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Adrenergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
It is structurally similar to prazosin with highly selective α1 receptor antagonism. It affects the subtypes namely α1D, α1B, and α1A. Similar to prazosin it acts by obstructing phosphodiesterases thereby activating the protein kinase bringing about an abatement in the tone of smooth muscles present in blood vessels causing vasodilation effect and fall in BP, resultant of declined peripheral resistance. Similar/analogous activity in tone of prostatic has been reported as a consequence of α1-adrenoceptor blockade relieving obstruction of bladder outflow (Fulton et al., 1995). Studies report that doxazosin (Fig. 4.4) produce increase in HDL level and decrease the LDL and total cholesterol levels; beneficial in insulin resistance and impaired glucose metabolism (Fulton et al., 1995; Grimm et al., 1996). The bioavailability and biotransformation in doxazosin is analogous to prazosin but has lengthy duration of activity extending as far as 36 h. The t½ is about 20 h with majority metabolites excreted/elimination via feces (Fulton et al., 1995; Li et al., 2015). Similar to terazosin it produces apoptosis of α adrenoceptors in the smooth muscles of prostate, hence utilized for treating urinary tract issues connected with BPH and hypertension. Adverse events are fatigue, dizziness, hypotension, and headache (Dutkiewicz, 1997; Lepor, 1995; Gugger, 2011).
Orthostatic Hypotension Induced by Drugs and Toxins
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
The selective α-blockers prazosin and terazosin are used primarily to treat hypertension, although they are also used to treat benign prostatic hyperplasia. Selective antagonists of ct\ receptors allow noradrenaline that is released as a sympathetic reflex response to hypotension to feedback on «2 receptors that are located presynaptically to further inhibit noradrenaline release. This minimizes the extent of reflex tachycardia as compared to that observed after treatment with nonselective α-blockers. Orthostatic hypotension is particularly a problem with the first dose of prazosin or terazosin, after which patients frequently become symptomatic of orthostatic hypotension (Figure 16.2) (Graham et al., 1976). Tolerance develops rapidly to the orthostatic hypotension, in part due to a compensatory expansion of the blood volume. First dose orthostatic hypotension may be minimized by starting therapy with low doses and administering the first dose at bed time. Patients should be warned about the first effect of the first dose and instructed to get up out of bed slowly and to lie down if they begin to feel dizzy or light-headed.
Adrenoceptor Antagonists
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
Terazosin has essentially the same activity as doxazosin. It has an affinity for α1-adrenoceptors of about one-third that of prazosin, and its selectivity for α1-adrenoceptors is illustrated by the fact that more than 100-fold higher concentration is required to displace [3H]rauwolscine from α2-adrenoceptor binding sites of rat brain than is needed to displace [3H]-prazosin from rat liver α1-adrenoceptors. Terazosin is more water soluble than prazosin and its absorption from the gastrointestinal tract is more complete and predictable than with prazosin, thus enabling better titration of the dose. Its elimination half-life is ∼12 hr, the effect lasting over 18 hr. It is therefore normally administered once daily for the treatment of hypertension, starting at a dose of 1 mg daily given at night to avoid the first dose effect. The daily dose is then increased gradually as the blood pressure stabilizes to a maximum dose of 20 mg daily (Titmarsh & Monk 1987).
Simple and high sample throughput LC/ESI-MS/MS method for bioequivalence study of prazosin, a drug with risk of orthostatic hypotension
Published in Drug Development and Industrial Pharmacy, 2022
Gabriel Onn Kit Loh, Emily Yii Ling Wong, Yvonne Tze Fung Tan, Hong Chin Wee, Ru Shing Ng, Haroon Khalid Syed, Kok Khiang Peh
The obtained precursor molecular ions [M + H]+ of prazosin and IS were 384.20 and 388.20 using Q1 and Q3 scans on drug standard solutions with concentration of 2000 ng/mL. Positive ionization mode was more favored by prazosin and IS due to the molecular structures of prazosin and IS having piperazine group, a six-membered ring with two nitrogen atoms at opposite positions in the ring. A proton donor was contributed with the use of formic acid in mobile phase. In the current study, two transitions were selected as quantification and confirmation product ions for prazosin and IS, m/z 95.00 and m/z 247.05 for prazosin, while m/z 71.10 and m/z 247.10 for IS. Terazosin was selected as IS as it is easily available and not costly. It showed similar chromatographic behavior as prazosin and its use has been reported in other studies [21,34].
How should future clinical trials be designed in the search for disease-modifying therapies for Parkinson’s disease?
Published in Expert Review of Neurotherapeutics, 2023
Abhishek Lenka, Joseph Jankovic
There is growing interest in the neuroprotective potential of the glycolysis-enhancing α-1 blockers. Large cohort studies and preclinical studies have reported favorable effects of α-1 blockers such as terazosin, doxazosin, and alfuzosin on PD [134,135]. These drugs enhance the production of ATP, resulting in positive bioenergetics. Importantly, a recent randomized pilot study on 13 PD patients reported that terazosin may engage its target and change ATP levels in the brain and blood of PD patients [136]. Given these promising results, it would be interesting to see how this class of drugs does in future randomized double blinded trials involving large number of patients.
Transdermal iontophoresis delivery system for terazosin hydrochloride: an in vitro and in vivo study
Published in Drug Delivery, 2021
Changzhao Jiang, Xiumei Jiang, Xiumin Wang, Jiaxu Shen, Mengjie Zhang, Leilei Jiang, Rui Ma, Tingting Gan, Yingbiao Gong, Jincui Ye, Wenyan Gao
In this study, we aimed to design a system capable of transdermally delivering terazosin hydrochloride, and the characteristics of this system were identified. Transdermal flux was mainly affected by current intensity, pH, drug concentration, and the type of chemical penetration enhancer used. In vivo experiments also confirmed the iontophoretic blood concentration efficacy as well as the antihypertensive effect. Based on these findings, further clinical studies should be conducted to validate the feasibility of delivering terazosin at therapeutic doses to hypertensive or benign prostatic hyperplasia patients.