Terazosin: Mechanism of action, uses, side effects and interactions

What is terazosin?

Terazosin is a selective alpha-1 adrenergic blocker. The drugs of this class cause relaxation of smooth muscle present in the walls of arteries and veins as well as those present in bladder neck and prostate.

Therefore these drugs are used in the treatment of hypertension and benign prostatic hyperplasia (BPH).

Terazosin is available as generic terazosin as well as several different brand names such as Hytrin, Zayasel amongst others. It is available as capsules commonly in strengths of 1 mg, 2 mg, 5mg and 10 mg.

Terazosin IUPAC name, molecular formula, weight, structure, drug class

IUPAC name: [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(oxolan-2-yl)methanone

Molecular formula: C19H25N5O4

Molecular weight: 387.44 g/mol

Molecular structure:

Terazosin - Side Effects, Dosage, Interactions

Drug class: Terazosin is an organic compound belonging to the group of n-arylpiperazines. These compounds contain piperazine ring where the nitrogen ring atom carries an aryl group.

Terazosin identification

Terazosin exists as a white, crystalline substance which is readily soluble in water and isotonic saline.

What is the mechanism of action of terazosin?

α1-receptors are present on a number of tissues in our body including blood vessels, sphincters of gastrointestinal and genitourinary tract and brain.

When epinephrine or norepinephrine binds with these receptors (Gq-linked receptors), there is intracellular stimulation of phospholipases C, A2, and D.

This will cause a release of Ca2+ from intracellular stores activating mitogen-activated kinase and inositol triphosphate kinase pathways and vasoconstriction.

Terazosin, being an α1-receptor blocker, binds with these receptors so that the original agonist (epinephrine and norepinephrine) does not bind with it. This will inhibit vasoconstriction and vasodilation.

What are the indications of terazosin?

Terazosin is indicated in following conditions:

  • Hypertension: When the smooth muscles of blood vessels are relaxed, the total peripheral resistance will fall. This will decrease blood pressure. Hence it is used along with other drugs to treat hypertension.
  • Benign prostatic hyperplasia: When the muscles of neck of bladder and prostate relax, there will be decreased resistance to urine outflow. As a result, there will be symptomatic relief in BPH with the use of terazosin.

What are the contraindications of terazosin?

  • Terazosin is absolutely contraindicated in patients with known hypersensitivity to terazosin or any other inactive ingredient of the capsule.
  • Terazosin is relatively contraindicated in patients with heart disease as it may cause reflex tachycardia in the initial days of its use.

Terazosin and orthostatic hypotension and syncope

All alpha-1 blockers have the capacity to produce a significant decrease in blood pressure. As a result there will reflex tachycardia.

The decrease is even more marked when the person stands from sitting position or sits from a lying position. This is called postural hypotension.

When the hypotension is so marked that the blood supply to the brain is affected, then patient may experience syncope.

Both postural hypotension and syncope are more common in the first few days of therapy or when therapy is restarted after a few days of interruption. That is why it is also referred to as ‘first-dose effect’.

The best way to decrease the risk of developing postural hypotension and syncope is to initiate terazosin with a 1 mg dose given at bedtime. Later the dose is gradually increased to as much as needed.

During this time the patient should be advised to avoid situations where syncope can be prove to be fatal such as driving or hazardous tasks.

Once the required dose is reached as there is no syncope on even that dose, the patient can be asked to resume his normal activity.

Terazosin and priapism

Priapism refers to a painful penile erection which is sustained for hours and not relieved by sexual intercourse or masturbation.

Although the probability of developing this condition is very low (probably less than once in every several thousand patients), the potential of this condition to cause permanent impotence is high so patient should be advised to seek immediate medical care if this develops.

Terazosin and intraoperative floppy iris syndrome (IFIS)

Patients currently taking or having a history of taking alpha-1 blockers may present with this syndrome during cataract surgery.

This syndrome is characterized by billowing of flaccid iris, progressive intraoperative miosis and in some cases prolapse of the iris toward the phacoemulsification incisions.

The ophthalmologist will then need to modify his technique. Therefore such patients should always inform their ophthalmologist if they are currently taking or having a history of taking alpha-1 blockers.

Terasazon and prostatic cancer

Patients with prostatic carcinoma and BPH can present with similar symptoms. Furthermore, these two diseases can frequently co-exist.

Therefore if a patient is diagnosed as having BPH, all examinations should be done to rule out prostatic carcinoma

Terazosin interactions with lab tests

Terazosin use has been associated with small decreases in hemoglobin, hematocrit white blood cells, albumin as well as total protein. If there is symptomatic anemia it is not due to terazosin and hence must be investigated and treated.

Terazosin pharmacokinetics

Absorption: After oral administration, almost the entire drug is absorbed from the GI tract. The drug has a high bioavailability as it undergoes minimal hepatic first-pass metabolism.

The amount of drug absorbed is not affected by meals, however, the time to reach peak plasma concentration was delayed by about 40 minutes.

Distribution: The plasma protein binding ability of the drug is very high and almost 90-94% of the drug is bound to plasma proteins at any given time. The volume of distribution is measured to be around 25 to 30 liters.

Metabolism and excretion: 70% of the parent drug is metabolized by the liver and then excreted in feces as well as urine while 30% of the parent drug is eliminated without being modified.

Overall 40% of the drug is excreted in urine while 60% is excreted in feces. The half-life of terazosin is 12 hours but is affected by age. The half-life of the drug in person above the age of 70 is expected to be around 14 hours.

How is terazosin stored?

Terazosin is stored at room temperature between 20 °C to 25 °C. The drug should be kept away from light as well as moisture (e.g. in washrooms)

Side effects of terazosin

The following side effects of terazosin do not need immediate medical attention:

  • headache
  • unusual tiredness
  • weakness

Less common side effects:

  • back pain
  • joint pain
  • blurred vision
  • drowsiness
  • nausea and vomiting
  • stuffy nose

The following side effects of terazosin need immediate medical attention as they might be fatal in the long run

More common

  • dizziness
  • Less common
  • chest pain
  • dizziness or lightheadedness when getting up from a lying or sitting position
  • syncopal episode
  • fast heartbeat
  • irregular heartbeat
  • pounding heartbeat
  • shortness of breath
  • swelling of feet or lower legs

Rare

  • weight gain
  • Anaphylaxis

What should I do if I overdose on terazosin?

Overdose of terazosin can lead to hypotension and circulatory collapse. If this ensues, support of the cardiovascular system is the most important step. Restoration of blood pressure and normalization of heart rate can be achieved by the following steps:

  • Put the patient in supine position
  • Give fluids. Crystalloids (e.g. ringer lactate) are given first, then colloids.
  • Vasopressors should then be given
  • Take RFTs. If they are effected, renal support can be provided. However, since more than 90% of drug is bound to plasma proteins, dialysis might not provide any benefit.

Terazosin dosage

Benign prostatic hyperplasia:

Initial dose: 1 mg given at night to all patients.

Subsequent dose: The doses are increased in a stepwise manner to 2 mg, 5 mg and then 10 mg. Usually, 10 mg daily for 4 to 6 weeks is needed to assess a beneficial response. If the desired urine flow rate is not achieved, a dose can be increased to 20 mg daily.

Hypertension:

Initial dose: 1 mg given at night to all patients.

Subsequent dose: The doses are slowly increased to attain the desired blood pressure. Usually, 1 mg to 5 mg is needed for good blood pressure control. There should be a gap of at least 12 hours between 2 doses.

Can I take terazosin if I am pregnant?

When terazosin was given to pregnant rats and rabbits at a dose which is approximately 280 times the maximum recommended human dose, teratogenicity was observed. Below this very high dose there was no malformation of the fetus.

Similarly, a study to assess the peri and postnatal development of pups after exposing them to high doses of terazosin while they were in their mother’s womb showed that significantly more pups died than in the control group during the three-week postpartum period.

In humans, there are no well-controlled studies to assess the safety of terazosin in pregnancy. As a result it is currently categorized as a category C drug, meaning they are only prescribed if the potential benefit justifies the potential risk to the mother and fetus.

Can I take terazosin if I am breastfeeding?

There has been no study on animals or on humans to check for the presence of terazosin in breast milk. However since many drugs do appear in the breast milk of humans while a mother is taking the drug, caution is advised.

Can I take terazosin if I have a liver impairment?

Scientific literature is not present on the pharmacokinetic profile of terazosin in patients with liver dysfunction.

However since most of the parent drug is known to be metabolized by the liver before excretion, caution is advised to the physician if he is prescribing terazosin to a patient with liver dysfunction.

Regular follow up is advised and the patient should be informed about the signs and symptoms of drug accumulation and advised to report to the ER if any of those signs and symptoms appear.

Can I take terazosin if I have kidney dysfunction?

Dose reduction is generally not needed if the sole complaint is mild to moderate kidney dysfunction. However, if there is severe kidney dysfunction dose will need to reduced.

Terazosin can cause acute renal failure especially if the patient is suffering from multiple myeloma and taking thiazide diuretics. So if the kidney dysfunction is due to multiple myeloma, terazosin should be completely stopped.

Does terazosin cause infertility?

A study to assess the effect of terazosin on infertility was carried out. It was found that while the drug did not affect the weight and morphology of testis, it reduced the number of sperms present in the semen.

When the dose was increased to more than 500 times the maximum recommended dose in humans, testicular atrophy was also seen.

Therefore it can be concluded that very high doses of terazosin can cause infertility. Another effect of terazosin is its ability to cause priapism which can cause impotence.

Can terazosin cause cancer?

Terazosin was given to rats for 2 years at the maximum tolerated dose and development of tumors was noted. Upon the conclusion of the study, it was found that at this dose terazosin is not oncogenic.

Another study in which the dose of the drug was well above the maximum tolerated dose, it was found that there was a significant increase in the development of benign adrenal medullary tumors in male rats.

Therefore it can be concluded that at the FDA recommended dose, there is no increased risk of developing cancer even with long-term use of the drug.

What are some drugs that can interact with terazosin?

Major drug interactions of terazosin include:

  • Sodium oxybate: Sodium oxybate has a CNS depressive action, therefore, it will augment the hypotensive effect of terazosin.
  • Tizanidine: Tizanidine will augment the hypotensive effect of terazosin.
  • Pollen allergen extract: Pollen extract can cause anaphylaxis. The treatment of anaphylaxis is epinephrine but terazosin interferes with epinephrine.
  • Antihypertensive drugs: All hypertensive drugs cause hypotension. This will increase the severity of postural hypotension.
  • Erectile dysfunction drugs: These drugs cause vasodilation and hence hypotension. Augments the hypotensive action of terazosin.

How long does terazosin stay in your system?

Terazosin has a half-life of 11.4 to 14 hours depending upon the age of the patient. Therefore it is expected that the entire drug would be completely removed from the body after 63.7 hours to 77 hours of complete cessation of drug.

Can I take terazosin with alcohol?

Avoid alcohol use during terazosin use. Using terazosin with ethanol can lower your blood pressure and cause hypotension.

This can cause symptoms such as dizziness or feeling like you might pass out, typically when getting up from a sitting or lying position. The likelihood to occur when you first start taking either of these medications.

Patients may need a dose adjustment or need their blood pressure checked more often if they take both medications.

Patients may develop flushing, warmth or redness under your skin or tingly feeling after alcohol intake which is more likely to occur in Asian descent and they should be advised to avoid alcohol or limit the intake.

Patients should tell their doctor about all other medications they use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Can I take terazosin with tizanidine?

Tizanidine may potentiate the hypotensive effect of terazosine secondary to its alpha-2 adrenergic activity.

Pharmacologic studies have found tizanidine to possess between 1/10 to 1/50 of the potency of clonidine, a structurally similar agent, in lowering blood pressure.

The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing, and was associated at times with bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely, syncope.

In clinical trials, the addition of tizanidine to antihypertensive therapy was associated with a 20% to 30% increase in the incidence of clinically significant decreases in systolic or diastolic blood pressure compared with placebo plus antihypertensive therapy or tizanidine alone. The incidence of orthostatic hypotension was also increased.

Can I take terazosin with codeine?

Many psychotherapeutic and CNS-active agents including codeine exhibit hypotensive effects, especially a the begining of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive drugs, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Can I take terazosin and lorazepam?

Lorazepam exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Concomitant use with terazosin may result in additive effects on blood pressure and orthostasis.

Can I take terazosin and Viagra or Cialis?

Viagra and Cialis may potentiate the hypotensive effect of alpha blockers, resulting in symptomatic hypotension in some patients.

These drugs inhibits phosphodiesterase-5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can cause peripheral vasodilation that may be additive with that induced by alpha blockers.

No events of symptomatic orthostasis or dizziness were reported in paients receiving Viagra or Cialis with a selective alpha-1A adrenergic blocker.

Can I take terazosin with lisinopril?

Additive hypotensive effects may occur when ACE inhibitors including lisinopril is used in combination with alpha-blockers such as terazosin.

In the presence of ACE inhibition, the risk and/or severity of first-dose effects associated with alpha-blockers such as postural hypotension and syncope may be increased.

Potentiation of first-dose response has also been reported with prazosin administered in the presence of enalapril.

Can I take terazosin with Garlic oil?

Garlic has been shown in some studies to lower blood pressure and may theoretically potentiate the effects of hypotensive agents.

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