プラゾシン

1.3

1.3

1.4

6.93e-01 g/L

277-280

279 °C

192.7 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

192 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；186.41 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；187.83 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]；H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (50%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, 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 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

IMAP assessments - Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)-: Environment tier I assessment；IMAP assessments - Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)-: Human health tier I assessment

Prazosin has been associated with a low rate of serum aminotransferase elevations that in controlled trials was no higher than with placebo therapy. These elevations were transient and did not require dose modification. No instances of clinically apparent acute liver injury due to prazosin have been published in the literature, but reports of cholestatic hepatitis have been received by the sponsor. Among the alpha adrenergic receptor antagonists, the most frequently implicated agent in causing liver injury has been alfuzosin with only single, and not well documented cases linked to other alpha blockers. Thus, acute symptomatic liver injury due to prazosin is quite rare, and severe hepatotoxicity must be exceeding rare, if it occurs at all.；Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury).

Serious Adverse Effects；Serious adverse effects include first-dose hypotension, and therefore it is recommended to take the initial dose at night. Also, patients may develop orthostatic hypotension and syncope. In cataract surgeries, patients taking prazosin may develop intraoperative floppy iris syndrome (IFIS) due to the drug's effect on the alpha receptors on the iris dilator muscle. However, some patients develop IFIS without using alpha-adrenergic receptor antagonists prior to surgery . Other serious adverse effects include priapism.；Common side effects found in 5 to 10% of patients are dizziness, headaches, drowsiness, lack of energy, weakness, palpitations, and nausea. An extensive list of side effects can be found below with their occurrence rates.；Serious Adverse Effects；* First dose hypotension；* Orthostatic hypotension；* Intraoperative Floppy iris syndrome；* Priapism；* Syncope；Common Adverse Effects (5 to 10% of patients) (Koola)；* Dizziness；* Headache；* Drowsiness；* Lack of energy；* Weakness；* Palpitations；* Nausea；Less Common Adverse Effects (1 to 4%)；* Vomiting；* Diarrhea

There is no direct toxicity with this medication. High doses and overdoses could lead to hypotension, and patients should be supported clinically with volume resuscitation if necessary or pressor support.；The literature reports a case of an overdose of prazosin in a pediatric patient with hypotension, which was refractory to volume resuscitation, epinephrine, and norepinephrine support. This patient had concomitant ingestion with naproxen and acetaminophen. Given the hepatic metabolism of both acetaminophen and prazosin, this likely led to the prolonged clearing of the medication. The patient did respond to vasopressin.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

prazosin

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

◉ Summary of Use during Lactation；Because little is available on the use of prazosin during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.；◉ Effects in Breastfed Infants；Relevant published information was not found as of the revision date.；◉ Effects on Lactation and Breastmilk；Relevant published information in nursing mothers was not found as of the revision date. Prazosin does not affect serum prolactin concentration in patients with hypertension. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

C02CA01

C - Cardiovascular system；C02 - Antihypertensives；C02C - Antiadrenergic agents, peripherally acting；C02CA - Alpha-adrenoreceptor antagonists；C02CA01 - Prazosin

QC - Cardiovascular system；QC02 - Antihypertensives；QC02C - Antiadrenergic agents, peripherally acting；QC02CA - Alpha-adrenoreceptor antagonists；QC02CA01 - Prazosin

**Effects on blood pressure** The pharmacodynamic and therapeutic effect of this drug includes is a decrease in blood pressure as well as clinically significant decreases in cardiac output, heart rate, blood flow to the kidney, and glomerular filtration rate. The decrease in blood pressure may occur in both standing and supine positions. Many of the above effects are due to vasodilation of blood vessels caused by prazosin, resulting in decreased peripheral resistance,. Peripheral resistance refers to the level resistance of the blood vessels to blood that flows through them. As the blood vessels constrict (narrow), the resistance increases and as they dilate (widen), and peripheral resistance decreases, lowering blood pressure. **Effects on sleep disturbance related to post-traumatic stress disorder (PTSD)** Some studies have suggested that this drug improves sleep in patients suffering from insomnia related to nightmares and post-traumatic stress disorder, caused by hyperarousal. This effect likely occurs through the inhibition of adrenergic stimulation found in states of hyperarousal.

Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha 1 and alpha 2, both play a role in regulating blood pressure. Alpha-1 receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle. These receptors, when activated, increase blood pressure. Prazosin inhibits the postsynaptic alpha-1 adrenoceptors. This inhibition blocks the vasoconstricting (narrowing) effect of catecholamines (epinephrine and norepinephrine) on the vessels, leading to peripheral blood vessel dilation. Through blood vessel constriction by adrenergic receptor activation, epinephrine and norepinephrine normally act to increase blood pressure.

XM03YJ541D

PRAZOSIN

Mechanisms of Action [MoA] - Adrenergic alpha-Antagonists

Established Pharmacologic Class [EPC] - alpha-Adrenergic Blocker

Prazosin is an alpha-Adrenergic Blocker. The mechanism of action of prazosin is as an Adrenergic alpha-Antagonist.

PRAZOSIN

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.

After administration of an oral dose, peak plasma concentrations are attained at approximately 3 hours. There is a linear association between the prazosin dose given and plasma concentration at steady state.

This drug is mainly excreted in the bile and the feces.

About 0.6 L/kg.

In patients with congestive heart failure, the clearance of this drug is decreased. Impairment of renal function does not have relevant effects on elimination.