Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

PURPOSE: Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. METHODS: Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. RESULTS: A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. CONCLUSIONS: Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis.

BACKGROUND: Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. RESULTS: Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]). CONCLUSIONS: Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.

Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel-Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697). CONCLUSIONS: Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Orthostatic hypotension in older adults: the role of medications.

Orthostatic hypotension (OH) is defined as an abnormal blood pressure reduction when standing and is frequently diagnosed in older adults. Pharmacological therapy is one of the main causes of orthostatic blood pressure impairment, leading to iatrogenic OH. Indeed, several medications may induce hypotensive effects and influence the blood pressure response to orthostatism. Hypotensive medications may also overlap with other determinants of OH, thus increasing the burden of symptoms and the risk of complications. Potentially hypotensive medications include both cardiovascular and psychoactive drugs, which are frequently prescribed in older patients. According to the available evidence, the antihypertensive treatment "per se" does not seem to predispose to OH, even if a higher risk is associated with polypharmacy and drug classes such as with diuretics and vasodilators. As concerns psychoactive medications, OH is a well-known adverse effect of tricyclic antidepressants, trazodone and antipsychotics. The knowledge of hemodynamic consequences of drug therapy may be helpful to improve OH treatment. A medication review is advisable in all patients presenting with OH, particularly at advanced age, aiming at optimizing medical treatment with a view to minimize the risk of iatrogenic OH.

Prevalence and Factors Associated with Analgesic Prescribing in Poly-Medicated Elderly Patients.

BACKGROUND: Pain is common in older patients and management guidelines rarely consider the effect of multiple comorbidities and concurrent medications on analgesic selection. OBJECTIVES: The objectives of this study were to identify the prevalence and pattern of analgesic prescribing and associated factors in older patients with polypharmacy. METHODS: Older patients (aged ≥ 75 years) admitted to the Royal Adelaide Hospital between September 2015 and August 2016 and with polypharmacy were included and their comorbidities and medications prescribed at discharge were recorded. Drug Burden Index and Charlson Comorbidity Index were calculated. The number of medications that increased the risk of orthostatic hypotension were recorded. Logistic regression was used to compute the association between analgesic use and participant characteristics, and results were presented as odds ratios and 95% confidence intervals, adjusted for age, sex, Charlson Comorbidity Index, Drug Burden Index and orthostatic hypotension. RESULTS: Over 15,000 admissions were identified, of which 1192 patients were included, 824 (69%) of whom were prescribed an analgesic medication. Paracetamol (used by 89% of analgesic users), opioids (34%) and adjuvants (17%) were used more frequently than non-steroidal anti-inflammatory drugs (8%). Analgesic users had a higher Drug Burden Index, were prescribed more medications and were less likely to be male compared with non-users. Charlson Comorbidity Index across the cohort was high (7.3 ± 1.9) but there was no difference between analgesic users and non-users, but analgesic users were more likely to have a documented diagnosis of osteoarthritis, osteoporosis and falls. Opioid use was associated with the Drug Burden Index, while adjuvant use was associated with orthostatic hypotension. Opioid use was associated with having a diagnosis of osteoporosis and falls. CONCLUSIONS: In our cohort of poly-medicated elderly patients, prescription of analgesic medications was common, and these patients are likely to have an increased rate of adverse drug reactions and falls compared with those who were not prescribed analgesic medications.

Preventing Radiation-Induced Injury by Topical Application of an Amifostine Metabolite-Loaded Thermogel.

PURPOSE: Despite the development of high-precision radiation therapy, ionizing radiation inevitably damages healthy tissues. Radiodermatitis and radioinduced oral mucositis are frequent and significant side effects among patients with breast and head and neck cancer, respectively. These radiation-related injuries negatively affect patient quality of life and can lead to unplanned therapeutic breaks and compromise treatment outcomes. Currently, no preventive or mitigating agent has emerged to address these issues. Although amifostine, a well-known free radical scavenger, has proven efficacy against specific radio- and chemo-induced toxicities, severe adverse side effects (reversible hypotension, nausea, emesis, etc) combined with logistical hurdles are associated with its recommended intravenous route of administration, limiting its use. METHODS AND MATERIALS: We developed a thermogel containing the active thiol metabolite of amifostine (CPh-1014) that polymerizes at body temperature and serves as a matrix for topical application onto the skin or mucosa. RESULTS: Applied before irradiation, CPh-1014 greatly reduced the severity of oral mucositis and dermatitis induced by either a single dose or fractionated irradiation regimens in in vivo mouse models. The cytoprotective effect of CPh-1014 was confirmed by the decrease in DNA double-strand breaks in the irradiated epithelium. Noticeably, CPh-1014 did not affect radiation therapy efficacy against tumors grafted at submucosal and subcutaneous sites. In contrast to the intravenous administration of amifostine, CPh-1014 oral application did not induce hypotension in dogs. CONCLUSIONS: CPh-1014 confers radioprotective effects in healthy tissues with reduced systemic side effects without compromising radiation therapy efficacy. We propose CPh-1014 as an easy-to-implement therapeutic approach to alleviate radiation therapy toxicity in patients with breast and head and neck cancer.

Medication Use and Fall-Related Hospital Admissions from Long-Term Care Facilities: A Hospital-Based Case-Control Study.

BACKGROUND: Falls are a leading cause of preventable hospitalizations from long-term care facilities (LTCFs). Polypharmacy and falls-risk medications are potentially modifiable risk factors for falling. OBJECTIVE: This study investigated whether polypharmacy and falls-risk medications are associated with fall-related hospital admissions from LTCFs compared with hospital admissions for other causes. METHODS: This was a hospital-based, case-control study of patients aged ≥65 years hospitalized from LTCFs. Cases were patients with falls and fall-related injuries, and controls were patients admitted for infections. Conditional logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between polypharmacy (defined as the use of nine or more regular pre-admission medications) and falls-risk medications (categorized as psychotropic medications and those that can cause orthostatic hypotension) with fall-related hospital admissions. RESULTS: There was no association between polypharmacy and fall-related hospital admissions (adjusted OR 0.97, 95% CI 0.63-1.48); however, the adjusted odds of fall-related hospital admissions increased by 16% (95% CI 3-30%) for each additional falls-risk medication. Medications that can cause orthostatic hypotension (adjusted OR 1.25, 95% CI 1.06-1.46), but not psychotropic falls-risk medications (adjusted OR 1.02, 95% CI 0.88-1.18) were associated with fall-related hospital admissions. The association between medications that can cause orthostatic hypotension and fall-related hospital admissions was strongest among residents with polypharmacy (adjusted OR 1.44, 95% CI 1.08-1.92). CONCLUSION: Polypharmacy was not an independent risk factor for fall-related hospital admissions; however, medications that can cause orthostatic hypotension were associated with fall-related hospital admissions, particularly among residents with polypharmacy. Falls-risk should be considered when prescribing medications that can cause orthostatic hypotension.

Factors associated with use of falls risk-increasing drugs among patients of a geriatric oncology outpatient clinic in Australia: a cross-sectional study.

Older people with cancer are at increased risk of falling. Falls risk-increasing drugs (FRIDs), comprising psychotropics and medications that cause orthostatic hypotension, are a potentially modifiable risk factor for falls. The objective of this study was to determine the prevalence and factors associated with use of FRIDs in older people with cancer. Patients aged ≥70 years who presented to a hospital outpatient clinic between January 2009 and July 2010 were included in the study. Information on current medication use, falls in previous 6 months, and frailty criteria was collected. Multinomial logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CIs) for factors associated with levels of FRID use. Overall, 76.1% (n = 293) of 383 patients used FRIDs. This comprised psychotropics (31.2%, n = 120) and medications causing orthostatic hypotension (69.9%, n = 269). In total, 24.0% (n = 92) patients reported falling in the previous 6 months. Risk factors for falling were associated with use of psychotropics but not orthostatic hypotension drugs. Patients with a history of falls had increased odds of using psychotropics (≥3 psychotropics; OR 13.50; 95%CI, 2.64-68.94). Likewise, frail patients had increased odds of using psychotropics (≥3 psychotropics; OR 27.78; 95%CI, 6.06-127.42). Risk factors for falling were associated with the use of psychotropics. This suggests that clinicians either do not recognize or underestimate the contribution of medications to falls in this high-risk patient group. Further efforts are needed to rationalize medication regimens at the time of patients' first presentation to outpatient oncology services.

Behavioral Disorders in Dementia: Appropriate Nondrug Interventions and Antipsychotic Use.

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Orthostatic hypotension and drug therapy in patients at an outpatient comprehensive geriatric assessment unit.

OBJECTIVE: To assess the rate of orthostatic hypotension and factors associated with it among elderly patients who underwent a comprehensive, ambulatory geriatric assessment. METHODS: The study included patients 65 years and older who were assessed in the outpatient comprehensive geriatric assessment unit. Data were collected from the computerized medical record including sociodemographic data, lifestyle, falls, blood pressure, BMI, functional and cognitive status, medications, and comorbidity. RESULTS: The study population consisted of 571 patients who underwent assessment over a nine-year period. The mean age was 83.7 ±â€Š6.1, 35.9% were men, and 183 (32.1%) were diagnosed with orthostatic hypotension. Multiple drugs, in general, and multiple drugs with the potential to cause orthostatic hypotension in particular increased the risk for orthostatic hypotension after adjustment for age, sex, chronic comorbidity, and supine systolic blood pressure ≥150 mmHg [odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.03-1.14 and OR = 1.22, 95% CI: 1.08-1.37, respectively]. In addition, α-blockers and calcium channel blockers increased the risk for orthostatic hypotension after similar adjustments (OR = 1.82, 95% CI: 1.01-3.16 and OR = 1.66, 95% CI: 1.11-2.48, respectively). Similarly, two additional drug types increased the risk for orthostatic hypotension: selective serotonin reuptake inhibitors (OR = 2.09, 95% CI: 1.33-3.19) and tricyclic antidepressants (OR = 4.36, 95% CI: 1.85-10.06). There were no specific associations between age, cognitive and functional state, morbidity (as measured by the Charlson Comorbidity Index), and specific diseases, and orthostatic hypotension. CONCLUSION: The results of the present study reinforce evidence of an association between drug therapy and orthostatic hypotension.

Phase I study assessing the safety, tolerability, and pharmacokinetics of avibactam and ceftazidime-avibactam in healthy Japanese volunteers.

Avibactam is a novel non-ß-lactam ß-lactamase inhibitor that has been shown to restore the in vitro activity of ceftazidime against pathogens producing Ambler class A, C, and some class D ß-lactamases. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of avibactam alone or with ceftazidime in healthy Japanese subjects. In this Phase I, double-blind study (NCT01291602), 16 healthy Japanese males, mean age 28.8 years, were randomized in a 2:2:1 ratio to receive avibactam 500 mg (n = 6), ceftazidime 2000 mg plus avibactam 500 mg (n = 7), or placebo (n = 3), each administered as a 100 ml intravenous infusion over 2 h, once on Day 1, every 8 h on Days 3-6, and once on Day 7. There were no deaths or serious adverse events. Nine treatment-emergent adverse events were reported in three subjects in the avibactam group - including one elevation in transaminase levels, and three vital signs events (tachycardia, palpitations, and orthostatic hypotension) - and one in the ceftazidime-avibactam group. All events were considered mild. After single or multiple dosing, plasma concentrations of avibactam and ceftazidime declined in a multi-exponential manner. No plasma concentration accumulation was observed, and the majority of avibactam was excreted unchanged in urine within 24 h. No clinically relevant changes in intestinal bacterial flora were observed. In conclusion, avibactam alone and ceftazidime-avibactam were generally well tolerated in healthy male Japanese subjects, and avibactam pharmacokinetics were comparable whether administered alone or in combination with ceftazidime.

Summer syncope syndrome redux.

BACKGROUND: While antihypertensive therapy is known to reduce the risk for heart failure, myocardial infarction, and stroke, it can often cause orthostatic hypotension and syncope, especially in the setting of polypharmacy and possibly, a hot and dry climate. The objective of the present study was to investigate whether the results of our prior study involving continued use of antihypertensive drugs at the same dosage in the summer as in the winter months for patients living in the Sonoran desert resulted in an increase in syncopal episodes during the hot summer months. METHODS: All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. This is a 3-year retrospective chart review study. They were defined as "cases" if they presented during the summer months (May to September) and "controls" if they presented during the winter months (November to March). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher's exact test. RESULTS: A total of 834 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened: 477 in the summer months and 357 in the winter months. In patients taking antihypertensive medications, there was a significantly higher number of cases of syncope secondary to dehydration during the summer months (40.5%) compared with the winter months (29%) (P = .04). No difference was observed in the type of antihypertensive medication used and syncope rate. The number of antihypertensives used did not increase the cases of syncope in either summer or winter. CONCLUSIONS: An increased number of syncope events was observed in the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. The data confirm our earlier observations that demonstrated a greater number of cases of syncope among people who reside in a dry desert climate who were taking antihypertensive medications during summer months. We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months.

Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine.

OBJECTIVE: To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine. METHODS: During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study. RESULTS: The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6 °C) and a moderate decrease in the toes (27.1±3.7 °C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. CONCLUSION: The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school.

Systolic and diastolic component of orthostatic hypotension and cardiovascular events in hypertensive patients: the Captopril Prevention Project.

OBJECTIVE: Impact of SBP vs. DBP decrement during orthostasis on cardiovascular events in hypertension is not clear. METHODS: We assessed prospective association of orthostatic hypotension with mortality and major cardiovascular events [myocardial infarction (MI) and stroke] among 8788 treated hypertensive patients (52.2% men; mean age 52 years, mean BP 161/99  mmHg) without history of MI or stroke at baseline. Orthostatic hypotension was defined according to combined international consensus criteria, and as either systolic (decrease ≥20  mmHg) or diastolic orthostatic hypotension (decrease ≥10  mmHg). Final Cox regression model was adjusted for age, sex, supine SBP and DBP, diabetes, smoking, and total cholesterol. RESULTS: A total of 1060 (12.1%) study participants fulfilled combined orthostatic hypotension criteria, of these 886 (10.1%) met systolic and 290 (3.3%) diastolic criterion. In the crude analysis, combined orthostatic hypotension criteria were predictive of the composite endpoint, major cardiovascular event, total mortality, and stroke but not MI. After full adjustment, combined orthostatic hypotension criteria and systolic orthostatic hypotension were independently associated with stroke only (hazard ratio: 1.48, 1.07-2.05, P = 0.019, and 1.53, 1.08-2.15, P = 0.015, respectively), whereas the composite endpoint tended in the same direction (hazard ratio: 1.21, 0.98-1.51, P = 0.075, and 1.24, 0.99-1.55, P = 0.066, respectively). In contrast, diastolic orthostatic hypotension was associated with increased risk of MI (hazard ratio: 2.04, 1.20-3.46, P = 0.008). CONCLUSION: Orthostatic hypotension has a dual role in cardiovascular events among hypertensive patients: SBP fall indicates higher risk of stroke, whereas DBP fall confers higher risk of MI.

The effect of udenafil on the hemodynamics of healthy male volunteers administered tamsulosin.

OBJECTIVE: The purpose of this study is to evaluate the hemodynamic interactions between udenafil and tamsulosin. METHODS: After a placebo lead-in period, 27 healthy volunteers received 200 mg udenafil + tamsulosin placebo, udenafil placebo +0.4 mg tamsulosin, or 200 mg udenafil +0.4 mg tamsulosin. Blood pressure and pulse rate (PR) were measured at 15 time points from 0 to 24 hours. RESULTS: A single dose of udenafil, when administered with multiple tamsulosin doses, produced statistically significant increases in PR (mean: 10.7; 95% confidence interval: 5.3, 16.2 bpm; p < 0.001) compared with tamsulosin administered with an udenafil placebo. Systolic and diastolic blood pressure measurements remained unchanged. Two subjects who took udenafil with tamsulosin had a decrease in standing systolic blood pressure (SBP) greater than 30 mmHg in comparison to their baseline SBP; however, compared with the frequency of a decrease in standing SBP greater than 30 mmHg in comparison to the baseline, there was no significant difference in frequency among the four treatments (p = 0.243). There was no difference in the Cmax, AUClast, or AUCinf of udenafil and its active metabolite DA-8164 between the administration of udenafil and udenafil with tamsulosin. CONCLUSION: The coadministration of udenafil and tamsulosin was not associated with clinically significant hemodynamic changes in healthy volunteers. Although this study was conducted on a small number of healthy young subjects, the use of udenafil for the treatment of erectile dysfunction in patients taking tamsulosin for the treatment of benign prostatic hyperplasia is not expected to cause significant safety problems.

[Orthostatic hypotension: implications for the treatment of cardiovascular diseases]. / Hypotension orthostatique : répercussions sur le traitement des maladies cardiovasculaires.

Several cardiovascular drugs may induce or worsen orthostatic hypotension especially in patients treated for hypertension, coronary artery disease and heart failure. Orthostatic hypotension is more frequent in polymedicated elderly patients with co-morbidities (prevalence 23%). In hypertensive elderly patients, the combination of three antihypertensive agents including a beta-blocker induces more frequently orthostatic hypotension. Supplementation in water and especially salt is generally not recommended in case of hypertension and heart failure. Education of patient to preventive counter-pressure maneuvers and muscle training of the lower limbs must be part of treatment. Midodrine causes supine hypertension in almost 25% of patients precluding to take this medication at the end of the afternoon. In severe heart failure, midodrine seems to be helpful to optimize drug treatment in patients suffering from hypotension.

Atrial fibrillation: an independent risk factor for nonaccidental falls in older patients.

BACKGROUND: Nonaccidental falls are often the result of a combination of factors including cardiovascular disorders such as orthostatic hypotension and unspecified cardiac arrhythmias. The objective of this study was to determine if there is an association between atrial fibrillation (AF) and nonaccidental falls. METHODS: We reviewed the records of 442 consecutive patients >65 years old who presented to the Emergency Department at the University of Utah Medical Center with a complaint of fall. RESULTS: Two-hundred eleven patients presented with nonaccidental fall, 231 patients with accidental fall. Patients with nonaccidental fall were more likely to be older, have a history of hypertension and neurological disorders, and taking five or more medications when compared to patients with accidental fall. Despite a similar prevalence of sinus rhythm at presentation, the prevalence of a history of AF was significantly higher in patients with nonaccidental fall compared to patients with accidental fall (26% vs 15%; P = 0.003). After adjusting for clinically and statistically significant predictors with a multivariate logistic regression analysis, AF, neurological disorders, and age ≤81 years were independent predictors of nonaccidental fall. In patients ≤81 years old (median age), the risk of nonaccidental falls was 2.5 times greater in patients with a history of AF when compared to those without a history of AF (odds ratio = 2.53 [confidence interval 95% 1.3-5], P = 0.007). CONCLUSION: AF is an independent risk factor for nonaccidental falls. Our results emphasize the need to screen for AF in patients presenting with nonaccidental fall.

Supplementation with hydrocortisone on the 3rd-5th day following dexamethasone premedicated chemotherapy eliminated severe dizziness and postural hypotension.

We present the case of a 60 year-old woman with a stage III fallopian tube cancer submitted to hysterectomy and bilateral salpingo-oophorectomy with partial omenectomy, followed by six courses of chemotherapy and revision surgery. After each course of chemotherapy (paclitaxel + carboplatin) preceded by premedication with dexamethasone, she suffered from side- -effects, of which the most unpleasant was severe dizziness appearing on the third, fourth and fifth day following the listed combination of drugs. It was revealed that dizziness with concomitant sweating and rapid pulse, noted in the standing position, was combined with marked postural hypotension. Considering the possibility of a temporary pituitary-adrenal axis suppression caused by premedication with a very large dose of dexamethasone, during those three days she was supplemented with small doses of hydrocortisone, which caused almost complete disappearance of the mentioned symptoms. Our conclusion is that postural hypotension causing severe dizziness initially linked with chemotherapeutic drugs can be eliminated or markedly reduced by three days supplementation with hydrocortisone applied after the expected wash out of the dexamethasone.

Medication-related dizziness in the older adult.

With increased medication use among the older adult population, adverse drug events and polypharmacy can be significant causes of dizziness in the elderly. The evidence evaluated in this review is helpful in clinical practice but requires an additional detailed investigation into the agents discussed to understand the risk/benefit ratio associated with medications. Examples of medications highly associated with dizziness in older adults and discussed in this review include cardiovascular and central nervous system agents. Several other medication classes associated with dizziness are among the medications most commonly used by older patients.