Srecko Marusic

Effect of a 36-month Pharmaceutical Care Program on the Coronary Heart Disease Risk in Elderly Diabetic and Hypertensive Patients

PURPOSE To examine the effect of a pharmaceutical care program on the coronary heart disease risk in elderly diabetic and hypertensive patients. METHODS A total of 200 elderly (> 60 years) diabetic and/or hypertensive patients were recruited into a randomized, controlled, prospective clinical trial with a 36-month follow-up, developed in a public primary health care unit in a municipality in the Brazilian State of Sao Paulo. A range of clinical measurements were evaluated at the baseline and up to 36 months afterwards. The intervention group patients received pharmaceutical care from a clinical pharmacist, whereas the control group patients received their usual care from the medical and nursing staff. The Framingham scoring method was used to estimate changes in the 10-year coronary heart disease risk scores of all the patients. RESULTS A total of 194 patients completed the study. Significant reductions (p < 0.05) in the mean values (baseline vs. 36 months) for the systolic blood pressure [156.7 mmHg vs 133.7 mmHg; P < 0.001), diastolic blood pressure (106.6 mmHg vs. 91.6 mmHg; P < 0.001),fasting glucose (135.1 mg/dL vs. 107.9 mg/dL; P < 0.001), hemoglobin A1C (7.7% vs. 7.0%; P <0.001), triglycerides (206.0 mg/dL vs. 152.5 mg/dL; P < 0.001), low-density lipoprotein (LDL)cholesterol (112.4 mg/dL vs. 102.0 mg/dL; P < 0.001), high-density lipoprotein cholesterol (55.5 mg/dL vs. 65.5 mg/dL; P < 0.001), total cholesterol (202.5 mg/dL vs. 185.9 mg/dL; P < 0.001), body mass index (26.2 kg/m2 vs. 26.1 kg/m2; P < 0.001), and abdominal circumference (103.2 cm vs. 102.5 cm; P= 0.001) were observed in the intervention group, whereas no significant changes were verified in the control group. The mean Framingham risk prediction score in the intervention group was 6.8% at baseline and decreased to 4.5%; P < 0.001) after 36 months, but remained unchanged in the control group. CONCLUSION The pharmaceutical care program resulted in better clinical measurements and reduced the cardiovascular risk scores in elderly diabetic and hypertensive patients over a 36-month period.

Acute interstitial nephritis due to mesalazine

SUMMARY:  A case of mesalazine‐induced acute interstitial nephritis (AIN) in a 41‐year‐old patient with ulcerative colitis (UC) is reported here. Clinical symptoms such as fever and arthralgia, and laboratory findings such as eosinophilia and renal failure suggested AIN, which was confirmed by biopsy. With withdrawal of mesalazine and intravenous methylprednisolone the patients renal function was recovered. It is observed that early discontinuation of mesalazine is associated with amelioration of interstitial nephritis in most patients, so the recommendation is that patients receiving mesalazine should undergo routine monitoring of renal function. Delayed diagnosis may lead to permanent renal function impairment.

The incidence of potential drug–drug interactions in elderly patients with arterial hypertension

Objective To assess the incidence and type of potential, clinically significant drug–drug interactions in elderly outpatients with arterial hypertension. Setting Three community pharmacies in Croatia. Method Eligible patients were aged 65 or older, treated for arterial hypertension and received 2 or more drugs. Potential interactions were identified by Lexi-Interact software. The software categorized each potential interaction according to clinical significance in five groups: (A) No known interaction; (B) Specified agents may interact, but there is little to no evidence of clinical concern; (C) Specified agents may interact in a clinically significant manner. Monitoring therapy is suggested; (D) The two medications may interact in a clinically significant manner. Modification of therapy is suggested; (X) Contraindicated combination. Interactions of level C, D and X were considered clinically significant. Main outcome measure The incidence and type of potential drug–drug interactions. Results There were 265 patients included in the study. Potential, clinically significant drug interactions were identified in 240 (90.6%) patients, out of which 97.9% had interactions with clinical significance C, 20.4% D, and 0.8% X. The median number of drug interactions per patient was 4. We identified 215 drug combinations with the potential to cause clinically significant interaction, out of which 83.3% had clinical significance C, 16.3% clinical significance D, and 0.4% clinical significance X. Conclusion Drug–drug interactions are common in elderly hypertensive patients. Computer-based screening could help pharmacists and physicians to recognize potential, clinically significant interactions.

Use of simulated patients to evaluate combined oral contraceptive dispensing practices of community pharmacists.

Background Combined oral contraceptive (COC) use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs) are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. Objective To evaluate the COC dispensing practices of CPs in a developing country. Method A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs) (with counseled audio recording) visited community pharmacies with a prescription for Ciclo 21® (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg). The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients’ medical and family history, and measuring of blood pressure) and provided counseling, as well as the quality of the screening and counseling, were evaluated. Results Of the 185 CPs contacted, 41 (22.2%) agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional), and all of the questions were closed-ended, viz., “do you smoke?” (n = 2) and “what is your age?” (n = 1). None of the CPs measured the patient’s blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP provided counseling regarding both aspects. Conclusion The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure.

Atorvastatin-related rhabdomyolysis and acute renal failure in a genetically predisposed patient with potential drug-drug interaction

Abstract Case description A 75-year-old man developed rhabdomyolysis and acute renal failure during atorvastatin therapy. All medications were discontinued and the patient was treated with intermittent hemodialysis throughout the course of hospitalization. After four weeks, patients kidney function tests and serum myoglobin levels decreased to normal values and muscle weakness gradually disappeared. Genotyping results showed that the patient had a single-nucleotide polymorphism within genes encoding the organic anion-transporting polypeptide 1B1 and ATP binding cassette sub-family B member 1, which predisposed him for statin-induced myopathy. He was also a poor metabolizer of cytochrome P450 2C19. Concomitant therapy with pantoprazole could have resulted in the inhibition of cytochrome P450 3A4-mediated metabolism of atorvastatin and contributed to the development of rhabdomyolysis. Conclusion The case illustrates the clinical relevance and relationship between pharmacogenetic and pharmacokinetic factors in the development of statin-induced myopathy.

Impact of Ceftriaxone De-restriction on the Occurrence of ESBL-Positive Bacterial Strains and Antibiotic Consumption

Abstract As a cost-saving measure, the Drug and Therapeutics Committee (DTC) removed ceftriaxone from the list of restricted antibiotics in May, 2008, which permitted its use as a first-line antibiotic. To evaluate the impact of this change, the occurrence of extended-spectrum beta-Iacta- mase (ESBL)-positive bacterial strains and antibiotic consumption were monitored for 2 years before and after the intervention. In the post-intervention period, ceftriaxone utilization increased, while total antibiotic utilization did not change significantly. The utilization of all restricted antibiotics decreased (p <0.05) in the post-intervention period. Utilization of carbapenems increased (p <0.05), while utilization of quinolones increased nonsignificantly. The density of resistant ESBLs increased (p = 0.001) from 0.99 to 1.34 per 1000 bed-days from the pre- to the post- intervention period. Ceftriaxone use was significantly correlated with ESBL occurrence (p <0.005). It can be concluded that ceftriaxone de-restriction increased the occurrence of ESBLs and the utilization of carbapemens.

Hyperkalaemia associated with hydroxyurea in a patient with polycythaemia vera

Hydroxyurea has been used for decades for the treatment of some types of malignancies [1]. It has been demonstrated to be very effective in preventing thrombosis and thus should be considered as first-line therapy in high-risk patients with myeloproliferative disorders [2]. An 81-year-old woman was admitted to hospital in December 2009 because of hyperkalaemia. Her medical history included essential hypertension for the last 15 years. She had been diagnosed with polycythaemia vera in April 2007 and an initial treatment consisted of phlebotomy and low-dose acetylsalicylic acid. In May 2009 the patient had developed iliofemoral vein thrombosis as a consequence of polycythaemia vera. To prevent further thromboembolic complications, therapy with hydroxyurea had been introduced. At the time of admission, the patients therapy included ramipril (2.5 mg), acetylsalicylic acid (100 mg) and hydroxyurea (1,000 mg) daily. Serum potassium level was 6.7 mmol/L (normal range 3.9–5.1 mmol/L). Levels of sodium, chloride, calcium, lactate dehydrogenase and creatine kinase were all within normal values. Haemoglobin concentration, haematocrit, white and red blood cells and platelet count were normal as were values for plasma aldosterone, plasma renin activity and 24-h urinary free cortisol. Arterial blood pH and bicarbonates were mildly decreased (pH 7.318, bicarbonates 18.9 mmol/L). Patients renal function was decreased with serum creatinine of 116 μmol/L and 24-h creatinine clearance of 41.7 ml/min. Electrocardiogram (ECG) showed no abnormality. Since there was no significant difference between the serum and plasma potassium levels, pseudohyperkalaemia could be excluded [3]. Because of the possibility that hyperkalaemia was caused by ramipril or acetylsalicylic acid, therapy with these drugs was discontinued. Repetitive administration of bicarbonate and insulin/glucose did not decrease the potassium level and after 7 days it remained high (5.8–6.4 mmol/L). The degree of hyperkalaemia could not have been explained by moderate renal insufficiency and the clinical investigation did not find any other possible cause. Thus, we suspected that it could have been caused by an adverse reaction to hydroxyurea. Therapy with hydroxyurea was discontinued and 2 days later the potassium level decreased to 5.0 mmol/L. Since hyperkalaemia was not listed as an adverse reaction in the Summary of Product Characteristics and no similar cases have been reported in the literature, we were not convinced that it was really caused by hydroxyurea. Hyperkalaemia was asymptomatic and caused no ECG changes in the presented case; thus, we believed that rechallenge would not endanger the patient. After Ethics Review Board approval she was re-administered 500 mg of hydroxyurea daily. After the second dose, the serum potassiS. Marusic (*) :N. Gojo-Tomic Department of Clinical Pharmacology, University Hospital Dubrava, Av. Gojka Suska 6, 10000 Zagreb, Croatia e-mail: srmarusic@inet.hr

Therapeutic efficacy of acenocoumarol in a warfarin-resistant patient with deep venous thrombosis: a case report

A case report of therapeutic efficacy of acenocoumarol in a warfarin-resistant patient with deep venous thrombosis.

Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study

AimHypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile.MethodsThe study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A—half an hour before breakfast; timing regimen B—an hour before the main meal of the day; timing regimen C—at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study.ResultsAltogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = −0.017 95% C.I. (−0.400–0.192); baseline vs. B = −0.325 95% C.I. (−0.562–0.023); baseline vs. C = −0.260 95% C.I. (−0.475–0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline.ConclusionThe three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.

Implementation of Venous Thromboembolism Prophylaxis Guidelines in Clinical Practice: A Retrospective Study in Two Croatian Hospitals

The aim of this study was to evaluate the implementation of the 9th edition of the American College of Chest Physicians (ACCP9) guidelines for prevention of venous thromboembolism in nonsurgical patients in clinical practice in one university and one general Croatian hospital. A retrospective study was conducted at Zadar General Hospital from Zadar and Dubrava University Hospital from Zagreb. Medical charts of all patients admitted to Medical Departments in two periods, before and after implementation of the ACCP9 guidelines, were analyzed. The ACCP9 guidelines were made available to all physicians through the hospital electronic information system immediately after the publication. The Hospital Drug Committees promoted implementation of the guidelines during their periodical clinical visits. Overall, 850 patients were included in the study in two periods. There was no statistically significant difference in the number of high-risk patients receiving thromboprophylaxis after the guidelines implementation in either hospital. In both periods, a signifi-cantly higher number of high-risk patients received thromboprophylaxis in Dubrava University Hos-pital in comparison with Zadar General Hospital (31.7% vs. 3.8% and 40.3% vs. 7.3%, respectively; p<0.001). This study revealed insufficient implementation of evidence-based thromboprophylaxis guidelines in clinical practice in two Croatian hospitals.