Non-adherence to antihypertensive medication is the most important cause of uncontrolled blood pressure and is influenced by multiple interrelating factors. Understanding the complexity of medication non-adherence and its associated factors is important to determine intervention strategies. Therefore, a systematic review was performed aimed to identify factors associated with antihypertensive medication non-adherence. Different databases were searched for observational studies reporting on factors associated with non-adherence to antihypertensive medication. Titles, abstracts and full texts were reviewed by three researchers. Subsequently, the methodological quality of each study was assessed. Factors that were extracted from the included studies were categorised as factors with consistent or inconsistent evidence to put their potential importance into perspective. Forty-four studies were included. Higher co-payment, side effects and a poor patient-provider relationship were identified as factors with consistent evidence since consistent significant relationships were found for these factors whenever studied. The relationships between non-adherence and multiple other factors were inconsistent among the reviewed studies. However, some of these factors deserve some consideration. Since multiple potentially relevant factors were identified, patient-tailored interventions focussing on identifying and addressing patients' specific barriers to adherence are needed. Further research should clarify the influence of inconsistent factors on adherence and their potential to be addressed in interventions.

Aims In 2001, the Association of Amsterdam Community Pharmacists adopted a programme to improve the pharmaceutical care of patients who were discharged from hospital with five or more drug prescriptions. A comprehensive protocol for pharmaceutical care at discharge (IBOM-1) was developed. The aim of the study was to evaluate the initial IBOM protocol and to study the effects of the protocol on drug therapy and patient satisfaction as well as on drug use compliance and mortality. Method A controlled intervention study involving 37 community pharmacies and 715 of their registered patients who were discharged from a hospital and using at least five prescribed drugs in the years [2001][2002][2003]. The intervention included an extensive medication review and drug counselling at the patient's home. Main outcome measure Pharmacy intervention activities, changes in medication, discontinuation of drugs prescribed at discharge, mortality, time spent on the intervention activities, and medication cost savings were all evaluated. Patient satisfaction was measured by means of a questionnaire. Results 379 and 336 patients were enrolled in the intervention and control groups, respectively. The mean number of drugs per patient not dispensed, concomitantly dispensed, or of which the quantity was changed was higher in the intervention group than in the control group (0.70 ± 1.74 vs. 0.40 ± 1.43, 0.11 ± 0.40 vs. 0.038 ± 0.26, and 0.29 ± 1.05 vs. 0.097 ± 0.52, respectively). The mean number of drugs for which the dose or dosage form was changed was similar in both groups. Substitution of brand for generic or vice versa was greater in the intervention group. Changes resulting from a PAIS signal were similar in both groups. The mean number of drugs per patient for which contact was required with the physician or the Pharmacy Hospital Service Desk was higher in the intervention group (0.35 ± 0.51 vs. 0.16 ± 0.38). About 40% of home visits resulted in the clearing of redundant drug supplies. The IBOM-1 intervention did not influence discontinuation of drugs prescribed at discharge, nor did it influence mortality. Medication costs were slightly reduced. More patients of intervention pharmacies than of control pharmacies indicated that they were (very) satisfied with the drug counselling by their community pharmacist upon delivery of their discharge medication (87% vs. 50%; v 2 \ 0.001). Conclusions Structured pharmaceutical care according to the IBOM-1 protocol led to more changes in drug therapy. Home visits resulted in the clearing of redundant home drug supplies. In addition, patients were highly satisfied with the counselling at discharge from hospital by their community pharmacist. Patient counselling at discharge from hospital by pharmacists, therefore, appears to be a meaningful pharmaceutical care activity.

In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the fi-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on fiadrenoceptor density in right atria (containing 70% PB-and 30% P2-adrenoceptors) and in lymphocytes (having only f2-adrenoceptors) was studied.2 fl-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (-)[1225I]-iodocyanopindolol (ICYP) binding; the relative amount of right atrial P,-and #2-adrenoceptors was determined by inhibition of ICYP binding by the selective #2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3 With the exception of pindolol, all f-adrenoceptor antagonists increased right atrial ,Badrenoceptor density compared to that observed in atria from patients not treated with fadrenoceptor antagonists. 4 All f-adrenoceptor antagonists increased right atrial fi-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial f2-adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5 Similarly, in corresponding lymphocytes, only sotalol or propranolol increased fi2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it.6 It is concluded that P-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte ,B-adrenoceptor subtypes. The selective increase in cardiac fi1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective fl-adrenoceptor antagonists.

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To differentiate beta 1- and beta 2-adrenoceptor-mediated effects in humans, we studied the effects of a 2-wk treatment of 12 male volunteers with the selective beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg/day) and the beta 2-selective antagonist ICI 118,551 (3 x 25 mg/day) on lymphocyte beta 2-adrenoceptor density and responsiveness [10 microM l-isoproterenol (IPN) evoked adenosine 3',5'-cyclic monophosphate (cAMP) increase] as well as on exercise- and IPN-induced changes in lymphocyte beta 2-adrenoceptor density, blood pressure, heart rate, and plasma norepinephrine levels. ICI 118,551 administration increased lymphocyte beta 2-adrenoceptor density and responsiveness by approximately 50%, whereas bisoprolol had no effect. Dynamic exercise on a bicycle and infusion of graded doses of IPN led to an approximately 100% increase in lymphocyte beta 2-adrenoceptor density; this was abolished by ICI 118,551 but not affected by bisoprolol. ICI 118,551 markedly attenuated IPN-induced decrease in diastolic blood pressure but did not affect increase in systolic blood pressure, whereas bisoprolol had opposite effects. The IPN-induced increase in heart rate, however, was antagonized by both bisoprolol and (to a greater extent) ICI 118,551. Finally, ICI 118,551 completely abolished the IPN-induced increase in plasma norepinephrine levels, whereas bisoprolol had no effect. These results indicate that bisoprolol and ICI 118,551 are suitable tools to differentiate in humans beta 1- and beta 2-adrenoceptor-mediated effects.