Terazosin


Article Author:
Cheng Yang


Article Editor:
Avais Raja


Editors In Chief:
Casey Ciresi


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
8/17/2019 9:29:05 PM

Indications

Terazosin was approved by the Food and Drug Administration (FDA) in 1987 initially as a treatment for hypertension and then approved in 1993 as a treatment for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia.[1][2] In more recent literature, terazosin, among other agents of its class been the subject of research as an off-label agent for the use of medical expulsive therapy (MET), a form of medical management for distal ureteral calculi.[3][4] The role of pharmacologic therapy in distal urinary tract stones is currently a focus of research, with terazosin and other alpha-1 antagonists under consideration for potential therapeutic value in addition to its traditionally accepted symptomatic relief effects[5]. Other off-label uses for terazosin currently being studied include: alleviation of nightmares associated with post-traumatic stress disorder (PTSD),[6] antihidrotic in patients suffering from hyperhidrosis related to selective serotonin reuptake inhibitor (SSRI) use[5] chronic prostatitis/chronic pelvic pain syndrome,[7] urethritis associated with radiation therapy,[8][9] and idiopathic oligozoospermia.[9]

Mechanism of Action

Terazosin is a selective, quinazoline-derived post-synaptic alpha-1 antagonist.[10][11] Alpha-1 adrenergic receptors subdivide into alpha-1A, alpha-1B, and alpha-1D.[12] Due to their nature as adrenergic receptors, they are a member of the G-protein coupled receptor category.  Terazosin is a competitive antagonist at these receptors, similar to other selective alpha-1 antagonists such as prazosin and doxazosin, notably at alpha-1A, which comprises the majority of alpha receptors in the urothelium.[13] The alpha-1 receptors are commonly located diffusely in smooth muscle tissue, to include vascular smooth muscle, sphincter smooth muscle, and urinary bladder smooth muscle.[14] Alpha-1 adrenergic receptors are also present in many other organ systems, including the central nervous system, endocrine system, and gastrointestinal system. The primary anti-hypertensive action occurs by blocking vascular smooth muscle in the arterioles, and the anti-obstructive urinary tract effects result from smooth muscle relaxation in the ureters, bladder, and urethral sphincter.  The exertion of anti-nightmare effect by terazosin does not have a clearly elucidated mechanism. However, a possible explanation could be because of the presence of presynaptic alpha-adrenergic receptors in the central nervous system.

Administration

Terazosin is available in the US in oral capsule formulation in the form of an HCl salt, available in 1 mg, 2 mg, 5 mg, and 10 mg formulations.

 For the FDA approved indications of hypertension and benign prostatic hyperplasia, the dosing route, frequency, and amount are as follows:

  • Hypertension:

The initial dose is 1 mg to 10 mg orally daily, titrated upwards as needed to a maximum of 20 mg daily. Considered a second-line agent due to adverse effects, additional consideration as an agent if the patient also experiences lower urinary tract symptoms associated with benign prostatic hyperplasia.[15][16]

  • Benign Prostatic Hyperplasia:

The initial dose is of 1 mg to 10 mg orally at bedtime, titrated upwards as needed based upon patient response up to 20 mg daily in 1 or 2 divided doses.[17]

 For Non-FDA approved indications, including medical expulsive therapy (MET), chronic prostatitis, hyperlipidemia, urethritis, hyperhidrosis, and oligospermia:

  • Medical expulsive therapy for distal ureteral calculi:

2 mg to 10 mg orally at bedtime. Most studies have indicated usage of 2 mg to 5mg, and only rarely have 10 mg doses been cited. For MET, the typical duration of terazosin is for up to 2 weeks, and the patient may discontinue therapy once the stone is expelled[3].

  • Chronic Prostatitis/Chronic Pelvic Pain Syndrome:

1 mg to 5 mg orally daily for 14 weeks. Terazosin was shown to be effective in a study comparing alpha-antagonist naïve patients with chronic prostatitis/chronic pelvic pain syndrome with placebo.[7]

  • Hyperlipidemia/Hypercholesterolemia:

5 mg, 10 mg, or 20 mg orally daily.  Studies demonstrating the lipid-lowering effects were subject to confounding factors due to titration of drug dosing to diastolic blood pressure or meeting maximum (20mg) dosage for terazosin. Additionally, there have not been studies to demonstrate a mortality benefit, as seen for other lipid-lowering drugs.[18][19]

  • Idiopathic oligozoospermia:

2 mg orally daily. One clinical study by Gregoriou et al. demonstrated a statistically significant improvement in spermatozoa count and seminal fluid volume after treatment with 6 months of terazosin. However, the study noted no change in mean percentage of abnormal spermatozoa, and also did not detect any significant difference in pregnancy rates.[9]

  • Urethritis associated with radiotherapy in prostate cancer

2 mg to 6 mg orally daily.  One study from Zelefsky et al. suggests improvement in urinary tract symptoms associated with radiotherapy for localized prostate cancer.[20]

  • Antidepressant-induced excessive sweating

1 mg to 6 mg orally daily.  A recent clinical trial demonstrated a positive response to hyperhidrosis associated with selective serotonin reuptake inhibitor use.[5]

Adverse Effects

Terazosin is generally well-tolerated. Many adverse effects of terazosin are explainable due to its blockade of alpha-1 adrenergic receptors.[16][11] Statistically significant adverse effects associated with terazosin detected in placebo-controlled trials listed in the FDA database include dizziness, headache, weakness, postural hypotension, and nasal congestion.[21][22] First-dose syncope is rare and may be mitigated by bedtime use. Orthostatic hypotension is common and should merit strong consideration when prescribing terazosin[23]. According to the FDA, post-marketing surveys also found priapism, atrial fibrillation, anaphylaxis, intraoperative floppy iris syndrome to be associated with terazosin use, though instances of such occurrences were extremely rare.

Contraindications

The only absolute contraindication to the usage of Terazosin is allergy or hypersensitivity to the medication.  Relative contraindications include usage in geriatric populations due to the potential for patient harm associated with syncope and/or postural hypotension as a result of Terazosin use,[24] patients with heart failure as well as general intolerance of the adverse effects associated with Terazosin as listed above. It is important to note that in geriatric patient populations, the occurrence of syncope or orthostatic hypotension can lead to falls, which are associated with increased mortality, morbidity, loss of functional capacity, and institutionalization for diagnostic workup/rehabilitation related to the syncope.[25] Though not contraindicated for use in pediatric populations, caution is advised to due limited data available regarding the use of terazosin in children, though there are small studies of safe usage in children without adverse outcomes[26][27][28].

Monitoring

The use of terazosin does not require plasma/blood drug level monitoring. Orthostatic vital signs should be obtained after the first dose to exclude postural hypotension. If used for hypertension, orthostatic blood pressures may be checked regularly during the titration interval to confirm efficacy. If used for lower urinary tract symptoms associated with benign prostatic hyperplasia, standard clinical assessment of patients may be used to determine efficacy.

Toxicity

Overdose of terazosin may lead to hypotension, and standard life-support protocols should be in place for instances of hemodynamic instability. There are no antidotes for terazosin toxicity specifically. Vasopressors may be used to support physiologic blood pressure parameters in the event of terazosin overdose. Terazosin is long-acting, with an elimination half-life of approximately 12 hours, and is highly protein-bound. Elimination is via renal excretion (40%) and via excretion of feces (60%).[29]

Enhancing Healthcare Team Outcomes

Medications are crucial components of the practice of medicine. In addition to procedural treatments, medications represent an essential aspect of therapy delivery. However, the process of delivering medication to a patient involves a complex interplay between healthcare team members of several roles. 

  • A qualified physician or mid-level practitioner must prescribe the medication with appropriate knowledge and assessment of the medication's efficacy and safety profiles according to the patient's demographics, comorbidities, and needs. 
  • The pharmacist that receives the prescription must verify that the dosage prescribed is appropriate and is responsible for communicating with the provider should any mistake or unsafe prescription be discovered, as well as checking for potential drug-drug interactions. 
  • The pharmacy technician assisting the pharmacist is encouraged to aid in this role and remaining vigilant when physically placing the pills in a bottle and ensuring the label is clear and correct. 
  • The nurse responsible for administrating the medication to the patient after prescription requires vigilance and awareness of the potential hypotension associated with terazosin, and should be meticulous in their measurement of orthostatic vital signs after administration.
  • A medical assistant may also have involvement in the measurement of vital signs and could be the first person to discover medication safety issues.
  • The patient and/or their caregiver are the crucial final step in the process, verbalizing any questions or concerns they may have regarding the use of the prescribed medication, as well as signs/symptoms for which they should be vigilant.

Though terazosin is relatively contraindicated in geriatric populations, it may still prove to be a useful drug that treats multiple co-morbidities at once to limit polypharmacy.[30][31][32] [Level III] As such, the patient and the rest of the healthcare team, to include their physician/mid-level, pharmacy team, and the nursing team, should remain vigilant and aware of the possibility of hypotension or arrhythmia associated with terazosin use. With this type of interprofessional team approach, there can be a maximal therapeutic benefit with minimal adverse events. [Level V]


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Terazosin - Questions

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Which of the following would be most important to include in instructions to patients who are receiving their first prescription for terazosin?



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Which of the following is a common unintended side effect of terazosin treatment of benign prostatic hyperplasia?



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A 76-year-old male patient is currently admitted to the hospital wards for an elbow fracture related to a golfing accident. The nurse responsible for his care takes a brief history and notes hypertension, well-controlled type 2 diabetes mellitus, and benign prostatic hyperplasia. On her examination, she notes a blood pressure of 154/96 mmHg. A few minutes later, the patient complains of urgency to void his bladder despite returning from the restroom 30 minutes ago. Which of the following drugs is best suited for treating an elderly man suffering from hypertension and BPH?



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Which of the following medications can cause epinephrine reversal?



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A 68-year-old male presents to the primary care clinic complaining of the gradual onset and worsening of slow urination and weak stream. The physician performs a prostate examination and palpates an enlarged, non-tender prostate without any focal nodularity. She diagnoses the patient clinically with benign prostatic hyperplasia. In addition to ordering the appropriate diagnostic tests to confirm her diagnosis, she considers prescribing Terazosin to the patient and explains the possible side effects and benefits. The patient is agreeable and asks how the medication works. What is the mechanism of action of terazosin?



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Which of the following drugs is an alpha-1 receptor antagonist?



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A patient was started on a new medication for her hypertension. He was sitting in a recliner watching television, and the phone rang. When he jumped up to answer it, he felt very dizzy and almost passed out. Which of the following drugs would be most likely to place the patient at risk of this event?



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A 46-year old male patient presents to the provider complaining of an inability to empty his bladder. The provider counsels him about starting a new medication. He is told to be aware of possible dizziness and syncope after taking the first dose of this medication. Which of the following medications is he likely taking?



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A 65-year-old male with hypertension and numerous food allergies was previously prescribed 2mg of terazosin taken orally every day 3 months ago. His blood pressure over the past several weeks has been in the range of 150/90 mmHg without any symptoms. His healthcare provider takes a concise history of the patient and prepares to counsel him regarding the use of terazosin. The patient inquires about the usage of the medication. Which of the following is the best response with regards to the drug?



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A 65-year-old male with essential hypertension presents to his healthcare provider. He does not smoke, and his family history is insignificant. On physical examination, he is afebrile with a pulse of 92/min, blood pressure 155/98 mmHg, and a respiratory rate of 20/min. The healthcare provider begins discussing the patient's concern for increased frequency of urination and his weak stream. The provider considers an alpha-1 adrenergic blocker as a possible pharmacologic treatment, such as terazosin. Given the patient's medical history, which of the following potential side effects, should he be counseled on?



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Terazosin - References

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Detweiler MB,Pagadala B,Candelario J,Boyle JS,Detweiler JG,Lutgens BW, Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center. Journal of clinical medicine. 2016 Dec 16;     [PubMed]
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