Terazosin Toxicity - An Overview

Introduction

Terazosin, a nonselective alpha-1 adrenergic antagonist, is used to treat hypertension and benign prostatic hypertrophy (age-associated prostate gland enlargement) by inhibiting the effects of adrenaline on nerve cells and causing blood vessels to relax and dilate. The second alpha-1 adrenergic antagonist to receive U.S. approval is Terazosin. Low transient blood aminotransferase increases, which are frequently raised with liver damage, and a very small number of cases of clinically obvious acute liver injury are both associated with treatment with Terazosin.

What Is Terazosin Used For?

Terazosin blocks alpha-adrenergic receptors on the smooth muscle in arterioles, as well as those in the bladder neck (group of muscles that connect the bladder to the urethra) and prostate, preserving mean arterial pressure and tissue perfusion. Arterioles are relaxed as a result of alpha-adrenergic receptors in blood vessels being inhibited, resulting in a lowering of blood pressure. Therefore, Terazosin is used to treat hypertension, and it is typically used with other antihypertensive medications. Terazosin is also used to treat the symptoms of urinary blockage caused by benign prostatic hypertrophy. Terazosin comes in tablet or capsule form in dosages of one, two, five, and ten milligrams. Terazosin is often started at a dose of one milligram per day at bedtime, and the dose is increased based on tolerance and clinical response to an average of five to ten milligrams per day in one dose per day, typically at bedtime. Research is currently focused on pharmaceutical treatment for distal urinary tract stones. Terazosin is currently being researched for the following off-label uses:

• For distal urethral calculi.

• For nightmares caused by post-traumatic stress disorder (PTSD).

• To treat hyperhidrosis caused by the use of selective serotonin reuptake inhibitors.

• Chronic prostatitis and chronic pelvic pain syndrome.

• Radiation therapy-related urethritis.

• Idiopathic oligozoospermia.

The following are the dosing route, frequency, and dosage instructions for the FDA-approved indications:

• Hypertension: The starting dose is 1 mg to 10 mg taken orally once daily, and it can be increased to a maximum of 20 mg once daily as needed. Due to side effects, it is regarded as a second-line drug; nevertheless, if the patient also exhibits symptoms of the lower urinary tract linked to benign prostatic hyperplasia, it is administered.

• Benign Prostatic Hyperplasia (BPH): The recommended starting dose is 1 mg to 10 mg taken orally at bedtime, and the dose can be increased as needed based on the treatment response up to 20 mg per day in one or two divided doses.

The following are the dosing route, frequency, and dosage instructions for the non-FDA approved indications:

• Medical Expulsive Therapy (MET) for Distal Ureteral Calculi: 2 to 10 mg orally before bed. Terazosin is often used for up to two weeks in the case of MET, after which the patient may stop taking it.

• Chronic Prostatitis and Chronic Pelvic Pain Syndrome: 1 to 5 mg taken orally every day for 14 weeks.

• Hyperlipidemia and Hypercholesterolemia: 5, 10, or 20 mg taken orally each day.

• Idiopathic Oligozoospermia: A daily dose of 2 mg. After therapy with Terazosin for six months, a study showed a statistically significant increase in spermatozoa count and seminal fluid volume.

• Urethritis Associated With Radiotherapy in Prostate Cancer: 2 to 6 mg each day. According to a study, radiation for locally advanced prostate cancer appears to relieve symptoms of the urinary tract.

• Antidepressant-Induced Excessive Sweating: 1 to 6 mg is used orally each day. Recent clinical research showed that selective serotonin reuptake inhibitor usage can effectively treat hyperhidrosis (excessive sweating).

What Is the Mechanism of Action of Terazosin?

The alpha-1 adrenergic receptors are further divided into alpha-1A, alpha-1B, and alpha-1D. They fall under the classification of G-protein coupled receptors. Terazosin works as a competitive antagonist at these receptors, much like other selective alpha-1 antagonists like prazosin and doxazosin, particularly at alpha-1A, which makes up the majority of alpha receptors in the urothelium. Alpha-1 receptors are mostly found in smooth muscle tissue, such as vascular smooth muscle, sphincter smooth muscle, and urinary bladder smooth muscle.

The digestive system, endocrine system, and central nervous system are just a few of the other organ systems that have alpha-1 adrenergic receptors. By inhibiting vascular smooth muscle in the arterioles, the main anti-hypertensive activity occurs. The ureters, bladder, and urethral sphincter's smooth muscles relax, which has an anti-obstructive impact on the urinary tract. Even though the anti-nightmare effect effected by Terazosin lacks a precisely defined mechanism, presynaptic alpha-adrenergic receptors in the central nervous system could be an explanation.

What Are the Side Effects of Terazosin?

The blockage of alpha-1 adrenergic receptors by Terazosin accounts for many of its side effects.

• Dizziness.

• Headache.

• Postural hypotension (from lying down to sitting up or standing up causes a reduction in blood pressure).

• Nasal congestion.

• Syncope.

• Priapism.

• Atrial fibrillation (irregular and rapid heart rhythm).

• Palpitations.

• Impotence.

• Incontinence.

• Gastrointestinal distress.

• Allergy.

• Intraoperative floppy iris syndrome (Poor preoperative pupillary dilation, gradual intraoperative pupillary constriction, flaccid stroma of the iris billowing, and iris prolapse to the surgical incisions).

What Is Terazosin Toxicity?

Terazosin overdose can result in hypotension, so it is important to follow basic life-support procedures in cases of hemodynamic instability. The toxicity of Terazosin particularly has no known antidotes. In the event of a Terazosin overdose, vasopressors (drugs that elevate mean arterial pressure) could be employed to support normal blood pressure levels. Terazosin is a highly protein-bound drug with an extended half-life and a long half-action (around 12 hours). And, Terazosin is excreted in both feces and urine, accounting for 60 % of elimination.

Conclusion

Although Terazosin is often contraindicated in senior populations, it may nevertheless be a helpful medication that manages several comorbidities concurrently to reduce polypharmacy (using five or more medications). Patients with BPH and hypertension typically receive Terazosin prescriptions. The potential for hypotension or arrhythmia associated with the use of Terazosin should be kept in mind by the patient as well as the rest of the healthcare team. This kind of interprofessional team approach has the potential to provide the most therapeutic effect with the fewest adverse outcomes.