Terazosin

1. Drug Name

• Generic Name: Terazosin

• Brand Names: Hytrin, Zayasel, others.

2. Drug Classification

• Class: Alpha-1 Adrenergic Blocker

• Subclass: Alpha-blocker, Antihypertensive

3. Mechanism of Action

Terazosin is a selective alpha-1 adrenergic antagonist. It works by blocking the alpha-1 receptors located on vascular smooth muscle and the smooth muscle of the prostate. This leads to:

• Vasodilation: By blocking alpha-1 receptors in the blood vessels, terazosin causes smooth muscle relaxation and vasodilation, leading to a decrease in peripheral vascular resistance and blood pressure.

• Prostatic Smooth Muscle Relaxation: In the prostate and bladder neck, terazosin induces relaxation of smooth muscle, improving urine flow and reducing the symptoms of benign prostatic hyperplasia (BPH).

The drug’s selective action on alpha-1 receptors results in reduced systemic vascular resistance (SVR) and improved urine flow in patients with BPH. Unlike non-selective alpha-blockers, terazosin is less likely to cause reflex tachycardia because of its peripheral vasodilation effects.

4. Pharmacokinetics

• Absorption: Terazosin is well absorbed after oral administration. It has an oral bioavailability of about 90%. Peak plasma concentrations are typically reached within 1-2 hours after administration.

• Distribution: The volume of distribution (Vd) of terazosin is approximately 2.5 L/kg. It is extensively protein-bound (approximately 93%).

• Metabolism: Terazosin is primarily metabolized in the liver via the cytochrome P450 enzyme system, particularly CYP3A4. It forms inactive metabolites that are excreted primarily in the urine.

• Excretion: Terazosin has a half-life (t½) of about 12 hours, allowing for once-daily dosing. It is primarily excreted in the urine (approximately 60%), with the remainder excreted in feces.

• Special Considerations:

  • Renal Impairment: In patients with renal impairment, the clearance of terazosin may be reduced, but dose adjustments are generally not required.

  • Hepatic Impairment: Since terazosin is metabolized by the liver, it should be used with caution in patients with liver dysfunction. Dose adjustment may be necessary in severe hepatic impairment.

5. Indications

• Primary Indications:

  • Hypertension: Terazosin is used for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents.

  • Benign Prostatic Hyperplasia (BPH): Used to improve urine flow and reduce symptoms associated with BPH, such as nocturia, frequency, and urgency.

• Off-Label Uses:

  • Post-Traumatic Stress Disorder (PTSD): Occasionally used in the treatment of nightmares associated with PTSD, although not a first-line treatment.

  • Raynaud’s Phenomenon: Occasionally used to manage vasospastic conditions like Raynaud's disease, although not FDA-approved for this indication.

• Special Populations:

  • Elderly: Often used in elderly patients for both hypertension and BPH management. However, caution is advised due to the potential for orthostatic hypotension.

  • Pediatrics: Not typically used in pediatric populations, as its safety and efficacy have not been established.

6. Dosage and Administration

• Adult Dosing:

  • Hypertension: The initial dose is typically 1 mg once daily, with gradual titration to 2 mg, 5 mg, and up to a maximum of 20 mg per day, depending on the patient’s response and tolerability.

  • Benign Prostatic Hyperplasia (BPH): The starting dose is generally 1 mg once daily, with titration to 2 mg, 5 mg, and up to 10 mg per day, depending on clinical response.

• Renal Impairment: In patients with renal dysfunction, no dose adjustments are generally necessary. However, caution should be exercised, especially in the elderly population, due to the risk of hypotension.

• Hepatic Impairment: Terazosin should be used cautiously in patients with hepatic impairment, and dosage adjustments may be necessary in patients with severe liver dysfunction.

• Administration: Terazosin should be taken orally once daily, preferably at bedtime, to reduce the risk of dizziness or orthostatic hypotension.

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity: Known hypersensitivity to terazosin or any components of the formulation.

  • Severe Hepatic Impairment: Terazosin should be avoided in patients with severe hepatic impairment due to the lack of sufficient data and potential for altered metabolism.

• Relative Contraindications:

  • Orthostatic Hypotension: Use with caution in patients prone to hypotension or those at risk of orthostatic hypotension.

  • Concomitant Use with PDE-5 Inhibitors (e.g., sildenafil): There is an increased risk of hypotension when terazosin is combined with PDE-5 inhibitors.

8. Warnings and Precautions

• Orthostatic Hypotension: Terazosin can cause a first-dose effect, leading to significant hypotension, especially when initiating treatment or increasing the dose. It is recommended to start at a low dose, with careful titration, and administer the first dose at bedtime to reduce the risk.

• Syncope: Rare cases of syncope have been reported, particularly when transitioning to higher doses or in patients who are volume-depleted.

• Priapism: Although rare, there is a risk of priapism (prolonged, painful erection), particularly in patients with BPH. If priapism occurs, medical attention is required immediately.

• Liver Function: Since terazosin is metabolized in the liver, caution is advised in patients with liver dysfunction. It should not be used in severe liver disease.

• Cataract Surgery: There is a potential for intraoperative floppy iris syndrome (IFIS) in patients undergoing cataract surgery, a condition characterized by iris atony and miosis during the surgical procedure. This is important to inform ophthalmologists about prior to surgery.

9. Adverse Effects

• Common Adverse Effects:

  • Dizziness (especially when standing up quickly)

  • Fatigue

  • Nasal congestion

  • Headache

  • Palpitations

• Less Common but Clinically Significant Side Effects:

  • Orthostatic Hypotension: Especially after the first dose, causing dizziness or fainting.

  • Edema: Swelling in the legs or ankles may occur.

  • Syncope: Episodes of fainting may occur, especially during dose titration or initiation.

• Rare/Serious Adverse Reactions:

  • Priapism: Painful and prolonged erection, requiring emergency intervention.

  • Liver Toxicity: Liver function should be monitored due to the rare occurrence of liver enzyme elevations.

10. Drug Interactions

• Major Drug Interactions:

  • Phosphodiesterase Type 5 Inhibitors (e.g., sildenafil, tadalafil): There is a risk of severe hypotension when terazosin is combined with these agents, so the combination should be used cautiously and under close supervision.

  • Other Antihypertensive Agents: Concomitant use with other antihypertensive drugs (such as diuretics or beta-blockers) may enhance the hypotensive effects of terazosin.

  • Cimetidine: The use of cimetidine may increase the plasma concentration of terazosin, potentially enhancing its effects.

• Food-Drug Interactions: Terazosin can be taken with or without food, although food may slightly reduce the rate of absorption.

11. Clinical Pharmacology

• Pharmacodynamics: Terazosin is an alpha-1 blocker that causes smooth muscle relaxation and vasodilation. This results in a decrease in peripheral vascular resistance (in hypertension) and improved urinary flow (in BPH).

• Additional Effects: Terazosin does not significantly affect heart rate or renal function at therapeutic doses. Its effect on vascular smooth muscle is well tolerated by most patients, and it does not affect serum glucose or lipid levels.

12. Special Populations

• Pregnancy: Category C. There are no adequate studies in pregnant women, but terazosin should only be used in pregnancy if the potential benefit justifies the risk to the fetus.

• Lactation: It is unknown whether terazosin is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

• Pediatrics: Terazosin is not typically recommended for pediatric use due to a lack of safety data.

• Geriatrics: Elderly patients may be more susceptible to the hypotensive effects of terazosin, particularly during dose initiation. Careful monitoring and dose adjustment may be necessary.

13. Therapeutic Uses

• Hypertension: Terazosin is used to treat hypertension, either as a monotherapy or in combination with other antihypertensive agents. It is generally considered a second-line agent after ACE inhibitors or calcium channel blockers.

• Benign Prostatic Hyperplasia (BPH): Terazosin is used to relieve the symptoms of BPH, such as urinary urgency, frequency, and weak stream.

• Off-Label Uses: Occasionally used in PTSD and Raynaud’s phenomenon, although not FDA-approved for these indications.

14. Monitoring and Follow-Up

• Blood Pressure: Regular monitoring of blood pressure is essential to evaluate the antihypertensive effect and adjust dosage accordingly.

• Liver Function: Periodic liver function tests should be done to monitor for possible hepatotoxicity, especially in patients with preexisting liver disease.

• Urinary Symptoms (BPH): Monitor urinary flow and symptom severity in patients with BPH to assess therapeutic effectiveness.

15. Overdose Management

• Symptoms of Overdose: Overdose may lead to severe hypotension, dizziness, tachycardia, and syncope.

• Treatment: Overdose treatment includes intravenous fluids, vasopressors if necessary, and close monitoring. In severe cases, activated charcoal may be used if ingestion occurred recently.

16. Patient Counseling Information

• Key Points:

  • Take the medication as prescribed, typically at bedtime to reduce dizziness.

  • Avoid standing up too quickly, especially after the first dose, to prevent dizziness or fainting.

  • Notify your doctor if you experience any persistent lightheadedness, swelling, or painful erections.

• Seek Immediate Medical Attention: If you experience severe dizziness, fainting, painful erections (priapism), or signs of liver problems (e.g., yellowing of skin or eyes, dark urine), seek immediate medical attention.