Search PubMed⌕ Search

Biomedical subjects

R Keith Campbell

Publications and source records attributed to R Keith Campbell.

18 recordsLinked to original sources
PubMed2006

Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus.

OBJECTIVE: To review advances in understanding the pathophysiologic basis of type 2 diabetes mellitus and the pharmacology and mechanism of action of dipeptidyl peptidase 4 (DPP-4) inhibition in correcting the underlying defects in glycemic control. DATA SOURCES: Articles were identified through MEDLINE for the period 1966 through November 2006. Abstracts and presentations from the American Diabetes Association Scientific Sessions and the European Association for the Study of Diabetes (2002-2006) were also searched for scientific reports on DPP-4 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Abstracts, original clinical and preclinical research reports, and review articles published in the English language were identified for review. Literature discussing glucose regulation, incretin hormones, type 2 diabetes pathophysiology, and DPP-4 inhibition were evaluated and selected based on consideration of their support for the proof of concept, mechanistic and in vivo findings, and timeliness. DATA SYNTHESIS: The search for new and effective therapies for type 2 diabetes has led to the identification of a novel therapeutic target, the incretin hormones, which play a role in mediating glucose homeostasis via effects on glucagon and insulin secretion from pancreatic islet alpha- and beta-cells, respectively. The incretins' glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitor agents act by blocking the active site of DPP-4, thereby preventing inactivation of and prolonging the duration of action of incretins, which in turn helps to correct the defective insulin and glucagon secretion that marks type 2 diabetes. Clinical studies to date indicate that DPP-4 inhibitors effectively stimulate insulin secretion, suppress glucagon release, and improve glucose control in patients with type 2 diabetes. These agents are well tolerated and have a low incidence of adverse effects. CONCLUSIONS: The DPP-4 inhibitors are novel agents for the treatment of type 2 diabetes. Compounds under development in this new class of oral antidiabetic drugs may be free of the limitations of current therapies.

Adenosine Deaminase↗
PubMed2006

Diabetes.

Explore the source record for details and available documents.

Blood Glucose↗
PubMed2006

Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus.

BACKGROUND: Exenatide is a subcutaneously injected incretin mimetic. It is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) who are already receiving therapy with metformin, a sulfonylurea, or both but continue to have suboptimal glycemic control. OBJECTIVE: This article reviews available information on the clinical pharmacology, comparative efficacy, tolerability, drug interactions, contraindications and precautions, dosage and administration, availability and storage, and cost of exenatide. METHODS: MEDLINE (1966-April 2006) and Web of Science (1995-April 2006) were searched for original research and review articles published in the English language. The search terms used were exenatide, exendin-4, glucagon-Like peptide-1, GLP-1, and incretin mimetic. The reference lists of identified articles were also consulted, as was selected information from the package insert for exenatide. All relevant comparative efficacy studies that were available in published form were included in the review. RESULTS: Naturally occurring incretins, such as glucagon-like peptide-1 (GLP-1), exhibit insulinotropic properties after release into the circulation from the gut. As a GLP-1 agonist, exenatide improves glucose homeostasis by mimicking the actions of naturally occurring GLP-1. It improves glycemic control by reducing fasting and postprandial glucose concentrations through a combination of known mechanisms, including glucose-dependent insulin secretion, restoration of first-phase insulin response, regulation of glucagon secretion, delaying gastric emptying, and decreasing food intake. Three Phase III comparative efficacy trials were identified that enrolled a total of 1,446 patients who received exenatide 5 pg SC BID, exenatide 10 mug SC BID, or placebo for 30 weeks in addition to their existing therapy with metformin, sulfonylurea, or both. In these trials, the addition of exenatide was associated with significant reductions in glycosylated hemoglobin (HbA(1c)) values (P < 0.001-P < 0.002), greater proportions of patients achieving an HbA(1c) 10% of patients receiving exenatide were hypoglycemia (19.6%), diarrhea (12.8%), and vomiting (12.8%). CONCLUSIONS: During clinical trials, exenatide added to existing metformin and/or sulfonylurea therapy in patients with T2DM reduced fasting and postprandial glucose concentrations, with improvements in HbA(1c) and modest weight loss. The main adverse effect associated with exenatide therapy was nausea.

Blood Glucose↗
PubMed2006

Pregabalin for the treatment of painful neuropathy.

Pregabalin is an alpha(2)-delta ligand that binds to and modulates voltage-gated calcium channels, exerting its intended effect to reduce neuropathic pain. Pregabalin is the second of only two medications that are US FDA approved for the treatment of neuropathic pain associated with diabetic peripheral neuropathy; it is also the third medication for the treatment of postherpetic neuralgia. Currently, there are three pivotal clinical studies documenting the efficacy and safety of pregabalin for the treatment of painful diabetic neuropathy, and three clinical studies regarding the use of pregabalin for pain associated with postherpetic neuralgia. This article will review each of these studies, as well as provide a clinical review for the use of pregabalin in the treatment of neuropathic pain.

Analgesics↗
PubMed2005

Phosphodiesterase 5 inhibitors for erectile dysfunction.

OBJECTIVE: To review the pharmacologic and clinical trial data of the Food and Drug Administration-approved phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction (ED). DATA SOURCES: Primary research and review articles were identified through a search of ScienceDirect, PubMed/MEDLINE, and International Pharmaceutical Abstracts (1990-August 2004). The following search terms were used in the Medicine Dentistry and Pharmacology, Toxicology, and Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5 inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil, prostatectomy, and diabetes. Web of Science (1990-August 2004) was used to search for additional abstracts using the same search terms as above. The package inserts for sildenafil, vardenafil, and tadalafil were also consulted. STUDY SELECTION AND DATA EXTRACTION: All identified research, review articles, and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports. DATA SYNTHESIS: ED is a common disorder in males with increased prevalence associated with age and presence of cardiovascular disease, prostatectomy, or diabetes mellitus. Sildenafil, vardenafil, and tadalafil are selective PDE5 inhibitors currently available for treatment of ED. Their pharmacology and pharmacokinetics vary slightly, but with potentially important clinical differences in duration of activity; all have similar clinical efficacy and adverse effect profiles in patients with ED of various causes. CONCLUSIONS: Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for the treatment of ED.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Diabetic neuropathy: an intensive review.

PURPOSE: The epidemiology, classification, pathology, and treatment of diabetic neuropathy are reviewed. SUMMARY: Diabetic peripheral neuropathy is a common complication of diabetes that can cause significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. Sensorimotor neuropathy is marked by pain, paresthesia, and sensory loss. Cardiac autonomic neuropathy (CAN) may contribute to myocardial infarction, malignant arrhythmia, and sudden death. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy. Genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder. The pathology of diabetic neuropathy involves oxidative stress, advanced glycation end products, polyol pathway flux, and protein kinase C activation; all contribute to microvascular disease and nerve dysfunction. For symptom management current evidence from clinical trials supports the use of desipramine, amitriptyline, capsaicin, tramadol, gabapentin, bupropion, and venlafaxine as preferred medications. Citalopram, nonsteroidal antiinflammatory drugs, and opioid analgesics may be used as adjuvant agents. Lamotrigine, oxcarbazepine, paroxetine, levodopa, and alpha-lipoic acid are alternative considerations. Evidence supporting the use of zonisamide, fluoxetine, mexiletine, dextromethorphan, and phenytoin is considered equivocal. Complementary therapies have also shown efficacy. The symptoms of CAN may be ameliorated with fludrocortisone, clonidine, midodrine, dihydroergotamine or caffeine, octreotide, and beta-blockers. Gastroparesis may be treated with metoclopramide or erythromycin. The most promising disease-modifying therapy is ruboxistaurin, which is in Phase III trials. Glycemic control remains the foundation of prevention and the prerequisite of adequate treatment. CONCLUSION: Diabetic neuropathy is a many-faceted complication of diabetes that can be managed symptomatically with an array of drugs.

Analgesics, Opioid↗
PubMed2003

Metformin hydrochloride in the treatment of type 2 diabetes mellitus: a clinical review with a focus on dual therapy.

BACKGROUND: Type 2 diabetes mellitus typically involves abnormal beta-cell function that results in relative insulin deficiency, insulin resistance accompanied by decreased glucose transport into muscle and fat cells, and increased hepatic glucose output, all of which contribute to hyperglycemia. OBJECTIVE: This review examines the pharmacology, pharmacokinetics, drug-interaction potential, adverse effects, and dosing guidelines for metformin hydrochloride, a biguanide agent for the treatment of type 2 diabetes. Clinical trial data are reviewed, including efficacy and tolerability information, with a focus on studies of dual metformin therapy (metformin plus another oral agent or insulin) published from 1998 to the present. Pharmacoeconomic considerations are also discussed. METHODS: Primary research and review articles were identified through a search of MEDLINE (1966-May 2003) and International Pharmaceutical Abstracts (1970-May 2003) using the terms metformin and/or Glucophage. Web of Science (1995-May 2003) was used to search for additional abstracts. The package inserts for metformin and metformin combination products were consulted. All identified articles and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports. RESULTS: Metformin is the only currently available oral antidiabetic/hypoglycemic agent that acts predominantly by inhibiting hepatic glucose release. Because patients with type 2 diabetes often have excess hepatic glucose output, use of metformin is effective in lowering glycosylated hemoglobin (HbA1c) by 1 to 2 percentage points when used as monotherapy or in combination with other blood glucose-lowering agents or insulin. Other metabolic variables (eg, dyslipidemia, fibrinolysis) may be improved with the use of metformin. Body weight is often maintained or slightly reduced from baseline. Metformin is well tolerated and is associated with few clinically deleterious adverse events. The most important and potentially life-threatening adverse event associated with its use is lactic acidosis, which occurs very rarely. CONCLUSIONS: Metformin has multiple benefits in patients with type 2 diabetes. It can effectively lower HbA1c values, positively affect lipid profiles, and improve vascular and hemodynamic indices. Adverse effects are generally tolerable and self-limiting. The availability of products combining metformin with a sulfonylurea or rosiglitazone has expanded the array of therapies for the management of type 2 diabetes.

Clinical Trials as Topic↗
PubMed2003

Biochemical pathways for microvascular complications of diabetes mellitus.

OBJECTIVE: To review the current biochemical theories on how diabetes contributes to microvascular disease. DATA SOURCES: MEDLINE search (1980-June 2003) and bibliographies of articles obtained on this topic. STUDY SELECTION AND DATA EXTRACTION: Articles identified from the data sources were evaluated and those deemed relevant to this review were incorporated. DATA SYNTHESIS: The prevailing biochemical theories on how diabetes leads to microvascular disease include increased polyol (sorbitol/aldose reductase) pathway flux, production of advanced glycation end-products, generation of reactive oxygen species, and activation of diacylglycerol and protein kinase C isoforms. These pathways contribute to endothelial damage and dysfunction and may alter gene functioning. CONCLUSIONS: Each pathway, via varied and often overlapping mechanisms, contributes to altered microvascular function that leads to the development of retinopathy, neuropathy, and nephropathy, the major microvascular complications associated with diabetes.

Animals↗
PubMed2003

Novel insulins and strict glycemic control. Analogues approximate normal insulin secretory response.

Our ability to gain strict glycemic control in diabetes has improved with the introduction of novel insulins. New formulations, novel insulin molecules, and various methods of insulin delivery are able to more closely approximate the normal physiologic insulin response than conventional preparations. In this article, the authors review the development of insulin formulations and the pharmacology of currently available insulin molecules and those soon to be on the market.

Humans↗
PubMed2002

Role of the pharmacist in diabetes management.

The role of pharmacists in diabetes management, including patient identification, assessment, education, referral, and monitoring, is described. Pharmacists can help identify patients with diabetes through screening and should target patients at high risk, people with a family history of the disease, and women with a history of gestational diabetes or who delivered a baby weighing more than nine pounds. Patient education should be provided immediately after diagnosis, at a second stage at which time a patient assessment can be performed, and at a third stage during which patients can receive continuing education to reinforce concepts and a motivational boost. One of the pharmacist's most important roles is the referral of patients to other members of the diabetes care team. Although the role of the pharmacist in monitoring diabetes is not well defined, it might include such things as ascertaining whether physician visits and testing to assess long-term glycemic control. Obtaining certification as a diabetes educator is recommended. This process requires at least 1000 hours of experience in providing disease-state management for patients with diabetes and successful completion of an examination. Implementing diabetes management services requires a commitment of time, effort, and resources and may necessitate training of staff and changes in work patterns. The pharmacist can play an important role in diabetes care by screening patients at high risk for diabetes, assessing patient health status and adherence to standards of care, educating patients to empower them to care for themselves, referring patients to other health care professionals as appropriate, and monitoring outcomes. Providing diabetes management services requires market savvy, communication skills, and a commitment of time, effort, and resources. Pharmacists who obtain training in diabetes management reap rewards in professional satisfaction and financial reimbursement.

Diabetes Mellitus↗
PubMed2002

Insulin glargine: a new basal insulin.

OBJECTIVE: To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine. DATA SOURCES: Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966-July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995-July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information. STUDY SELECTION AND DATA EXTRACTION: All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature. DATA SYNTHESIS: Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies. CONCLUSIONS: Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.

Amino Acid Sequence↗
PubMedDate not supplied

Assessing diabetes patients' healthcare needs.

Pharmacists who possess the proper skills and knowledge can intervene with patients in a proactive manner by initiating a dialogue at the point of dispensing medication. After patients complete the DPAQ and the pharmacist assesses the information, a plan of care is developed. Proper documentation (e.g., using the SOAP format) is the first and most important step in caring for patients with diabetes. Such encounters impact on the level of care provided and are professionally and financially rewarding for the pharmacist.

Delivery of Health Care↗
PubMedDate not supplied

Insulin lispro update.

PURPOSE: This paper provides a review of the literature and clinical studies for insulin lispro and updated information on its advantages over regular insulin for various populations of people with diabetes. METHODS: Information was gathered from a search of Medline articles and from review of clinical studies. RESULTS: Patients in various special populations using insulin lispro, with proper adjustment of basal insulin, had a greater reduction in hemoglobin A1C and fewer episodes of hypoglycemia than patients on regular insulin. CONCLUSIONS: More recently published literature shows that due to its faster onset and shorter duration of action, insulin lispro is useful for not only lowering A1C values, but also for reducing hypoglycemic events in various populations with diabetes, including pediatric and pregnant patients, those with gastroparesis, and insulin pump users.

Blood Glucose↗
PubMedDate not supplied

Counseling patients with type 2 diabetes and insulin resistance in the outpatient setting.

Insulin resistance is a major health concern. Besides being a leading risk factor for type 2 diabetes, it is also associated with hypertension, dyslipidemia, obesity, and cardiovascular disease. Making lifestyle changes can reduce insulin resistance and help prevent the onset of diabetes. For those with type 2 diabetes, treatment with insulin-sensitizing drugs, such as the TZDs and biguanides, can improve glycemic control and prevent some of the adverse consequences of the disease. Adherence to both lifestyle and medication regimens is very important and should be actively supported by all members of the healthcare team. Diabetes educators, including pharmacists, can increase awareness of the underlying pathophysiology and clinical implications of insulin resistance. Diabetes educators also play a vital role in counseling patients with type 2 diabetes on strategies that reduce their risk of hyperglycemic complications and in providing support, education, and guidance. By understanding the disease and its management, diabetes educators can contribute to improved outcomes and help to reduce the impact of this worldwide epidemic.

Aging↗
PubMedDate not supplied

Insulin therapy in type 2 diabetes.

OBJECTIVE: To review the increasingly common use of insulin therapy in patients with type 2 diabetes and the practical aspects of initiating insulin therapy in these patients. DATA SOURCES: Recent scientific and clinical literature identified through MEDLINE searches for the years 1995-2001 using the terms oral agents, type 2 diabetes, insulin therapy, glycemic control and diabetic complications, glucose toxicity, insulin lispro, insulin aspart, and insulin glargine. STUDY SECTION: Reports of key large (1,000 patients or more) and significant smaller, randomized, controlled clinical trials were reviewed. For studies comparing insulin analogs, the authors reviewed a sampling of the identified trials for their characteristics and clinical importance. DATA SYNTHESIS: Tight blood glucose control can help reduce the risk of diabetes complications. Evidence suggests that early insulin therapy can help correct the underlying pathogenetic abnormalities in type 2 diabetes and improve long-term glycemic control. For these reasons, some diabetes experts advocate the initiation of insulin therapy earlier in the course of type 2 diabetes than has been common in the past. Insulin regimens should be designed to mimic the body's natural physiologic secretion of insulin, including the basal amounts released continuously by the pancreas and the insulin surges produced in response to glucose loads. Using new insulin analogs is a useful approach to achieving this ideal. Insulin glargine provides a nearly constant, peakless release of insulin when injected subcutaneously once daily. Two new rapid-acting insulin analogs, insulin lispro (Humalog--Lilly) and insulin aspart (NovoLog--Novo Nordisk), enhance patients' flexibility in terms of meals by permitting injection immediately before meals, rather than 30 minutes before meals, as with regular insulin. CONCLUSION: Patients should be reassured that early initiation of insulin therapy is a positive event that should improve their long-term health and does not represent a decline in the course of their disease.

Amino Acid Sequence↗
PubMedDate not supplied

Unraveling the mysteries of syndrome X. As the number of Americans with insulin resistance grows, pharmacists can help patients prevent the onset of type 2 diabetes and cardiovascular disease.

The prevalence of insulin resistance and type 2 diabetes is rapidly increasing, primarily because of rising rates of obesity and physical inactivity. Insulin resistance syndrome is a metabolic disorder that often leads to a cluster of serious clinical conditions, including type 2 diabetes and cardiovascular disease. Optimal management of diabetes requires not only tight glycemic control but also stringent management of cardiovascular risk factors. Because of their ready access to patients, pharmacists are well positioned to help detect and manage the many conditions associated with insulin resistance.

Cardiovascular Diseases↗