Priapism is a condition characterized by a prolonged and often painful erection that persists without sexual stimulation. Although uncommon, it is a recognized side effect of numerous medications used to treat a variety of common ailments. Understanding the connection between certain pharmacological agents and this condition is important for both patients and healthcare providers. Drug-induced priapism can rapidly lead to serious complications.
Understanding the Condition
Priapism is defined as an erection lasting four hours or longer that is not related to sexual excitement or activity. This persistence distinguishes it from a normal erection, which subsides once stimulation ends.
The most prevalent form is ischemic priapism, also known as low-flow priapism, accounting for approximately 95% of all cases. This type involves a failure of blood to drain adequately from the corpora cavernosa, the twin chambers that fill with blood. The trapped blood quickly becomes deoxygenated, leading to hypoxia, acidosis, and pain, making ischemic priapism a medical emergency. In contrast, non-ischemic priapism, or high-flow priapism, results from uncontrolled arterial inflow, often due to trauma creating a fistula. This high-flow type is usually less rigid and painless, and it does not carry the same immediate risk of permanent tissue damage as the ischemic form.
Identifying High-Risk Drug Categories
Therapeutic and recreational substances are implicated in causing priapism by disrupting the vascular and neurological controls of the penis. Antidepressants, particularly those with strong alpha-adrenergic blocking properties, are a significant category of causative agents. Trazodone is historically the agent most frequently cited in case reports of drug-induced priapism, though the overall incidence remains low.
Antipsychotic medications, including both typical and atypical agents like risperidone and chlorpromazine, are another high-risk class. These drugs often share the same mechanism of action as the implicated antidepressants. Alpha-adrenergic blockers, commonly prescribed to manage hypertension or benign prostatic hyperplasia (BPH), directly interfere with the body’s natural detumescence process. Examples include prazosin, terazosin, and tamsulosin, which relax smooth muscle throughout the body, including the penile vasculature.
Medications used to treat erectile dysfunction (ED) also carry a risk, especially when administered via intracavernosal injection. These injectable vasoactive agents, such as alprostadil, papaverine, and phentolamine, bypass systemic controls to directly induce smooth muscle relaxation. Improper dosing can lead to a prolonged erection. Even oral ED medications, like phosphodiesterase type 5 (PDE5) inhibitors, are occasionally cited as a cause. Recreational drugs, including cocaine and cannabis, and various anticoagulants like warfarin and heparin, have also been linked to priapism.
The Pharmacological Mechanism of Action
Drug-induced priapism results from the disruption of the balance between neurological signals that cause and end an erection. Normal detumescence is primarily mediated by the sympathetic nervous system, which releases neurotransmitters that act on alpha-1 adrenergic receptors located on the smooth muscle lining the penile blood vessels.
When these alpha-1 receptors are activated, the smooth muscle contracts, constricting the vessels and allowing blood to drain out of the corpora cavernosa. Many psychiatric and antihypertensive medications cause priapism because they function as alpha-adrenergic blockers, preventing this muscle contraction. By blocking the alpha-1 receptors, the drug maintains smooth muscle relaxation, which keeps the venous outflow channels closed and traps blood, leading to low-flow priapism.
Medications for erectile dysfunction, particularly intracavernosal injections, work through a different direct mechanism. These vasoactive substances directly cause the smooth muscle to relax, increasing blood flow into the penis while simultaneously impeding venous outflow. When the medication’s effect is prolonged or excessive, the resulting sustained relaxation traps the blood, causing the ischemic condition. The final common pathway for both mechanisms is the mechanical obstruction of venous drainage, which causes the blood to stagnate and become ischemic.
Immediate Action and Clinical Management
Priapism lasting four hours or longer should be treated as a medical emergency. The urgency stems from the risk of permanent cavernous tissue damage due to prolonged oxygen deprivation. The chance of preserving future erectile function decreases significantly after the four-hour mark.
Upon arrival, the physician will first determine if the priapism is ischemic or non-ischemic, often by analyzing a sample of blood drawn from the penis. For ischemic priapism, a stepwise approach is initiated to rapidly decompress the corpora cavernosa. The first-line intervention typically involves therapeutic aspiration, where blood is drained from the penis using a needle.
Aspiration is often followed by the intracavernosal injection of an alpha-agonist medication, such as phenylephrine, directly into the corpora cavernosa. Phenylephrine works by overriding the causative drug’s blocking effect, stimulating the smooth muscle to contract and allowing the trapped blood to drain. Patients must communicate all current medications, including recreational drug use or supplements, to the treating physician to guide management and prevent recurrence.