What medications can cause priapism and how does it occur?

Medications That Can Cause Priapism and Their Mechanisms

Several commonly used medications can cause priapism, with alpha-adrenergic blockers, antipsychotics, and erectile dysfunction drugs being the most frequent culprits. 1, 2

Definition and Types of Priapism

Priapism is a persistent penile erection that continues for more than 4 hours beyond, or unrelated to, sexual stimulation. It is a urological emergency that requires prompt evaluation and management. 1

There are three main types:

• Ischemic (veno-occlusive, low flow) priapism: A non-sexual, painful persistent erection with little or no cavernous blood flow and abnormal blood gases (hypoxic, hypercarbic, acidotic). The corpora cavernosa are rigid and tender. This is a true emergency. 1

• Non-ischemic (arterial, high flow) priapism: A persistent erection caused by unregulated cavernous arterial inflow. The penis is typically neither fully rigid nor painful. Often associated with trauma. 1

• Stuttering (intermittent) priapism: Recurrent episodes of ischemic priapism with periods of detumescence in between. 1

Medications Associated with Priapism

1. Erectile Dysfunction Medications

• PDE-5 Inhibitors (sildenafil, tadalafil, vardenafil)
  • Mechanism: Inhibit phosphodiesterase type 5, preventing breakdown of cGMP, leading to prolonged smooth muscle relaxation and increased blood flow 1, 3
  • Risk factors: Anatomical deformation of the penis, sickle cell anemia, multiple myeloma, leukemia 3
  • Incidence: Reported infrequently during post-marketing surveillance 1

2. Psychotropic Medications

• Antipsychotics (both typical and atypical)

  • Mechanism: Alpha-adrenergic blockade in the corpora cavernosa 4, 5
  • Risk factors: Not dose-dependent; can occur at any time during treatment 5
  • Note: Approximately 50% of drug-related priapism cases are due to antipsychotics 5

• Antidepressants (particularly trazodone)

  • Mechanism: Alpha-adrenergic blockade 6, 2
  • Warning: Priapism with trazodone can result in irreversible damage to erectile tissue if not treated promptly 6

3. Antihypertensives

• Alpha-blockers (particularly prazosin)
  • Mechanism: Alpha-adrenergic blockade preventing detumescence 7, 2
  • Warning: Prolonged erections and priapism have been reported with alpha-1 blockers including prazosin 7

4. Other Medications

• Anticoagulants (particularly heparin) 2
• Intracavernosal injection therapies for erectile dysfunction (papaverine, phentolamine, alprostadil) 1, 8
  • Highest incidence: 1.4% of patients using intracavernosal drugs reported priapism events in one study 8

Pathophysiological Mechanism

The primary mechanism for drug-induced priapism involves:

• Alpha-adrenergic blockade: Most implicated drugs have alpha-adrenergic blocking properties that interfere with the normal detumescence mechanism 2, 4

• Normal erection physiology: Erection involves relaxation of smooth muscles in the corpora cavernosa and increased arterial blood flow. Detumescence requires sympathetic nervous system activation via alpha-adrenergic receptors 1, 2

• Disrupted detumescence: When drugs block alpha-adrenergic receptors, the normal detumescence mechanism fails, leading to persistent erection 2, 4

Risk Factors and Prevention

• Pre-existing conditions that increase risk: Sickle cell anemia, leukemia, multiple myeloma, anatomical deformation of the penis 3, 7

• Drug combinations: Risk may increase when combining medications with alpha-blocking properties or adding new drugs to an existing regimen 4

• Patient education: Informing patients about this potential side effect is crucial for early reporting and treatment 4, 5

Clinical Implications

• Medical emergency: Ischemic priapism requires immediate treatment to prevent permanent erectile dysfunction 1, 9

• Treatment approach:

  • Local measures and etilefrine may be effective for drug-induced priapism 8
  • More invasive procedures may be necessary if conservative measures fail 9

• Medication selection: For patients with a history of priapism, consider medications with lower alpha-adrenergic blocking properties (e.g., amisulpride has been suggested as an alternative antipsychotic with minimal alpha-adrenergic affinity) 5

Key Takeaways

• Drug-induced priapism accounts for approximately 30% of all priapism cases 2

• Alpha-adrenergic blockade is the primary mechanism for most drug-induced priapism 2, 4

• Priapism is a urological emergency requiring prompt intervention to prevent permanent erectile dysfunction 1, 9

• Patient education and awareness are essential for early reporting and treatment 4, 5