What Is Terazosin HCl?

For the treatment of benign prostatic hyperplasia. Terazosin hydrochloride can also be used to treat hypertension and can be used alone or in combination with other antihypertensive drugs such as diuretics or b-adrenergic blockers. This product is a selective 1 receptor blocker, which can reduce peripheral vascular resistance and reduce systolic and diastolic blood pressure. It is usually not accompanied by tachycardia, has no adverse effects on electrolytes, blood sugar, liver and kidney function, and has a certain effect on improving blood lipids. You can selectively block smooth muscle 1 receptors in the bladder neck, prostate gland, and capsule, thereby reducing smooth muscle tension, reducing lower urinary tract resistance, and alleviating symptoms such as frequent urination, urgency, and dysuria due to benign prostatic hyperplasia.

Drug Name: Terazosin
Alias: Gottling
Main indications: Benign prostatic hyperplasia

Main medication contraindications: Use with caution in lactating women
Dosage form: Tablets or capsules
Drug type: Prostate disease medication

Terazosin compound profile

Terazosin Basic Information

Chinese name: terazosin

Chinese alias: TERAZOSIN (HYTRIN); 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4-[(tetrahydrofuran-2-formyl) piperazine; tetrazolid Gortrin; Antihypertensive tablets; Masani; Terazosin hydrochloride dihydrate; Tetrazosin hydrochloride

English name: terazosin

English alias: [4- (4-amino-6,7-dimethoxyquinazolin-2-yl) piperazin-1-yl]-(oxolan-2-yl) methanone; Terazosin Hydrochloride; Heitrin; Hytrin; Hytrinex

CAS number: 63590-64-7

Molecular formula: C ₁₉ H ₂₅ N ₅ O ₄

Molecular weight: 387.43300

Exact mass: 387.19100

PSA: 103.04000

LogP: 1.64090

Terazosin physicochemical properties

Appearance and properties: powder

Density: 1.332 g / cm ³

Melting point: 281-283 ° C

Boiling point: 664.5ºC at 760 mmHg

Flash point: 355.7ºC

Stability: stable under normal temperature and pressure

Storage conditions: sealed and stored in a cool, dry place

Terazosin Safety Information

Symbol: GHS07

Signal Word: Warning

Hazard statement: H302

WGK Germany: 3

Danger category code: R22

Safety instructions: S26; S36

RTECS number: TK8044925

Dangerous goods mark: Xn ^[1]

Terazosin production method

Using furoic acid as raw material, chlorination with thionyl chloride produces furoyl chloride, and then mono-acylation of piperazine. The mono-acylated product is reduced with 4-amino-2-chloro-6,7-dimethoxyquine The oxazoline is condensed in the presence of triethylamine to obtain terazosin. Acidification with hydrochloric acid in ethanol can give terazosin hydrochloride containing two crystal waters ^[1] .

Terazosin uses

It is used to treat hypertension and to improve micturition symptoms in patients with benign prostatic hyperplasia ^[1] .

Terazosin Pharmacopoeia Standard

Terazosin main active ingredients

1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (tetrahydrofuran-2-formyl) piperazine hydrochloride dihydrate, calculated as dry product, containing C ₁₉ H ₂₅ N ₅ O ₄ HCl should be 98.0 102.0%.

Terazosin traits

White or off-white powder, slightly bitter, almost odorless.

Slightly soluble in water, slightly soluble in ethanol.

The absorption coefficient is taken from this product and accurately weighed. Add methanol: water: hydrochloric acid (300: 700: 0.9) to make a quantitative solution containing about 5g per 1ml. Spectrophotometry (Appendix 24 of the Chinese Pharmacopoeia 1990 edition, page 24) at 246nm The absorbance is measured at the wavelength of

Terazosin identification

(1) Take the solution under the measurement of absorption coefficient and measure it by spectrophotometry (Appendix 24 of Chinese Pharmacopoeia 1990 Edition), it has the maximum absorption at the wavelengths of 211nm and 246nm.

(2) The infrared light absorption spectrum should be consistent with the reference spectrum.

(3) Identification of chlorides in aqueous solution. Page 35, Appendix 2 of Chinese Pharmacopoeia 1990 Edition).

Terazosin test

The acidity is 0.2g of this product. After adding 20ml of water to dissolve, the pH value should be determined according to law (Chinese Pharmacopoeia 1990 Edition Appendix page 44). The pH value should be 3.0 4.5.

Relevant substances are taken from this product, and methanol is added to make a solution containing 20.0mg per 1ml, which is used as the test solution; the precise amount is the appropriate amount. Dilute with methanol to a solution containing 0.2mg per 1m1. As a control solution, perform a thin-layer chromatography (Chinese Pharmacopoeia 1990 Edition, Part Two Appendix, page 30) test. Take 5l of each of the two solutions and point them under the same silica gel. Ethyl acetate-methanol-diethylamine (40: 20: 3) is used as a developing agent on a 254nm thin-layer plate. After being developed, it is dried and inspected under an ultraviolet lamp (254nm). No more than two, the color must not be darker than the main spots displayed by the control solution.

Take 1.0g of this product after weightlessness and check it according to law (Chinese Pharmacopoeia 1990 Version Two Appendix Appendix 56). The residual residue shall not exceed 0.1%.

Take the residues left by the burning residue under heavy metals and inspect them in accordance with law (the second method on page 51 of Appendix 2 of the 1990 edition of the Chinese Pharmacopoeia). The content of heavy metals must not exceed 10 parts per million.

Determination of terazosin

Take about 0.35g of this product, accurately weigh, add 25ml of glacial acetic acid and 6ml of mercury acetate test solution, shake to dissolve, add 15ml of acetic anhydride, shake well, add 1 drop of crystal violet batch solution, and use perchloric acid (0.1mol / L) Titrate until the solution becomes blue, and correct the titration result with a blank test. Each 1ml of perchloric acid solution (0.1mol / L) is equivalent to 42.39mg of C ₁₉ H ₂₅ N ₅ O ₄ · HCl ^[2] .

Terazosin drug description

Terazosin classification

Circulatory System Drugs> Cardiovascular Expansion Drugs> Angiotensin II Receptor Antagonists

Terazosin dosage form

Tablet or capsule: 1mg; 2mg; 5mg.

Terazosin pharmacology and toxicology

A. Benign Prostatic Hyperplasia (BPH) The symptoms associated with BPH involve bladder outlet obstruction, which includes two basic components: a static portion and a dynamic portion. The static part is the result of an enlarged prostate. Over time, the prostate will keep expanding. However, clinical studies have shown that the size of the prostate has nothing to do with the severity of BPH symptoms or the degree of urethral obstruction. The dynamic part is a function of increased tension in the smooth muscles of the prostate and bladder neck, leading to narrowing of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nerve stimulating effect of 1-adrenergic receptors, which are abundant in the prostate, prostate sac, and bladder neck. The reduction in symptoms and improvement in urinary flow after terazosin administration is associated with smooth muscle relaxation caused by 1-adrenergic receptor blockade in the bladder neck and prostate. Because there are relatively few 1-adrenergic receptors in the bladder body, terazosin can reduce the obstruction of the bladder outlet without affecting the contraction of the bladder. The overall function and symptoms of urination were comprehensively evaluated, and patients treated with terazosin had a significant (p0.001) overall improvement compared to patients treated with blanks. In long-term trials, terazosin significantly improved symptoms and maximum urine flow scores, suggesting that terazosin relaxes smooth muscle cells. Although blocking 1-adrenergic receptors also lowers blood pressure in hypertensive patients due to increased peripheral vascular resistance, normal blood pressure BPH male patients do not cause clinically significant blood pressure reduction when treated with terazosin.

B. Hypertension In animals, terazosin increases blood pressure by reducing total peripheral vascular resistance

Terazosin reduce. Terazosin's vasodilation and blood pressure lowering effects seem to be mainly caused by 1-adrenergic receptor blockade. Within 15 minutes after administration, terazosin gradually reduced blood pressure. Patients with mild (approximately 77%, diastolic blood pressure 95-105mmHg) or moderate (approximately 23%, diastolic blood pressure 105-115mmHg) hypertension at a total dose of 5-20mg / day once or twice daily Terazosin was administered for clinical trials. As with all antagonists, because terazosin rapidly decreases blood pressure after the first or previous doses, the starting dose is 1 mg and then adjusted to a fixed dose or to a specific blood pressure endpoint ( The diastolic pressure in the supine position is usually 90 mmHg). Blood pressure was measured at the end of the dosing interval (usually 24 hours), and the results showed that the antihypertensive effect continued throughout the interval. Generally, the systolic blood pressure reduction in the supine position was 5-10 mmHg larger than that in the blank, and the diastolic blood pressure decreased 3.5-8 mmHg. Measured 24 hours after dosing, heart rate did not change. The blood pressure response is similar to prazosin but less than hydrochlorothiazide. The terazosin low-dose group statistically significantly reduced patients' total cholesterol, low density, and very low density lipoproteins, but did not significantly change high density lipoproteins and triglycerides. 2. Toxicology Carcinogenic, mutagenic and reproductive toxicity Terazosin has no mutagenic effect. There is also no evidence to support the carcinogenic effects of terazosin. Treatment has no effect on testicular weight and morphology. At 30 and 120 mg / kg / day, the sperm content of the uterine smear was reduced compared to the control smear and the number of sperm had a better correlation with subsequent conception. When rats were given orally at doses of 40 and 250 mg / kg / day (29 and 175 times the maximum recommended human dose) for one or two years, the incidence of testicular atrophy increased significantly, but at 8 mg / kg / day (> 6 times the maximum recommended human dose) No increase in dose. In dog experiments, testicular atrophy was also observed at 300 mg / kg / day (> 500 times the maximum recommended human dose) for 3 months, but at a dose of 20 mg / kg / day (> 38 times the maximum recommended human dose) ) No testicular atrophy was observed. Teratogenicity during pregnancy has not been adequately and well controlled in pregnant women and the safety of terazosin during pregnancy has not been determined. Terazosin is not recommended during pregnancy unless proven to be more beneficial than maternal and fetal risk.

Terazosin pharmacokinetics

The male patient absorbed it almost completely after taking the medicine. Immediately after a meal, the effect on absorption is minimal, but the time to peak plasma concentration is delayed by about 40 minutes. Terazosin has a small first pass metabolism in the liver. It peaks about 1 hour after taking the drug and has a half-life of about 12 hours. Terazosin medications at age

Terazosin A study of the effects of aerodynamics found that patients with 70 and 20-39 years of age had plasma half-life of 14.0 and 11.4 hours, respectively. The plasma protein binding rate is 90-94%. About 40% are excreted in the urine, and about 60% are excreted with feces.

Terazosin indications

Terazosin hydrochloride can be used to treat benign prostatic hyperplasia. Terazosin hydrochloride can also be used to treat hypertension and can be used alone or in combination with other antihypertensive drugs such as diuretics or -adrenergic blockers ^[3] .

Terazosin dosage usage

If terazosin hydrochloride is discontinued for a few days, the first dosing regimen should be reused.

Benign Prostatic Hyperplasia 1. The first dose The first dose is 1mg, and the medicine is taken before bedtime. Patients should be closely monitored during the first dose to avoid severe hypotension reactions. 2. The maintenance dose should be gradually increased to 2mg, 5mg or 10mg once a day until satisfactory symptoms and / or flow rate improvement are obtained. 3. The usual dose is 10mg once daily. For 4 to 6 weeks, it is unclear whether higher doses can be used for patients with inappropriate or unresponsive 20 mg daily doses. If the drug is discontinued for several days or longer, treatment should be restarted using the first dosing regimen. 4. When combined with other antihypertensive drugs, especially the calcium channel blocker verapamil, special care should be taken to avoid causing significant hypotension and the amount of this product should be reduced.

Hypertension 1. First dose The first dose is 1 mg, taken before bedtime. Patients should be closely monitored during the first dose to avoid severe hypotension reactions. 2. The maintenance dose should be increased slowly until a satisfactory blood pressure is obtained. The recommended dose is usually 1 mg-5 mg once daily; however, some patients may be effective at a dose of 20 mg daily. Doses above 20 mg do not appear to affect blood pressure further, and doses above 40 mg have not been studied. Blood pressure should be monitored between doses. If the antihypertensive effect becomes smaller after 24 hours of administration, a twice daily dosing regimen may be considered. If the drug is discontinued for several days or longer, treatment should be restarted using the first dosing regimen. In clinical trials, in addition to the first medication before bedtime, other medication time should be in the morning.

Terazosin adverse reactions

Six benign prostatic hyperplasias of terazosin and blank control clinical trials have shown that terazosin 1-20 mg once daily with an adverse reaction rate of at least 1%, which is higher than that of the blank control group, or has clinical significance Adverse reactions include weakness, orthostatic hypotension, dizziness, drowsiness, nasal congestion / rhinitis, and impotence. The incidence of urinary tract infections in the terazosin group was significantly reduced (Table 1). The risk of a hypotensive adverse event is greatest during the first 7 days of treatment and including each dosing interval. Table 1 Adverse reactions that occurred during the blank-controlled trial in the treatment of benign prostatic hyperplasia. Human system terazosin (N = 636) Blank (N = 360) Systemic reactions # Weakness, flu complications, headache 7.4% * 2.4% 4.9% 3.3 % 1.7% 5.8% Cardiovascular system hypotension Cardiac orthostatic hypotension syncope 0.6% 0.9% 3.9% * 0.6% 0.6% 1.1% 0.8% 0.0% Digestive system nausea 1.7% 1.1% Metabolic and nutritional disorders Peripheral edema Weight gain 0.9% 0.5% 0.3% 0.0% Nervous system dizziness, drowsiness, dizziness 9.1% * 3.6% * 1.4% 4.2% 1.9% 0.3% Respiratory dyspnea nasal congestion / rhinitis 1.7% 1.9% * 0.8% 0.0% Special sense blurred vision / amblyopia 1.3% 0.6% Urogenital system Impotence Urinary tract infection 1.6% 1.3% 0.6% 3.9% * # Includes weakness, fatigue, burnout and fatigue. * Comparison between two groups, p? 0.05. Adverse events are usually transient and mild or moderate, and treatment must be discontinued when serious adverse reactions occur. In the blank-control trial, the proportion of premature treatment discontinuations due to adverse reactions was not significantly different between the blank and terazosin groups. 2. Hypertensive 4 terazosin blank control clinical trials for treating hypertension show that terazosin 1 ~ 40mg once a day, the combination of unilateral electricity and other antihypertensive drugs, terazosin than the blank control group Significantly increased adverse reactions were weakness, blurred vision, dizziness, nasal congestion, nausea, peripheral edema, palpitations, and lethargy. In controlled or published short-term or long-term clinical trials, adverse reactions that occurred in at least 1% of the 1987 patients taking the drug or were reported after marketing include: systemic reactions: chest pain, facial edema, fever, abdominal pain, neck pain, Shoulder pain; cardiovascular system: arrhythmia, vasodilation; digestive system: constipation, diarrhea, dry mouth, indigestion, flatulence, vomiting; metabolic / nutrition disorders: gout; muscular and skeletal system: joint pain, arthritis, Arthropathy, myalgia; nervous system: anxiety, insomnia; respiratory system: bronchitis, cold symptoms, nosebleeds, flu symptoms, worsening cough, pharyngitis, rhinitis; skin and accessories: itching, rash, sweating; special feelings: Visual abnormalities, conjunctivitis, tinnitus; urogenital system: frequent urination, urinary incontinence (mainly seen in postmenopausal women), urinary tract infections. Post-marketing shows occasional patient allergies and reports of abnormal penile erections. Adverse reactions are usually mild or moderate, but sometimes severe, and treatment must be discontinued.

Terazosin precautions

1. Prostate Cancer Prostate cancer and BPH cause many of the same symptoms. These two diseases often coexist. Therefore, it is believed that patients with BPH should be examined before treatment with terazosin hydrochloride to rule out the possibility of prostate cancer. 2. Orthostatic hypotension Although syncope is the most serious orthostatic effect of terazosin, other symptoms of hypotension are more common, such as dizziness, palpitations, and in clinical trials of hypertension, 28% of patients have this symptom. In the BPH trial, 21% of patients experienced one or more of the following symptoms: dizziness, hypotension, orthostatic hypotension, syncope, and dizziness. Patients should be informed that this product may cause syncope and orthostatic hypotension, especially at the beginning of treatment, and to avoid driving or hazardous work 12 hours after the first dose, after increasing the dose or restarting after interrupted treatment. Patients should be advised to sit or lie down when symptoms of hypotension occur, although these symptoms are not always upright, and care should be taken when the patient stands up from a sitting or lying position. If the symptoms of dizziness, dizziness, or palpitations are uncomfortable, you should tell your doctor to consider adjusting the dose. 3. Patients should be informed that treatment with terazosin may cause symptoms of drowsiness or drowsiness, and those who must drive or operate heavy machinery should be careful. 4. Patients should be informed that treatment with terazosin hydrochloride or other similar supine treatments may cause abnormal penile erections. Patients should be aware that this response is fairly rare, but if not brought to the attention of a doctor in time, it may lead to permanent erectile dysfunction (impotence). 5. Laboratory tests In controlled clinical trials, terazosin was observed to decrease hematocrit, hemoglobin, white blood cells, total protein mass, and albumin slightly, but it was statistically significant. This suggests that terazosin has the potential to dilute blood.

Medication for pregnant and lactating women

In studies conducted before and after childbirth in rats, the death of the young rats in the 120 mg / kg / day (> 75 times the maximum recommended human dose) group was significantly higher in the 3 weeks after delivery than in the control group. Whether terazosin is secreted in breast milk is unclear. Because many drugs are secreted in breast milk, terazosin should be given attention when administered to lactating women.

Medication for children

In controlled trials, terazosin was added to diuretics and certain adrenergic blockers, and no unexpected interactions were observed. Terazosin has been administered in combination with: analgesics / anti-inflammatory drugs, antibiotics, anticholinergic / sympathomimetic drugs, anti-gout drugs, cardiovascular drugs, corticosteroid drugs, gastrointestinal drugs, Glycemic drugs, sedatives and tranquilizers. When co-administered with other drugs, terazosin and verapamil, the average AUC0-24 of terazosin increased by 11% when first administered verapamil, and increased after 3 weeks of treatment with verapamil 24%, and at this time the average Tmax of terazosin decreased from 1.3 hours to 0.8 hours. No significant effect was found on verapamil. When terazosin is combined with captopril to reach steady state, the maximum plasma concentration of terazosin increases linearly with dose.

Terazosin contraindications

Those who are allergic to terazosin are contraindicated.

Terazosin overdose

Terazosin hydrochloride excess can cause hypotension. The patient can be kept supine to restore blood pressure and normal heart rate. If this method is not effective, the method of volume expansion should be adopted. If necessary, use booster drugs and monitor and maintain renal function. Laboratory data indicate that the plasma binding rate of terazosin is 90-94%; therefore, dialysis treatment may not be beneficial for drug overdose.

Terazosin Drug Interactions

In controlled trials, terazosin was added to diuretics and certain b-adrenergic blockers, and unexpected interactions were not observed. Terazosin has been administered in combination with: analgesics / anti-inflammatory drugs, antibiotics, anticholinergic / sympathomimetic drugs, anti-gout drugs, cardiovascular drugs, corticosteroid drugs, gastrointestinal drugs, Glycemic drugs, sedatives and tranquilizers. When co-administered with other drugs, terazosin and verapamil, the average AUC0-24 of terazosin increased by 11% when first administered verapamil, and increased after 3 weeks of treatment with verapamil 24%, and at this time the average Tmax of terazosin decreased from 1.3 hours to 0.8 hours. No significant effect was found on verapamil. When terazosin is combined with captopril to reach steady state, the maximum plasma concentration of terazosin increases linearly with dose.

Terazosin Expert Reviews

Avoid driving and operating the machine within 12 hours after the first dose and increased dose or when the medicine is discontinued. When combined with other antihypertensive drugs or diuretics, the dosage should be reduced. It is not recommended to use ^[4] .