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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).
Pheochromocytoma and Paraganglioma
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Andrzej Januszewicz, Jacques W.M. Lenders, Graeme Eisenhofer, Aleksander Prejbisz
Preoperative alpha-blockade has been advocated for 7 up to 14 days to minimise intraoperative hypertension by preventing catecholamine-induced alpha-adrenoreceptor-mediated vasoconstriction. The medication should be started at a minimum dose (2 dd 10 mg) with slow uptitration to get the optimal therapeutic response (1,3,5) (Table 63.4). Traditionally, the irreversible, noncompetitive alpha-adrenoceptor blocker phenoxybenzamine has been used, but nowadays competitive alpha-blockers such as doxazosin are also used as alternatives. On the basis of current evidence, there is no superior alpha-adrenoceptor blocker for the pretreatment of patients with PPGLs. Perioperative hemodynamics seem to be slightly better controlled with phenoxybenzamine, at the cost of more pronounced postoperative hypotension. However, side effects occurred less often in the group receiving doxazosin (46). Evidence from randomized controlled clinical studies regarding the comparable effectiveness of noncompetitive versus competitive adrenergic receptor blockers is unavailable at this time.
Cardiovascular drug therapy in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
William H. Frishman, Wilbert S. Aronow, Angela Cheng-Lai
Alpha-adrenergic blockers are effective treatments for patients with hypertension and have become first-line treatments for males with symptomatic prostatism. Caution should be exercised when using these agents because of a significant incidence of postural hypotension, especially in patients receiving diuretics or other vasodilator drugs (78,120). A more selective alpha1-blocker, tamsulosin, has become available, which improves prostatism symptoms without having vasodilator effects (121). However, the National Heart, Lung, and Blood Institute withdrew doxazosin from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial after an interim analysis showed a 25% greater rate of a secondary endpoint, combined cardiovascular disease, in patients on doxazosin than in those on chlorthalidone, largely driven by the increased risk of congestive HF (122). These findings have cast a shroud over the use of doxazosin in the elderly particularly if it is being contemplated as monotherapy in a hypertensive elderly patient.
Image-based computer modeling assessment of microwave ablation for treatment of adrenal tumors
Published in International Journal of Hyperthermia, 2022
Jan Sebek, Grazia Cappiello, George Rahmani, Nooshin Zeinali, Muireann Keating, Michael Fayemiwo, Jim Harkin, Liam McDaid, Bryan Gardiner, Declan Sheppard, Russell Senanayake, Mark Gurnell, Martin O’Halloran, M. Conall Dennedy, Punit Prakash
All patients underwent standardized screening and diagnostic approach for endocrine hypertension. PA was diagnosed according to Endocrine Society Guidelines [25]. Screening used a mid-morning aldosterone renin ratio (ARR) following two hours of ambulation with each patient seated for 15 min prior to venesection. Washout of interfering medications was performed on all patients. Confirmatory testing was performed using the seated saline infusion test (SSIT) [26,27]. Blood pressure was controlled during screening and diagnosis using a combination of doxazosin and a calcium channel antagonist. Potassium was corrected where necessary in advance of all blood sampling. Threshold ARR and aldosterone values are reported according to locally determined laboratory reference ranges: suppressed plasma renin activity (PRA) was accepted at values <1.0 ng/mL/h, and direct renin concentrations (DRC) <9.0 mIU/L; raised aldosterone renin ratio (ARR) was accepted at values >800 pmol/L:ng/mL/h when calculated using the PRA and >35 pmol:mIU when using the DRC.
Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant
Published in The American Journal of Drug and Alcohol Abuse, 2020
Daryl I. Shorter, Xuefeng Zhang, Coreen B. Domingo, Ellen M. Nielsen, Thomas R. Kosten, David A. Nielsen
All participants were randomly assigned to placebo (n = 29; 19 AA vs. 10 AT/TT) or doxazosin (n = 47; 21 AA vs. 26 AT/TT). A single dose of doxazosin (8 mg/day) was used in the active medication arm with titration up to 8 mg occurring over a 2-week period (6). This dosage of doxazosin was chosen because it is well tolerated and approved by the FDA for both benign prostatic hyperplasia and hypertension (30). In addition, prior studies have showed a reduction of cocaine use after the doxazosin treatment at the same dose (8mg daily) (6, 13). All participants who met study inclusion criteria underwent a standard physical examination, psychiatric evaluation, and laboratory assessment. Participants attended thrice-weekly clinic visits for 12 weeks with urine toxicology screening at each visit. Urines were tested for six categories of drugs: cocaine, amphetamine, methamphetamine, tetrahydrocannabinol, opiates, and benzodiazepines, using a one-step drug screen card (Acon DOA-754 5-Panel Card. San Diego, CA).
Impact of maternal pheochromocytoma on the fetus and neonate
Published in Gynecological Endocrinology, 2019
When PCC removal is planned for after delivery, the patient uses medications and breastfeeds her baby before surgery. In this case, however, there is concern about drugs being transferred to breast milk. Table 3 indicates the drugs used to treat PCC during preoperative breastfeeding. There are no data regarding phenoxybenzamine transmission via breast milk or its effects on the breastfed neonate. However, less than 1% of the maternal dose is available to the neonate. The potential effects of this exposure on a breastfed neonate are unknown [46]. Moreover, data regarding transfer of doxazosin to human milk are limited, and no data show the effects of doxazosin on breastfed neonates. Although some have advised avoiding breastfeeding during doxazosin therapy because of the results of animal studies [67], the physicochemical properties of doxazosin suggest low transfer to breast milk [47,68]. In addition, a single case study involving a breastfeeding mother receiving doxazosin reported a neonatal doxazosin exposure of <0.1% of the maternal dosage and suggested that maternal doxazosin therapy might be compatible with breastfeeding [68]. However, the neonate may experience additional adverse effects such as hypoglycemia and bradycardia. Although most β-blockers pass to the milk of lactating women, propranolol is highly bound to proteins in the bloodstream and is passed to breast milk at very low levels. These low levels are not expected to pose any risk to the breastfed infant, and the American Academy of Pediatrics considers propranolol to be compatible with breastfeeding [69].