartrate, a narcotic analgesic with antagonist properties, are reviewed. When administered intramuscularly or intravenously, butorphanol tartrate appears to be as effective for relieving moderate to severe pain as are pentazocine, meperidine and morphine. Butorphanol produces sedation more commonly and, at therapeutic dosages, depresses respiration as much as these other narcotic analgesics. A limited number of long-term clinical studies suggest a lower physical dependence liability with butorphanol than with other narcotic analgesics. Butorphanol is more expensive than morphine and, for most patients, offers no significant advantages over morphine for short-term use. Because butorphanol's cardiovascular effects are not completely understood, morphine also remains the drug of choice for pain associated with myocardial infarction.     

Drug therapy reviews: clinical pharmacology of antiepileptic drugs.

The absorption, distribution, biotransformation, excretion and clinical pharmacokinetics of antiepileptic drugs are reviewed. Six guidelines for the therapeutic use of these drugs are given: (1) when therapy with an antiepileptic drug is initiated or when dosage is raised or lowered, the new steady-state drug serum concentration and the full effect of the dosage change will not occur for five elimination half-lives; (2) a loading dose is usually necessary to immediately achieve a steady-state serum drug concentration equal to the usual maintenance steady-state serum drug concentration; (3) the choice of dosage intervals for antiepileptic drugs is determined in part by the range of fluctuation in drug concentration between doses that is acceptable; (4) addition of a drug to an existing antiepileptic regimen may raise or lower the serum concentration of prior drugs by inhibition or induction of their metabolism; (5) if possible, make only one change at a time in an antiepileptic drug regimen; and (6) antiepileptic drugs should not be given by the i.m. route in emergency situations.     

Drug therapy reviews: management of the disulfiram-alcohol reaction.

A review of the proposed mechanisms of the disulfiram-alcohol interaction and recommended management of the interaction is presented. The efficacy of disulfiram in the management of alcoholism, the signs and symptoms of the disulfiram-alcohol interaction, and other agents with disulfiram-like activity are discussed. Recommended treatment consists of supportive measures such as Trendelenberg posture, administration of oxygen and intravenous infusion of fluid, solute, colloid, and, if needed, a pressor agent such as norepinephrine. Iron salts, ascorbic acid, antihistamines and phenothiazines are of no established benefit.     

Drug therapy reviews: methenamine mandelate and methenamine hippurate.

The mechanism of action, spectrum of antimicrobial activity, pharmacokinetics, adverse effects, therapeutic use, and dosage of methenamine hippurate and methenamine mandelate are reviewed. The antimicrobial activity of methenamine depends on its conversion in the urine to formaldehyde. Formaldehyde's spectrum of antibacterial activity encompasses all urinary tract pathogens. Urinary concentrations of formaldehyde vary with pH and urine volume; however, there is no documentation that acdification of the urine enhances methenamine's therapeutic activity. Adverse reactions to methenamine, including gastrointestinal intolerance and skin reactions, are mild and reversible and occur infrequently. Methenamine mandelate and hippurate are effective in the prevention of recurrent urinary tract infections except in patients with Foley catheters or who require intermittent catheterization.     

Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy.

Combinations of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are discussed with regard to general toxicity, drug interactions, animal studies, clinical reports, efficacy of combination therapy and usage conditions. Although MAOI-TCA combinations are usually considered contraindicated, informed opinion has shifted to cautious recommendation for the combination. Only refractory patients in whom less hazardous treatment has failed should be considered for combination therapy. The preferred dosage regimen is administration of the MAOI t.i.d. during the day and the entire TCA dose at bedtime. Patients should be informed of the immediate need for medical advice should side effects occur. It is concluded that the simultaneous administration of these agents is potentially efficacious and safe is carefully monitored and controlled.     

Drug therapy reviews: dietary fiber and fiber supplements in the therapy of gastrointestinal disorders.

Dietary fiber and fiber supplements are reviewed, with particular emphasis on their sources, composition and properties; physiological actions on gastrointestinal functions; and uses in gastrointestinal disease states (functional bowel disease, diverticular disease and other conditions). Adverse effects and contraindications, and the hypothesis of diet's effect on colon cancer also are discussed. Dietary fiber supplements may relieve symptoms of constipation, spastic colon, and diverticular disease; in the two latter disorders, colonic pressure relationships are altered. It is concluded that current evidence does not support other therapeutic uses for dietary fiber sonstituents, except possibly in patients with anal fissures and hemorrhoids, which can be helped by the passage of a softer stool.