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Kareus Therapeutics has an active diabetes program targeted to treat insulin resistance and the underlying cardiovascular disease.
Based on the latest figures from the International Diabetes Federation about 366 million people worldwide have diabetes; up from 300 million estimated in 2009. In animal models of diabetes and insulin resistance, KU-5039 demonstrated robust insulin sensitization and glucose lowering within one week. Insulin resistance (IR) is the condition in which normal amount of insulin gives inadequate biological response. Kareus Therapeutics has identified a novel series of orally available insulin sensitizers with potential CV benefits. AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular AMP-to-ATP ratio. Content in this special section was created or selected by the Everyday Health editorial team and is funded by an advertising sponsor. As treatment options evolve, keeping your blood sugar under control is becoming safer and easier. Thanks to the latest generation of diabetes treatments, there are entirely new approaches to treating type 2 diabetes. People with type 2 diabetes have elevated blood sugar (glucose) levels because their bodies can’t make enough insulin or process it the way they should to keep their blood sugar at healthy levels.
The first diabetes drugs, such as injected insulin and sulfonylureas, attacked the problem by increasing the amount of insulin in the body to help control blood sugar. For example, one of the most popular traditional types of diabetes drugs, biguanides, works by reducing the amount of glucose produced by the liver and increasing insulin sensitivity.
And unlike sulfonylureas, which can trigger weight gain in some people with diabetes, SGLT2 inhibitors can promote weight loss.
However, because SGLT2 inhibitors increase the amount of sugar in urine, they can also increase the chance of bladder and yeast infections and can make people thirstier, says Celia Levesque, RN, a certified diabetes educator and an advanced practice nurse at the University of Texas MD Anderson Cancer Center in Houston. Two new classes of diabetes treatments that work in a similar manner are DPP-4 inhibitors and GLP-1 receptor agonists and are available only by injection.
An advantage of these drugs is that they can also promote weight loss, which can help with diabetes management. Like other new classes of diabetes medications, incretin mimetic drugs can help promote weight loss. Cagliero says that, in some cases, these new diabetes treatments are less powerful than older diabetes drugs. This post is an overview on calcium channel blockers, in this first part we will discuss their classification, mechanism of action as well as clinical indications. Phenilalkylamines: verapamil is the only drug in this group, it binds to the V binding site.
Dihydropyridines: the prototype agent in this group is nifedipine, a first generation dihydropyridine that binds to the N binding site. Calcium channel antagonists block the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature. Dihydropiridines have minimal effect on cardiac conduction or heart rate, while they have potent actions as arteriolar vasodilators.
On the other hand, verapamil and diltiazem slow AV conduction and decrease SA node automaticity, they also decrease heart rate.
CCB’s  effectiveness in the treatment of hypertension is  related to a decrease in peripheral resistance accompanied by increases in cardiac index. CCB are also useful in the treatment of hypertensive patients with comorbidities such as: asthma, diabetes, angina, ond or peripheral vascular disease.
Calcium channel blockers act as coronary vasodilators, producing variable and dose-dependent reductions in myocardial oxygen demand, contractility, and arterial pressure. In the presence of heart failure, the use of calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Verapamil and diltiazem are class IV antiarrhythmics, according to Vaughan and Williams’ classification of antiarrhythmic drugs. Calcium channel blockers act as coronary vasodilators, producing variable and dose-dependent reductions in myocardial oxygen demand, contractility, and arterial pressure. In the presence of heart failure, the use of calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. European Association for the Study of Diabetes (EASD) estimates 4.6 million deaths from the disease annually. IR is the underlying defect in >90% of patients with type 2 diabetes mellitus and is the key pathologic mechanism for associated susceptibility to premature cardiovascular disease (CVD).
The content is subject to Everyday Health’s editorial standards for accuracy, objectivity, and balance.
People with diabetes and their doctors now have the opportunity to customize diabetes treatment plans to best manage blood sugar and reduce the risk of complications because of several new classes of recently approved diabetes medications. The goal of type 2 diabetes treatment is to keep blood sugar under control to reduce the long-term risk of complications from the disease, such as heart disease, kidney failure, and blindness. As researchers have learned more about how the body processes glucose, new diabetes treatments have emerged. The latest diabetes treatments take that approach one step further by targeting glucose metabolism in the kidneys and other organs. This class of oral medications blocks absorption of glucose in the kidneys and allows it to be removed from the body in urine.
They breakdown an enzyme called GLP-1, which is produced by the pancreas to regulate glucose in the body. Side effects of the drugs include nausea and low blood sugar, especially when used in conjunction with a sulfonylurea medication.
These medications mimic incretin hormones normally produced by the body to trigger the release of insulin after eating. Diltiazem is used in the treatment of variant angina because of its coronary antispasmodic properties. These combined pharmacologic effects are advantageous and make these agents as effective as beta blockers in the treatment of angina pectoris. These combined pharmacologic effects are advantageous and make these agents as effective as beta blockers in the treatment of angina pectoris.


Global diabetes market was over $24B in 2008 and the top ten products generated $21 billion sales. The molecule exhibited rapid absorption, high oral bioavailability (>75%), good plasma exposure levels and low clearance across species. In long-term follow-up of patients with type 2 diabetes, IR is an independent predictor of CVD. An advantage of SGLT2 inhibitors versus older diabetes treatments is that they're not associated with hypoglycemia, where the blood sugar becomes too low.
These drugs also help suppress the liver’s glucose output to keep blood sugar under control.
Food and Drug Administration is investigating a possible link between these drugs and inflammation of the pancreas and precancerous changes in the pancreas. They also decrease cardiac contractility (negative inotropic effect) ,automaticity at the SA node and conduction at the AV node. They are indicated when beta blockers are contraindicated, poorly tolerated, or ineffective. Their ability to inhibit the AV node is employed in the management of supraventricular tachyarrhythmias, such as: atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia. They are indicated when beta blockers are contraindicated, poorly tolerated, or ineffective. In the setting of the ongoing proliferation of anti-hyperglycaemic therapeutic classes and formulations with myriad therapeutic options for the treatment of T2DM presently available,2 this uncertainty has prompted regulatory agencies in both Europe and the USA to reassess the approval process for new T2DM medications, with changes focused primarily on excluding with a specified degree of statistical certainty incremental CV risk prior to new drug approval.3 Long-term randomized clinical outcome trials with both new and presently available medications are recommended, but not mandated. Despite accessibility of many agents (insulin, sulfonylureas, TZDs and biguanides), many patients (~40%) fail to achieve long term glycemic goals.
One unit increase in IR, assessed by homeostasis model, is associated with a 5.4% increase in risk for CVD.
In liver, activation of AMPK leads to inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In the absence of definitive CV risk assessment from randomized trials for presently available drug classes and individual drugs within each class, critical analyses of existing databases are both imperative and informative.In this context, Schramm et al. In addition, although hyperglycemia is the primary risk factor for microvascular complications; cardiovascular disease remains the major cause of death in diabetics. Many anti-diabetic drugs in market do not have any insulin sensitization effect and do not offer protection for diabetic CVD.
In addition, activation of AMPK pathway plays an important role in the myocardial response to ischemia, pressure overload, and heart failure and pharmacological activation of AMPK shows promise as a therapeutic strategy in the treatment of heart disease.
Analysts reviewed medication-error events mentioning students submitted to the Pennsylvania Patient Safety Authority from July 2010 through June 2015. Insulin resistance and inflammation may be the key contributing factors to cardiovascular diseases in diabetics.
Although TZD class of drugs (pioglitazone and rosiglitazone) show insulin sensitization their major site of action is adipose, thus induce weight gain and edema. The overall results of the study suggest that most but not all insulin secretagogues (sulphonylureas and meglitinides) are associated with worse outcomes compared with metformin.
Analysts also found that students caught or discovered the error in 16.2% (n = 115) of reports. Tolbutamide, glibenclamide (known as glyburide in the USA and Canada), glipizide, and glimepiride were all associated with significantly increased mortality and CV risk compared with metformin, but outcomes with gliclazide and repaglinide were not statistically different from those with metformin.In interpreting these data, it is of key importance to note that the observation of less benefit with most sulphonylureas in the study compared with metformin should not be interpreted as causing harm. The most common node of origin for the medication error was administration (75.9%, n = 540). Given the fact that metformin has an estimated risk reduction of ?40% for major adverse cardiac events and death compared with placebo,5 when comparing outcomes associated with other drugs against metformin, hazard ratios of up to 1.7 would suggest treatment effects similar to or better than placebo, especially when considered in the context of favourable effects on microvascular disease risk associated with improved glucose control. Therefore, beyond the direct comparisons with metformin of each secretagogue, the most important and novel finding of the present study is the variability of the estimates of hazard associated with individual insulin secretagogues, suggesting that some may be better than others with regard to the outcomes assessed.
High-alert medications, including insulin, opioids, and anticoagulants, were reported in 40.9% (n = 291) of events. Of course, as noted by the investigators, such interpretations are limited by the non-randomized observational nature of the present analyses deriving from an administrative database, with some variance in the propensity to prescribe the specific secretagogues analysed that may confound associations beyond the ability to adjust completely for differences in patient mix between the secretagogue groups.
The apparent paradox of superior outcomes with metformin, a drug with modest glucose-lowering properties, compared with sulphonylureas that are approximately twice as potent raises the possibility that some benefit of glucose control with sulphonylureas may be offset by adverse effects of the drugs.Sulphonylureas are the oldest non-insulin drug class presently available for the treatment of T2DM, having been used for more than half a century.
In 1971, the University Group Diabetes Project (UGDP) randomized trial reported increased CV and all-cause mortality with tolbutamide, a first-generation sulphonylurea,6 prompting early termination of that arm of the trial and modification of the US product label to include a ‘special warning on increased risk of CV mortality’. Direct patient-care experiences are vital for students to prepare for the real world.1-2 This hands-on experience places them in a position to be involved in errors as well as catch potential or actual errors. Gliclazide, glipizide, and glimepiride were deemed preferable, the use of chlorpropamide and glibenclamide (glyburide) was discouraged explicitly because of their greater risk of hypoglycaemia and prolonged pharmacodynamic effects, and the use of other sulphonylureas was discouraged implicitly by omission. Students ranging in experience from first-year healthcare students to students in their final year before graduation will be involved, either directly or indirectly, in the care of patients in Pennsylvania.
However, in the absence of data on clinical trial mortality and CV disease outcomes, these specific recommendations remain grounded primarily on clinical judgement. Pennsylvania Patient Safety Authority analysts have not previously explored the role students play in contributing to and intercepting medication errors reported through the Authority’s Pennsylvania Patient Safety Reporting System (PA-PSRS). This analysis identified events that mention the involvement of students, including those that reached the patient, and some in which the student detected the error.MethodsAnalysts queried the PA-PSRS database for medication errors that occurred from July 2010 through June 2015 that included the word “student” in the narrative. Drug binding leads to inhibition of K+ efflux and triggers a cascade of intracellular events resulting in increased insulin release, independent of circulating glucose concentrations.
Events that included students but also mentioned that the instructor was involved in an error were included in the analysis.
Impaired ischaemic pre-conditioning is a potential explanation for the increased myocardial infarction case-fatality rate in patients treated with sulphonylureas in some studies;13,14 however, this remains highly speculative and has not been supported by other analyses. Of course, apparently conflicting data from clinical studies could be attributable to the use of different sulphonylureas, further underscoring the importance of considering individual drugs rather than the entire drug class in future analyses.
The medication name, route of administration, patient care area, and harm score, adapted from the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) harm index,10 were provided by the reporting facility. For example, the increased mortality signal observed in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial15 associated with more intensive glucose control leading to early termination of the study was not observed in the similarly designed Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial,8 with glyburide as the most prevalent sulphonylurea used in ACCORD and gliclazide prescribed by study protocol in ADVANCE.
When a medication-name data field was left blank but the name was provided in the event description, an analyst adjusted the medication name field. The reports were evaluated to determine the factors associated with medication errors involving students.


Sulphonylureas bind to sulphonylurea receptor proteins (SURs), subunits of the hetero-octameric ATP-sensitive K+ (KATP) channels. Analysts classified reports by the type of student involved, node of origin, presence of the instructor, and whether the student caught or was involved in the error.
Drug binding inhibits KATP channel-mediated K+ efflux, triggering a cascade of events leading to glucose-independent insulin release from pancreatic ?-cells, but also to impaired ischaemic pre-conditioning in cardiac myocytes. KATP channel inhibition in other cells and tissue types may also contribute to the overall effects of individual sulphonylureas. Overall, 63 unique patient care areas were associated with student-involved events and event reports; the most common areas are shown in Table 1.
The most common nodes of origin for the reported events, as identified by the analysts, are shown in Figure 2.  Figure 1. The study by Schramm et al.4 once again highlights the high degree of clinical uncertainty that exists regarding the CV effects of presently available drugs, underscoring the importance of the recent shift in regulation towards requiring CV assessment of emerging glucose-lowering therapies.
Harm Scores for Student-Related Medication Errors,  as Reported to the Pennsylvania Patient Safety Authority,  July 2010 through June 2015 (N = 711)   Table 1.
Care Areas Most Commonly Reported in   Student-Related Medication Errors, as Reported to  the Pennsylvania Patient Safety Authority,  July 2010 through June 2015 (N = 711)  Figure 2.
Student nurse and instructor relied on paper MAR [medication administration record], which did not reflect medication signed off as given, without checking the computer system to determine if medication had previously been given. Upon further investigation, found students do not have access into the computer system, they work directly under the supervision of their instructor. Cardiovascular disease and type 2 diabetes mellitus: regulating glucose and regulating drugs.
Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study.
After seeing this syringe, the student indicated that he gave the prior patient the wrong dose using a 100-unit syringe. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
Student-Related Medication Error Events by Month,  as Reported to the Pennsylvania Patient Safety Authority,  July 2010 through June 2015 (N = 711) The majority of students involved in errors were nursing students (see Table 2).   Table 2. Type of Student Identified in Student-related Medication  Error Reports, as Reported to the Pennsylvania Patient Safety Authority,  July 2010 through June 2015 (N = 711)Nearly 4% (n = 28) of reports did not involve students, but rather involved instructors. Following are examples of events involving instructors and nursing or pharmacy students:Nursing instructor removed the wrong patient’s medication and tubing from the patient medication bin, and the student nurse scanned the dose [barcode], flushed the syringe pump tubing, and connected the Rocephin® (cefTRIAXone) dose to the IV. Instructor noted the wrong patient name on another medication removed from bin and stopped the Rocephin [infusion].
Both patients were receiving same dose of Rocephin.One Percocet® [oxyCODONE and acetaminophen] tablet was given to the wrong patient by an unattended nursing student. The patient was confused and unable to communicate that she received duplicate medications.Patient told pharmacy student that she was taking fluticasone nasal spray. Pharmacy student accidentally logged fluticasone as fluticasone 50 mcg inhalation powder instead of the nasal spray.
When a healthcare professional student was found to have been involved in the error, the instructor or preceptor was noted to be involved or present 28.9% of the time (n = 164 of 568).
In the subset of nursing students, instructors were commonly present when these students were involved in medication errors (92.1%, n = 151 of 164).
Following are examples of reports of student-involved events:Patient received medication in error. Patient medicated improperly by nursing student working under this RN’s supervision.Nursing student documented giving oxyCODONE but the documentation was not co-signed by the instructor. A pharmacy student was on the team and identified the dosing error prior to the patient getting the second dose and therefore the patient received the appropriate amount based on renal status.
Patient had no harm.DiscussionAlthough healthcare students may not intend to harm a patient, they are sometimes involved in medication errors that require intervention.
When the preceptor is with another student, the responsibility of supervision often falls to the staff nurse.3 This responsibility, added to typical patient care responsibilities, may create situations in which direct student supervision may not be realistic. Communication breakdowns regarding who will administer the prescribed medications, what medications have been administered, and which medications should be held, have resulted in dose omissions and the administration of extra doses.
Communication between students, nursing instructors, and facility staff needs to be planned carefully to ensure a model that considers the safety hazards associated with dual assignments.15 Numerous additional conditions exist in the hospital setting that may contribute to medication errors involving students.
A few include communication and documentation issues, monitoring issues, preparing drugs for multiple patients, and medication administration records (MARs) not referenced.12,15-16 Improper or limited access to the electronic health record (EHR) may limit students’ ability to read about or document patient-care activities.
As with all reporting systems, the type and number of reports collected depend on the degree to which facility reporting is accurate and complete.
The reporting cultures and patterns in each facility, and their interpretations of what occurrences are reportable, can lead to reporting variations.Risk Reduction StrategiesProfessional organizations, healthcare facilities, and professional schools can strive to identify system-based causes of errors involving healthcare students and instructors and implement effective types of risk-reduction strategies to prevent harm to patients. Verbally confirm actions of medication administration in presence of instructor or preceptor. Ensure that staff complete documentation in a timely fashion if students are involved in patient care.
Design healthcare professional education programs to include multidisciplinary clinical simulation training before clinical rotations to develop the ability to work in teams and reduce medication errors.3,4,18 Establish an orientation and training process for students and faculty. Enhancing patient safety: the importance of direct supervision for avoiding medication errors and near misses by undergraduate nursing students.
Characteristics of medication errors made by students during the administration phase: a descriptive study. Effect of pharmacy students as primary members on inpatient interdisciplinary mental health teams.
Standards for accreditation of baccalaureate and graduate degree nursing programs [online].



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Teaching care plan for diabetes type 2 diabetes
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