Prazosin
Encyclopedia
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic
drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth muscle
. These receptors are responsible for the vasoconstrictive action of norepinephrine
, which would normally raise blood pressure and cause increase in anxiety and panic. By blocking these receptors, prazosin reduces blood pressure and reduces anxiety and panic.
In addition to its alpha-blocking
activity, prazosin is an antagonist
of the MT3 receptor
(which is not present in humans), with selectivity
for this receptor over the MT1
and MT2 receptor
s.
at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases.
The antihypertensive characteristics of prazosin make it a second-line choice for the treatment of high blood pressure.
Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia
, blocking alpha-1 receptors, which control constriction of both the prostate
and ureters. Although not a first line choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with both problems concomitantly.
This medication has shown to be effective in treating severe nightmares in children, associated with PTSD symptoms.
Veterans have also been treated successfully at the Oregon VA for sleep disturbance related to PTSD. Doses are lower for this purpose than for control of blood pressure.
Prazosin holds promise as a pharmacologic treatment for alcohol dependence after a 2009 pilot trial l was completed. A larger controlled Phase II trial "Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence" is currently underway, set to be completed November 2013.
, syncope, and nasal congestion
. The orthostatic hypotension and syncope are associated with the body's poor ability to control blood pressure without active alpha-adrenergic receptors. Patients on prazosin should be told not to stand up too quickly, since their poor baroreflex may cause them to faint as all their blood rushes to their feet. The nasal congestion is due to dilation of vessels in the nasal mucosa.
One phenomenon associated with prazosin is known as the "first dose response", in which the side effects of the drug, especially orthostatic hypotension and fainting, are especially pronounced in the first dose.
One very rare side effect of prazosin (and doxazosin) is priapism
.
Another possible side effect is dreaming while awake or hallucinations of wakefulness while falling asleep on the medication (see oneirophrenia
) .
s.
undergoes heterocyclation into 2,4-dihydroxy-6,7-dimethoxyquinazoline. Substituting hydroxyl groups of this compound with chlorine atoms by reaction with thionyl chloride
, or a mixture of phosphorus oxychloride with phosphorus pentachloride gives 2,4-dichloro-6,7-dimethoxyquinazoline. Upon subsequent reaction with ammonia, the chlorine atom at C4 of the pyrimidine ring is replaced with an amino group, which leads to the formation of 4-amino-2-chloro-6,7-dimethoxyquinazoline. Introducing this into a reaction with 1-(2-furoyl)piperazine gives prazosin.
Sympatholytic
A sympatholytic drug is a medication which inhibits the postganglionic functioning of the sympathetic nervous system . They are indicated for various functions, for example they may be used as antihypertensives...
drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth muscle
Vascular smooth muscle
Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels.Vascular smooth muscle contracts or relaxes to both change the volume of blood vessels and the local blood pressure, a mechanism that is responsible for the...
. These receptors are responsible for the vasoconstrictive action of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, which would normally raise blood pressure and cause increase in anxiety and panic. By blocking these receptors, prazosin reduces blood pressure and reduces anxiety and panic.
In addition to its alpha-blocking
Alpha blocker
Alpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...
activity, prazosin is an antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
of the MT3 receptor
Melatonin receptor 1C
Melatonin receptor 1C, also known as MTNR1C, is a protein that is encoded by the Mtnr1c gene. This receptor has been identified in fish, amphibia, and birds, but not in humans.- References :...
(which is not present in humans), with selectivity
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
for this receptor over the MT1
Melatonin receptor 1A
Melatonin receptor type 1A is a protein that in humans is encoded by the MTNR1A gene.-Further reading:...
and MT2 receptor
Melatonin receptor 1B
Melatonin receptor 1B, also known as MTNR1B, is a protein that in humans is encoded by the MTNR1B gene.-Function:This gene encodes the MT2 protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane...
s.
Use
Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. However, when prazosin is initially started, heart rate and contractility go up in order to maintain the pre-treatment blood pressures because the body has reached homeostasisHomeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases.
The antihypertensive characteristics of prazosin make it a second-line choice for the treatment of high blood pressure.
Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
, blocking alpha-1 receptors, which control constriction of both the prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
and ureters. Although not a first line choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with both problems concomitantly.
This medication has shown to be effective in treating severe nightmares in children, associated with PTSD symptoms.
Veterans have also been treated successfully at the Oregon VA for sleep disturbance related to PTSD. Doses are lower for this purpose than for control of blood pressure.
Prazosin holds promise as a pharmacologic treatment for alcohol dependence after a 2009 pilot trial l was completed. A larger controlled Phase II trial "Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence" is currently underway, set to be completed November 2013.
Side effects
Side effects of prazosin include orthostatic hypotensionOrthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
, syncope, and nasal congestion
Nasal congestion
Nasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can range from a...
. The orthostatic hypotension and syncope are associated with the body's poor ability to control blood pressure without active alpha-adrenergic receptors. Patients on prazosin should be told not to stand up too quickly, since their poor baroreflex may cause them to faint as all their blood rushes to their feet. The nasal congestion is due to dilation of vessels in the nasal mucosa.
One phenomenon associated with prazosin is known as the "first dose response", in which the side effects of the drug, especially orthostatic hypotension and fainting, are especially pronounced in the first dose.
One very rare side effect of prazosin (and doxazosin) is priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...
.
Another possible side effect is dreaming while awake or hallucinations of wakefulness while falling asleep on the medication (see oneirophrenia
Oneirophrenia
Oneirophrenia is a hallucinatory, dream-like state caused by several conditions such as prolonged sleep deprivation, sensory deprivation, or drugs . From the Greek words "ὄνειρο" and "φρενός"...
) .
Prazosin in management of PTSD
Prazosin has been reported to be useful in management of anxiety, such as PTSD. Raskin and colleagues studied the efficacy of prazosin for PTSD among ten Vietnam combat veterans in a 20-week double-blind crossover protocol with a two-week drug washout to allow for return to baseline. The CAPS and the Clinical Global Impressions-Change scale (CGI-C) were the primary outcome measures. Patients who were taking prazosin had a robust improvement in overall sleep quality (effect size, 1.6) and recurrent distressing dreams (effect size, 1.9). In each of the PTSD symptom clusters the effect size was medium to large: .7 for reexperiencing or intrusion, .6 for avoidance and numbing, and .9 for hyperarousal. The reduction in CGI-C scores (overall PTSD severity and function at endpoint) also reflected a large effect size (1.4). Prazosin appears to have promise as an effective treatment for PTSD-related sleep disturbance, including trauma-related nightmares, as well as overall Anxiety and PTSD symptoms.Prazosin in scorpion stings
Since 1983 prazosin has revolutionized the management of severe scorpion stingScorpion sting
Scorpion stings are a cutaneous condition caused by the stinging of scorpions, usually resulting in pain, paresthesia, and variable swelling. The anatomical part of the scorpion that delivers the sting is called a "telson".- See also :* Scorpion venom...
s.
Chemistry
Prazosin, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl)-piperazine, is synthesized from 2-amino-4,5-dimethoxybenzoic acid, which upon reaction with sodium cyanateCyanate
The cyanate ion is an anion with the chemical formula written as [OCN]− or [NCO]−. In aqueous solution it acts as a base, forming isocyanic acid, HNCO. The cyanate ion is an ambidentate ligand, forming complexes with a metal ion in which either the nitrogen or oxygen atom may be the electron-pair...
undergoes heterocyclation into 2,4-dihydroxy-6,7-dimethoxyquinazoline. Substituting hydroxyl groups of this compound with chlorine atoms by reaction with thionyl chloride
Thionyl chloride
Thionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
, or a mixture of phosphorus oxychloride with phosphorus pentachloride gives 2,4-dichloro-6,7-dimethoxyquinazoline. Upon subsequent reaction with ammonia, the chlorine atom at C4 of the pyrimidine ring is replaced with an amino group, which leads to the formation of 4-amino-2-chloro-6,7-dimethoxyquinazoline. Introducing this into a reaction with 1-(2-furoyl)piperazine gives prazosin.
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- Pfizer & Co., Inc., (1970).
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