Biomedical subjects
T H Self
Publications and source records attributed to T H Self.
Is theophylline use justified in acute exacerbations of asthma?
Despite widespread use of theophylline in the hospital management of asthma, supportive data justifying its use are sparse. Clinical research in the 1980s has forced a serious new examination of the drug's role in acute exacerbations of asthma. Because of the morbidity, mortality, questionable value, and overall cost of theophylline therapy, this reevaluation is of particular importance. Enhanced knowledge of the value of treatment with intensive inhaled beta agonists, systemic glucocorticoids, and inhaled ipratropium should prompt elimination of the routine, initial use of theophylline in emergency room care of most asthmatics. Further research is necessary to justify the routine, initial use of the drug in hospitalized asthmatics.
Calcium channel blockers as inhibitors of drug metabolism.
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Interaction of rifampin and glyburide.
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Hypothyroidism: effect on warfarin anticoagulation.
Although our observation is not the first case of reduced PT response to oral anticoagulants associated with hypothyroidism, it is the only such interaction reported since 1963, and the first case involving warfarin therapy in a human being. We submit this case as a reminder of a potentially forgotten interaction, and to stress the importance of close monitoring in patients receiving warfarin therapy who have concomitant changes in thyroid function.
The effect of pneumococcal vaccine on the disposition of theophylline.
Pneumococcal vaccine is frequently given to chronic obstructive airway disease patients who are maintained on theophylline therapy. Several studies demonstrating the effect of viral and bacterial vaccines on drug metabolism prompted our evaluation of the effect of pneumococcal vaccine on theophylline pharmacokinetics. Six healthy volunteers, acting as their own controls, received 250 mg of theophylline every 8 h for 12 days. Plasma area under the concentration-time curves (AUC) were measured on Days 4, 6, and 12. On Day 5 pneumococcal vaccine (0.5 ml) was given intramuscularly. No significant difference in elimination rate constant, AUC, or apparent oral clearance of theophylline was found at one or seven days after vaccine administration. These results indicate that intramuscular pneumococcal vaccine does not alter the pharmacokinetics of theophylline during chronic oral administration.
Effect of calcium channel blockers on theophylline disposition.
Twelve healthy subjects received a single oral dose of theophylline, 5 mg/kg alone, and after 7 days of oral verapamil, 120 mg every 8 hours, diltiazem, 90 mg every 8 hours, and nifedipine, 20 mg every 8 hours, in randomized crossover fashion. Mean theophylline oral clearance decreased 18% and 12% after verapamil and diltiazem, respectively (p less than 0.05). No significant change in theophylline oral clearance was observed after nifedipine. Increases in mean theophylline half-life were observed after verapamil (10.8 +/- 3.2 hours) and diltiazem (9.9 +/- 2.4 hours) (p less than 0.05) but not after nifedipine (8.6 +/- 2.4 hours) when compared with control (8.6 +/- 1.9 hours). Apparent volume of distribution was unchanged. Urinary excretion data showed that the relative formation rate constants of 3-methylxanthine and 1,3-dimethyluric acid were decreased during verapamil and diltiazem (p less than 0.05) but not during nifedipine. No change in 1-methyluric acid excretion was observed. Increases in urinary elimination of unchanged theophylline were observed after verapamil, diltiazem, and nifedipine. The modest reduction in theophylline clearance observed after verapamil and diltiazem is not likely to produce clinically significant increases in theophylline concentrations in most patients.
Update on rifampin drug interactions.
Rifampin, a potent inducer of the hepatic microsomal system, has been shown to cause clinically important interactions when combined with other drugs, including oral anticoagulants, oral contraceptives, digitoxin, methadone hydrochloride, sulfonylureas, and barbiturates. Additional literature on previously described interactions has been published recently on quinidine, glucocorticoids, digoxin, and theophylline. New rifampin interactions have been described for cyclosporine, ketoconazole, chloramphenicol, beta-blockers, verapamil, and phenytoin. These interactions seem to be of clinical significance.
The effect of ranitidine and cimetidine on imipramine disposition.
The pharmacokinetic characteristics of imipramine were studied after a single, oral, 100 mg dose was taken by 12 healthy male subjects following 3 days of pretreatment with placebo, cimetidine (300 mg every 6 h), and ranitidine (150 mg every 12 h) in a randomized, double blind, crossover trial. After each imipramine dose plasma samples were collected for 72 h and assayed for imipramine, desipramine, 2-hydroxyimipramine and 2-hydroxydesipramine by HPLC. Cimetidine preadministration statistically prolonged imipramine t 1/2 compared to ranitidine (22.7 vs. 13.0 h) or placebo (10.8 h). Mean imipramine area under the curve (AUC) following cimetidine pretreatment was more than double that following placebo (2.633 vs. 0.966 micrograms X h X ml-1) or ranitidine (1.14 micrograms X h X ml-1) pretreatment. Imipramine apparent oral clearance was reduced in all 12 subjects after cimetidine. Compared to ranitidine or placebo, cimetidine pretreatment was associated with an increased imipramine/desipramine AUC ratio, suggesting cimetidine-induced impairment of demethylation of imipramine. Ranitidine was not observed to alter imipramine pharmacokinetics.
Isoniazid interactions.
Isoniazid is an antituberculous drug that is usually administered for nine to 12 months. The potential for clinically important interactions exists because this drug is a potent inhibitor of drug metabolism. Studies and case reports have shown that isoniazid inhibits the metabolism of several drugs, including phenytoin, carbamazepine, anticoagulants, benzodiazepines, and vitamin D. Furthermore, isoniazid inhibits both monoamine oxidase and diamine oxidase (histaminase). Additional study is required to document the clinical significance of other isoniazid interactions. Future investigations will identify new isoniazid interactions.
Early use of oral theophylline in hospitalized chronic obstructive pulmonary disease patients: cost-containment through medical education.
This study measured the impact of an education program conducted by a clinical pharmacist on early conversion from intravenous to oral theophylline in hospitalized chronic obstructive pulmonary disease patients. Two separate two-month audit periods were conducted on the pulmonary medicine service (PMS) of a teaching hospital. During the first audit period (pre-ed), no education was provided. Prior to each month of the second two-month audit period (post-ed), an education program and handout outlining the rationale for early conversion from intravenous to oral theophylline was presented to medicine residents rotating onto the PMS. The results of this preliminary study suggest that the education program was responsible for a statistically significant decrease in intravenous aminophylline therapy from three days (pre-ed) to one day (post-ed). As a result of the reduction in length of intravenous therapy, both drug costs and patient charges were reduced by a statistically significant amount.
Rifampin drug interactions.
Rifampin, an antituberculosis agent, is usually administered for nine to 12 months with other antituberculosis drugs or drugs from other classes. A potential for drug interactions often exists because this drug is a potent inducer of drug metabolism. Rifampin causes a proliferation of the smooth endoplasmic reticulum and an increase in the cytochrome P-450 content in the liver. Rifampin's enzyme-induction effect is selective; therefore, it is not always clear which agents will be affected. Studies and case reports have demonstrated that rifampin accelerates the metabolism of several drugs, including oral anticoagulants, oral contraceptives, glucocorticoids, digitoxin, quinidine, methadone, hypoglycemics, and barbiturates. Rifampin interacts with other agents, but further study is needed to demonstrate the clinical importance of these interactions. In addition to inducing drug-metabolizing enzymes, rifampin may cause alterations in absorption and hepatic uptake. Future investigations will probably identify new rifampin drug interactions.
Effect of rifampin on theophylline disposition.
The concentrations of theophylline from single 400-mg oral doses were evaluated both before and after 7 days of oral rifampin administration (600 mg/day) in six healthy, nonsmoking adults. The mean oral clearance of theophylline was significantly increased from 54.9 +/- 21.2 to 68.9 +/- 26.5 ml/h/kg. The elimination rate constant was significantly increased in five of the six subjects, with a mean increase of approximately 25%. Although intersubject variability was large, these data indicate the potential need to increase theophylline doses in some patients receiving rifampin.
Medical education provided by a clinical pharmacist: impact on the use and cost of corticosteroid therapy in chronic obstructive pulmonary disease.
The impact of medical education provided by a clinical pharmacist on the use and cost of corticosteroid therapy in acute exacerbations of chronic obstructive pulmonary disease was evaluated. Three separate two-month audits of corticosteroid use were conducted on the pulmonary medicine service (PMS) of a teaching hospital. For the first audit period, no education was given and no clinical pharmacist was on the PMS. During the second audit period, no education was given, but a clinical pharmacist was on-service. For the third audit period, education (brief discussion and a handout) was given to new house staff members by the clinical pharmacist on the PMS. A significant reduction in the mean number of intravenous steroid doses, steroid cost per day, and patient steroid charges per day occurred in the third vs. the first period. Steroid cost per day and patient steroid charges per day were lower in the third period than the second, but the difference was not statistically significant.
Pharmacist's role when dispensing pressurized aerosols for asthma.
Pharmacists should ensure that patients with asthma know how to use their pressurized aerosol medication, including bronchodilators and steroids. Inappropriate inhalation technique with these agents is common and may result in suboptimal response or therapeutic failure. Instruction by the pharmacist should include demonstration of the inhalation technique as well as the use of verbal and printed information. After demonstrating the use of the inhaler, the pharmacist should observe the patient to verify proper use. Instructions should be reinforced when prescriptions are refilled or if the patient is readmitted to the hospital. For patients who cannot learn proper inhalation technique, extension devices are now available.
The value of demonstration and role of the pharmacist in teaching the correct use of pressurized bronchodilators.
The use of an improper technique with metered-dose inhalers decreases the efficacy of the bronchodilators being administered. There is evidently a need for patients to watch a demonstration. Twenty-nine adult asthmatic patients from an allergy clinic were divided into three groups, each receiving a different form of instruction: an information sheet, personal instruction or a videotape presentation. Subsequently each patient was tested for correct use of the inhaler. There was no difference in mean scores for inhalation technique between the groups instructed in person and by videotape, but both were significantly better than the mean score of the group given only an information sheet. There was also no significant change in the scores at a follow-up test in the groups who saw the technique demonstrated. These results indicate the need for and value of the demonstration of proper technique with pressurized inhalers. A pharmacy-generated education system using videotape equipment or personal instruction by a pharmacist could readily solve the problem.
Spiking fever induced by isoniazid.
In a 48-year-old man, a consistent pattern of spiking fever occurred ten days after the initiation of therapy with isoniazid and rifampin. The fever recurred upon rechallenge with isoniazid, but not with rifampin. Isoniazid has the potential to induce fever, and this is thought to be a hypersensitivity reaction.
Cimetidine drug interactions.
Cimetidine is a widely used antiulcer medication that is also a potent inhibitor of the mixed-function oxidase enzymes in the liver. This effect results in a number of clinically important interactions with other drugs, which are now being appreciated. Other effects of cimetidine, such as raising of gastric pH, alteration of liver blood flow, or alterations in renal secretory mechanisms, may also contribute to or result in clinically significant interactions. Current data document appreciable alterations in the metabolism or excretion of warfarin, theophylline, phenytoin, lidocaine, certain beta-adrenoceptor antagonists, certain benzodiazepines, and probably narcotic analgesics and procainamide. Thus, effects of these drugs and serum levels, where available, should be more closely followed when used in combination with cimetidine. Cimetidine appears to exacerbate the myelosuppressive effects of the nitrosoureas, and may also significantly alter the absorption of ketoconazole. Though other drugs may affect the absorption or elimination of cimetidine, the clinical implication of these effects is uncertain.