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Know Your Genetic Risk for PDE5 Inhibitor Side Effects

Phosphodiesterase-5 inhibitors (also called “PDE5 inhibitors”) are a class of drugs used primarily to treat erectile dysfunction (ED). PDE5 inhibitors block cGMP specific phosphodiesterase type 5 (PDE5) from degrading cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the male penis. When sexual stimulation occurs, Nitric oxide is released, increasing concentration of cGMP. This causes smooth muscle relaxation and an erection. Both NO and cGMP are needed in increased concentration for erection to occur. Source: International Journal of Clinical Practice “Comparison of Phosphodiesterase Type 5 (PDE5) Inhibitors” (Aug 2006).

 

Serious Adverse Reactions

 

While relatively uncommon, severe adverse reactions to PDE5 inhibitors do occur. These include:

 

  • Heart attack
  • Priapism (painful erection)
  • Seizures
  • Syncope (fainting)

 

Source: Clinical Cornerstone “The efficacy and safety of PDE5 inhibitors” (Jul 2005).

 

Common Side Effects

 


PDE5 inhibitors are associated with a number of side effects. Common side effects of ED medications such as theses include headache, facial flushing, nasal congestion, and dyspepsia. Other reported side effects include:


 

  • Palpitations
  • Tachycardia (increased heart rate)
  • Angina (chest pain)
  • Myocardial infarction (heart attack)
  • Hypotension (low blood pressure)
  • Headache (up to 15%)
  • Dizziness
  • Paresthesia (pins and needles)
  • Somnolence (sleepiness)
  • Syncope
  • Amnesia
  • Seizures
  • Erythema (red skin)
  • Rash
  • Allergic edema (swelling)
  • Dyspepsia (indigestion)
  • Nausea
  • Gastrointestinal and abdominal pain
  • Dry mouth
  • Vomiting
  • Back pain
  • Myalgia (muscle pain)
  • Fly syndrome
  • Tinnitus (ringing in ears)
  • Vertigo
  • Dyspnea (cough)
  • Sinus congestion

 

Less Common Side Effects

 

Rare side effects of PDE5 inhibitors, in addition to the aforementioned serious adverse reactions, include:

 

  • Hypertension (high blood pressure)
  • Increased lacrimation (tears)
  • Epistaxis (nosebleed)

 

There also may be interactions with other medications metabolized in a similar way, such as erythromycin and HIV protease inhibitors.
 

Source: International Journal of Clinical Practice “Current Safety And Tolerability Issues In Men With Erectile Dysfunction Receiving PDE5 Inhibitors” (Sep 2007).

 

Understand Your Risk for Side Effects with the Rxight® Genetic Test

 

Pharmacogenetic testing with Rxight® is designed to identify genetic polymorphisms and may help reduce the probability of developing side effects when taking medications. Specifically, Rxight® relies on the sequencing of 18 genes for 60 alleles. This is used to establish how a patient is likely to react to hundreds of drugs across over 50 medication classes, including PDE5 inhibitors. All the is required is a simple cheek swab of your DNA, which will be sequenced. After your sample is processed at our labs you will receive a detailed report listing medications which you may have a reaction to or not benefit from. This can then guide current and future prescribers in finding a safe and appropriate dose.

 

How Does Pharmacogenetic Testing Work?

 

Some patients never suffer from adverse effects when taking PDE5 inhibitors while others are not as fortunate. This inter-patient variability is caused by a number of factors, one of which being the genetic differences between patients. A number of genes controlling the NO and cGMO pathways have been associated with a drug response to PDE5 inhibitors. Source: Pharmacogenomics “Pharmacogenetics of erectile dysfunction: navigating into uncharted waters” (Aug 2014).

 

Variable rates of metabolism of PDE5 inhibitors may also be associated with development of adverse reactions. The drug is metabolized by the cytochrome P450 superfamily of enzymes. Polymorphisms in these enzymes may increase the probability of developing adverse effects when taking the drug. Identifying these alleles can aid doctor’s decision making when prescribing PDE5 inhibitors.

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