https://orcid.org/0000-0002-3963-4057
Abstract
Ischemic priapism is a rare event, but represents a medical emergency requiring aggressive treatment. While clinicians associate priapism with phosphodiesterase-5 (PDE-5) inhibitors, antipsychotics and α adrenergic antagonists represent a higher number of cases. We present the case of a 52-year-old male who experienced an episode of ischemic priapism secondary to acute overdose of perphenazine. We were unable to locate any prior case of priapism associated with acute perphenazine overdose in the literature. When managing a patient with acute overdose of a first-generation antipsychotic with α-blocking effects such as perphenazine, clinicians should consider this uncommon but serious complication.
Introduction
Priapism is a rare condition with an incidence of 1.5 per 100,000 patient-years [Citation1]. Drug-induced priapism may represent 30% of these cases [Citation2]. A 2020 query of the FDA Adverse Event Reporting System (FAERS) demonstrated that priapism represents 0.7% of the reported side effects for sildenafil, tadalafil, and vardenafil. In a literature search and systematic review of 2,960 abstracts related to priapism, 240 cases of drug-induced priapism were identified. PDE-5 inhibitors were implicated in 7 (2.9%) of cases. Second-generation antipsychotics (33%), α-adrenergic antagonists (8.8%), and first-generation antipsychotics (7.9%) accounted for a higher number of cases [Citation3]. Perphenazine is a first generation piperazinyl phenothiazine antipsychotic which is known to exhibit α-adrenergic blockade in addition to its primary effects on dopamine, histamine, and serotonin receptors [Citation4]. As all previously published cases of perphenazine associated priapism are related to therapeutic use or an associated drug interaction, the current case presents a unique addition to the literature.
Case report
A 52-year-old male presented to the emergency department after ingesting 30 tablets of perphenazine 16 mg as an attempt at self-harm. His past medical history included heart failure, asthma, substance use disorder (cocaine), hypertension, hyperlipidemia, depression, schizoaffective disorder, nicotine dependence, and multiple suicide attempts. He was on perphenazine as a chronic home medication for management of his schizoaffective disorder. His other home medications are listed in . Upon presentation, the patient had a Glasgow Coma Scale (GCS) of 12, a blood pressure of 102/69 mmHg, pulse of 116 beats per minute, temperature of 95.9° F, respiratory rate of 16 breaths per minute, and oxygen saturation of 94% on room air. Initial ECG showed a QRS of 98 ms and a QTc of 492 ms. He denied other ingestions. Urine toxicology screen was negative, as were ethanol, acetaminophen, and salicylate concentrations. Activated charcoal was not administered due to depressed GCS. The patient was admitted to the hospital on cardiac telemetry for monitoring. On hospital day three, urology was consulted for a persistent erection noticed by the internal medicine team. The patient had a prior history of priapism secondary to cocaine use. He denied recent use, which was corroborated with a negative urine metabolite screen. The urologist performed a dorsal penile block as well as a penile ring block with 1% lidocaine. Blood was aspirated from the penis, and penile blood gas showed a pH of 7.16, a pCO2 of 64 mmHg, and a pO2 of 35 mmHg which is consistent with ischemic priapism. 2 mL of 500 mcg/mL phenylephrine was injected into the cavernosa with partial detumescence achieved. Irrigation was performed, and another 2 mL of phenylephrine was injected with further detumescence. The patient was re-evaluated throughout the day and maintained flaccidity. He was discharged on hospital day four. Psychiatry recommended continuing perphenazine, and per outpatient pharmacy records, the medication was filled once more after discharge. The medicine was subsequently stopped and it is unclear if patient ever took a dose, or why the medication was discontinued. He was maintained on his other maintenance medications without any additional medication to replace perphenazine. No further episodes of priapism have been documented in the patient’s electronic medical record after 15 months of follow up ().
Figure 1. Home medication list at time of admission (based on pharmacy fill history).
Figure 2. Timeline.
We present, in accordance with the CARE Guidelines (https://www.care-statement.org), a case of priapism following acute overdose of perphenazine.
Discussion
Priapism is defined as a prolonged erection unrelated to sexual stimulation which can be ischemic or non-ischemic. Ischemic priapism is more prevalent and can have serious consequences including loss of erectile function if left untreated. Therefore, it is considered a urologic emergency. Diagnosis is based on a physical exam, a detailed patient history, as well as a penile blood gas if available. Current guidelines recommend against conservative management such as observation or a cool compress. Ischemic priapism should be treated with intracavernosal administration of phenylephrine as soon as the diagnosis is made. Phenylephrine is the preferred agent due to its selective α stimulation [Citation5]. This mechanism appeared to directly counteract the effects of the drug-induced priapism in our patient case.
While parasympathetic stimulation primarily influences erection, detumescence is achieved through sympathetic stimulation [Citation6]. Alpha receptors are found in both cavernosal tissue, as well as in the cavernosal artery [Citation7]. Blockade of alpha sympathetic receptors, which are necessary to achieve detumescence, has been described to produce a prolonged erection [Citation6].
A PubMed search using the terms “priapism AND perphenazine” yielded only three case reports. All published cases are related to chronic therapeutic use [Citation8–10]. We were unable to locate any prior case of priapism associated with acute perphenazine overdose in the literature search.
Though our patient’s condition was otherwise consistent with the reported ingestion and confirmed by pill count, this case is limited by lack of confirmatory perphenazine serum levels, which are not readily available in our institution.
When managing a patient with acute overdose of a first-generation antipsychotic with α-blocking effects such as perphenazine, clinicians should consider this uncommon but serious complication. Patients should receive a full physical exam on initial presentation to look for signs and symptoms of priapism. If priapism is suspected, an emergent consult to urology should be placed if these services are available, and management with vasoactive medications as outlined above should be started as soon as possible. Patient counseling should occur upon initiation of any new medication with priapism as a known side effect. The patient should be informed to seek emergent medical attention if they sustain an erection for longer than four hours.
The data that support the findings of this study are available at the following resources:
Disclosure statement
No potential conflict of interest was reported by the authors.
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References
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