Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes.

The impact of Parkinson's disease (PD) and its pharmacologic treatment on health-related quality of life (HRQL) and economic outcomes is reviewed. PD is a chronic and progressive neurologic disorder characterized by specific motor deficits resulting from the degeneration of dopaminergic neurons in the substantia nigra. The cardinal symptoms are tremor, rigidity, bradykinesia, and loss of postural reflexes. PD markedly reduces HRQL and places an economic burden on society of up to $25 billion per year. Patients' inability to move freely and to perform everyday tasks restricts their independence and leads to increased reliance on caregivers and assistive devices. Emotional and psychosocial well-being is also negatively affected. As the disease progresses, the response to levodopa typically decreases and various motor complications develop; these are difficult to treat and result in further declines in HRQL. The economic costs of PD include both direct health care costs (for drugs, physician services, and hospitalization) and indirect costs (for lost worker productivity). Economic analyses of PD and its treatments can help guide effective allocation of health care resources. Various antiparkinsonian agents and formulations, such as extended-release levodopa-carbidopa and pramipexole, have been found to be cost-effective relative to other agents. The newest antiparkinsonian drugs, cathechol-O-methyltransferase inhibitors, also have the potential to improve HRQL and economic outcomes, although more study is needed to confirm this. The total impact of PD and its treatment can be fully appreciated only when HRQL and economic outcomes, in addition to clinical outcomes, are examined.

Successful orchestration of antiparkinsonian pharmacotherapy.

As is true with the orchestration of essentially all forms of pharmacotherapy, the overall quality of therapy should not be judged as a simple binary function (it is either good or bad). Rather, it should be judged along a continuum, spanning adequate through excellent and peaking at truly elegant, where two or more disease states are optimally managed with a single, simple drug. Because the difference between adequate and elegant therapy often depends on fine-tuning the drug choice, dosage, and route of administration, it is no surprise that pharmacists are often intimately involved in many highly successful specialty clinics, including Parkinson's disease clinics.

Photosensitizing potential of ofloxacin.

BACKGROUND: The relative phototoxic risk of ofloxacin, one of the newer fluoroquinolones, was compared with that of an active control of known but low phototoxic risk, naproxen. METHODS: A randomized, controlled, open-label trial was used with a standardized phototoxic assay completed at baseline, midway through, and at the termination of the 12-day trial. The trial was held at a dermatology research laboratory located at a large tertiary referral and teaching hospital. Thirty healthy volunteers who met the inclusion criteria and met none of the exclusion criteria were enrolled. Twenty-seven patients completed the trial. Three subjects failed to complete the trail. One subject developed an exaggerated response to the initial photoexposure and was dropped from the study. The other two subjects failed to return for follow-up visits. RESULTS: Both ofloxacin and the active control agent, naproxen, significantly increased the subjects' response to the tested solar and ultraviolet irradiation. There was, however, no significant difference between the responses observed for ofloxacin versus naproxen at any time. CONCLUSIONS: Ofloxacin possesses a definite but low potential to cause phototoxic reactions in humans. These study data, in concert with surveillance data, suggest a hierarchy of phototoxic risk among the fluoroquinolones: fleroxacin >> lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin, ofloxacin. The impact that phototoxicity risk will have on selecting the optimum member of a large drug family appears to be substantial in outpatient and ambulatory settings and minimal in inpatient settings.

Isopropyl alcohol intoxication.

Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and laboratory findings.

Protein binding: what does it mean?

Protein binding can enhance or detract from a drug's performance. As a general rule, agents that are minimally protein bound penetrate tissue better than those that are highly bound, but they are excreted much faster. Among drugs that are less than 80-85 percent protein bound, differences appear to be of slight clinical importance. Agents that are highly protein bound may, however, differ markedly from those that are minimally bound in terms of tissue penetration and half-life. Drugs may bind to a wide variety of plasma proteins, including albumin. If the percentage of protein-bound drug is greater when measured in human blood than in a simple albumin solution, the clinician should suspect that the agent may be bound in vivo to one of these "minority" plasma proteins. The concentration of several plasma proteins can be altered by many factors, including stress, surgery, liver or kidney dysfunction, and pregnancy. In such circumstances, free drug concentrations are a more accurate index of clinical effect than are total concentrations. Formulary committees must grasp the clinical significance of qualitative and quantitative differences in protein binding when evaluating competing agents.

Intrathecal administration of natural human interferon alpha in amyotrophic lateral sclerosis.

Ten patients with amyotrophic lateral sclerosis were given intrathecal injections of natural interferon alpha, 1 million units weekly for 7 to 24 weeks. Six patients completed the trial. Four voluntarily withdrew after 7 to 13 injections. The slopes of deterioration for 40 quantitative tests of neuromuscular function for the control and treatment periods were compared by paired t test in the six patients who completed the trial and in the patient who withdrew after 13 injections. No significant differences were found. The patients tolerated treatment well. The CSF reaction was modest and spontaneously reversible. Indomethacin and ibuprofen blocked interferon side effects.

A double-blind controlled trial of bovine brain gangliosides in amyotrophic lateral sclerosis.

We conducted a double-blind controlled study of the effect of brain gangliosides in amyotrophic lateral sclerosis. Nineteen patients received intramuscular gangliosides (40 mg/d) for 6 months, and 21 received placebo. The deterioration rates for approximately 120 clinical and electrophysiologic parameters of neuromuscular function were analyzed, but no statistically significant beneficial effect of the drug was demonstrated. However, the large coefficient of variation for each item indicated that a sample size of several hundred patients would have been necessary to exclude the possibility that the drug produced a 25% slowing of progression of the disease.

Bacampicillin hydrochloride: chemistry, pharmacology, and clinical use.

Bacampicillin hydrochloride is an orally administered ester of ampicillin that is rapidly and completely hydrolyzed in vivo to ampicillin. The most notable advantage of bacampicillin over ampicillin is its superior bioavailability--bacampicillin achieves significantly higher blood and tissue levels and attains peak blood levels more rapidly than equimolar doses of oral ampicillin. In addition, the percentage of an oral dose of ampicillin that is absorbed decreases sharply as the size of the dose is increased from 500 mg to 2 g; this phenomenon is not observed with equipotent doses of bacampicillin. The enhanced absorption of bacampicillin in the upper gastrointestinal tract results in a frequency of diarrhea that appears to be markedly lower than that of ampicillin and similar to that observed with amoxicillin. Apart from the sizable differences between bacampicillin and ampicillin with regard to oral absorption, the pharmacokinetic and pharmacologic profiles of these two agents are essentially identical. Twice daily dosing (pulse dosing) with bacampicillin has been shown in numerous clinical trials to be of equivalent efficacy to ampicillin given four times daily or amoxicillin given three times daily in the treatment of infections of the upper respiratory tract, lower respiratory tract, skin and soft tissues, and urinary tract. The unanswered question is whether twice daily ampicillin or amoxicillin would yield similar results.

Cost comparison of two antimicrobial regimens for treating mixed aerobic-anaerobic infections.

The costs of cefoxitin sodium therapy and clindamycin phosphate plus amikacin sulfate therapy for mixed aerobic-anaerobic infections were compared. A randomized, prospective study was undertaken with 70 adult patients with documented or suspected serious aerobic-anaerobic infections. It had been shown that the two therapies did not differ in efficacy or incidence of toxicity. The cost to the pharmacy for one day's therapy was chosen as the unit of cost comparison. Cost-per-day data were calculated by the unit-price and price-allocation methods with and without a sterile-products charge. Amikacin was added to the cefoxitin regimen when resistant organisms were cultured. To extend the analysis to other aminoglycosides, rough comparisons were made for "equivalent" doses of tobramycin sulfate and gentamicin sulfate. Fifty-four patients completed the trial (77%). The cost of cefoxitin therapy was significantly less than that of clindamycin plus amikacin therapy and cefoxitin plus amikacin therapy (p less than 0.001) by both pricing methods. When gentamicin and tobramycin were substituted for amikacin sulfate, the cost per day for therapy, according to the price-allocation method, was still significantly less for cefoxitin (p less than 0.001). Cost analysis is an important component in the selection of the appropriate therapy after the efficacy and toxicity of therapeutic regimens have been shown to be equivalent.

Myasthenia gravis: signs, symptoms, diagnosis, immunology, and current therapy.

Myasthenia gravis is a neuromuscular disease that presents clinically as fluctuating weakness of one or more skeletal muscle groups. Weakness becomes more severe with exercise and improves with rest. The disease is caused by an autoimmune reaction at or near the post-synaptic nicotinic acetylcholine receptor. The results of this immune reaction are the lytic destruction of the post-synaptic membrane and a reduction in the number of acetylcholine receptors. Myasthenia gravis can be diagnosed by repetitive exercise of the involved muscles, administration of edrophonium (Tensilon), electrophysiologic testing, or demonstration of anti-acetylcholine receptor antibodies. When the myasthenic weakness is mild or limited to the extraocular muscles, it may be treated with acetylcholinesterase inhibitors. When the weakness is more severe and/or more generalized, immunotherapy is most often indicated. Prednisone or prednisone plus thymectomy is the most frequently used form of immunotherapy. Azathioprine, 6-mercaptopurine, plasmapheresis, or gamma globulin injections are other immunotherapeutic options that may be useful in selected patients. A large number of drugs may precipitate or exacerbate myasthenic weakness.

Migraine headache: signs and symptoms, biochemistry, and current therapy.

The classification, biochemistry, precipitating factors, differential diagnosis, treatment of acute attacks, and prophylactic therapy of migraine headaches are reviewed. The biochemistry of both classic (prodromal symptoms) and common (no prodromal symptoms) migraines is poorly understood, but appears to involve serotonin. Although their clinical importance is not clear, common precipitating factors include coffee, tea, and cola beverages; chocolate, cheese, and alcohol; light stimulation, stress, fasting, lack of sleep, and fever; and reduced estrogen levels. The symptomatic treatment of acute attacks with ergot preparations, isometheptene, flufenamic acid, analgesics and sedatives is reviewed. Prophylactic therapy with methysergide maleate, tricyclic compounds, monoamine oxidase inhibitors, propranolol, and 5-hydroxytryptophan is also discussed.

Drug therapy reviews: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics--part 4: aminoglycosides.

The aminoglycoside antibiotics are reviewed with regard to mechanism of action, bacterial resistance, antimicrobial spectrum, combinations with other agents, pharmacology, dosages in patients with normal and impaired renal function, adverse reactions, therapeutic use, prophylatic use and selection. Streptomycin is suggested in the therapy of tuberculosis, brucellosis, tularemia and yersinia infections; several of these require the coadministration of another agent. The choice between streptomycin and gentamicin for combination therapy of enterococcal endocarditis may be simplified by knowledge of the prevalence of high-level streptomycin-resistant strains in the hospital or by use of an in vitro screening test. Neomycin is the agent used orally in the treatment of hepatic encephalopathy. Paromomycin is indicated only for the treatment of amebic infections. The major difference among gentamicin, tobramycin and amikacin lies in the low but increasing prevalence of gram-negative bacilli which are resistant to gentamicin and tobramycin and susceptible to amikacin. In those institutions in which gentamicin-resistant strains are of concern, amikacin is the aminoglycoside of choice in high-risk patients until the infecting bacterium has been determined.

Pharmacotherapy of Parkinson's disease.

The pathophysiology, anticholinergic therapy and dopaminergic therapy of Parkinson's disease are reviewed; an emphasis is placed on the structure and function of the basal ganglia because of their importance in understanding the pharmacotherapy of parkinsonism. The pharmacologic management of Parkinson's disease is limited primarily to manipulation of the dopamine-acetylcholine system. Levodopa, with or without a peripheral dopa decarboxylase inhibitor, is the current drug of choice in the management of idiopathic and postencephalitic Parkinson's disease. Modification of the serotonin-histamine system via the use of antihistamines may be useful in some patients. There are also many adjunctive agents which may be employed in combination with or in place of levodopa. Levodopa clearly has no place in the treatment of neuroleptic-induced Parkinson's disease; anticholinergics and antihistamines are the agents of choice.