Precautions

A number of common factors can increase the risk of adverse events when using PDE5 inhibitors. Therefore, everyone should be medically evaluated for overall health, fitness for sexual activity and underlying causes of erectile dysfunction prior to initiating treatment with a PDE5 inhibitor like Viagra®, Cialis® or Levitra®.

Sexual activity can pose a very small but measurable cardiovascular risk even for healthy individuals. Aging, disease and medications can increase this risk. Patients who experience: angina pectoris, dizziness or nausea during sexual activity should stop activity and seek medical advice.

Endothelial dysfunction and cardiovascular disease are often found to be comorbidities in patients with erectile dysfunction. Emergency room nurses will need to include PDE5 use into patient assessment and history taking. A brief description of the risk associated with combining PDE5 and a number of common cardiac treatments may help elicit disclosure.

PDE5 contraindications:

The use of a PDE5 inhibitor is contraindicated in patients with known hypersensitivity to any component of the medication.
Recent exposure to or use of organic nitrates in any form is a contraindication to PDE5 treatment due to the increased risk of life threatening hypotension.
Health care professionals need to warn patients of the significant risk posed by the recreational use of PDE-5 inhibitors combined with nitrates like amyl nitrate.

Organic nitrates like nitroglycerine and amyl nitrate are used worldwide to treat ischemic heart disease. The primary medical use of nitrates is as a vasodilator. Organic nitrates increase the level of available nitric oxide in the system. A study by Feelisch and Kelm demonstrated the ability of vascular endothelium and vascular smooth muscle to metabolize organic nitrates to nitric oxide (NO). The amount of NO correlated strongly with the amount of cGMP produced by cells. Increased cGMP concentration is known to induce vascular dilation through the relaxation of vascular smooth muscle. Therefore, PDE-5 inhibitors can exaggerate the vasodilatory effects of nitrates and increase the risk of profound life threatening hypotension by blocking the normal enzymatic degradation of cGMP.

Warnings:

PDE5 inhibitors produce a small effect on supine blood pressure in healthy individuals.
PDE5 inhibitors may induce a slight reduction in cardiac output
PDE5 inhibitors are not recommended or used only with caution for the following populations:
- patients with a myocardial infarction within the last 90 days
- patients with unstable angina or angina occurring during sexual intercourse
- patients with New York Heart Association Class 2 or greater heart failure in the last 6
  months
- patients with uncontrolled arrhythmia, hypotension (<90/50 mm Hg), or uncontrolled
  hypertension (>170/100 mm Hg)
- patients with a stroke within the last 6 months
- patients with left ventricular outflow obstruction
Anti-hypertension medications - can cause an additive effect when taken with PDE5 inhibitors. Concomitant use of organic nitrates present the most serious hypotensive risk but alpha-adrenergic blocking agents may also cause significant vasodilation when taken with a PDE5 inhibitor. Combining PDE5 inhibitors and a vasodilator can result in symptomatic hypotension (e.g. syncope or dizziness). When PDE5 and antihypertension agents are taken together the dosage of each drug may need to be adjusted. Intravascular volume and vascular tone can also effect the cardiovascular response to these medications.
Hepatic insufficiency- The cytochrome P450 enzyme CYP3A4 is the primary mechanism for the metabolism and elimination of PDE5 medications from the system. Each pass through the a healthy liver reduces the concentration of PDE5 inhibitors and active metabolites. Therefore, disease or drugs that affect these enzymes will necessarily alter circulating time and concentration of drugs cleared by this enzyme pathway.
- Cimetidine is a non-specific CYP inhibitor that can cause a 56% increase in sildenafil plasma concentration.
- CYP3A4 inhibitors that reduce the clearance of PDE5 inhibitors include:
  - erythromycin
  - ketoconazole
  - itraconazole
  - ritonavir
  - grapefruit
  - starfruit
- CYP3A4 inducers enhance the clearance of PDE5 inhibitors. They include:
  - bosentan
  - rifampin
Age - plasma levels of PDE5 inhibitors are increased in healthy patients >65 years. Lower dosage may be considered
Renal insufficiency - plasma levels of PDE5 inhibitors are increased in patients with severe renal insufficiency (e.g. creatinine clearance <30 mL/min)
Special Senses
- Vision-
  - Nonarteritic anterior ischemic optic neuropathy (NAION), is of unknown etiology. NAION can cause temporary attenuation or permanent loss of vision, usually unilaterally. NAION has been associated with PDE5 inhibitor use. Patients taking PDE5 inhibitors for ED who experience visual disturbances should stop taking the medication and seek medical advice.
  - It is also recommended that sildenafil be administered with caution to patients with retinitis pigmentosa. PDE-6 is known to be present in the photoreceptors of the retina. It is presumed that sildenafil has some effect on PDE-6 which might explain the color perception problems that occur at high doses.
  - Dose related color discrimination impairment (blue/green tinge) is presumed to be a result of the overlapping of effect on PDE6. Sildenafil seems to have a greater crossover effect than the longer acting PDE5 inhibitors.
- Hearing- Sudden attenuation, loss of hearing and tinnitus have been reported by people taking PDE5 inhibitors. Patients taking PDE5 inhibitors for ED who experience auditory disturbances should stop taking the medication and seek medical advice.
Priapism - is a persistent erection of the penis. In most cases, the arterial supply is excessive, the venous drainage is inadequate, or there is a combination of the two conditions (Lechtenberg and Ohl, 1994). Sickle cell anemia, leukemia, and multiple myeloma are conditions known to predispose patients to priapism. It is recommended that PDE5 inhibitors be used with caution in patients that have anatomical deformation of the penis and in patients who have conditions which may predispose them to priapism.
Combining treatment - Sildenafil is not recommended that it be taken in combination with other ED drugs or treatment methods.
Coagulopathy - PDE5 is known to be present in platelets. Sildenafil should be administered with caution in patients that have a bleeding disorder or peptic ulcer disease.

Instant Feedback:

The use of sildenafil concurrently with any form of nitrate is contraindicated due to: