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Biomedical subjects

K D Lake

Publications and source records attributed to K D Lake.

17 recordsLinked to original sources
PubMed1992

Postmortem changes and pharmacokinetics: review of the literature and case report.

OBJECTIVE: To review the mechanisms and sequence of events that occur during ischemia and cell death and following death of the human body. The impact of these postmortem events on the distribution and pharmacokinetic behavior of drugs is described. The case study presented illustrates a possible situation where such postmortem changes could have affected the pharmacokinetics of procainamide. DATA SOURCES: English-language journal articles and reference texts identified from pertinent data sources. DATA SYNTHESIS: Postmortem changes in the human body begin at the cellular level with the onset of ischemia. As the length of time of ischemia increases and death ensues, more changes occur and lead to deterioration in tissue and organ function. These changes may affect the pharmacokinetic and distribution behavior of certain drugs. Drugs particularly affected are those whose distribution is dependent on molecular size, lipophilicity, pH, energy-dependent transport, and tissue binding. Such drugs include the tricyclic antidepressants, digoxin, and cimetidine. Other drugs with similar characteristics, such as procainamide, may also demonstrate like changes in distribution and pharmacokinetics. CONCLUSIONS: When measuring drug concentrations after death, it is important to consider the phenomenon of postmortem redistribution. Postmortem drug concentrations may not be a true reflection of antemortem concentrations and as a result, wrong conclusions could be made about the cause of death. More studies characterizing the postmortem distribution and pharmacokinetic characteristics of specific drugs are necessary.

Antidepressive Agents, Tricyclic↗
PubMed1992

Over-the-counter medications in cardiac transplant recipients: guidelines for use.

OBJECTIVE: The purpose of this article is to review the pathophysiology of the denervated heart and the factors that need to be considered before recommending the use of over-the-counter (OTC) medications in the cardiac transplant recipient. DATA SOURCES: Pharmacology and therapeutic textbooks, English-language journal articles, and physiology textbooks published between 1969 and 1991. DATA EXTRACTION: Case reports, controlled case studies, and textbook chapters evaluating drug interactions with immunosuppressive agents were reviewed. The effects of various OTC medications on the denervated heart were examined and relevant material was extrapolated. DATA ANALYSIS: The number of cases or studies in which a particular effect or interaction occurred was reported. Those findings that were less well documented were either identified as such or were not included in the review. DATA SYNTHESIS: Common pharmacokinetic and pharmacodynamic interactions with the primary immunosuppressive agents (e.g., cyclosporine, azathioprine, prednisone) are reviewed. The physiology and altered responses of the denervated heart to various medications are also explained. Using this information recommendations are given for the use and monitoring of OTC analgesics, antacids, laxatives, sleep aids, stimulants, and other medications that may be used in the cardiac transplant recipient. CONCLUSIONS: Many OTC medications can be used safely in the cardiac transplant recipient. In each situation, risk/benefit assessments must always be made and therapy should be monitored closely. Most important, patients should always notify the transplant team before adding an OTC product to their immunosuppressive regimen.

Analgesics↗
PubMed1992

The pharmacokinetics and pharmacodynamics of immunosuppressive agents.

Designing immunosuppressive regimens for the pediatric transplant patient is challenging because one must balance the need to provide adequate immunosuppression without interfering with normal growth processes or causing long-term adverse consequences. To optimize immunosuppressive therapy and minimize toxicity, it is necessary for the nurse to be knowledgeable of the pharmacokinetic and pharmacodynamic characteristics of the various agents. It is also important to understand which drugs interact with immunosuppressive agents and how to manage these interactions.

Adrenal Cortex Hormones↗
PubMed1991

Mechanical circulatory assistance after heart transplantation.

From October 1985 through December 1989, 92 heart transplant procedures were performed in 89 patients. Nine patients (aged 19 to 66 years; 7 male, 2 female) required mechanical circulatory support after transplantation because of primary idiopathic organ failure (n = 2), implant difficulty (2), poor organ quality (2), or acute right heart failure (3). Devices used included the intraaortic balloon pump (6), centrifugal right ventricular assist device (2), left ventricular assist (1), biventricular assists (2), and total artificial heart (1). Two patients required multiple devices. One patient underwent retransplantation. Implant time ranged from 1 to 18 days. One early death occurred owing to right heart failure 6 days after transplantation, 7 hours after removal of a right ventricular assist device, for an overall mortality of 11%. The remaining 8 patients are alive 4 months to 28 months after transplantation. The actuarial 1-year survival of 89% +/- 10% compares well with the survival of 87% +/- 4% for the entire transplant group. All surviving patients are in functional class I. Echocardiographic examination in all patients revealed left ventricular ejection fraction to be normal in 7 and depressed in 1. Extending the criteria for organ donors or difficulty with the implant procedure can lead to early organ failure, which may be reversible with circulatory assistance allowing excellent survival.

Adult↗
PubMed1991

Management of drug interactions with cyclosporine.

Major advances in transplantation and in the treatment of autoimmune disorders have been achieved with the use of cyclosporine (CsA). During the past 10 years a variety of drug interactions have been reported to occur with CsA. These may be classified as either pharmacokinetic or pharmacodynamic in origin. Pharmacokinetic interactions are manifested by either an increase or decrease in the CsA concentration. The predominant mechanism of interaction is alteration in the cytochrome P-450 metabolism of CsA, however, some of the drugs may also affect its absorption, distribution, and elimination. Pharmacodynamic interactions include enhanced nephrotoxicity. Management of these events mandates proactive measures such as assessing the interactive potential of each new agent, measuring CsA concentrations more frequently when either initiating or discontinuing other agents, adjusting the dosage of CsA as necessary, and monitoring patients' clinical status to ensure efficacy and minimize the risk of toxicity.

Animals↗
PubMed1988

Evaluation of a method for initiating vancomycin therapy: experience in 205 patients.

This study evaluated a dosing method for initiating vancomycin therapy in a large population based on patients' age, weight, and renal function. The aims were to determine the method's efficacy in achieving predetermined peak and trough serum concentrations, and to calculate the cost savings incurred by individualizing therapy. Average doses +/- 1 SD of 7.93 +/- 0.29 mg/kg corrected body weight (lean body weight + 40% excess weight) were administered at intervals predicted by the patients' estimated creatinine clearances (range 22-130 ml/min). The calculated mean dose +/- SD was 558 +/- 83 mg (range 350-750 mg) and the calculated median interval was 12 hours (range 6-24 hr). Peak and trough concentrations +/- SD measured at steady state averaged 26.0 +/- 5.4 and 7.3 +/- 2.3 micrograms/ml, respectively. Peak and trough serum concentrations fell within the predetermined therapeutic range in 311 (76%) of 410 samples. Peak concentrations were in the range of 20-30 micrograms/ml in 145 (71%) of 205 samples. Trough concentrations were in the range of 5-10 micrograms/ml in 166 (81%) of the 205 samples. This simplified dosing method successfully individualized therapy in most patients, and produced a significant savings to the pharmacy in reduced drug acquisition costs and to patients in reduced drug charges.

Adult↗
PubMed1988

Ganciclovir pharmacokinetics during renal impairment.

Limited information is available concerning the use of ganciclovir (GCV) in patients with severe renal impairment. The pharmacokinetics of GCV were studied in a heart transplant recipient requiring hemodialysis. The total body clearance was calculated to be approximately 5% of that previously reported for patients with normal renal function. GCV was removed by hemodialysis; a single 4-h procedure decreased the concentration in plasma by approximately 50%. GCV can be safely administered to patients with renal insufficiency if concentrations in plasma are monitored.

Acyclovir↗
PubMed1987

Immunizing the pregnant woman. Risks versus benefits.

No substance should be administered unnecessarily during pregnancy. However, when a pregnant woman is not immune to serious disease, the risk of maternal and fetal infection must be weighed against the risk of vaccination. Whenever possible, an inactivated (killed) vaccine should be selected and immunization delayed until the second trimester. Only rarely is an attenuated (live) vaccine indicated.

Bacterial Vaccines↗
PubMed1987

Antibiotic prophylaxis in open-heart surgery patients: comparison of cefamandole and cefuroxime.

The efficacy of cefamandole and cefuroxime in preventing postoperative wound infections was compared in 3037 patients undergoing open-heart surgery. Antibiotic prophylaxis in 1467 patients having coronary artery bypass and valve replacement surgery was cefamandole 2 g iv preoperatively followed by 2 g q6h for five days postoperatively; 1570 patients received cefuroxime 1.5 g iv preoperatively then 1.5 g iv q 12h for three days postoperatively. Postoperative wound infections (sternal and leg wounds) were studied in each treatment group. In the cefamandole study group, 27 patients (1.8 percent) developed postoperative wound infections (9 sternal and 18 leg wounds). In the cefuroxime treatment group, 19 patients (1.2 percent) developed postoperative wound infections (9 sternal and 10 leg wounds). Overall, no statistical difference was found between the two antibiotics in preventing postoperative wound infections. However, in patients having valve replacement surgery, cefuroxime was found statistically more effective than cefamandole prophylaxis in preventing sternal wound infections (no infections in 284 patients compared with five infections in 205 patients, respectively, p = 0.01). The most common organism isolated from infected wounds with cefamandole was Staphylococcus aureus followed by S. epidermidis compared with cefuroxime which had S. epidermidis followed by S. aureus. Cefuroxime was found to be as effective as cefamandole and considerably less expensive in preventing postoperative wound infections in patients undergoing open-heart surgery.

Cardiac Surgical Procedures↗
PubMed1986

Reducing prophylactic antibiotic costs in cardiovascular surgery: the role of the clinical pharmacist.

A project was undertaken to demonstrate significant drug cost savings from clinical pharmacy services. The method of identifying and documenting the problem and the presentation and implementation of the project are discussed. The cost savings of the project are presented, including the economic impact on the patient and institution. The clinical pharmacist, the key figure in the success of the project, presented a complete pharmacological and financial analysis of the project to the medical staff. The project resulted in a financial savings of approximately $600 000/yr to patients in decreased drug charges, $200 000/yr in decreased drug purchases/inventory, and $105 000/yr to the hospital in an improved revenue/expense statement. This project represents an example of the important role of the clinical pharmacist in helping a hospital identify areas to reduce drug therapy costs. A future role for clinical pharmacists will be to work closely with the director of pharmacy, hospital administration, and medical staff in identifying and implementing cost-effective drug therapy.

Anti-Bacterial Agents↗
PubMedDate not supplied

A simplified dosing method for initiating vancomycin therapy.

Vancomycin dosing regimens should be individualized for each patient. The routine use of standard doses 500 mg every 6 hours or 1.0 g every 12 hours regardless of patients' age, weight or kidney function is no longer appropriate. A simplified method for initiating vancomycin therapy was developed and evaluated prospectively in 30 patients. Average doses of 8.3 +/- 0.6 mg/kg lean body weight (rounded to the nearest 50 mg) were administered to patients with varying degrees of renal function (estimated creatinine clearances 19-113 ml/min). The dosing interval was predicted by the patient's estimated creatinine clearance. Our simplified schedule resulted in desired serum levels and required no modification in 25 of 30 patients. Only slight dosage changes were needed in the remaining five patients. Mean peak and trough serum concentrations of vancomycin were 26.9 +/- 5.8 micrograms/ml (range 18.8-39.7 micrograms/ml) and 7.7 +/- 2.0 micrograms/ml (range 4.5-11.8 micrograms/ml) respectively. Our regimen is practical and simple and requires limited patient information.

Adult↗
PubMedDate not supplied

New drug therapy for kidney stones: a review of cellulose sodium phosphate, acetohydroxamic acid, and potassium citrate.

Kidney stones have an overall incidence of two to three percent in western countries. In many patients, the disease process is difficult to control and recurrence rates are high: 20 to 50 percent over the subsequent ten years. The pathogenesis and standard methods of treatment for the five major types of stones (i.e., calcium oxalate, struvite, calcium phosphate, uric acid, and cystine) are reviewed. Three new drugs are reviewed in the context of their roles in the selective treatment of kidney stones. Cellulose sodium phosphate (Calcibind) is a nonabsorbable ion-exchange resin with a limited indication for the treatment of calcium stones associated with absorptive hypercalciuria Type I. Acetohydroxamic acid (Lithostat) is an urease-inhibitor that is indicated as adjunctive therapy in patients with chronic urea-splitting urinary tract infections and struvite stones. Potassium citrate (Urocit) is an investigational agent that has clinical efficacy in patients with calcium oxalate and calcium phosphate stones who are hypocitraturic. In addition, potassium citrate is an alkalinizing agent that can be used in patients with uric acid stones.

Adult↗
PubMedDate not supplied

Steroid-free maintenance immunotherapy: Minneapolis Heart Institute experience.

Recent advances in immunotherapy have resulted in improved survival after heart transplantation. The use of OKT3 as an induction agent has allowed the identification of a subset of patients who can be successfully withdrawn from prednisone and maintained on only cyclosporine and azathioprine. The latter regimen offers several theoretic advantages in terms of freedom from complications of long-term steroid therapy. To compare both the long-term efficacy and toxicity of steroid-free maintenance immunosuppression with triple-drug therapy, the medical records of 68 patients undergoing transplantation at the Minneapolis Heart Institute during a 3-year period (1988 through 1990) were reviewed. Thirty-six patients were treated with OKT3 induction immunotherapy, 29 were successfully tapered off prednisone by 114 +/- 44 days after transplantation, whereas 32 patients were maintained on triple-drug therapy. The incidence of treated rejection was equivalent in both groups; however, the time to first rejection was longer in patients treated with OKT3/steroid-free maintenance (205 +/- 214 vs 27 +/- 17 days) (p = 0.02). Bacterial infections during the early posttransplant period were more common in the OKT3/steroid-free maintenance group (p = 0.008); however, fungal and viral infections were equally distributed between both groups. The incidence of hypertension was slightly higher in patients maintained on prednisone (67% vs 51%; p = 0.242).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMedDate not supplied

OKT3 induction and steroid-free maintenance immunosuppression for treatment of high-risk heart transplant recipients.

A group of high-risk heart transplant patients (n = 35) were treated from May 1987 through June 1990, with murine-derived monoclonal CD3 antibody (OKT3) induction therapy and steroid-free maintenance immunosuppression. This group was compared with a group of transplant patients (n = 47) who were not considered high risk and who were treated simultaneously with triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone). The 1- and 3-year actuarial survival rates were similar: 97% and 91% for the OKT3 and 92% and 85% for the triple-drug immunosuppression groups, respectively. The overall incidence of rejection was equal for both groups (56%). No rejection occurred during the OKT3 course and rejection episodes occurred significantly later in patients treated with OKT3, with a mean first rejection episode of 111 +/- 104 days versus 27 +/- 21 days for the triple-drug immunosuppression group (p less than or equal to 0.05). Bacterial infections were seen more frequently (29% vs 6% of the patients treated) in the early period (less than 3 months) in the OKT3 group (p = 0.01) and were associated with the use of mechanical assistance in this group. The incidence of late infections or cytomegalovirus disease was similar for both groups. Patients treated with OKT3 and subsequent steroid-free maintenance immunosuppression had no significant posttransplantation increases of serum cholesterol levels, and hypertension was less common. Initial hospitalization was longer (p less than or equal to 0.05) in the OKT3 group (23 +/- 19 vs 13 +/- 5 days) but after the initial discharge the number of hospital days for the first year was similar for both groups (8 +/- 14 vs 9 +/- 13 days). Ventricular function at 1 year after transplantation was similar for both groups with average ejection fraction of 57% and 59% for the OKT3 and triple-drug immunosuppression groups, respectively. In conclusion, high-risk patients treated with OKT3 and steroid-free maintenance immunosuppression were managed on smaller doses of immunosuppressive drugs in the early postoperative period, and had excellent long-term survival rates. In this group of patients, rejection was delayed and the incidence of hypercholesterolemia, hypertension, and steroid-induced complications was decreased. Such a regimen offers a relatively drug-free period in the early posttransplant stages and freedom from the long-term complications of steroids.

Actuarial Analysis↗