Pheochromocytoma and Paraganglioma
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
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.
Complications of Laparoscopic Adrenal Surgery
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
Prazosin and doxazosin are selective alpha-1 antagonists which can avoid the effects that phenoxybenzamine has on the presynaptic blockade of alpha-2-adrenoceptors. The starting dose for prazosin is 1 mg every 8 hours and can be increased to a maximal dose of up to 12 mg daily. Doxazosin is given in once-a-day or twice-a-day dosing and is started at 1 mg and can be titrated up to 16 mg daily (45,46). It’s advantage over phenoxybenzamine is that blood pressure returns to normal quickly postoperatively compared with patients given phenoxybenazamine who tend to have more prolonged postoperative hypotension, often refractory to large doses of adrenoceptor agonists and requiring more fluid loading (46). Preoperative alpha blockade results in varying degrees of expansion of the circulating blood volume and the more that the blood volume is increased, the more significant the hypotension is following the removal of the pheochromocytoma (50).
Adrenergic Antagonists
Sahab Uddin, Rashid Mamunur in 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).
Chitosan-TPP nanoparticles stabilized by poloxamer for controlling the release and enhancing the bioavailability of doxazosin mesylate: in vitro, and in vivo evaluation
Published in Drug Development and Industrial Pharmacy, 2019
Bader M. Aljaeid, Khalid M. El-Say, Khaled M. Hosny
Doxazosin mesylate (DM), is a drug used for treatment of benign prostatic hyperplasia and hypertension [1]. The dose of DM varies from 1 to 16 mg/daily and its kinetics follow the linear approach within the therapeutic dosage range [2]. DM is absorbed after oral administration and reach the maximum plasma level within 2–3 h which in some cases leads to sudden hypotension, and also requires to be given in low doses with high frequent dosing manner [3]. In order to avoid sudden plasma high concentration after administration of immediate tablets, and to decrease the frequency of dosing especially if the drug used in treatment of chronic diseases, a controlled-release gastrointestinal therapeutic system is recommended in order to enhance the therapeutic efficacy of the drug and to enhance the patient compliance [4].
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].
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