Trends of Over-the-Counter and Prescribed Medication Use During Pregnancy: A Cross-Sectional Study.

Background: Globally, unjustified medication use during pregnancy, a critical phase in human life, is a threat that compromises the safety of both, the mother and the child. We aim to investigate the prevalence of over-the-counter (OTC) or non-prescription and prescription medication use during pregnancy in women from the city of Riyadh, Saudi Arabia, the level of prior knowledge, and the sources of their information about medication hazard/safety. Methods: A cross-sectional study was performed using a self-administered questionnaire for 287 pregnant women visiting King Saud Medical City (KSMC) - outpatient departments for routine antenatal care during 3 months (1st Mar-31st May 2021). The questionnaire was developed by Navaro et al with 4 sections: socio-demographic data, medication use during pregnancy, level of knowledge, and relevant sources of information. Results: The participants had a mean age of 32.21 years ± 6.41 (SD), and gestational age of 23.67 weeks ± 8.47. About 76.66% of them reported using medication during their current pregnancy: predominantly prescribed (86.36%). Women who used medication during pregnancy were slightly older; the mean difference was 1.97 years (95% CI 0.23-3.71) (P=0.027). Women living in an urban environment as compared with rural had a higher prevalence of medication use (79.01% vs 52%) (P=0.002). Overall, 58.19% reported using non-prescribed medications during pregnancy, with analgesics as the most frequently used class (70.30%). The mild nature of the illnesses and availability of an old prescription and information from pharmacists were the main reasons for self-medication. About 40.77% denied receiving any information about medication use during pregnancy. Conclusion: The prevalence of the medication use during pregnancy in our population is alarmingly high. Analgesics were the most frequently used. Lack of adequate information from treating physicians appears to be contributory to self-medication during this critical time.

Effect of low dose allopurinol on glycemic control and glycemic variability in patients with type 2 diabetes mellitus: A cross-sectional study.

Background: Type 2 diabetes mellitus (DM), gout, and asymptomatic hyperuricemia are inter-connected pathologies. Glycemic control (GC), involving a range of treatments is central to the management of DM, whereas allopurinol continues to be the most widely recommended urate lowering agent. Allopurinol has been shown to possess anti-oxidant properties: this study explores the potential effect of allopurinol on glucose homeostasis. Methods: This is an observational study with a cross-sectional design performed on patients with type 2 diabetes mellitus (DM), recruited from centers in Saudi Arabia. Patients were divided into two groups; allopurinol users; (for gout or asymptomatic hyperuricemia) and a matching disease control group. Patient demographics, co-morbid conditions, biochemical tests, and pharmacological treatments were extracted from electronic records to investigate the effect of allopurinol therapy on Glycemic control (GC), as assessed by glycated haemoglobin (HbA1c as primary endpoint), and on parameters of glycaemic variability (GV) (secondary endpoints). Results: A total of 194 patients with type 2 DM were recruited (97 in both groups). The two groups were matched for age, sex, and duration of DM: mean age: 59.4 years, 73% males, and 122 months in the allopurinol group vs 59.6 years, 73% males, and 113 months in the control group. Antidiabetic medications were matched between the two groups. In the allopurinol group, it was prescribed with a daily dose of 100 mg, for 77% of the patients, with median duration of 39.5 months. HbA1c values were; 6.90% (6.20, 7.80) in the allopurinol group vs 7.30% (6.60, 8.40) in the control group (P = 0.010). Parameters of GV were calculated from 3 consecutive fasting blood sugar (FBS) readings: variability independent of the mean (VIM) was 0.140 in the allopurinol group vs 0.987 in the control group (P < 0.001). Conclusion: Concomitant low-dose allopurinol therapy in patients with type 2 DM was associated with modest but significant improvements in GC and GV.

Erectile Dysfunction: Pharmacological Pathways with Understudied Potentials.

Erectile dysfunction (ED) is a public health concern worldwide. In the past, it was perceived as a phenomenon attributed to age advancement. However, more individuals are affected every year that do not fall under that age criterion. Epidemiological research revealed that this abnormality has an association with endothelial dysfunction connected to several cardiovascular (CV) risk factors. Currently, ED is interpreted as a clinical marker for future adverse events and not only as a present health issue that negatively affects the quality of life. The management of ED involves lifestyle modifications, therapeutic optimization for comorbid conditions, and pharmacological and psychosexual therapy. Phosphodiesterase type 5 (PDE5) inhibitors are the first-line pharmacological agents to be prescribed for such a condition. Nonetheless, other pharmacological pathways and agents remain underinvestigated or were investigated at some stage. This review aimed to present to future researchers interested in this field with some pharmacological agents that showed favorable effects on a limited number of studies on human subjects or experimental models.

Clinical, Echocardiographic, and Therapeutic Characteristics of Heart Failure in Patients with Preserved, Mid-Range, and Reduced Ejection Fraction: Future Directions.

BACKGROUND: Heart failure (HF) is recognized as a worldwide epidemic. Definitions and risk stratification are usually based upon measurements of left ventricular ejection fraction (LVEF) but such classifications reflect an underlying spectrum of different pathologic, phenotypic, and therapeutic patterns. METHODS: This was a retrospective cohort study of HF patients in Saudi Arabia. Patients were divided into three categories based on LVEF: those with preserved ejection fraction (EF) (EF≥50%, HFpEF); those with mid-range EF (EF 40-49%, HFmrEF); and those with reduced EF (EF <40%, HFrEF). Their demographics, co-morbid conditions, echocardiographic findings, pharmacological treatments and all-cause mortality (ACS) after a follow-up period of 24 months were compared. RESULTS: A total of 293 HF patients were identified (mean age: 63 years). In total, 65% were males, 79% were Saudi nationals, and 70% had type 2 diabetes mellitus (DM). Classification based on EF was established in 288 patients: HFpEF (105 patients, 36.5%), HFmrEF (49, 17.0%), and HFrEF (134, 46.5%). The 3 groups differed in sex distribution: 51% females in the HFpEF group and 78% males in the HFrEF group (P<0.001). Body mass index (BMI) was highest in the HFpEF group and lowest in the HFrEF group (31.5 vs 26.6; P<0.001). Although systolic blood pressure (SBP in mmHg) was highest in patients with HFpEF, left ventricular mass index (LVMI in g/cm2) was highest in patients with HFrEF 121.00 (94.50, 151.50), and eccentric hypertrophy was the dominant LV geometrical characteristic (54.6%). HFrEF patients had the highest use of ACE inhibitors (60.5%), loop diuretics (79.9%), and aldosterone receptor antagonists (56.7%) (P values; 0.009, 0.007, and <0.001, respectively). A total of 42 deaths occurred during follow-up: HFpEF (17 events), HFmrEF (3 events) and HFrEF (22 events) (Logrank test P=0.189). CONCLUSION: This Saudi HF population shows similarities to other populations: EF category distribution, sex distribution, therapeutic trends, and survival outcomes. However, findings related to the underlying risk factors, namely type 2 DM and obesity, have identified HFpEF as an emerging threat in this (relatively) young population.

Predictors of Mortality in Patients with Chronic Heart Failure: Is Hyponatremia a Useful Clinical Biomarker?

BACKGROUND: Chronic heart failure (CHF) is a global health burden. Despite advances in treatment, there remain well-recognised morbidity and mortality. Risk stratification requires the identification and validation of biomarkers, old and new. Hyponatremia has re-emerged as a prognostic marker in CHF patients. METHODS: This is a retrospective cohort study on 241 CHF patients recruited from King Fahd Hospital of the University, Al-Khobar, Saudi Arabia (January 2005-December 2016). Their serum sodium and biochemical parameters were measured at baseline, along with 2-D echocardiographic assessments of left ventricular mass and ejection fraction. The primary endpoint was the association between hyponatremia and all-cause mortality (ACM) after a follow-up period of 24 months. RESULTS: Mean age of patients was 60.61 ± 12.63 (SD) years; 65.1% were males, and type 2 diabetes mellitus (DM) was present in 71%. Baseline serum sodium was 138.00 (136, 140) (median and interquartile range). Hyponatremia (<135 meq/L) was present in 14.1%. After follow-up, 46 deaths had occurred. Multivariate Cox-proportional hazard model showed that type 2 DM, New York Heart Association (NYHA) class (III-IV vs I-II), age, and left ventricular mass index (LVMI) were significant and independent predictors of ACM, with HR 3.03 (95% CI; 1.13, 8.16) (P=0.028), HR 2.31 (95% CI; 1.11, 4.82) (P=0.026), HR 1.06 (95% CI; 1.03, 1.09) (P<0.001), and HR 1.01 (95% CI; 1.00, 1.02) (P=0.039), respectively. Estimated glomerular filtration rate (eGFR) was not a significant predictor. Kaplan-Meier survival analysis was used for the analysis of NYHA class and hyponatremia interactions and showed that hyponatremia had an association with poorer survival in patients with NYHA class III-IV rather than I-II (Log-rank test, P= 0.0009). CONCLUSION: Hyponatremia was a feature in CHF patients, and ACM was predicted by type 2 DM, NYHA class, age, and LVMI. Hyponatremia impact on survival was in patients with more advanced disease.

Effect of Long-Term Allopurinol Therapy on Left Ventricular Mass Index in Patients with Ischemic Heart Disease; A Cross-Sectional Study.

BACKGROUND: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? METHODS: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. RESULTS: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. CONCLUSION: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.

Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets.

Chronic heart failure (CHF) is a complex syndrome that results from structural and functional disturbances that affect the ability of the heart to supply oxygen to tissues. It largely affects and reduces the patient's quality of life, socio-economic status, and imposes great costs on health care systems worldwide. Endothelial dysfunction (ED) is a newly discovered phenomenon that contributes greatly to the pathophysiology of numerous cardiovascular conditions and commonly co-exists with chronic heart failure. However, the literature lacks clarity as to which heart failure patients might be affected, its significance in CHF patients, and its reversibility with pharmacological and non-pharmacological means. This review will emphasize all these points and summarize them for future researchers interested in vascular pathophysiology in this particular patient population. It will help to direct future studies for better characterization of these two phenomena for the potential discovery of therapeutic targets that might reduce future morbidity and mortality in this "at risk" population.

Effect of Xanthine Oxidase Inhibition on Arterial Stiffness in Patients With Chronic Heart Failure.

BACKGROUND: The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. RESULTS: A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 (P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. CONCLUSIONS: We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen.The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.

Allopurinol and endothelial function: A systematic review with meta-analysis of randomized controlled trials.

AIM: Oxidative stress and endothelial dysfunction are two inter-related conditions commonly seen in patients with cardiovascular risk factors. The enzyme, xanthine oxidase, is an important contributor to these phenomena but to a variable degree in different patient populations. This meta-analysis will summarize the effect of allopurinol, an established xanthine oxidase inhibitor, on endothelial function among patients with different comorbidities. METHODS: Medline Complete, PubMed, ProQuest, ClinicalKey, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till July 29, 2017. Meta-analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on endothelial function. A random effect model was used to calculate the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information: Q statistics, I2 statistic, Tau-squared (T2 ), and Tau (T). RESULTS: Thirty eligible studies were identified; 12 were included in the final analysis and subdivided among 3 patient's groups: patients with chronic heart failure (CHF; 197 patients), patients with chronic kidney disease (CKD; 183 patients), and patients with type 2 diabetes mellitus (DM; 170 patients). Allopurinol was found to have a statistically significant benefit on endothelial function in patients with CHF and CKD but not in type 2 DM. The standardized mean differences and CI in the three patient's groups were 0.776 (0.429, 1.122), 0.350 (0.009, 0.690), and 1.331 (-0.781, 3.444), respectively. CONCLUSION: Allopurinol has an antioxidant property that might partially reverse endothelial dysfunction in patients with certain comorbidities. The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies.

Comparison of the effects of diuretics on blood pressure and arterial stiffness in patients with stroke.

OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used in patients with stroke. We compared their effects on arterial blood pressure (BP) and arterial stiffness in a group of patients with stroke. METHODS: In a prospective, randomized, double-blinded study we investigated the effect of 28-day treatment with BDZ (2.5 mg once daily) or IND (2.5 mg once daily) on BP and arterial stiffness in a group of patients with first-ever ischemic stroke. RESULTS: All data are expressed as mean (SD). In all, 23 patients completed the protocol (age 70.0 +/- 9.55 years). Group I (IND) and group B (BDZ) comprised 13 and 10 patients, respectively. Groups were well matched for demographics and baseline characteristics. Mean arterial pressure reduction from baseline was I = 14.3 +/- 10.3 mm Hg (P < .001) versus B = 9.1 +/- 11.2 mm Hg (P = .03). Augmentation index (AI) was reduced by: I = 4.94 +/- 7.22% (P = .037) versus B = 6.17 +/- 7.85% (P = .035). Time to reflection was increased by I = 3.22 +/- 9.57 milliseconds (P = .268) versus B = 4.71 +/- 5.30 milliseconds (P = .020). There was no significant difference between the two drugs with regard to change in BP or arterial stiffness. Pooled data showed a reduction in mean arterial pressure by 12.1 +/- 10.77 mm Hg (P < .0001) and in AI by 5.5 +/- 7.36% (P = .002), and a small increase in time to reflection by 3.9 +/- 7.79 milliseconds (P = .029). The change in BP explained up to 28% of the change in AI. CONCLUSION: Both diuretics altered hemodynamic parameters to a similar extent. The results are consistent with a direct effect of diuretic therapy on vascular function. The influence of both diuretics on arterial stiffness was similar.

Comparison of the effect of diuretics on carotid blood flow in stroke patients.

OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used in the management of blood pressure after stroke. There are theoretical reasons why these agents may differ with regard to their cardiovascular effects. We compared the effect of these agents on blood pressure and cerebral blood flow in a group of stroke patients. METHODS: In a prospective, randomized, double-blinded study we investigated the effect of 28 days' treatment with BDZ 2.5 mg od or IND 2.5 mg od on blood pressure and cerebral blood flow in a group patients with recent first-ever ischemic stroke. Using extracranial carotid and transcranial ultrasound we assessed carotid blood flow and intracranial hemodynamics. RESULTS: All data are expressed as mean (SD). Twenty-five patients completed the protocol (age 68.8 +/- 10.6 y). Groups I (IND) and B (BDZ) comprised 13 and 12 patients, respectively. Groups were well matched for demography and baseline characteristics. Percent change in mean arterial pressure reduction from baseline was (I = -14.7 +/- 12.5, P < 0.001 vs. B = -7.7 +/- 9.16 mm Hg, P = 0.02). There was a trend toward increased carotid blood flow in both groups (I = +10% +/- 47, P = 0.4 vs. B = +33% +/- 47, P = 0.12). No significant change in middle cerebral artery mean flow velocity or pulsatility index was observed. There was no significant difference between the 2 drugs with regard to change in blood pressure (95% confidence interval for difference -2.5 to 16.3 mm Hg, P = 0.14) or carotid blood flow (95% confidence interval for difference -58 to 27 mL/s, P = 0.45). CONCLUSIONS: Both diuretics reduced blood pressure to a similar and significant degree. There was no evidence of an adverse effect on cerebral blood flow or intracranial hemodynamics induced by either agent. No significant difference between the effect of IND and BDZ was observed.