Agent For Erectile Dysfunction Research Articles

Investigation of Cissus populnea as a Potential Therapeutic Agent for Erectile Dysfunction.

Cissus populnea (CP) is a plant reported to possess an erection-enhancing ability, though mechanisms remain unclear. Drugs targeting phosphodiesterase 5 (PDE5) inhibition, such as sildenafil, have been employed to treat erectile dysfunction (EDRF), but they are associated with several complications. This study investigated the effect of C. populnea extracts (aqueous and saponin-rich) on the activity and gene expressions of proteins related to erection. PDE5, Nitric oxide synthase (NOS) and androgen receptor (AR) genes were studied using RT-PCR on CP-treated paroxetine-induced ERDF-rats. It also employed Schrödinger suites for investigations such as molecular and induced-fit docking, MMGBSA, ADMET, and QSAR profiling of CP-phytocompounds. C. populnea extracts reduce the activity and downregulate the expression of the PDE5 gene while upregulating the expressions of AR and NOS genes in the ERDF-rats relative to the control group. Five (leading) compounds with induced-fit docking (IFD) scores in kcal/mol, namely, stigmasterol (-638.73), daucosterol (-644.73), furostanol (-639.29), papaverine (-639.03), and capsaicin (-642.88), had better docking scores of -9.936, -9.824, -9.064, -8.863, and -8.736 kcal/mol, respectively, compared with those of sildenafil (-8.611 kcal/mol). They also showed an excellent ADMET profile, satisfying Lipinski's rule of five. The MMGBSA predictions revealed that stigmasterol, daucosterol, papaverine, and capsaicin had binding free energies of -45.29, -59.14, -50.63, and -50.47 kcal/mol, respectively, suggesting that they are significant inhibitors of PDE5. The QSAR model revealed that lead compounds possess good pIC50 values. These results indicate that C. populnea is a more promising possible treatment for controlling EDRF and deserves further research.

(108) Evaluation the Efficacy and Safety of Hyperbaric Oxygen Therapy in Sildenafil Citrate Non Responder Organic Erectile Dysfunction Patients: a Randomized Double Blinded Controlled Clinical Trial

Abstract Introduction Although the phosphodiesterase 5 inhibitors (PDE5i) are the first-line oral agents for erectile dysfunction (ED) treatment, there is growing number of PDE5i- non responder patients. Management of those patients is challenging and one of the new suggested regenerative therapies is the hyperbaric oxygen therapy (HBOT). HBOT is the application of oxygen under pressure to increase tissue oxygen levels. Few clinical reports were published about HBOT and ED. Objective To evaluate the efficacy and safety of HBOT in sildenafil citrate non- responder organic ED patients. Methods The current study included 30 sildenafil citrate non-responder ED patients. Patients were divided into two groups (randomly assigned and comparably cross-matched for age). Both patients and the investigators were blinded as regards the treatment until the end of the study. Group 1: Patients assigned to the HBOT group (20 patients) were treated with (30) sessions in 5 days/week (90 minutes of 100% oxygen at 2.2 ATA); Group 2: Patients assigned to the control group (10 patients) were exposed to (30) sessions of air oxygen tension at 1 ATA with room oxygen. Baseline laboratory investigations were done (random blood sugar, lipid profile, total & free testosterone). All patients were evaluated with the sexual health inventory for men (SHIM), erection hardness score (EHS), the sexual health encounter profile (SEP), and penile color Doppler initially, at 1 & 3 months after the end of treatment. Results The age mean ± SD in the HBOT group was 56.35±7.43 years and in the control group was 61.7±7.14 years. The current study showed that sildenafil citrate non-responders ED patients with 30 sessions of HBOT in 5 days/week, demonstrated a significant improvement of the total SHIM score, EHS, and SEP after 1 month of stoppage of treatment as compared to the control group. Also, penile color Doppler evaluation showed a significant improvement of 10 &20 minutes peak systolic velocity (PSV) between patients receiving HBOT compared to the control after 1 month of stoppage of treatment. More interestingly, the improvement of the total SHIM score, EHS, and SEP continued after 3 months of stoppage of the HBOT treatment as compared to the baseline evaluation. In addition, 10 &20 minutes PSV with penile color Doppler evaluation demonstrated maintained improvement after 3 months of stoppage of the HBOT treatment as compared to the baseline evaluation. In addition, the linear regression analysis was done for factors affecting SHIM score improvement (1 month/baseline) in the HBOT treatment group, revealing that hypertension was an independent predictor for SHIM score improvement. Hypertensive patients showed 4.6 times more SHIM score improvement as compared to non-hypertensive patients. As regards HBOT safety, there was no significant difference in adverse effects between the HBOT treatment group and the control group. Conclusions HBOT might be a potential therapeutic modality for sildenafil citrate non-responder ED patients especially in hypertensive patients with good safety profile. Further a multi-centric trial with a larger sample size and a longer follow-up period is recommended. Disclosure No.

A pilot RCT of an online mindfulness‐based cognitive intervention for chemsex

AbstractObjectivesChemsex is a term used to describe sex acts using psychoactive substances to enhance the sexual experience/arousal and predominates among men who have sex with men (MSM). Chemsex drugs predominantly include γ‐hydroxybutyric acid (GHB) and analogues, methamphetamine, mephedrone and erectile dysfunction agents (e.g., Sildenafil). Mindfulness‐based cognitive therapy (MBCT) combines cognitive therapy and mindfulness and has been shown to help support both sexual functioning and methamphetamine use. However, limited clinical trials have evaluated the use of cognitive mindfulness for chemsex in MSM. The present study assessed the effectiveness of an online mindfulness‐based cognitive intervention (MBCI) among 29 MSM aged 18–30 years engaged in chemsex.Design and SettingA mixed methods approach consisted of a randomised waitlist‐controlled trial and a content analysis reviewing participants' feedback on MBCI. The design of the intervention was based on a behavioural taxonomy mapped to selected behaviour change techniques (BCTs) to support the reliability of MBCI in its delivery.Main Outcome MeasuresParticipants completed assessments measuring levels of chemsex, mindfulness, sexual self‐efficacy and well‐being, taken at Weeks 0, 8 and 12 (follow‐up).ResultsParticipants reported lower levels of chemsex and higher levels of cognitive mindfulness, sexual self‐efficacy and well‐being postintervention and at the 12‐week follow‐up. The content analysis feedback responses yielded favourable outcomes, suggesting that participants developed a sense of self‐compassion, confidence and positive identity.ConclusionsThe MBCI effectively reduced chemsex; however, this study warrants replication with a larger, more diverse group of participants.

Combination vardenifil and tadalifil drug induced liver injury; case report and review of the literature of liver injury associated with phosphodiesterase type 5 inhibitors.

Phosphodiesterase type 5 inhibitors (PDE5I) are prescribed for erectile dysfunction and pulmonary hypertension. Despite its widespread use, there are only seven cases of drug-induced liver injury (DILI) associated with PDE5I, none associated with vardenafil or avanafil. We report a patient who had taken vardenafil and tadalafil individually for several years without developing symptoms of liver injury. However, after taking vardenafil and tadalafil together on 2 consecutive days, he developed severe cholestasis. Causality was determined using Roussel Uclaf causality assessment method (RUCAM). The patient is a 72-year-old White man in excellent health who drank 2 units of alcohol, three times/week. Previously, he had used vardenafil for more than 2 years and tadalafil for 3 months as single agent for erectile dysfunction without any complications. He took vardenafil and tadalafil for 2 consecutive days and 5 days later, he developed dyspepsia, loss of appetite, jaundice, and intense itching. Liver tests showed mixed cholestatic/hepatocellular pattern of injury. Histology showed marked cholestasis with minimal inflammation. He remained cholestatic for 5 weeks before a full recovery 2 months later. The patient then resumed vardenafil monotherapy with no recurrent liver dysfunction. RUCAM causality score 7 indicates that the combination of PDE5I is probable cause of liver injury. The similarities among the eight cases of PDE5I DILI include a relatively short latency, cholestatic histological features, and complete recovery. Biochemical pattern of liver injury is variable. PDE5I DILI is a rare event that can result in severe acute liver injury.

Do ART and Chemsex Drugs Get Along? Potential Drug-Drug Interactions in a Cohort of People Living with HIV Who Engaged in Chemsex: A Retrospective Observational Study.

People living with HIV (PLWH) who engaged in chemsex are at risk of potential drug-drug interactions (pDDIs) with recreational drugs. This study aimed to characterize pDDIs between antiretroviral treatment (ART) and chemsex drugs and evaluate their association with unscheduled relevant hospital consultations. We conducted a single-center, retrospective, observational study in a series of gay, bisexual, and other men who have sex with men (gbMSM) living with HIV who engaged in chemsex and who attended a tertiary hospital in Barcelona, Spain, from February 2018 through August 2019. Associations between all recorded pDDIs and relevant unscheduled consultations were estimated using the incidence rate (IR) per 100 person-years of those events compared between patients with no pDDI (green flag) or moderate severity pDDI (orange flag) with patients with high severity pDDI (red flag) using the incidence rate ratio (IRR). Among 172 PLWH engaged in chemsex, 249 ART regimens were prescribed: 44% based on integrase inhibitors, 30% on boosted ART, and 26% based on non-nucleoside reverse transcriptase inhibitors. The substances and recreational drugs most frequently used were erectile dysfunction agents (83%), methamphetamine (79%), GHB (77%), and alkyl nitrites (71%). Polydrug use was reported in 52%. We observed 2048 pDDIs. Of these, 23% were orange flag pDDIs; 88% related to boosted ARTs. The IR of the 285 unscheduled relevant episodes in patients with orange flag pDDIs was 64.67 (95%CI 40.07-89.28). The IRR of green flag pDDIs was 1.05 (95%CI 0.60-1.8; p = 0.876). One in four pDDIs were of moderate severity but no significant increase in the incidence of unscheduled relevant consultations was observed. A high number of unscheduled consultations, predominantly for psychiatric events and intoxication, were observed. Beyond using non-boosted ART to minimize pDDIs, other factors related to the practice of chemsex must be addressed, in order to offer a better approach.

Drug Therapies Affecting Renal Function: An Overview.

Undesirable side effects of medication are inevitable. Due to the role of the kidneys in clearance and filtration, the renal system faces a unique situation when it comes to the side effects of drugs. It has an important role for different classes of drugs to be excreted, and drugs are a key factor for this system to be at risk. Medications in articles were divided into classes using the standard set by the Saudi Pharmaceutical Journal. Many drug classes cause renal insults. The top six classes were pain killers, antibiotics, proton pump inhibitors, antidiabetics, antihyperlipidemics, and agents for erectile dysfunction. Renal insults caused by these agents could vary in severity. Some drugs could cause nephrotoxicity from one dose, while others may only need continuous monitoring. Different populations also operate under different rules, as some people need dose adjustments while others who are medically free of major illnesses do not. A variety of unfavorable outcomes for the kidney could take place, such as acute kidney injury, chronic kidney disease, and end-stage renal disease, and unfortunately, some of these issues could lead to the need for renal replacement therapies. The outcome of this review paper will help multidisciplinary physicians to understand the renal side effects of the most used drug classes in the Kingdom of Saudi Arabia, their destructive mechanisms, and most importantly, the clinical presentations of renal dysfunction in relation to each class. Emphasizing these adverse effects will prevent future unfavorable outcomes, especially in commonly used drugs that are frequently prescribed for different age groups. Moreover, some of these drugs are considered to be over-the-counter medications, which makes them a serious problem that needs to be handled cautiously.

Delineation of chemsex patterns of men who have sex with men in association with their sexual networks and linkage to HIV prevention

BackgroundPrevious studies have shown that men who have sex with men (MSM) and who engage in drug use in sexualized contexts (chemsex) were more likely to be HIV positive. Their social networks and adoption of HIV prevention measures have, however, not been fully investigated. We aim to compare the sexual behavior, HIV prevention efforts and social networks of MSM by the intensity and patterns of their drug use. MethodsData from respondents of a community-based, cross-sectional survey (PRiSM) conducted among MSM in Hong Kong in 2017 were collected retrospectively. Characteristics of MSM engaged and not engaged in chemsex were compared in logistic regressions, delineated by latent class analysis (LCA) and compared in multinominal logistic regression. FindingsOf 4133 respondents, 3044 were sexually active with an HIV prevalence of 6.5%. The prevalence of chemsex engagement in the preceding 6 months was 12%, after excluding use of poppers or erectile dysfunction agents (EDA) alone. Four types of drug user were identified by LCA: Minimal (mainly poppers), low-threshold (mainly poppers and EDA), medium-threshold (mainly methamphetamine, GHB, poppers and EDA) and intense (extensive use of different types of drug). Medium-threshold and intense drug users were more likely to be HIV positive, be diagnosed with sexually transmitted infections, make gay friends through mobile apps and sex parties, and intend to take pre-exposure prophylaxis (PrEP). Medium-threshold drug users had a more influential role in their social network, as shown by their higher centrality in mobile apps network. ConclusionChemsex engagement in MSM is significantly associated with HIV infection in Hong Kong. The HIV transmission risk could however be offset by the inclination of MSM belonging to medium-threshold and intense drug users to take PrEP, should the intervention become accessible to the community. Further mobile apps could be a good channel to access MSM who are medium-threshold drug users.

The herbal formula KH-204 is protective against erectile dysfunction by minimizing oxidative stress and improving lipid profiles in a rat model of erectile dysfunction induced by hypercholesterolaemia

BackgroundHypercholesterolaemia (HC) is a major risk factor for ischemic heart disease and is also known to be a risk factor for erectile dysfunction (ED). ED caused by HC is thought to be related to HC-induced oxidative stress damage in the vascular endothelium and erectile tissue. KH-204 is an herbal formula with a strong antioxidant effect. We evaluated the effects of KH-204 on erectile function in a rat model of HC-induced ED.MethodsMale Sprague-Dawley rats (6 weeks old) were divided into normal control, high-fat and cholesterol diet (HFC), and HFC with KH-204 treatment (HFC + KH) groups (n = 12 each). Normal control group rats were fed normal chow diet. HFC and HFC + KH group rats were fed high-fat and cholesterol diets and treated with or without daily oral doses of KH-204 for 12 weeks. Subsequently, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured, and lipid profiles, expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase, oxidative stress (8-hydroxy-2-deoxyguanosine), and ratio of smooth muscle cells and collagen fibres were evaluated in the serum and corpora tissue.ResultsCompared to the HFC group, the HFC + KH group showed statistically significant increases in peak ICP and ICP/MAP ratio, expression of eNOS and nNOS, and ratio of smooth muscle cells and collagen fibres (p < 0.05). The HFC + KH group also showed statistically significant decreases in oxidative stress (p < 0.05). Further the lipid profiles of this group were ameliorated compared to those of the HFC group (p < 0.05).ConclusionsThe current study shows that the antioxidant and hypolipidemic effects of KH-204 are effective in ameliorating ED by restoring endothelial dysfunction and suggests that KH-204 may be a potential therapeutic agent for ED by correcting the fundamental cause of ED.

健康食品中の強壮、ダイエット、催眠および血糖降下薬に関連する医薬品15成分の液体クロマトグラフ/タンデム質量分析計(LC/MS/MS)による一斉分析法の検討

健康食品中の強壮、ダイエット、催眠および血糖降下薬に関連する医薬品15成分の液体クロマトグラフ/タンデム質量分析計(LC/MS/MS)による一斉分析法の検討

Sildenafil enhances locomotor activity in young mice and exerts anxiogenic effects in both young and aged mice

BackgroundSildenafil is a selective PDE5 inhibitor that increases cGMP levels in the target tissues and is an effective treatment agent for erectile dysfunction. The nitric oxide-cGMP pathway might be implicated in regulation of certain CNS functions, including locomotor activity and anxiety.Material/MethodsThe aim of the current study was to investigate effects of sildenafil (3 and 10 mg/kg) on anxiety and locomotor activity in open field and elevated plus maze (EPM) tests in young and aged mice.ResultsSildenafil (3 and 10 mg/kg) significantly decreased the percent of time spent in the open arms compared to the control group in young animals in the EPM test, but only the 10 mg/kg dose significantly decreased the percentage of total number of entries to the open arms in young animals. Sildenafil (3 and 10 mg/kg) significantly decreased the percentage of total number of entries to the open arms in aged animals in the EPM test, but it significantly increased total distance moved and speed of the animals in the locomotor activity test in young animals. The total distance moved and the speed of the animals significantly decreased in aged animals compared to the young control group, although sildenafil (3 and 10 mg/kg) did not alter these parameters in aged mice.ConclusionsOur results show that sildenafil had anxiogenic effects in young as well as aged mice, but it enhanced locomotor activity only in the young mice in the EPM test. Thus, sildenafil seems to exert different effects on anxiety and locomotion in young and aged animals.

Simple and sensitive liquid chromatography–tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction. Tadalafil and acebutolol (internal standard) were extracted by liquid-liquid extraction with tert-butyl methyl ether. The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0.1 % formic acid and acetonitrile (45:55, v/v) at a flow rate of 0.3 mL/min. The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro™ API mass spectrometer. The calibration curve was linear over a concentration range of 2-2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV %) of 10.9 %. Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL). Tadalafil was found to be stable in a battery of studies, including bench top, freeze-thaw, and autosampler conditions. The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg.

Effects of Experimental Hyperlipidemia on the Pharmacokinetics of Tadalafil in Rats

Hyperlipidemia is associated with an increased risk of erectile dysfunction. In this study, we investigated the effects of hyperlipidemia on the pharmacokinetics of tadalafil, a novel therapeutic agent for erectile dysfunction, in rats with experimental hyperlipidemia. Tadalafil (1 mg/kg) was administered to control rats and rats with poloxamer-407-induced hyperlipidemia (1 g/kg, i.p.). In addition, we performed in vitro studies to determine the hepatic metabolism in S9 fractions, intestinal absorption, and plasma protein binding. Hyperlipidemia dramatically increased tadalafil's the total area under the plasma concentration-time curve from time 0 to infinity after intravenous (2.09-fold) and oral (11.9-fold) administration, and decreased total body clearance (0.537-fold) and apparent volume of distribution at the steady state (0.438-fold) after intravenous administration of tadalafil. Further, we observed decreased in vitro hepatic S9 metabolism, intestinal first-pass metabolism, and unbound fraction of tadalafil. The alterations in the pharmacokinetics of tadalafil observed in rats with poloxamer 407-induced hyperlipidemia may be attributable to a decrease in hepatic and intestinal metabolism and unbound fraction of tadalafil in the plasma. These findings have potential therapeutic implications for predicting the pharmacokinetic responses of humans to hyperlipidemia. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Vardenafil and Resveratrol Synergistically Enhance the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway in Corpus Cavernosal Smooth Muscle Cells and Its Therapeutic Potential for Erectile Dysfunction in the Streptozotocin‐Induced Diabetic Rat: Preliminary Findings

Phosphodiesterase type 5 (PDE5) inhibitors are very effective agents for erectile dysfunction; however, specific patient populations are hard to treat. The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Resveratrol, a plant polyphenol, is reported to activate endothelial NO synthase (eNOS) through activation of sirtuin 1. We previously reported that human corpus cavernosal smooth muscle cells (CCSMCs) express eNOS and synthesize cyclic guanosine monophosphate (cGMP) via the NO/cGMP pathway. To investigate the ability of resveratrol and/or vardenafil to increase cGMP in an in vitro model using CCSMCs and to improve erectile function in an in vivo rat model of streptozotocin (STZ)-induced diabetes. CCSMCs were treated with resveratrol and/or vardenafil. Twenty male Sprague-Dawley rats were randomly divided into five groups (N = 4 in each group): age-matched controls, diabetic controls, and diabetic rats treated with resveratrol, vardenafil, or both in combination for the last 4 weeks of an 8-week period of diabetes induction. Intracellular cGMP measurement, intracovernous pressure (ICP)/mean arterial pressure (MAP) ratio, and smooth muscle/collagen ratio. Intracellular cGMP level was elevated by resveratrol treatment in CCSMCs. The combination treatment of resveratrol and vardenafil had a synergistic effect. Diabetic rats showed impairment of erectile function. Treatment with either resveratrol or vardenafil improved ICP/MAP ratio, and combination therapy with resveratrol and vardenafil had a synergistic effect in improvement of ICP/MAP. Treatment with either resveratrol or vardenafil elevated cGMP level in CCSMCs and improved erectile function in STZ-induced diabetic rats. Furthermore, a synergistic effect was observed in vitro and in vivo. Resveratrol or combination therapy of resveratrol and vardenafil can improve erectile function in which NO release is impaired, although further study is needed to confirm the results.

A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil

A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION) 12 hours after receiving sildenafil citrate (Viagra®). Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs.

A NOVEL CLINICAL ENTITY OF OBSTRUCTIVE AZOOSPERMIA: PHENOTYPIC ANALYSIS OF TESTICULAR GERM CELL-SPECIFIC GENE MEICHROACDIN-DISRUPTED MICE AND GENOTYPIC ANALYSIS OF HUMAN MEICHROACIDIN IN MALE INFERTILE POPULATION

Phosphodiesterase type 5 (PDE5) inhibitors are very effective agents for erectile dysfunction; however, specific patient populations are hard to treat. The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Resveratrol, a plant polyphenol, is reported to activate endothelial NO synthase (eNOS) through activation of sirtuin 1. We previously reported that human corpus cavernosal smooth muscle cells (CCSMCs) express eNOS and synthesize cyclic guanosine monophosphate (cGMP) via the NO/cGMP pathway.To investigate the ability of resveratrol and/or vardenafil to increase cGMP in an in vitro model using CCSMCs and to improve erectile function in an in vivo rat model of streptozotocin (STZ)‐induced diabetes.CCSMCs were treated with resveratrol and/or vardenafil. Twenty male Sprague‐Dawley rats were randomly divided into five groups (N = 4 in each group): age‐matched controls, diabetic controls, and diabetic rats treated with resveratrol, vardenafil, or both in combination for the last 4 weeks of an 8‐week period of diabetes induction.Intracellular cGMP measurement, intracovernous pressure (ICP)/mean arterial pressure (MAP) ratio, and smooth muscle/collagen ratio.Intracellular cGMP level was elevated by resveratrol treatment in CCSMCs. The combination treatment of resveratrol and vardenafil had a synergistic effect. Diabetic rats showed impairment of erectile function. Treatment with either resveratrol or vardenafil improved ICP/MAP ratio, and combination therapy with resveratrol and vardenafil had a synergistic effect in improvement of ICP/MAP.Treatment with either resveratrol or vardenafil elevated cGMP level in CCSMCs and improved erectile function in STZ‐induced diabetic rats. Furthermore, a synergistic effect was observed in vitro and in vivo. Resveratrol or combination therapy of resveratrol and vardenafil can improve erectile function in which NO release is impaired, although further study is needed to confirm the results. Fukuhara S, Tsujimura A, Okuda H, Yamamoto K, Takao T, Miyagawa Y, Nonomura N, and Okuyama A. Vardenafil and resveratrol synergistically enhance the nitric oxide/cyclic guanosine monophosphate pathway in corpus cavernosal smooth muscle cells and its therapeutic potential for erectile dysfunction in the streptozotocin‐induced diabetic rat: Preliminary findings.

Clinical applications of centrally acting agents in male sexual dysfunction

Currently available agents for erectile dysfunction (ED) share the same mechanism of action and pharmacologic properties. Therefore, they share the same limitations, including a principal focus on erection as an end-organ process. One of the relatively unexplored areas of research has been the potential for centrally acting agents to improve male sexual response. A variety of neurohormones and neurotransmitter systems are involved in the male sexual response, including testosterone, dopamine, serotonin and the melanocortin systems. Investigations to determine the utility of centrally acting agents as monotherapy or adjunctive therapy in men with ED or other forms of sexual dysfunction are underway. Bremelanotide, a melanocortin agonist, has been tested in men with ED and may prove to be one of the first centrally acting agents to have clinical utility in male sexual dysfunction.

Salvage Strategies for Nonresponders to Phosphodiesterase-5 Inhibitor Treatment for Erectile Dysfunction in the Aging Male

This article reviews contemporary treatment strategies for the aging male who does not demonstrate a satisfactory response to first-line oral phosphodiesterase-5 inhibitor agents for erectile dysfunction. More than half of men aged 40–70 years are unable to attain or maintain a penile erection sufficient for satisfactory sexual performance, with the prevalence of erectile dysfunction climbing to more than 75% among those aged over 70 years. However, the aging male may fail to respond to or express dissatisfaction with oral on-demand treatment. Clinically effective phosphodiesterase-5 inhibitor salvage strategies include patient re-education, lifestyle changes, correction of risk factors, dose adjustment, agent switching, androgen replacement and/or psychosexual or relationship counseling. Important new data supporting the safe and efficacious use of daily phosphodiesterase-5 inhibitor dosing schedules are reviewed. If required, progression to second- and third-line treatments is appropriate for most men, and may include intracavernous penile injections, vacuum erection devices, multimodality therapy or implantation of a penile prosthesis.

Mechanisms of Pharmacokinetic and Pharmacodynamic Drug Interactions Associated with Ritonavir‐Enhanced Tipranavir

Tipranavir is a nonpeptidic protease inhibitor that has activity against human immunodeficiency virus strains resistant to multiple protease inhibitors. Tipranavir 500 mg is coadministered with ritonavir 200 mg. Tipranavir is metabolized by cytochrome P450 (CYP) 3A and, when combined with ritonavir in vitro, causes inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in addition to induction of glucuronidase and the drug transporter P-glycoprotein. As a result, drug-drug interactions between tipranavir-ritonavir and other coadministered drugs are a concern. In addition to interactions with other antiretrovirals, tipranavir-ritonavir interactions with antifungals, antimycobacterials, oral contraceptives, statins, and antidiarrheals have been specifically evaluated. For other drugs such as antiarrhythmics, antihistamines, ergot derivatives, selective serotonin receptor agonists (or triptans), gastrointestinal motility agents, erectile dysfunction agents, and calcium channel blockers, interactions can be predicted based on studies with other ritonavir-boosted protease inhibitors and what is known about tipranavir-ritonavir CYP and P-glycoprotein utilization. The highly complex nature of drug interactions dictates that cautious prescribing should occur with narrow-therapeutic-index drugs that have not been specifically studied. Thus, the known interaction potential of tipranavir-ritonavir is reported, and in vitro and in vivo data are provided to assist clinicians in predicting interactions not yet studied. As more clinical interaction data are generated, better insight will be gained into the specific mechanisms of interactions with tipranavir-ritonavir.

Ocular Adverse Effects Associated with Systemic Medications

This article reviews several retrospective case series and reported adverse events regarding common ocular adverse effects related to systemic therapy. It is not intended as a comprehensive summary of these well described adverse drug reactions, nor is it intended to cover the complete spectrum of all ocular adverse effects of systemic therapy. Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications. For this review, the certainty of the adverse effect profile of each medication was evaluated according to the WHO Causality Assessment Guide.A certain relationship has been established for pamidronate and alendronate as causes of scleritis, uveitis, conjunctivitis and blurred vision. Topiramate has been established as adversely causing symptoms consistent with acute angle-closure glaucoma, typically bilateral. Vigabatrin has been shown to cause bilateral irreversible visual field defects attributed to underlying medication-induced retinal pathology. Isotretinoin should be considered in the differential diagnosis of any patient with pseudotumour cerebri. Patients taking amiodarone and hydroxychloroquine should be monitored and screened regularly for development of optic neuropathy and maculopathy, respectively. Sildenafil has been reported to cause several changes in visual perception and is a possible, not yet certain, cause of anterior ischaemic optic neuropathy. Patients taking tamoxifen should also be monitored for development of dose-dependent maculopathy and decreased colour vision. COX-2 inhibitors should be included in the differential diagnosis of reversible conjunctivitis. Several herbal medications including canthaxanthine, chamomile, datura, Echinacea purpurea, Ginkgo biloba and liquorice have also been associated with several ocular adverse effects. It is the role of all healthcare professionals to detect, treat and educate the public about adverse reactions to medications as they are an important health problem.

Electrospray Ionisation - Mass Spectrometry (ESI-MS) and Liquid Chromatography -Electrospray Ionisation - Mass Spectrometry (LC-ESI-MS) of Selected Pharmaceuticals

This review surveys recent publications on the Electrospray Ionisation - Mass Spectrometry (ESI-MS) of drugs of small molecular mass taken from selected drug classes using the Web of Knowledge database. The structural classes are antibiotics/antibacterials, steroids, cannabinols, antidiabetics, immunosuppressants, antitumour drugs, antiretroviral drugs, nonsteroidal antiinflammatories, mucolytic drugs, anticoagulants, cyclooxygenase inhibitors, stimulants, noradrenergic agents, anti-TB drugs and erectile dysfunction agents. Fragmentation information that these drugs exhibit in-source and in ion-trap, triple quadrupole and time-of flight mass spectrometers is also provided. An appraisal of applications for the period 2004-2005, again taken from the Web of Knowledge database, of the technique liquid chromatography - electrospray ionization - mass spectrometry (LC-ESI-MS) to the detection and determination of these drugs, primarily in biomatrices, is then made. Information on such aspects as sample concentration, LC separation conditions, recoveries from biological media and limits of detection (LODs) are provided. Keywords: Elect rospray ionis ation mass spect rometry (ESI- MS), Fragm entation patte rns, Drug analy sis by liqui d chrom atography- electrospr ay ionis ation mass spect rometry (LC-E SI-MS), Drugs of small molec ular mass