Adrenoceptor Antagonists
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Phentolamine is used in the short-term management of hypertensive crises that occur in phaeochromocytoma. In common with all non-selective α-adrenoceptor antagonists, phentolamine has been notably ineffective, however, in the control of primary (essential) hypertension. Although the blockade of postjunctional vascular α1-adrenoceptors will inhibit sympathetic vasomotor tone and favour a lower blood pressure, the blockade of prejunctional α2-adrenoceptors will enhance neurotransmitter release. This will have a two-fold effect. (1) The increase in baroreceptor-mediated reflex sympathetic activity to the heart arising from the fall in blood pressure will lead to unopposed tachycardia via β-adrenoceptors, which will tend to restore blood pressure. (2) The enhanced release of noradrenaline from sympathetic neurones will compete with the antagonist at the postjunctional α-adrenoceptors thus reducing its effectiveness. A consequence of this is that these non-selective antagonists are more effective against the responses to exogenous noradrenaline than those to sympathetic nerve stimulation. Thus, side-effects such as nasal congestion, reflex tachycardia and ejaculation failure and low effectiveness make the non-selective antagonists unsuitable for use in essential hypertension. Phentolamine may be used to counteract hypertension associated with MAO inhibitor/sympathomimetic amine interactions (ie the ‘cheese effect’, Chapter 2) or to prevent tissue necrosis when adrenaline injections are inadvertently made outside the vein.
Complications of Radical Retropubic Prostatectomy
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
ICI was first presented to the urologic community in the early 1980s. The first drugs used for ICI were papaverine and phentolamine. Papaverine is a synthetic opium alkaloid, which acts primarily as a phosphodiesterase inhibitor, increasing the intracavernosal levels of cAMP and cGMP. The elevated levels of cyclic adenosine monophosphate (cAMP) and cGMP relax the vascular smooth muscle of the corpora, facilitating an erection. Virag reported the first use of papaverine as an ICI in 1982. It is a relatively inexpensive drug with priapism and fibrosis being the primary side effects, both of which are dose dependent. Barada and McKimmy reported up to 35% incidence of priapism and 33% incidence of corporal fibrosis (117). Phentolamine is a nonselective, competitive alpha-adrenergic blocker. By relaxing arterial and venous smooth muscle, it allows increased blood flow to the penis. Most of the side effects of phentolamine are related to its inhibition of serotonin receptors and subsequent histamine release. These include hypotension, tachycardia, nasal congestion, and dyspepsia. These two drugs have been combined to increase the spectrum of action and limit the dose of each agent necessary for erectile function. Multiple studies quote a 70% to 87% efficacy rate with the combination compared with about a 40% efficacy rate for a single agent (118,119). Additionally, the combination therapy allowed for lower doses of each agent, limiting the side effect profile. The studies reported a 1% to 23% incidence of priapism and 1.4% to 16% incidence of fibrosis.
Pharmacological diagnostic tests
Harald Breivik, William I Campbell, Michael K Nicholas in Clinical Pain Management, 2008
Whilst there is more acceptance that pain is sympathetically maintained in some patients, efficacy of phentolamine has not yet been adequately tested.42 Despite this, the authors feel that the test is useful and that it helps to identify a group of patients who may respond to other types of sympathetic blockade. We will continue to use the test in our pain management center until further evidence is available. For studies on the effect of sympatholytic therapies, it is essential that the patient has sympathetically maintained pain or components of a complex pain that are sympathetically maintained. The phentolamine test is one way of selecting appropriate patients for such studies.
A review on pharmacological options for the treatment of erectile dysfunction: state of the art and new strategies
Published in Expert Opinion on Pharmacotherapy, 2023
Mattia Longoni, Alessandro Bertini, Nicolò Schifano, Emanuele Zaffuto, Paolo Maggio, Rossi Piercarlo, Sara Baldini, Giulio Carcano, Gabriele Antonini, Andrea Salonia, Francesco Montorsi, Federico Dehò, Paolo Capogrosso
Phentolamine is a nonselective α-adrenergic antagonist that decreases arterial resistance and promotes vasodilatation by inhibiting smooth muscle cell contraction [75]. The commercial preparation of Bimix, approved for clinical use in some European countries, contains papaverine hydrochloride (15 mg/mL) and phentolamine mesylate (0.5 mg/mL) in 2-mL vials [61]. The combination of these two drugs has shown the same efficacy and equal rate of prolonged erection compared to PGE1 30 μg alone, whereas it caused significantly less injection pain (15% vs 35%, p < 0.05) [76]. The addition of alprostadil (Trimix) provides the highest efficacy rates, reaching up to 92% [77,78]. This three-drug combination has similar adverse effects as alprostadil monotherapy, although fibrosis is more common when a higher dose of papaverine is used (5–10%) [77]. Noteworthy, hypotension could potentially occur with higher concentrations of the compounds [53]. In a randomized clinical trial, the combination of papaverine 17.64 mg + phentolamine 0.58 mg + PGE1 5.8 μg had a twofold efficacy rate compared to PGE1 40 μg monotherapy (50% vs 22%), with very low pain (12.5% vs 22%) due to the reduced dose of alprostadil being used [79]. Therefore, Trimix could be a suitable option for patients who underwent radical pelvic surgery as pain or tenderness after PGE1 is accentuated by an underlying cavernous nerve injury [53,63]. Unfortunately, no commercially marketed preparation for Trimix is available, due to the low stability of the combined agents.
Management of a patient with unintended intravenous dihydroergotamine infusion extravasation causing brachial artery vasospasm
Published in Baylor University Medical Center Proceedings, 2023
Extravasation injuries occur in 0.1% to 6% of adult patients and up to 11% of pediatric patients.9,10 The physicochemical properties of an infiltrated substance will typically determine the propensity for tissue damage after infiltration. Nitropaste, nitroprusside infusions, and intradermal phentolamine injections were initially attempted in our patient with minimal results. Nitropaste has been well documented in effectively treating cerebral vasospasms and vasospastic conditions such as Raynaud’s phenomenon11,12 via relaxation of the smooth muscles within the arterioles and venules.13 Nitroprusside infusions can be helpful in relieving cerebral vasospasms and have been reported in treating systemic ergotism induced limb ischemia with some efficacy.7,8 Phentolamine is a competitive nonselective alpha-adrenergic receptor antagonist and is the drug of choice in treating sympathomimetic vasopressor extravasation, such as epinephrine and norepinephrine.14,15 There is currently minimal literature on the effectiveness of intradermal phentolamine in treating extravasation of other medications with vasopressor properties, such as DHE. This patient ultimately required invasive intervention in the operating room to manage the iatrogenic vasoconstriction of the brachial artery.
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
Adverse effects associated with α2 agonists include hypotension, bradycardia, dry mouth, and sedation. At high doses, respiratory depression may occur. Clonidine withdrawal has also been reported to produce rebound hypertension and elevated plasma catecholamine concentrations. This side effect can be reversed with IV phentolamine. Other clonidine withdrawal symptoms include headache, agitation, nervousness, and rarely hypertensive encephalopathy, cerebrovascular accident, and even death [12]. Epidural clonidine can cause severe hypotension, especially in women and those of low body weight, and it is not recommended for perioperative, obstetrical, or postpartum pain due to concerns regarding hemodynamic instability [13].
Related Knowledge Centers
- Adrenergic Antagonist
- Baroreflex
- Dromotropic
- Heart Rate
- Hypotension
- Tachycardia
- Norepinephrine
- Vasodilation
- Alpha-1 Blocker
- Myocardial Contractility