Prazosin Hydrochloride
19237-84-4COc1cc2nc(N3CCN(C(=O)c4ccco4)CC3)nc(N)c2cc1OC.ClWFXFYZULCQKPIP-UHFFFAOYSA-NPrazosin Hydrochloride is a synthetic piperazine derivative with hypotensive antiadrenergic properties, Prazosin Hydrochloride reduces peripheral resistance and relaxes vascular smooth muscles as a selective adrenergic alpha-1 antagonist by a mechanism not completely known. It is used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. (NCI04)
19237-84-4Soluble at ambient temperatures (mg/ml): acetone, 0.0072; methanol, 6.4; ethanol, 0.84; dimethylformamide, 1.3; dimethylacetamide, 1.2; chloroform, 0.041
In water, 1.4 mg/ml @ pH approx 3.5
61.9 [ug/mL] (The mean of the results at pH 7.4)
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
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Warning
H302 (56.6%): Harmful if swallowed [Warning Acute toxicity, oral]
P203, P260, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 76 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prazosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Khoury AF, Kaplan NM; Alpha-blocker Therapy of Hypertension. An Unfulfilled Promise. JAMA 266 (3): 394-8 (1991). For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. A summary of the published data on efficacy, side effects, and special properties of alpha 1-receptor blockers indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.
Animal studies indicate that prazosin does not have its antihypertensive effect in the CNS. Prazosin does not interfere with nerve impulse transmission across sympathetic ganglia nor does it cause adrenergic neuronal blockade.
The exact mechanism of the hypotensive action of prazosin is unknown. Prazosin causes a decrease in total peripheral resistance and was originally thought to have a direct relaxant action on vascular smooth muscle. Animal studies have suggested that the vasodilator effect of prazosin is also related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). Unlike conventional alpha- blockers, the antihypertensive action of prazosin is usually not accompanied by reflex tachycardia.
Prazosin ... is a very potent and selective alpha 1-adrenergic antagonist. ... Interestingly, the drug also is a relatively potent inhibitor of cyclic nucleotide phosphodiesterases...
Elimination half-life approx 3 hr.
The plasma half-life of prazosin after oral administration has been reported to be 2-4 hr.
Animal studies show that prazosin hydrochloride is metabolized extensively in the liver, principally by demethylation and conjugation, and excreted as unchanged drug (5-11%) and metabolites. Four of the metabolites have been shown to possess 10-25% of the hypotensive activity of prazosin and they may contribute to the antihypertensive effect of the drug.
The 6-O-demethyl and 7-O-demethyl analogues of the new antihypertensive drug prazosin [2-[4-(2-furoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate 10-step reaction sequences starting from isovanillin and vanillin, respectively. The 6-O-demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7-O-demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline and 2,4-diamino-6,7-dimethoxyquinazoline, are also described. All 4 metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.
Wird geladen…
DTXSID50172822CHEMBL1558SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
When prazosin is administered with diuretics or other hypotensive agents, particularly beta-adrenergic blocking agents (eg, propranolol), the hypotensive effect of prazosin may be increased.
... prazosin hydrochloride has been administered without any adverse drug interaction in limited clinical experience to date with the following: cardiac glycosides -- digitalis and digoxin; hypoglycemics -- insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; tranquilizers and sedatives -- chlordiazepoxide, diazepam, phenobarbital; antigout -- allopurinol, colchicine, and probenecid; antiarrhythmics -- procainamide, propranolol and quinidine; analgesics, antipyretics and anti-inflammatories -- propoxyphene, aspirin, indomethacin, and phenylbutazone.
/HUMAN EXPOSURE STUDIES/ In overdosage, hypotension and CNS depression ranging from lethargy to coma are reported. In addition, priapism may occur.
/CASE REPORTS/ Ingestion of at least 50 mg of prazosin by a 2 yr old child produced profound drowsiness and depressed reflexes. There was no decrease in blood pressure and recovery was uneventful. A 19 yr old man who ingested approximately 200 mg of prazosin had normal CNS responses and slightly decreased blood pressure.
Drug Induced Liver Injury Rank (DILIrank 2.0)
Prazosin hydrochloride
Ambiguous-DILI-concern
3
Adverse reactions
DOI:10.1016/j.drudis.2016.02.015
/LABORATORY ANIMALS: Acute Exposure/ ... Prazosin has been shown to exacerbate canine narcolepsy-cataplexy, probably secondary to inhibition of a subtype of alpha1-adrenergic receptor (eg, alpha1b) in the CNS.
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No carcinogenic potential was demonstrated in an 18 month study in rats with /prazosin hydrochloride/ ... at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day.
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ /prazosin hydrochloride/ ... has been shown to be associated with decreased litter size at birth 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose respectively.
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Decreased fertility has occurred in male and female rats receiving prazosin dosages of 75 mg/kg but did not occur in those receiving 25 mg/kg. Testicular changes consisting of atrophy and necrosis have occurred in rats and dogs receiving prazosin dosages of 25 mg/kg daily for a year or longer but no such changes occurred in those receiving 10 mg/kg daily.
For more Non-Human Toxicity Excerpts (Complete) data for PRAZOSIN HYDROCHLORIDE (6 total), please visit the HSDB record page.
Treatment with supportive care including intravenous fluid boluses and vasopressors such as dopamine were effective in the few overdose cases reported.
Maintain an open airway and assist ventilation if necessary.Hypotension usually respondes to supine positioning and iv crystalloid fluids. Occasionally pressor therapy is needed. there is no specific antidote. Administer activated charcoal.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prazosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
PRAZOSIN HCL
alpha-Adrenergic Blocker [EPC]; Adrenergic alpha-Antagonists [MoA]
PRAZOSIN HYDROCHLORIDE
Adrenergic alpha-Antagonists [MoA]; alpha-Adrenergic Blocker [EPC]
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
There is intraindividual and interindividual variation in the rate of absorption and plasma concentrations of prazosin. The absolute oral bioavailability of prazosin is also variable but is reported to average about 60% (range: 43-82%). Results of one study indicate that the presence of food may delay absorption of the drug in some patients, but does not affect the extent of absorption.
Following oral administration of prazosin hydrochloride, plasma concentrations of the drug reach a peak in 2-3 hrs in most fasting patients. Plasma concentrations of prazosin generally do not correlate with therapeutic effect. One manufacturer reports that plasma concentrations of the drug after a single 5 mg dose range from 0.01-0.075 ug/ml. Blood pressure begins to decrease within 2 hr after an oral dose; the maximum decrease occurs in 2-4 hr. The hypotensive effect of prazosin lasts less than 24 hr.
Animal studies indicate that prazosin is widely distributed in body tissues. After iv administration in dogs, highest concentrations of the drug are found in the lungs, coronary arteries, aorta, paw arteries and heart; the lowest concentrations are in the brain. During prazosin therapy, approximately 97% of the drug in plasma is bound to proteins. It is not known whether the drug crosses the placenta. Prazosin is distributed into milk in small amounts.
Approximately 6-10% of a dose is excreted in urine and the remainder in feces via bile.
The drug /prazosin hydrochloride/ is tightly bound to plasma proteins (primarily alpha1-acid glycoprotein), and only 5% of the drug is free in the circulation; diseases that modify the concentration of this protein (e.g., inflammatory processes) may change the free fraction. Prazosin is extensively metabolized in the liver, and little unchanged drug is excreted by the kidneys.
MEDICATION
Use (kg; approx.) in Germany (2009): >10
Oral Capsules, 1 mg (of prazosin), Minipress, Pifizer; 2 mg (of prazosin), Minipress, Pifzer; 5 mg (of prazosin), Minipress, Pifizer.
Oral Capsules, 1 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 1, Pifizer; 2 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 2, Pfizer; 5 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 5, Pfizer.
Capsules, 1, 2, and 5 mg /Prazosin HCl/
1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine.
2-(4-(2-FUROYL)PIPERAZIN-1-YL)-4-AMINO-6,7-DIMETHOXYQUINAZOLINE
VerwendenPrazosin Hydrochloride (Terazosin EP Impurity K) is an antihypertensive. α1-Adrenergic blocker.