Pharmacologic Therapy PDF

10/18/23, 4:54 AM Realizeit for Student Pharmacologic Therapy Phosphodiesterase type 5 (PDE-5) inhibitors (oral medications that are used to treat erectile dysfunction) are first-line therapy (Allen, 2019). Currently available PDE-5 inhibitors include sildenafil, vardenafil, and tadalafil. Each of...

10/18/23, 4:54 AM Realizeit for Student Pharmacologic Therapy Phosphodiesterase type 5 (PDE-5) inhibitors (oral medications that are used to treat erectile dysfunction) are first-line therapy (Allen, 2019). Currently available PDE-5 inhibitors include sildenafil, vardenafil, and tadalafil. Each of these agents has a similar mechanism of action but a different pharmacologic action and clinical use. Erection involves the release of nitric oxide in the vasculature of the corpus cavernosum as a result of sexual stimulation. This subsequently leads to smooth muscle relaxation in blood vessels supplying the corpus cavernosum, resulting in increased blood flow and an erection. During sexual stimulation, PDE-5 inhibitors increase blood flow to the penis (Norris, 2019). When PDE-5 inhibitors are taken about 1 hour before sexual activity, they are effective in producing an erection with sexual stimulation; the erection can last about 1 to 2 hours. The most common side effects of these medications include headache, flushing, dyspepsia, diarrhea, nasal congestion, and lightheadedness. These agents are contraindicated in men who take organic nitrates (e.g., isosorbide, nitroglycerin), because taken together, these medications can cause side effects such as severe hypotension (Cheng et al., 2019; Norris, 2019). In addition, PDE-5 inhibitors must be used with caution in patients with retinopathy, especially in those with diabetic retinopathy. Patient education about the use of these medications and their side effects is summarized in Table 53-3. For patients in whom PDE-5 inhibitors are contraindicated or ineffective, other pharmacologic measures to induce erections include injecting vasoactive agents, such as alprostadil, papaverine, and phentolamine, directly into the penis. Complications include priapism (a persistent abnormal erection) and development of fibrotic plaques at the injection sites. Alprostadil is also formulated in a gel pellet that can be inserted into the tip of the urethra with an applicator to create an erection. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IXpO%2fe0zb8VXpgr8WpGa5yIKHGedfP1dqOEseKVJL%2… 1/5 10/18/23, 4:54 AM Realizeit for Student Phosphodiesterase Type 5 Inhibitors Prescribers commonly order PDE5 inhibitors as the first-line treatment for ED. These drugs do not cause an erection but help maintain the erection resulting from sexual stimuli by enhancing the vasodilatory effect of endogenous nitric oxide, increasing blood flow to the penis. The prototype PDE5 inhibitor is sildenafil (Viagra). Pharmacokinetics Sildenafil is significantly protein bound and is rapidly absorbed by the oral route. The drug is metabolized in the liver and is primarily excreted in the feces and to a lesser extent by the kidneys. The onset of action is 20 to 60 minutes, with a duration of up to 4 hours. Action Sildenafil improves erectile function by inhibiting the enzyme responsible for the breakdown of cyclic guanosine monophosphate (cGMP), a vasodilatory neurotransmitter in corporal tissues of the penis. This causes a vasodilatory effect in the smooth muscle of the corpus cavernosum that allows for a harder and longer-lasting erection. Use Sildenafil is used for the treatment of ED in men healthy enough for sexual activity. The U.S. Food and Drug Administration (FDA) has also approved the drug for the treatment of pulmonary arterial hypertension in men. The drug should not be administered to women and children. Use in Patients With Hepatic Impairment Caution is warranted with the use of sildenafil with hepatic impairment. Patients with cirrhosis or other significant liver dysfunction should start with a lower dose to minimize worsening of the hepatic impairment. Adverse Effects Adverse reactions to sildenafil commonly include headache, facial flushing, dyspepsia, nasal congestion, and dizziness. Rarely, clinicians have reported nonarteritic ischemic optic neuropathy (NAION) due to obstruction of blood flow to the optic nerve, resulting in irreversible loss of vision in one or both eyes, as well as sudden permanent hearing loss accompanied by dizziness and tinnitus. Priapism is rare and usually associated with excessive dosing or concurrent use with another erectogenic drug (capable of causing an erection). Contraindications Contraindications to sildenafil include a known hypersensitivity to the drug. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IXpO%2fe0zb8VXpgr8WpGa5yIKHGedfP1dqOEseKVJL%2… 2/5 10/18/23, 4:54 AM Realizeit for Student QSEN Alert: Safety Prescribers should not order it for men who also take organic nitrates, commonly used to treat angina, because the sildenafil–nitrate combination can cause severe hypotension resulting in dizziness, syncope, heart attack, or stroke. Also, men who are not healthy enough to engage in sexual activity should not take sildenafil. Nursing Implications Preventing Interactions Sildenafil, like other PDE5 inhibitors, is primarily metabolized by the cytochrome P450 (CYP) enzyme CYP3A4. Many medications and herbs interact with sildenafil, increasing or decreasing its effects. Alcohol increases the risk of orthostatic hypotension, tachycardia, dizziness, and headache. Administering the Medication Administration is generally oral. It is important not to take sildenafil more than once in a 24-hour period. A recent high-fat meal may delay drug action. QSEN Alert: Evidence-Based Practice Sexuality is a significant quality-of-life consideration for all individuals. Age-related changes, chronic disease, treatment protocols, and concurrent health conditions can increase the risk of sexual dysfunction in men. In a prospective study of 161 men receiving orchiectomy and radiation therapy for early-stage testicular cancer, researchers explored the short-term effects of treatment on body image and sexual dysfunction (Wortel et al., 2015). Although the cancer itself is not associated with sexual dysfunction, treatment is associated with sexual dysfunction in about one third of patients. Findings demonstrated that more than 60% of the patients reported change in their body image following orchiectomy that was associated with sexual dysfunction. Six months after treatment, more than 20% of men reported a reduction of sexual activity, interest, and pleasure. Because testicular cancer (the most common cancer in men between the ages of 20 and 34 years) often affects men of reproductive age who are sexually active, the nurse should assess for the presence of body image disturbance and sexual dysfunction early in treatment to explore the impact, if present, on quality of life. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IXpO%2fe0zb8VXpgr8WpGa5yIKHGedfP1dqOEseKVJL%2… 3/5 10/18/23, 4:54 AM Realizeit for Student Assessing for Therapeutic and Adverse Effects The nurse should assess that the patient reports the ability to initiate or maintain a penile erection for satisfactory sexual relations. Additionally, the nurse assesses for signs of adverse effects, including headache, facial flushing, dyspepsia, nasal congestion, and dizziness. Patients with symptoms of NAION or sudden decrease or loss of hearing should discontinue sildenafil and seek immediate medical care. Although rare, persistent priapism requires prompt medical treatment to avoid permanent penile damage. Because ED is a strong predictor of coronary artery disease, it is recommended that a cardiovascular assessment be completed in a noncardiac patient who presents with ED. Other Drugs in the Class Three other FDA-approved PDE5 inhibitors have similar effectiveness and safety profiles. Avanafil (Stendra), the newest PDE5 inhibitor, is a fast-acting and highly selective member of the class. The drug reaches its peak in 30 minutes, with a duration of 6 hours. Meals do not affect absorption rate or peak levels. Absorption and metabolism of the drug occurs in the liver through the CYP450 system. Excretion takes place in the feces through the bile. Adverse effects, common to other PDE5 inhibitors, include headache, flushing of the face, nasal congestion, and back pain. Tadalafil (Cialis) has a longer half-life, which gives men the option of taking the drug up to 12 hours before sexual intercourse or as a lower dose, once-a-day daily medication. The drug reaches its peak in 2 hours, with a duration of 24 to 36 hours. Meals do not affect absorption rate or peak levels. Adverse effects, which may linger because of in this longer-acting drug, include back and muscle pain. Vardenafil (Levitra) has a time to peak effect of 1 hour and a duration of action of 4 hours. As with sildenafil, a high-fat meal delays absorption and reduces peak levels. The drug is available in an oral disintegrating tablet. QSEN Alert: Safety Vardenafil is the only PDE5 inhibitor that prolongs the QT interval and should not be used with other drugs with similar effect, particularly class I and II antidysrhythmics. Like sildenafil, vardenafil reduces blood pressure and to a lesser degree increases the risk of light sensitivity, blurred vision, and loss of blue–green color discrimination. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IXpO%2fe0zb8VXpgr8WpGa5yIKHGedfP1dqOEseKVJL%2… 4/5 10/18/23, 4:54 AM Realizeit for Student Adjuvant Medications Used to Treat Erectile Dysfunction Clinicians consider adjuvant drugs second-line therapy in the management of ED and generally reserve them for patients who manifest insufficient response to or adverse effects from PDE5 inhibitors. Alprostadil is a synthetic enzyme that causes relaxation of cavernosal smooth muscle and dilation of cavernosal arterioles leading to increased penile blood flow. It is a prostaglandin, specifically a prostaglandin E1. Administration of alprostadil occurs in two ways: either as an injection into the penis or as a pellet inserted into it (via the urethral opening at the end of the penis). Box 8.7 presents notes about administering the drug. Intracavernosal alprostadil (Caverject) relaxes trabecular smooth muscle and dilates cavernosal arteries, resulting in penile engorgement and reduced venous outflow. Intraurethral alprostadil (Muse) is less efficacious than the intracavernosal drug (60% or less). Administration by either route can produce dose–response improvements in frequency of an erection sufficient for intercourse. The onset of action is immediate following injection, and erection should not last longer than 1 hour with proper dosing (determined in a provider’s office). Intracavernosal injection of alprostadil is associated with a burning sensation, prolonged erection, and priapism, and long-term use is associated with penile fibrosis. Caution is warranted in patients concurrently receiving anticoagulants due to risk of bleeding and in patients at risk for priapism (e.g., sickle cell anemia or trait, multiple myeloma, leukemia). Intraurethral use of the drug is associated with penile pain and minor urethral bleeding. Experts do not recommend alprostadil for concurrent use with other vasoactive agents. Clinical Application 8.2 After an evaluation, the nurse practitioner suspects that Mr. Johnson's erectile dysfunction may result from the combination of obesity and antihypertensive medications. He receives a prescription for lisinopril, an angiotensin-converting enzyme inhibitor, which he will take along with hydrochlorothiazide. What patient teaching guidelines should the nurse discuss with Mr. Johnson and his wife? https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IXpO%2fe0zb8VXpgr8WpGa5yIKHGedfP1dqOEseKVJL%2… 5/5