Prazosin
 | |
| Clinical data | |
|---|---|
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | ~60% |
| Protein binding | 97% |
| Elimination half-life | 2–3 hours |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.038.971 |
| Chemical and physical data | |
| Formula | C19H21N5O4 |
| Molar mass | 383.401 g/mol g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
Prazosin, trade names Minipress,Vasoflex,Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure (hypertension). It belongs to the class of alpha-adrenergic blockers, which lower blood pressure by relaxing blood vessels. 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. By blocking these receptors, prazosin reduces blood pressure.
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. This is because the body has reached homeostasis at this abnormally high blood pressure. The blood pressure lowering effect is apparent however 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.[1]
Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia by 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.[1]
This medication has shown to be effective in treating severe nightmares in children, associated with PTSD symptoms.[2] Also veterans have 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.[2]
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 hypotension, 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 after the first dose.
Another common side effect of prazosin (and doxazosin) is priapism.[3][4]
Another possible side effect is dreaming while awake or hallucinations of wakefulness while falling asleep on the medication (see oneirophrenia) .
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.
Raskind MA, Peskind ER, Kanter ED, et al: Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo controlled study. American Journal of Psychiatry 160:371–373, 2003
Prazosin in scorpion stings
Since 1983 prazosin has revolutionized the management of severe scorpion stings.[5]
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 cyanate 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.
- H.-J.E. Hess, U.S. patent 3,511,836 (1970).
- H.-J.E. Hess, U.S. patent 3,635,979 (1972).
- H.-J.E. Hess, U.S. patent 3,663,706 (1972).
- Pfizer & Co., Inc., GB 1156973 (1970).
- E. Honkanen, A. Pippuri, P. Kairisalo, M. Koivisto, S. Tuorni, J. Heterocycl. Chem., 17, 797(1980).
- H.-J.E. Hess, U.S. patent 3,935,213 (1976).
- Ph.D. Hammen, U.S. patent 4,062,844 (1977).
- R.R. Crenshaw, G.M. Luke, R.A. Portike, U.S. patent 4,138,561 (1979).
- A.K. Pippuri, E.J. Honkman, BE 861821 (1977).
- A.K. Pippuri, E.J. Honkman, BE 861822 (1977).
References
- ^ a b Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 13. ISBN 1-59541-101-1.
- ^ a b "Drug Helps PTSD Nightmares" (Press release). Department of Veteran Affairs. March 30, 2008. Retrieved 2009-03-16.
- ^ Bhalla AK, Hoffbrand BI, Phatak PS, Reuben SR (1979). "Prazosin and priapism". Br Med J. 2 (6197): 1039. doi:10.1136/bmj.2.6197.1039. PMC 1596841. PMID 519276.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Avisrror MU, Fernandez IA, Sánchez AS, García-Pando AC, Arias LM, del Pozo JG (2000). "Doxazosin and priapism". J. Urol. 163 (1): 238. doi:10.1016/S0022-5347(05)68018-4. PMID 10604360.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Bawaskar HS, Bawaskar PH (2007). "Utility of scorpion antivenin vs prazosin in the management of severe Mesobuthus tamulus (Indian red scorpion) envenoming at rural setting". J Assoc Physicians India. 55: 14–21. PMID 17444339.
{{cite journal}}: Unknown parameter|month=ignored (help)
Raskind MA, Peskind ER, Kanter ED, et al: Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo controlled study. American Journal of Psychiatry 160:371–373, 2003