Article, Urology

Priapism associated with pregabalin

a b s t r a c t

Priapism is defined as a prolonged erection of the penis for at least 4 h without sexual stimulation. It may occur in all age groups. Drugs are the most common cause in adults. A 64-year-old male patient was admitted to the emer- gency department with painful erection that had lasted for 2 days without sexual stimulation. Our patient had used pregabalin for around 1 year due to Neuropathic pain. The dose of the drug was increased as his pain scaled up recently. Approximately 30 cc of dark blood was drained from the corpus cavernosum with an 18 Gauge nee- dle in the emergency department. Cavernous blood aspiration and irrigation resulted in significant recovery and relief. We present this report of priapism associated with pregabalin as it is a rare case with insufficient number of studies in the literature.

Introduction

Priapism is defined as a prolonged erection of the penis for at least 4 h without sexual stimulation. Priapism affects quality of life, sexual function and physical health negatively. Although rare, it may occur in all age groups and is more common in patients with Sickle cell anemia. There are three types of priapism: ischemic, non-ischemic and recur- rent. ischemic priapism is more common [1].

Penile erection begins with the smooth Muscle relaxation of the cavernosal tissue and arteries, leading to increased blood inflow and de- creased Venous outflow. Corpora cavernosum is clogged due to blood accumulation resulting in a continuous painful erection [2]. The under- lying cause has not been described in most cases (primary or idiopathic priapism), but some of them presented with specific medications and diseases (secondary priapism). Drug use is the most common cause in adults, particularly intracavernous injections accounting for 25% of the cases [3].

In our case, the patient had been using pregabalin for 1 year due to neuropathic pain and applied to the emergency department following the occurence of priapism due to increased dose of pregabalin. We pres- ent this report of priapism associated with pregabalin as it is a rare case with insufficient number of studies in the literature.

* Health Science University Antalya Training And Research Hospital, Kazim Karabekir Street, 07100 Muratpasa, Antalya, Turkey.

E-mail address: [email protected].

Case

A 64-year-old male patient was admitted to the emergency depart- ment with painful erection that had lasted for 2 days without sexual stimulation. His history revealed that he had been using 75 mg pregabalin twice a day for neuropathic pain for 1 year. However, the dose of pregabalin was increased to 300 mg twice a day by the physical therapist by whom the patient was examined due to the continious neuropathic pain he had experienced for the last 4 days. Painful erec- tions started after increasing the drug dosage and had not regressed for 2 days. He applied to our emergency department about 36 h after his complaints started. Approximately 30 cc of dark blood was drained from the corpus cavernosum with an 18 Gauge needle in the emergency department.

The patient did not have any previous history of priapism, hemoglo- binopathy, cancer or any other neurological diseases except for a cere- brovascular event he experienced 2 years ago. The patient did not have a history of perineal injury, drug allergy, previous surgery, alcohol or substance use. Other than pregabalin, he used 100 mg of coraspin daily. The color of the penis was normal on examination. There was no bruising, ecchymosis, trauma and prosthesis. He had a rigid, erectile, sensitive penis. The glans penis was soft. Anal tone and rectal touch ap- peared normal. Neurological examination revealed 3/5 motor loss on the left (previously). Other systemic examinations were normal. Com- plete blood count, electrolytes, kidney and liver function tests were within normal limits. Cavernous blood aspiration and irrigation resulted in significant recovery and relief. No new attack of priapism occured at 6-hour follow-up. Thereafter, the patient was discharged 2 days later

https://doi.org/10.1016/j.ajem.2019.11.027

with the suggestion of outpatient follow-up. He was advised to stop using pregabalin. No new attack of priapism was observed on the sec- ond day. At 1 month follow-up, the patient did not report any other at- tack of priapism.

Discussion

Pregabalin is chemically related to gabapentin and has multiple si- multaneous mechanisms of action, such as gabapentin. It binds to the alpha-2-delta subunits of voltage-gated Calcium channels and reduces calcium transfer to other cells [4]. Pregabalin is also a presynaptic inhib- itor of the release of many excitatory neurotransmitters including gluta- mate, noradrenaline, and substance P. Neuronal excitability appears to be inhibited as a result of the effect of pregabalin [5].

Pregabalin is used for the treatment of Focal seizures, diabetic pe- ripheral neuropathy, postherpetic neuralgia and various neuropathic pains. Pregabalin is excreted from the kidneys and is not metabolized in the liver. It has an elimination life of about 6 h. It is not expected to interact pharmacokinetically with other drugs as it does not bind to plasma proteins [6].

Priapism most frequently occurs as a side effect of drugs. These gen- erally include intracavernous injections, antipsychotics, antidepres- sants, cocaine and alcohol. Some studies have demonstrated that adrenergic ? receptor blockers are also associated with priapism be- cause of its effect on cavernous smooth muscles [7-9]. The first case of priapism, which was thought to be associated with pregabalin, was pub- lished in 2014 [10]. A case of priapism associated with increased pregabalin dose has been presented in this report for the first time.

A randomized clinical trial showed that increased dose of pregabalin resulted in a clear dose-related increase in efficacy as well as an increase in the incidence of many adverse events in the treatment of neuropathic pain. The most common adverse events were dizziness, drowsiness and peripheral edema [11]. Pregabalin-induced priapism can be explained by 2 different mechanisms. Pregabalin reduces intracellular free cyto- solic calcium levels by inhibiting voltage-gated calcium channels, which can induce penile erection by loosening cavernous smooth mus- cles. The other way is that pregabalin affects the voltage-gated calcium channels of the adrenergic nerves, which leads to a reduction in the re- lease of intracellular calcium stores, thereby inducing erection by relax- ation of the cavernous smooth muscles [7].

Conclusion

Pregabalin is commonly prescribed by physical therapists and neu- rologists. Although priapism is rarely seen, it still bears some risk, so we recommend that patients should be informed accordingly.

Sources of support

None.

Declaration of competing interest