Life-Threatening Hyperkalemia from Cream of Tartar Ingestion

Introduction

Cream of tartar (potassium bitartrate) has a long history as a cooking aid and medicinal purgative. Despite containing large amounts of potassium, there are no well-documented cases of it causing toxicity. We report two cases in which intentional ingestions of cream of tartar resulted in life-threatening hyperkalemia. In addition, we briefly review the use of cream of tartar as a historical purgative.

Case Reports

In both cases, individuals ingested a large quantity of cream of tartar in an effort to “clean themselves out”. They manifested similar initial symptoms (vomiting), abnormal serum potassium (>8.0 mmol/L), and EKG’s with peaked T waves. Both patients were treated for hyperkalemia and recovered without complication. A search for articles on an academic internet database failed to identify any cases specifically dealing with ill effects of potassium bitartrate and numerous websites continue to purport its beneficial health effects.

Conclusion

Ingestion of cream of tartar can potentially result in life-threatening hyperkalemia.     

Acute Oral Potassium Overdose: The Role of Hemodialysis

Introduction

Hyperkalemia is a common condition, particularly in the setting of renal dysfunction. Hyperkalemia due to intentional oral potassium overdose is not commonly reported.

Case Report

We present a case of acute intentional potassium overdose in a patient with normal renal function resulting in significant hyperkalemia, with a maximum serum potassium concentration of 11 mEq/L. Despite an initial course complicated by various unstable cardiac rhythms, including ventricular tachycardia, ventricular fibrillation, and pulseless electrical activity, the patient was discharged from the hospital neurologically intact. Treatment for hyperkalemia included hemodialysis.

Discussion

The role of dialysis in potassium overdose is poorly defined.

Conclusion

Based on this case and a review of the medical literature, we recommend hemodialysis for cases of potassium overdose with hemodynamic instability and significantly elevated serum potassium concentrations that do not respond promptly to medical therapy. Hemodialysis should also be considered in cases with underlying renal dysfunction.     

Comparison of Hyperkalemic Risk in Hospitalized Patients Treated with Different Angiotensin Receptor Blockers

Background and Aim

Clinical use of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) is associated with hyperkalemia as an adverse drug reaction. Although it has significant clinical implications, the incidence and relative risks of hyperkalemia with various ARBs have not yet been fully evaluated. The purpose of this study was to determine the risk of hyperkalemic events in hospitalized patients treated with different ARBs and to compare the risk among them.

Methods

We constructed a retrospective cohort composed of hospitalized adult patients who took ARBs in a single tertiary teaching hospital between April 2004 and March 2010. We estimated the incidence of hyperkalemia (serum potassium level >5.5 mEq/L) with various ARBs, and then compared the risk between them using a multivariate Cox proportional hazard model based on age, sex, Charlson co-morbidity score, baseline serum potassium, underlying diseases, and concomitant drugs.

Results

We identified 6992 evaluable intervals from 5449 patients treated with one of the seven ARBs during hospitalization over the 71-month study period with 2521.6 patient-months. We found 381 hyperkalemic events (5.4%) during the study period and an overall event rate of 15.1/100 patient-months. Moderate to fatal hyperkalemia was relatively rare (>6.0 mEq/L, 2.1% [moderate]; >6.5 mEq/L, 0.9% [severe]; >7.0 mEq/L, 0.3% [fatal]). After adjustment for covariates, telmisartan showed a lower risk of hyperkalemia (hazard ratio 0.67; 95% confidence interval 0.51, 0.89) compared with all other ARBs.

Conclusion

The risk of hyperkalemic events in hospitalized patients treated with different ARBs was defined. Telmisartan showed a relatively lower hyperkalemic risk profile in hospitalized patients compared with other ARBs.     

Drug-induced life-threatening potassium disturbances detected by a pharmacovigilance program from laboratory signals

Purpose

Detection and reporting of drug-induced life-threatening potassium disturbances and the study of associated factors under a Pharmacovigilance Program using Laboratory Signals at a Hospital (PPLSH) during a 2-year period.

Methods

All serum potassium levels <2 mmol/l or >7 mmol/l detected at admission to the hospital, including those of patients who died in the emergency ward or during hospitalization, were monitored prospectively from January 2009 through to December 2010. The incidence rate of each etiology of potassium disturbances was calculated. Factors associated with drug-induced potassium disturbances were detected using a multiple logistic regression model.

Results

The incidence of true life-threatening drug-induced hyper- and hypokalemia events was 3 and 4.32 (Poisson 95 % confidence interval 1.62–10.24), respectively, per 10,000 admissions. Of the severe potassium disturbances, 32.3 % were drug-induced, and 23 % were lethal. We identified previously undescribed pharmacological causes of hyperkalemia (risedronate, doxazosin) and hypokalemia (acyclovir, teicoplanin, cefepime, meropenem, dexketoprofen colistimethate). Significant predictor factors associated with drug-induced hyperkalemia were the use of polypharmacy (>5 drugs), age (>74 years), sex (female) and kidney disease (glomerular filtration rate <60 ml/min) with the presence of ≥4 comorbid conditions. The only predictor of drug-induced hypokalemia was the use of >5 drugs. The triggering factor associated with drug-induced hyperkalemia and hypokalemia was azotemia and hypoalbuminemia, respectively.

Conclusions

Drug-induced life-threatening potassium disturbances remain a relevant problem. Potential strategies for prevention are to avoid polypharmacy, early discontinuation of treatment of drugs causing hyperkalemia or nephrotoxicity in cases of various clinical situations (cardiac descompensation, infection, hypovolemia) or obstructive causes, and insistence on albumin control during hospitalization.     

Local and systemic immune responses in gingivitis and periodontitis

Objective

The aim of this study was to determine the effect of gingivitis and periodontitis on white blood cell (WBC) count and differential WBC count in gingival microvascular blood (GMB) and in venous blood (VB).

Material and methods

102 systemically healthy adult patients — 32 with gingivitis, 36 with periodontitis, and 34 controls — underwent evaluation of the total WBC count, and the count of different types of WBC in VB and GMB.

Results

Inflammation of periodontal tissues was persistently associated with a systemic (in VB) elevation of the WBC count (p<0.05 in gingivitis and p<0.01 in periodontitis), compared to that in control group subjects, and with elevated systemic and local lymphocyte counts (p<0.05), compared to the analogous cell count in the control group. Patients with periodontitis were found to have reduced polymorphonuclear leucocyte (PMN) counts in GMB, compared to patients with gingivitis.

Conclusion

Persistent chronic bacterial infection affects the systemic elevation of WBC in subjects with gingivitis and periodontitis. A local decrease in PMN in periodontitis patients and a systemic increase in lymphocytes in gingivitis and periodontitis patients may indicate the inability of these patients’ organisms to defend against periodontopathic bacteria — and thus susceptibility to disease.     

Cardioactive steroid poisoning: A comparison of plant- and animal-derived compounds

Introduction

Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+−K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides. A systematic review of CAS poisoning was performed to compare the mortality rate of cardenolides and bufadienolides.

Methods

MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.

Results

Fifty-nine articles, describing 924 patients, were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a 5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n = 8). The difference in mortality rates was statistically significant (p < 0.001, [X²]). CASs with 6-member rings accounted for the highest percentage of nonsuicidal exposures.

Conclusion

Although cardenolides accounted for the majority of exposures, bufadienolides were five times more lethal than cardenolides.     

Diagnostic value of serum tumor markers for adnexal masses

Objective

The study aim was to investigate the diagnostic value of measuring preoperative serum tumor markers in patients with adnexal masses.

Methods

The study included all (358) consecutive patients treated for adnexal tumors at the Clinic of Obstetrics and Gynecology, Clinical Center of Serbia during 12 months. Tumor-marker levels (Ca 125, CEA, HE 4, Ca 19.9 and Ca 15.3) obtained from all women on admission were compared with histopathological findings in cases in which tumors were removed.

Results

Women with malignant tumors had the highest levels of Ca 125, CEA and HE 4 (p<0.01). Mucinous adenocarcinoma produced the highest amounts of Ca 19.9 and CEA. Ca 15.3 was the highest in women with endometrioid carcinoma. There were no significant differences in the levels of all serum tumor markers between women with benign and borderline tumors (p>0.05). Malignant forms of tumors were well indicated by Ca 125, HE 4 and Ca 15.3 levels. The combination of Ca 125 and HE 4 resulted in the highest sensitivity, specificity, and positive or negative predictive value (91.04%, 87.6%, 67.9%, 77.2%, respectively).

Conclusions

Blood levels of tumor markers can be effective? predictors of the nature of adnexal masses. For the most precise evaluation, a combination of serum tumor markers should be used.     

Effect of testosterone replacement or duration of castration on baroreflex bradycardia in conscious rats

Background

In this study, we tested the hypothesis that 17β-estradiol contributes to testosterone-mediated restoration of baroreflex-mediated bradycardia in short-term (3 weeks) castrated rats. Further, a reported increase in serum testosterone after long-term (6 weeks) castration constituted a basis for testing the hypothesis that a spontaneous increase in serum testosterone or androstenedione in this model causes a commensurate increase in baroreflex-mediated bradycardia.

Results

Testosterone (1 week) replacement enhanced baroreflex-mediated bradycardia in short-term castrated rats without changing 17β-estradiol level. A spontaneous recovery of baroreflex-mediated bradycardia occurred following long-term castration, although circulating testosterone and androstenedione remained suppressed.

Conclusion

The data suggest: 1) 17β-Estradiol does not contribute to testosterone restoration of the baroreflex-mediated bradycardia in short-term castrated rats. 2) The long-term modulation of baroreflex-mediated bradycardia occurs independent of androgens, or the baroreflex mechanism may become adapted to low levels of circulating androgens.     

Complications of Oral Exposure to Fentanyl Transdermal Delivery System Patches

Purpose

Fentanyl is a synthetic opioid available therapeutically as an intravenous, transbucal, or transdermal preparation. It is also used as a drug of abuse through a variety of different methods, including the oral abuse of transdermal fentanyl patches. This is a series of patients with oral fentanyl patch exposure reported to our center and represents the first series of oral fentanyl patch exposures collected outside of the postmortem setting.

Methods

In this series, we examined the New York Poison Control Center database for all cases of oral abuse of fentanyl reported between January 2000 and April 2008.

Results

Twenty cases were reported, nine were asymptomatic or had symptoms of opioid withdrawal; 11 had symptoms of opioid intoxication. Eight patients were administered naloxone and all showed improvement in clinical status. Only one case resulted in a confirmed fatality—this patient had an orally adherent patch discovered at intubation.

Conclusions

Oral exposure may result in life-threatening toxicity. Patients should be closely assessed and monitored for the opioid toxidrome, and if symptomatic, should be managed with opioid antagonists and ventilatory support.     

The Toxicology Investigators Consortium Case Registry—The 2010 Experience

Introduction

The American College of Medical Toxicology Case Registry was established in 2010 as a method of identifying cases cared for by medical toxicologists at participating institutions. The Registry allows for the extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. The current report is a summary of the data collected in 2010.

Methods

All cases seen by medical toxicologists at participating institutions were entered on a database. Information characterizing patients entered in 2010 was tabulated.

Results

Over the course of 2010, the number of institutions contributing cases grew from 4 to 50. Three thousand nine hundred forty-eight cases were entered. Emergency departments were the most common source of consultations, accounting for approximately 50% of the cases. The most common reason for consultations was for pharmaceutical overdoses, which occurred in 42% of the patients. The most common classes of agents were non-opioid analgesics (14%), sedative/hypnotics/muscle relaxants (10%), ethanol (8%), and opioids (8%). N-acetylcysteine was the most common antidote used, followed by opioid antagonists, sodium bicarbonate, and physostigmine. Anti-crotalidae Fab fragments were administered in 72% of the cases in which an antivenin was used. Signals were detected suggesting the possibility that amlodipine and metoprolol were associated with greater toxicity than had been previously recognized.

Conclusions

The Registry can identify and characterize patients who have sufficient toxicity to require a consultation by a medical toxicologist. Hypotheses for further investigation emerged from the data. The Registry appears to be a potentially powerful tool for toxicovigilance and research.     

Dermal Exposure to a Compounded Pain Cream Resulting in Severely Elevated Clonidine Concentration

Introduction

Clonidine is an imidazoline derivative antihypertensive medication that is also used as adjunctive therapy for neuropathic pain disorders via topical administration. Clonidine overdose can manifest both central and peripheral alpha-adrenergic agonist effects.

Case Report

A 23-year-old man presented to an emergency department with altered mental status, bradycardia, and hypertension after suspected overdose. He had rubbed a specially compounded medicinal cream over his entire body containing clonidine 0.2 % (w/w), gabapentin 6 %, imipramine 3 %, ketamine 10 %, lidocaine 2 %, and mefenamic acid 1 %. The patient presented with severe hypertension, bradycardia, and altered mental status. He was found to have a subarachnoid hemorrhage and was treated for hypertensive emergency. Toxicological analysis of initial blood samples revealed a serum clonidine concentration of 5,200 ng/ml. At 6-month follow-up, the patient had made a full recovery.

Discussion

There are limited reports of topical clonidine toxicity, and to our knowledge, this case involves the highest concentration yet reported following clonidine overdose by any route of exposure. The severely elevated serum clonidine concentration found in our patient demonstrates the possibility of toxicity resulting from inappropriate use of such a product. At high serum concentrations, the pharmacodynamic effects of clonidine appear to cause significant peripheral alpha-1 adrenergic stimulation. Toxicologists should be aware of the increasing use of topical clonidine preparations for the treatment of neuropathic pain and the potential for toxicity.     

Retrospective Review of Digoxin Exposures to a Poison Control System following Recall of Digitek® Tablets

Background

In April 2008, Digitek® digoxin tablets were recalled by the manufacturer as possibly containing double the labeled amount of drug. The recall to March 2006 involved 800 million tablets.

Objective

The aim of this study was to evaluate whether there was any increase in the number of calls to a poison control system, and any increase in the severity of exposures after the recall compared with before the recall.

Methods

A retrospective review of all digoxin exposures to a poison control system from March 2004 to February 2008 was conducted, with data extracted from an electronic database (California Poison Control System). Total numbers of exposures were identified. Cases with moderate, major, and death outcomes were also identified and tallied. Chi-squared analysis was performed.

Results

Prior to the recall, there were 679 digoxin exposures. 148 (22%) were listed with moderate, major, or death as outcome. After the recall, there were a total of 610 cases, 165 (27%) with moderate, severe, or death as outcome. There was a statistically significant increase in the total number of moderate, major, and death outcomes after the period of the manufacturing error compared with before (p = 0.028).

Conclusion

During the period of manufacturing error, there was a statistically significant increase in digoxin exposures with moderate, major, or death outcomes. The recall of Digitek® tablets may have increased moderate, major, or death outcomes from digoxin exposures in a poison control system database.     

Increased aortic stiffness in ulcerative colitis

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Currently, there is an increased scientific interest in the evaluation of early functional vascular alterations, especially in inflammatory disorders. The present study was aimed to examine whether UC is associated with abnormalities in aortic elasticity.

Methods

The study was comprised of 11 UC patients (mean age 39 ± 12 years, 7 males), their results were compared to 22 age- and gender-matched controls. All subjects underwent a complete two-dimensional transthoracic Doppler echocardiography including evaluation of aortic elastic properties. The oscillometry-based Arteriograph device was used in all cases to measure aortic pulse-wave velocity (PWV) and augmentation index (Aix).

Results

Despite similar blood pressure values, aortic stiffness index, PWV and Aix were significantly increased, while pulsatile change in aortic diameter, aortic strain and aortic distensibility were significantly decreased in UC patients compared to controls.

Conclusion

Abnormal echocardiographic aortic elastic properties and Arteriograph-derived pulse-wave velocity could be demonstrated in patients with ulcerative colitis.     

Efficacy and Safety of Fenofibric Acid Co-Administered with Low- or Moderate-Dose Statin in Patients with Mixed Dyslipidemia and Type 2 Diabetes Mellitus

Background

Monotherapy with lipid-modifying medication is frequently insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia and type 2 diabetes mellitus.

Objective

To evaluate the efficacy and safety of fenofibric acid + statin combination therapy in this population.

Study Design

A pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week trials.

Setting

Multiple clinical research facilities in the US and Canada.

Patients

Patients with mixed dyslipidemia and type 2 diabetes (n= 586).

Intervention

Fenofibric acid (Trilipix®) 135 mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor®] 10, 20, or 40 mg; simvastatin [Zocor®] 20, 40, or 80 mg; or atorvastatin [Lipitor®] 20, 40, or 80 mg); or fenofibric acid + low- or moderate-dose statin.

Main Outcome Measure

Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events.

Results

Fenofibric acid + low-dose statin resulted in significantly (p<0.001) greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C) [16.8%] and triglycerides (?43.9%) than low-dose statin monotherapy (4.7% and ?18.1%, respectively) and significantly (p<0.001) greater reductions in lowdensity lipoprotein cholesterol (LDL-C) [?34.0%] than fenofibric acid monotherapy (?5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in significantly (p≤0.011) greater mean percentage changes in HDL-C (16.3%) and triglycerides (?43.4%) than moderate-dose statin monotherapy (8.7% and ?24.2%, respectively) and significantly (p<0.001) greater reductions in LDL-C (?32.6%) than fenofibric acid monotherapy (?5.3%). Compared with low- or moderate-dose statin, fenofibric acid + low- or moderate-dose statin resulted in over 5-fold higher percentages of patients achieving optimal levels of LDL-C, non-HDL-C, apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse events was generally similar among treatments.

Conclusion

Fenofibric acid + statin combination therapy in patients with mixed dyslipidemia and type 2 diabetes was well tolerated and resulted in more comprehensive improvement in the lipid/apolipoprotein profile than either monotherapy.     

Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia

Objective

Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia.

Materials and methods

We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale.

Results

BDNF levels were significantly lower in patients than controls (p?p?p?>?0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia.

Conclusion

Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory.     

Intraarticular and serum vancomycin concentration added to acrylic cement

Background

Vancomycin is the antibiotic of choice in therapy of orthopaedic implant infections caused by methicillin-resistant bacteria but its use poses a risk of toxicity, especially in patients with renal insufficiency. Addition of vancomycin to acrylic cement may cause systemic exposition to this drug eluting from cement to serum, which may require high-flux hemodialysis.

Methods

A patient hemodialysed twice a week underwent implantation of a spacer due to methicillin-resistant S. epidermidis infection of knee prosthesis. The spacer was made of acrylic cement loaded with 0,55 g of gentamicin per 40 g of cement and 6 g of vancomycin into totally 120 g of cement. The measurements of vancomycin concentration in serum within 9 days and in intraarticular fluid within 2 days were performed.

Results

Maximal intraarticular vancomycin concentration was reached 7 hours after surgery ( 120 μg/ mL) and was over Minimal Inhibitory Concentration for 47 hours. The serum concentration reached maximal value (2,6 μg/mL) 13 hours after implantation of spacer and was 2,3 μg/mL on 9-th postoperative day.

Conclusion

This composition of acrylic cement spacer containing gentamicin and vancomycin was found therapeutically effective and not necessitating high-flux hemodialysis in a hemodialysed patient with chronic renal failure.     

Single dose of H3 receptor antagonist - ciproxifan - abolishes negative effects of chronic stress on cognitive processes in rats

Rationale

The role of histamine neurons in stress evoked cognitive impairments remains unclear. Previous research has indicated that the blockade of H(3)-type histamine receptors may improve attention and memory in naïve rodents.

Objectives

The purpose of this study was to determine if ciproxifan, (cyclopropyl-(4-(3-1H-imidazol-4-yl) propyloxy) phenyl) ketone, an H(3) receptor antagonist, could alleviate cognitive deficits observed in chronically stressed rats.

Methods

Specifically, we attempted to characterize the preventive action of single dose of ciproxifan (3 mg/kg, i.p.) against an impairment caused by chronic restraint stress (2 h daily for 21 days) on recognition memory tested in an object recognition task and on the long-term memory tested in a passive avoidance test.

Results

We found that administration of ciproxifan potently prevented deleterious effects of chronic restraint stress, when administered prior to learning, or immediately after learning, or before retrieval on both the recognition (p<0.001) and the passive avoidance behavior (p<0.001).

Conclusions

These data support the idea that modulation of H(3) receptors represents a novel and viable therapeutic strategy in the treatment of stress evoked cognitive impairments.     

Extent of Control of Cardiovascular Risk Factors and Adherence to Recommended Therapies in US Multiethnic Adults with Coronary Heart Disease

Background

Guidelines for cardiovascular risk factor control in people with coronary heart disease (CHD) focus on compliance with β-adrenoceptor antagonists (β-blockers), angiotensin receptor blockade (ACE inhibitors/angiotensin II receptor antagonists [angiotensin receptor blockers; ARBs]) [ACE/ARBs], and lipid-lowering agents, with goals for BP of <140/90 mmHg and low-density lipoprotein cholesterol (LDL-C) levels of <2.6 mmol/L (100 mg/dL). Most data derive from registries of hospitalized patients or are from clinical trials. Little data exist on goal attainment and adherence with therapy among CHD survivors of major US ethnic groups in the real-world setting.

Objective

We assessed levels of cardiovascular risk factor control and adherence with recommended therapies among US CHD survivors.

Methods

We identified 364 US adults (representing 12.8 million in the US with CHD) aged 18 years and over in the National Health and Nutrition Examination Survey 2005–6 with known CHD. We calculated proportions of patients who were receiving recommended treatments, and who achieved goal targets for BP, LDL-C levels, glycosylated hemoglobin (HbA_1c), and nonsmoking status, and differences between actual and goal levels (‘distance to goal’), stratified by sex and ethnicity.

Results

Overall, 58%, 38%, and 60% of CHD survivors were receiving β-adrenoceptor antagonists, ACE/ARBs, and lipid-lowering medications, respectively (22% received all three). However, treatment rates for β-adrenoceptor antagonists and lipid-lowering agents were lower (p< 0.05 to p< 0.01) in Hispanics (36% and 27%, respectively) and non-Hispanic Blacks (47% and 42%, respectively) than in non-Hispanic Whites. Moreover, lipid-lowering treatment rates were lower in females (50%) than in males (67%) [p< 0.01]. Overall, 78% were nonsmokers while 68% achieved goal levels for BP, 57% for LDL-C levels, and, if diabetic, 67% for HbA_1c. Only 12% met all four goals. Non-Hispanic Whites had the lowest SBP and DBP as well as HbA_1c (p<0.05 to p<0.01 across ethnicity). In those who did not achieve goal levels, distance to goal averaged 1.0 mmol/L (37.0 mg/dL) for LDL-C levels, 15.6 mmHg for SBP, and 1.3% for HbA_1c.

Conclusion

Despite clear treatment guidelines, we show that many US adults with CHD, especially Hispanics and non-Hispanic Blacks, are neither receiving recommended treatments nor adequately treated in terms of BP, LDL-C levels, and HbA_1c. Greater efforts by healthcare systems to disseminate and implement guidelines are needed.     

A pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers

Purpose

Ticagrelor is a reversibly binding P2Y₁₂ receptor antagonist for the prevention of atherothrombotic events in patients with acute coronary syndrome. Previous in vitro studies showed that ticagrelor is a substrate and inhibitor of P-glycoprotein (ABCB1). Therefore, we examined the potential interaction between digoxin, a P-glycoprotein substrate, and ticagrelor by evaluating the pharmacokinetics, safety, and tolerability.

Methods

This was a randomized, double-blind, two-period crossover study in healthy volunteers (n?=?20). Pharmacokinetic parameters of digoxin and ticagrelor were evaluated following co-administration of ticagrelor 400 mg qd or placebo on days 1–16, and digoxin (0.25 mg bid on day 6 and 0.25 mg qd on days 7–14).

Results

Co-administration of ticagrelor increased the digoxin maximum plasma concentration by 75 %, from 1.8 ng/ml to 3.0 ng/ml (Gmean ratio [GMR] 1.75 [95 % CI, 1.52–2.01]); minimum plasma concentration by 31 %, from 0.5 ng/ml to 0.7 ng/ml (GMR 1.31, 1.13–1.52); and mean area under the curve by 28 %, from 16.8 ng?·?h/ml to 21.0 ng?·?h/ml (GMR 1.28, 1.12–1.46), compared with placebo. Renal clearance of digoxin was unaffected by the presence of ticagrelor. Digoxin had no effect on the pharmacokinetics of ticagrelor or its active metabolite, AR-C124910XX. Co-administration of ticagrelor and digoxin was well tolerated.

Conclusions

Collectively, these results indicate that ticagrelor is a weak inhibitor of the P-glycoprotein transporter. Based on these findings, it is recommended that serum concentrations of drugs like digoxin (P-glycoprotein transporter substrates with a narrow therapeutic range) are monitored when initiating or changing ticagrelor therapy.