Can you take viagra twice in one day

The world lost an iconic rock legend in October 2017 when Tom Petty died. Originally determined to be a cardiac arrest, his death was recently revealed to be caused by an accidental drug overdose. The rock star, best known for classic songs such as “Free Fallin’” and “American Girl,” had been taking a variety of medications, including pain medications for a recent hip fracture, according to a statement from his family on his website.

Unfortunately, the story may sound familiar by now. Drug overdoses killed 42,000 people in the U.S. in 2016 (the most recent year for which data is available) and accidental overdoses continue to claim the lives of both icons and non-celebrities every year.

According to the CDC, prescription opioid painkillers (such as oxycodone) are involved in 40 percent of all opioid overdose deaths.

Opioid and opiate drugs bind to and activate opioid receptors in your brain, gut, and spinal cord. These are normally activated by versions of opioids that your body makes naturally and are involved in the way we perceive pain. Opioid receptors are located in parts of the brain that are also heavily involved in the reward system and interact with the neurotransmitter dopamine.

In addition to altering your perception of pain, when taken in large doses, opioid drugs can slow your breathing and make you sedated. That can eventually prevent your brain from getting the oxygen it needs and, in extreme cases, it can kill you. Taking other drugs that also affect this neural system can enhance the effects of opioid drugs without you realizing it, making it that much more likely that you’ll accidentally overdose.

“I tell my patients that when it comes to mixing an opioid pain reliever with another drug, one plus one does not equal two—one plus one equals 11,” Sharon Stancliff, M.D., medical director for the Harm Reduction Coalition in New York City, tells SELF. “The risk of overdose is significantly higher if you are mixing different types of drugs.”

When taking any prescription pain medication—especially opioids—it’s vital to know about all possible drug interactions.

Opioids have a particularly dangerous reaction with prescription drugs called benzodiazepines, or “benzos” for short. While prescription opioids (such as oxycodone and hydrocodone) are used to relieve pain, benzodiazepines (such as alprazolam, clonazepam, diazepam, clobazam, lorazepam, or chlordiazepoxide) are typically prescribed to treat anxiety or to help people sleep.

The problem is that, as SELF previously reported, both drugs cause sedation and breathing issues. Together, they can be fatal. According to the National Institute on Drug Abuse (NIDA), over 30 percent of overdoses involving opioids also involve a benzodiazepine.

Alcohol is another drug that’s dangerous to mix with opioids or benzodiazepines. A CDC analysis of drug overdose deaths concluded that over 22 percent of opioid-related deaths and 21 percent of benzodiazepine-related deaths involved mixing with alcohol, which is also a depressant.

Benzodiazepines and alcohol are the two drugs you should be most careful not to mix with opioids. But the FDA also warns that doctors limit their prescribing of other depressants, muscle relaxants, antipsychotic drugs, and sleep medications alongside opioids for similar reasons. There’s even evidence that antihistamines, which can also cause drowsiness and sedation, may be problematic when combined with opioids.

Additionally, the FDA warns patients to be careful when taking opioids along with antidepressants (e.g. fluoxetine, sertraline, and citalopram) and migraine medications (e.g. sumatriptan) because the combination may cause a dangerous buildup of serotonin in the brain as well as issues with the adrenal gland and sex hormones. The agency also warns about the risks of taking opioids with antiemetic medications (such as ondansetron) and other serotinergic drugs (such as St. John’s wort).

The recognition that blood flow into the corpora cavernosa is regulated by vascular smooth muscle tone and that this tone can be pharmacologically altered with a variety of agents is regarded as one of the most significant advances in the treatment of ED. Initial therapy for ED should ideally be determined by etiology but also evidence based, depending on factors such as treatment efficacy, adverse effects, patient and partner acceptance, psychological effect, reversibility and cost. The ideal treatment for ED must be simple to take, non-invasive, non-painful, have a high success rate and cause few minor side effects.12 Of the treatment options currently available, sildenafil most closely fulfils these criteria. The majority of ED sufferers currently choose oral therapy as a first line treatment and are prescribed sildenafil, the only PDE5 inhibitor currently available.

Response to sildenafil is reduced in chronic ED caused by either severe vasculogenic ED or post radical prostatectomy ED. Steers et al reported that only 55 and 59% of patients with severe ED achieved a response score of 4 or 5 to questions 3 and 4, respectively, of the IIEF inventory erectile function domain when treated with sildenafil 100 mg. Improved erections were reported by only 57% of patients with diabetes mellitus treated with sildenafil in a 3 month flexible dose study.13 McMahon et al have reported that sildenafil is less effective in patients with CVOD as opposed to patients with arteriogenic ED. They demonstrated an inverse relationship between the severity of CVOD as determined by the DICC parameter, flow-to-maintain (FTM), and the response to sildenafil, as judged by patient scores to IIEF erectile function domain questions 3 and 4. They concluded that only patients with mild CVOD and a FTM ≤30 ml/min are likely to respond to sildenafil or combined sildenafil/ICI.14 This is contrary to that reported by Shabsigh who suggested that sildenafil is effective in improving erectile function in patients with ED regardless of the etiology in a randomised placebo controlled study of 329 consecutive patients.15 Shabsigh reported that although responses to questions 3 or 4 of the IIEF in patients treated with sildenafil were superior to placebo, responses did not differ in patients with organic, psychogenic or mixed ED.

The majority of the 30–35% of ED sufferers who fail to respond to the maximum recommended dose of sildenafil (100 mg), chose ICI therapy as second line therapy. Shabsigh et al reported that alprostadil therapy can be used effectively and safely in patients who fail initial therapy with sildenafil. In 67 patients who did not respond satisfactorily to sildenafil, alprostadil ICI resulted in significant improvement in questions 3 and 4 of the IIEF inventory erectile function domain in 60 (89.6%) and 57 (85.1%) patients, respectively.16 Combined sildenafil and ICI therapy has been previously reported as effective salvage therapy for sildenafil non-responders. Twenty nine of 61 patients (47.5%) who failed to respond to sildenafil monotherapy, responded to combined therapy with sildenafil (100 mg) and Trimix ICI with an erection suitable for sexual intercourse.14 Clearly ICI, despite lacking the obvious appeal of an oral medication, remains one of the major elements in the ED treatment armamentarium.

This study group comprised an unselected heterogenous population of chronic ED sufferers and included patients with psychogenic ED and organic ED of a predominantly vasculogenic aetiology. This study demonstrates that administration of sildenafil at doses of 150–200 mg results in sufficient rigidity to achieve vaginal intromission and complete satisfactory sexual intercourse in 24.1% of ED sufferers who had previously failed a trial of sildenafil 100 mg. This is contrary to the manufacturer sponsored pre-marketing studies, where the erectile response to a dose of 200 mg was not differentiable from 100 mg.17 In this study, the response to sildenafil was independent of patient age and duration of ED but was highly dependent on etiology of ED. Rigidity sufficient for satisfactory sexual intercourse was reported by 80% of patients with psychogenic ED but only 18.4% of patients with organic ED. As has been reported previously, patients with CVOD appear less likely to respond to sildenafil as is the case with ICI treatment. Patients with CVOD, either as pure CVOD or as MVED, had significantly lower responses to sildenafil 200 mg than patients with arteriogenic ED (P<0.05). Clearly, our concepts about the etiology and mechanism of CVOD may need revision. CVOD is probably a multi-etiological condition involving not only degenerative cavernous myopathy, incompetence of the tunica albuginea or corporo-spongiosal shunts but also possibly disturbances of penile innervation or neurotransmitter release, failure in prostanoid synthesis or signal transduction via gap junctions, malfunctions of the enzymes nitric oxide synthase, adenylcyclase or guanylate cyclase or malfunction of the potassium channels. If this is in fact correct, it seems reasonable to assume that different etiologies of CVOD may respond to different treatments, that combination treatments may have a role and that our future management of patients with ED may re-focus on an evidence based etiological diagnosis approach in order to identify the most rational etiology specific treatment(s).

A failure to respond to sildenafil was common in patients with post RRP ED for prostate cancer. This parallels the experience of the Sildenafil Study Group who reported that only 43% of patients who had had RRP responded to sildenafil and suggested surgical damage to the cavernous nerves, with subsequent failure to activate the NO-cGMP pathway as the probable mechanism.6 Our study group was unselected, relatively small and comprised a majority of patients who had undergone non-nerve sparing procedures. Improved results would be expected following a nerve sparing procedure. Lowentritt et al reported improved erections in 53% and improved capacity for sexual intercourse in 40% of patients taking sildenafil after nerve sparing RRP which was dependent on patient age, pathological stage and degree of nerve sparing surgical technique.18 Hong et al suggested that the response to sildenafil was dependent upon the interval between nerve sparing RRP and reported that the treatment satisfaction increased to a peak at 60% 18–24 months after surgery.19

Adverse effects were reported more frequently by participants in this study than by participants in the earlier studies although the adverse effect severity profile was similar.6,8,9,20 Headaches, facial flushing, nasal congestion and dyspepsia remained the most common adverse effects. The higher incidence of reported adverse effects in this study clearly relates to the higher dose of sildenafil used. Adverse effects reflect the pharmacological action of sildenafil as a PDE-5 inhibitor and a weak PDE-6 inhibitor. Of particular interest is the fact that 31% of sildenafil responders were not prepared to continue treatment with sildenafil due to intolerable adverse effects. This contrasts significantly to that reported previously (2.6% and 9%).6,11 This is, however, less than the reported alprostadil ICI drop-out rate of 37%.21 As such, the role of high dose salvage therapy is limited by patient acceptance of a higher incidence of adverse effects.

This study reports a lack of major cardiovascular adverse effects associated with taking high dose sildenafil confirming the previously reported excellent safety profile of sildenafil. An increased risk of developing coronary artery disease and myocardial infarction in patients suffering ED is also demonstrated. An association between atherosclerotic coronary artery disease (CAD) and ED has been reported by several investigators. This is not surprising as the majority of patients with ED have vasculogenic ED due to atherosclerosis of the hypogastrico-cavernous axis. Furthermore, both clinical entities share the same risk factors including cigarette smoking, hypertension, hyperlipidaemia and diabetes mellitus. The incidence of acute myocardial infarction and cardiac death in this study exceeds that reported in the general community.22

Several authors have suggested an increased incidence of silent myocardial ischaemia in patients with vasculogenic ED over the general community and identified vasculogenic ED as a possible independent risk factor for coronary artery disease.23,24,25,26 Matsuzawa et al reported that 5 out of 20 patients with ED and no prior history of coronary artery disease, had exercise electrocardiogram changes suggestive of silent coronary artery disease.24 Similarly, Kawanishi et al reported a 20.7% incidence of abnormal stress electrocardiograms in 58 patients with ED and no history of coronary artery disease. They reported abnormal stress electrocardiogram findings in 54.8% of patients with penile CDU evidence of vasculogenic ED as opposed to only 3.7% of patients with normal penile CDU.25 Unfortunately the results of coronary angiography were not reported in either study so the high incidence of abnormal stress electrocardiogram findings reported almost certainly overstates the true incidence of silent myocardial ischaemia. Physicians must consider the cardiovascular status of ‘at risk’ patients with vasculogenic ED and significant vascular risk factors prior to initiating any treatment for ED including sildenafil. Sildenafil prescribing guidelines proposed by the ACC/AHA should be followed and ‘at risk’ patients may require cardiological assessment with exercise electrocardiography, stress echocardiography or persantin thallium stress testing.27

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *