Visceral afferents innervating the perineum discount rumalaya gel 30 gr overnight delivery, distal rectum discount generic rumalaya gel uk, anus cheapest generic rumalaya gel uk, distal urethra purchase 30gr rumalaya gel with mastercard, vulva, and distal third of vagina converge at the ganglion. Four to 8 mL of local anesthetic is used for diagnostic block and 8% to 10% phenol or 50% alcohol is used for neurolysis. Similar to superior hypogastric plexus blocks, there are no controlled studies on its efficacy, although case reports confirm its effectiveness in relieving perineal pain secondary to cancer. Pharmacologic Management of Pain Opioids Morphine is the standard for opioid therapy for cancer pain (see Chapter 20, Opioids). The metabolites of morphine include morphine-6-glucuronide, which causes additional analgesia, and morphine-3-glucuronide, which can cause adverse effects. Controlled-release preparations are available, reducing the need to take the drug frequently. Hydromorphone, a μ-receptor agonist, is three to five times more potent than morphine when given orally and five to seven times more potent when given parenterally. Pruritus, sedation, nausea, and vomiting occur less frequently compared with morphine. Its metabolite, hydromorphone-3- glucoronide, lacks analgesic property but possesses properties similar to that of morphine-3-glucuronide. Methadone has a 60% to 95% bioavailability, high potency, and a long duration of action. Its potency compared with morphine ranges from 1:1 to 1:2 on acute dosing but can be 1:4 with chronic dosing. It has a long and unpredictable half-life of 8 to 80 hours that makes it difficult to achieve steady-state plasma concentrations, increasing the risk of accumulation and the need for careful and individualized dosing. There has been an “epidemic” of deaths due to 4050 unintentional overdose from methadone111 because many physicians do not appreciate the consequences of the drug’s long and unpredictable half-life. Most reports are based on high-dose maintenance (>120 mg) for the treatment of addiction; however, such occurrences have also been reported with lower dosages. It has a high bioavailability (60%) and is associated with a low incidence of itching and hallucinations. The controlled-release preparation (OxyContin, Purdue Pharma) has good analgesic characteristics but became a popular drug for abuse prior to its reformulation to include abuse-deterrent technologies. Oxymorphone has greater affinity to the μ-receptor than morphine and has little or no affinity to the κ-opioid receptor. Due to extensive first-pass hepatic metabolism, the bioavailability of oxymorphone is only 10%. It should not be taken with alcohol because this increases its plasma concentration by as much as 300%. The efficacy of oxymorphone in chronic and cancer pain is similar to other opioids. Buprenorphine is a partial agonist at the μ-receptor, a κ-antagonist, and a weak δ-agonist. It has a rapid onset (30 minutes) when given orally and a long duration of action of 6 to 9 hours. Buprenorphine antagonizes the opioid effects of full agonists such as morphine or hydromorphone due to its partial opioid agonist pharmacodynamics. Approximately 9% of Caucasians do not have the enzyme and do not experience analgesia from codeine. Children under 12 years of age lack maturity of the enzyme and cannot convert the drug to morphine, experiencing the drug’s side effects with minimal analgesia. It has bioavailability of 80% to 90%, low abuse potential, low incidence of constipation, and minimal risk of fatal respiratory depression, which is possibly limited to patients with severe renal failure. Tapentadol is similar to tramadol and also has a dual mode of action as a μ- opioid agonist and a norepinephrine reuptake inhibitor. Tapentadol has side effects and adverse reactions that are similar to those of tramadol, but has a higher risk of addiction and respiratory depression due to its opioid agonism. The oral equianalgesic doses of morphine 10 mg intravenously or 30 mg orally are (1) 200 mg of codeine, (2) 30 mg of hydrocodone, (3) 20 mg of oxycodone, (4) 150 mg of tramadol, and (5) 75 mg of tapentadol. A 2013 study determined, contrary to older studies, that individuals receiving stable doses of 20 mg of morphine or equivalent are at increased risk for motor vehicle collisions and this risk increases substantially at doses above 120 mg. Opioids are commonly used for cancer pain, with long-acting opioids supplemented by short-acting ones for breakthrough pain. Opioid monotherapy in cancer pain is rarely successful and adjuvants and procedural interventions are usually added for increased efficacy. The use of opioids for acute or short-term pain (<3 months) following surgery or traumatic injuries is well accepted and supported by the literature. The use of opioids for treatment of chronic (>3 months) noncancer pain is controversial. To date, there has been no randomized clinical trial establishing the efficacy of chronic opioid therapy for greater than 3 months. Studies show them to be effective in the treatment of neuropathic pain, although at higher doses. Because of the undesirable issues associated with the use of opioids, such as addiction, aberrant behaviors, and regulatory issues, opioids are a third-line drug for neuropathic pain. The combination of a gabapentin 4052 and an opioid has been shown to result in better analgesia, fewer side effects, and lower doses of each drug. It should be noted that although individual studies show the efficacy of opioids in low back pain in the short term, a meta-analysis did not show reduced pain when compared with a placebo or a nonopioid control group. Other opioids, including pure opioid agonists, should not be used in the treatment of fibromyalgia and chronic widespread pain. The long-term use of opioids is associated with tolerance and physical dependence. The rates of substance-use disorders or opioid misuse reported in studies vary widely. A body of evidence suggests that among chronic pain patients receiving opioid therapy, 6% to 37% will exhibit aberrant drug-related behaviors, 8% to 16% will abuse their drugs, and approximately 2% to 14% may become addicted. Recent literature has supported the hypothesis that a subset of patients self-medicate with opioids to manage depression independent of pain. Second-line recommendations included capsaicin 8% patches, lidocaine patches, and tramadol. Antidepressants also inhibit the histaminic, cholinergic, muscarinic, and nicotinic receptors, resulting in sedation, dry mouth, and urinary retention. Venlafaxine has more serotonergic effects at lower doses but with greater noradrenergic activity at higher dosages. Duloxetine and milnacipran have preferential noradrenergic effect, have longer half-lives (12 and 8 hours respectively), and have no active metabolites. The side effects of antidepressants include cholinergic effects such as dry mouth, sedation, and urinary retention. A gradual withdrawal is recommended for duloxetine to prevent agitation, anxiety, confusion, and hypomania. The recommended doses for the commonly used antidepressants are shown in Table 56-2. Anticonvulsants Neuropathic pain is associated with changes in sodium and calcium channel subunit expression, resulting in functional changes. In chronic nerve injury, there is redistribution and alteration of subunit compositions of sodium and 4054 calcium channels, resulting in spontaneous firing at ectopic sites along the sensory pathway. Most anticonvulsants block sodium channels, explaining their efficacy in neuropathic pain syndromes. The other drugs directly block calcium channels (lamotrigine), T-type calcium channels (topiramate and zonisamide) and α -delta subunits (gabapentin and2 pregabalin). Compared to gabapentin, pregabalin has an improved linear pharmacokinetic profile. The maximum dose of pregabalin is 600 mg/day in patients with creatinine clearance more than 60 mL/min or 300 mg in patients with clearance of 30 to 60 mL/min. The popularity of gabapentin and pregabalin relates to the lack of drug interactions and their perceived speed of onset. Oxcarbazepine is similar in chemical structure to carbamazepine and noted to be effective in trigeminal neuralgia with fewer side effects; its analgesic effect is fast and pain relief may be noted within 24 to 48 hours. The side effects of anticonvulsants include dizziness, fatigue, somnolence, weight gain, peripheral edema (gabapentin and pregabalin); rash (lamotrigine); paresthesia, cognitive effects, weight loss (topiramate); hyponatremia; and low thyroid concentrations (oxcarbazepine). Lidocaine Patch, Capsaicin Patch, Mexiletine, and Intravenous Lidocaine The 5% lidocaine patch delivers lidocaine locally at the site of neuropathic pain generation, limiting its systemic effects and reducing its interactions with other concomitantly administered medications; analgesia is by local sodium channel blockade and not by its systemic effects. It is recommended that a maximum of three patches be applied for a maximum of 12 hr/day.
The result is that order genuine rumalaya gel on line, during their initial introduction to practice purchase rumalaya gel 30 gr on line, the functionality of the devices in the sickest of patients is not necessarily well characterized or understood buy cheap rumalaya gel 30gr on line. It is our sickest patients who have the most to gain from devices that allow us to assess their clinical condition more rapidly and less invasively purchase 30 gr rumalaya gel amex, but it is our sickest patients who are the most vulnerable should the devices tend to become inaccurate under just those clinical conditions. The 1811 limits of the reliability and clinical applicability of these devices must be a matter of concern for the practicing anesthesiologist. Though devices are becoming “smarter,” that knowledge does not excuse us of the knowledge to know how to employ them wisely. The oxygen analyser: applications and limitations–an analysis of 200 incident reports. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Pulse oximeters demonstrate different responses during hypothermia and changes in perfusion. Diagnosis of clinically unrecognized endobronchial intubation in paediatric anaesthesia: which is more sensitive, pulse oximetry or capnography? Perioperative anaesthetic morbidity in children: a database of 24,165 anaesthetics over a 30-month period. Clinical evaluation of a Raman scattering multiple gas analyzer for the operating room. The capnograph: applications and limitations–an analysis of 2000 incident reports. Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic concentration-awake. Prospective randomized controlled multi-centre trial of cuffed or uncuffed endotracheal tubes in small children. Accuracy of a new low-flow sidestream capnography technology in newborns: a pilot study. The fast flush test measures the dynamic response of the entire blood pressure monitoring system. Perioperative spinal cord infarction in nonaortic surgery: report of three cases and review of the literature. Thrombotic complications of umbilical artery catheters: A clinical and radiographic study. Coarctation of the abdominal aorta and renal artery stenosis related to an umbilical artery catheter placement in a neonate. Evaluation of distal radial artery cross- sectional internal diameter in pediatric patients using ultrasound. Incidence and clinical outcome of iatrogenic femoral arteriovenous fistulas: Implications for risk stratification and treatment. Surgical intervention for complications caused by femoral artery catheterization in pediatric patients. Ultrasound-guided versus landmark-guided 1814 femoral vein access in pediatric cardiac catheterization. Complications resulting from use of arterial catheters: Retrograde flow and rapid elevation in blood pressure. Arterial fast bolus flush systems used routinely in neonates and infants cause retrograde embolization of flush solution into the central arterial and cerebral circulation. Retrograde air embolization during routine radial artery catheter flushing in adult cardiac surgical patients: An ultrasound study. Retrograde blood flow in the brachial and axillary arteries during routine radial arterial catheter flushing. Pressurized bag pump and syringe pump arterial flushing systems: An unrecognized hazard in neonates? Oscillometric blood pressure measurements by different devices are not interchangeable. Particular Requirements for the Safety, Including Essential Performance, of Automatic Cycling Non-Invasive Blood Pressure Monitoring Equipment. A comparison of two automated indirect arterial blood pressure meters: With recordings from a radial arterial catheter in 1815 anesthetized surgical patients. Comparison of two automatic methods and simultaneously measured direct intra-arterial pressure. Sampling intervals to record severe hypotensive and hypoxic episodes in anesthetised patients. Comparison of non-invasive blood pressure measurements on the arm and calf during cesarean delivery. Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures. Impact of the pulmonary artery catheter in critically ill patients: Meta-analysis of randomized clinical trials. American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Practice guidelines for pulmonary artery catheterization: an updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Summary of recommendations: Guidelines for the prevention of intravascular catheter-related infections. Central venous access sites for the prevention of venous thrombosis, stenosis and infection in patients requiring long-term 1816 intravenous therapy. Central venous catheters in pediatric patients—subclavian venous approach as the first choice. Minimizing complications associated with percutaneous central venous catheter placement in children: recent advances. Percutaneous femoral venous catheterizations: a prospective study of complications. Comparison of the Fick and dye injection methods of measuring the cardiac output in man. Measurement of cardiac output in anaesthetized animals by a thermodilution method. A multicenter evaluation of a new continuous cardiac output pulmonary artery catheter system. Effect of injectate volume and temperature on thermodilution cardiac output determination. Clinicians’ abilities to estimate cardiac index in ventilated children and infants. Clinical assessment of cardiac performance in infants and children following cardiac surgery. Clinical validation of cardiac output measurements using femoral artery thermodilution with direct Fick in ventilated 1817 children and infants. A comparison of pulmonary and femoral artery thermodilution cardiac indices in paediatric intensive care patients. The effectiveness of right heart catheterization in the initial care of critically ill patients. Arterial waveform analysis for the anesthesiologist: Past, present, and future concepts. Validation of the mostcare pulse contour cardiac output monitor: Beyond the bland and altman plot. Digest of the 10th International Conference on Medical and Biological Engineering; Dresden1973. Translation of Otto Frank’s paper “Die Grundform des Arteriellen Pulses” Zeitschrift fur Biologie 37: 483–526 (1899). The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model. The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements. Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine. Cardiac output measurement in patients undergoing liver transplantation: pulmonary artery catheter versus 1818 uncalibrated arterial pressure waveform analysis. Arterial pressure-based cardiac output in septic patients: Different accuracy of pulse contour and uncalibrated pressure waveform devices. Uncalibrated pulse contour- derived stroke volume variation predicts fluid responsiveness in mechanically ventilated patients undergoing liver transplantation. Uncalibrated arterial pulse contour analysis versus continuous thermodilution technique: Effects of alterations in arterial waveform.
If the organism is unable to ferment lactose or sucrose discount rumalaya gel 30gr overnight delivery, the slant will revert to alkaline (red) when the glucose is used up and alkaline amines are produced in the oxidative decarboxylation of peptides (derived from protein in the medium) near the surface of the agar purchase rumalaya gel 30 gr visa. If acid slant–acid butt (yellow–yellow): glucose and sucrose and/or lactose fermented buy 30gr rumalaya gel amex. The presence of black precipitate (butt) indicates hydrogen sulﬁde production and presence of splits or cracks or air bubbles indicates gas production cheap rumalaya gel. Early readings may result in false acid–acid results, while delayed readings may result in false alkaline–alkaline results. The utilization of sucrose may suppress the enzyme mechanism that results in the production of H2S. Trace amounts of H2S may not be detectable with the ferrous sulfate indicator in the agar [1, 15]. Following the incubation, add 4–5 drops of 10 % ferric chloride solution to the slant. The development of green color on the surface of the slant indicates positive reaction. Decarboxylase (Moeller’s Method) Decarboxylases are a group of substrate-speciﬁc enzymes that are capable of decar- boxylate (or hydrolyze) amino acids to form alkaline-reacting amines. Lysine, ornithine, and arginine are the three amino acids used routinely in the identiﬁcation of Enterobacteriaceae, Aeromonas, Plesiomanas, and Vibrio species. The decarboxylation of lysine and ornithine yields cadaverine and putrescine, respectively. A control tube containing the base without an added amino acid to verify that the organism utilizes glucose must accompany all decarboxylase tests. Since decarboxylation is an anaerobic reaction, the tubes must be overlaid with mineral oil prior to incubation. If the organism is viable, both the control and the test tube with amino acid should turn yellow because of fermentation of the small amount of glucose in the medium. If the amino acid is decarboxylated, the alkaline amines cause the indicator (bromcresol purple) in the acid medium to revert back to its original purple color. Inoculate a Moeller decarboxylase broth containing ornithine, lysine, and/or arginine. The low protein-to-carbohydrate ratio in the medium prevents the neutralization of weak acids by the alkaline products if the protein is utilized, thus allowing small quanti- ties of acid to be detected. Acid production results in a pH shift that changes the color of the bromthymol blue indicator from green to yellow. Non-saccharolytic organisms produce slight alkalinity (blue-green color) in the tube without oil overlay, but the tube with oil will not exhibit a color change and will remain green [15 ]. Acid production from carbohydrate metabolism results in a pH shift that changes the color of the bromthymol blue indicator from green to yellow. A yellow color indicates carbohy- drate utilization and no color change (green) or blue color indicates no carbohydrate utilization. The acid reaction produced by oxidative organisms is detected ﬁrst at the surface and gradually extends throughout the medium. When oxidation is weak or slow, it is common to observe an initial alkaline reaction at the surface of the tube that may persist for several days. Commercial Microbial Identi ﬁ cation System The commercial microbial identiﬁcation system is the backbone of microbial identiﬁcation in the clinical microbiology laboratories. It provides an advantage over conventional identiﬁcation systems by requiring little storage space and having an extended shelf life, rapid turnaround, low cost, standardized quality control, and ease of use. These systems require simultaneous inoculation and incubation of a series of min- iaturized biochemical reactions which are either based on detecting bacterial enzymes or cellular products that do not require microbial growth and have fairly rapid turnaround time (2–4 h) or based on metabolic activity that requires microbial growth and requires several hours to overnight incubation. In either case, the 6 Biochemical Pro ﬁ le-Based Microbial Identi ﬁ cation Systems 115 Table 6. The majority of metabolic based automated commercial identiﬁcation systems also incorporate antimicrobial susceptibilities testing. Despite their extensive database, they remain less than optimal in identifying fastidious slow-growing esoteric organisms. A suspension of the test organism is prepared in the inoculum ﬂuid and then used to ﬁll the reaction wells in the base. The substrates are rehydrated when the base and lid are aligned and snapped into place. Following the recommended incubation time, the wells are manually examined for color changes or the presence of ﬂuorescence. The resulting pattern of positive and negative test scores is the basis for identiﬁcation [17, 18 ]. It is intended for the identiﬁcation of clinically signiﬁcant aerobic gram-negative bacteria that belong to the family Enterobacteriaceae as well as most pathogens isolated from stool specimens. It is intended for the identiﬁcation of Neisseria, Haemophilus, Moraxella, Gardnerella vaginalis, as well as other fastidious bacteria. It is intended for the identiﬁcation of gram-positive bacteria isolated from clinical specimens. Both growth-based and enzymatic sub- strates are employed to cover the different types of reactivity. The tests are based on microbial utilization and degradation of speciﬁc substrates detected by various indicator systems. Acid production is indicated by a change in phenol red indicator when an isolate is able to utilize a carbohydrate substrate. Chromogenic substrates produce a yellow color upon enzymatic hydrolysis of either p -nitrophenyl or p-nitroanilide compounds. Enzymatic hydrolysis of ﬂuorogenic substrates results in the release of a ﬂuorescent coumarin derivative. Organisms that utilize a speciﬁc carbon source reduce the resazurin-based indicator. The system utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Continuous measure- ments of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. The system includes an inoculation station for panel setup and an incubator/ reader carousel module. The carousel houses four horizontal tiers of 26 panel carri- ers to accommodate a tier-speciﬁc Normalizer and 25 Phoenix Panels. Susceptibility testing is performed with an inoculum concentration of 3–7 × 10 cfu/5 ml. Kinetic measurements of bio-reactivity within individual micro-wells via red, green, blue, and ﬂuorescence readings are collected and comparatively analyzed with the Phoenix database [18 ]. It requires the user to prepare a suspension of the isolate in saline and verify the organism concentration with a densitometer. The sample identiﬁcation number is entered into the Carrier via barcode or keypad and electronically linked to the supplied barcode on each test card. All information entered at the bench is then transported to the instrument in a memory chip attached to the cassette. The panels are then incubated at 35 °C for 16–42 h, depending on panel, organism type, and results of readings. At the appropri- ate time, the WalkAway System automatically dispenses reagents into the appropri- ate biochemical wells and incubates the panels for an additional period of time (approximately 2–20 min, depending on the panel type). The identiﬁcation of bacteria is based on measuring a series of biochemicals contained in panels designed for the speciation of most medically signiﬁcant bacteria. The panels contain identiﬁcation media consisting of substrates and/or growth inhibitors, which, depending on the species of the bacteria present, will exhibit color changes or increases in turbidity after incubation. The panel may also contain series of antibiotic that are present in speciﬁed con- centrations in the wells of applicable MicroScan panels. The panel is then incubated for an additional period of time (approximately 5–30 min) depending on the panel type. If additional incubation 6 Biochemical Pro ﬁ le-Based Microbial Identi ﬁ cation Systems 119 is necessary for the biochemicals, the susceptibilities and certain biochemicals will be read ﬁrst and stored. The reagents will not be added until after additional incu- bation, at which time biochemicals not previously read will be determined. The automated system is ﬂuorescent based and detects bacterial growth by monitoring the activity of speciﬁc surface enzyme produced by the test organism. Growth is determined by generating a ﬂuorescent product from a nonﬂuorescent substrate.
Unlike the findings with intravenous nitrovasodilators (see below) purchase genuine rumalaya gel online, tolerance to fenoldopam’s antihypertensive effects does not appear to occur 30 gr rumalaya gel overnight delivery. Rebound hypertension has also not been observed with abrupt discontinuation of the drug buy 30gr rumalaya gel amex. The most common adverse effects of fenoldopam are related to its effects as a vasodilator and include hypotension discount rumalaya gel 30gr with mastercard, tachycardia, flushing, dizziness, headache, tachycardia, and nausea. Sympathomimetics Ephedrine The sympathomimetic drug ephedrine exerts both direct and indirect actions on adrenoceptors. Endocytosis of ephedrine into α - and β -adrenoceptor1 1 presynaptic postganglionic nerve terminals displaces norepinephrine from the synaptic vesicles. The displaced norepinephrine is then released to activate the corresponding postsynaptic receptors to cause arterial and venous vasoconstriction and increased myocardial contractility, respectively. Indeed, ephedrine’s initial cardiovascular effects resemble those of epinephrine because dose-related increases in heart rate, cardiac output, and systemic vascular resistance are observed. However, ephedrine is less potent than epinephrine, and the indirect acting sympathomimetic’s duration of action is longer than that of the endogenous catecholamine. Ephedrine also directly stimulates β -adrenoceptors, which limits the increases in arterial pressure2 that occur as a result of α -adrenoceptor activation. Tachyphylaxis to1 ephedrine’s hemodynamic effects occurs with repetitive administration of the drug because presynaptic norepinephrine stores are quickly depleted and ephedrine is released from synaptic vesicles as a false neurotransmitter instead. In contrast, tachyphylaxis does not occur with epinephrine because 827 the endogenous catecholamine directly stimulates α- and β-adrenoceptors independent of norepinephrine displacement and release. The most common clinical use of ephedrine during anesthesia is treatment of acute decreases in arterial pressure concomitant with bradycardia. Ephedrine was previously used for the treatment of hypotension in laboring parturients because the drug increases uterine blood flow, but phenylephrine may be preferred in this setting because ephedrine crosses the placenta and may cause fetal acidosis. As a result of this minor structural difference, phenylephrine almost exclusively stimulates α -adrenoceptors to1 increase venous and arterial vasomotor tone while exerting little or no effect on β-adrenoceptors. In contrast to ephedrine, phenylephrine acts directly on the α -adrenoceptor and is not dependent on presynaptic norepinephrine1 displacement to produce its cardiovascular effects. Phenylephrine constricts venous capacitance vessels and causes cutaneous, skeletal muscle, mesenteric, splenic, and renal vasoconstriction. Phenylephrine55 also increases pulmonary artery pressures through pulmonary arterial vasoconstriction and greater venous return. Unlike endogenous or synthetic catecholamines, phenylephrine is not arrhythmogenic. Intravenous boluses or infusions of phenylephrine are most often used for treatment of hypotension in the presence of normal or elevated heart rate. The presence of α -adrenoceptor blockade also has1 the potential to cause unopposed β - and β -adrenoceptor activity. For1 2 example, epinephrine will activate only β - and β -adrenoceptors because the1 2 α -adrenoceptor agonist effects of the catecholamine are inhibited. As a1 result, epinephrine produces pronounced tachycardia (a β effect) and severe1 hypotension (activation of β receptors causing arterial and venous2 vasodilation) when administered in the presence of an α -adrenoceptor1 blocker. Similarly, norepinephrine and ephedrine only activate β -1 adrenoceptors because their α -adrenoceptor agonist actions are inhibited. The response of a given vascular bed to an α -adrenoceptor antagonist is dependent on its intrinsic level of1 vasoconstriction, as blood vessels with higher vascular smooth muscle tone will generally be more responsive to α -adrenoceptor blockade. Because phenoxybenzamine’s actions at α-adrenoceptors are irreversible, synthesis of new receptors is required to reverse the drug’s effects as a vasodilator. Phenoxybenzamine’s prolonged half-life after oral administration also contributes to its sustained actions at the α-adrenoceptor. Phenoxybenzamine is used almost exclusively to normalize arterial pressure before surgery in patients with pheochromocytoma. The slow onset of α-57 adrenoceptor blockade produced by phenoxybenzamine occurs because the molecule requires structural modification to become pharmacologically active. As a result, several weeks of treatment may be required to obtain adequate control of arterial pressure. Restoration of normal intravascular volume status is also an important goal of phenoxybenzamine therapy because hypovolemia resulting from elevated serum norepinephrine and epinephrine concentrations contributes to hemodynamic instability during pheochromocytoma resection. Subsequent addition of a β-adrenoceptor antagonist also helps in achieving these goals and also serves to protect the myocardium from the adverse effects of chronic catecholamine stimulation. These combined interventions facilitate greater cardiovascular stability during pheochromocytoma resection, which is usually associated with additional 829 release of norepinephrine and epinephrine into the circulation during tumor manipulation. The most prominent side effect of phenoxybenzamine therapy is orthostatic hypotension, which may be especially severe in the presence of pre-existing hypertension or hypovolemia. Vasopressin may be required to treat refractory hypotension associated with phenoxybenzamine overdose. The competitive α - and α -adrenoceptor antagonist phentolamine is also1 2 used in patients with pheochromocytoma. In contrast to phenoxybenzamine, the effects of phentolamine are reversible (half-life less than 10 minutes) and new receptor synthesis is not required to restore α-adrenoceptor activity and vascular smooth muscle tone. Phentolamine is a potent intravenous vasodilator that rapidly decreases arterial pressure, but in doing so, also causes baroreceptor reflex-mediated tachycardia. Blockade of cardiac α -2 adrenoceptors by phentolamine may contribute to the development of arrhythmias. Phentolamine also exerts antihistamine and cholinergic activity, the latter of which may produce abdominal cramping and diarrhea. Because the drug causes hypotension and tachycardia, phentolamine is relatively contraindicated and should only be used with extreme caution in patients with flow-limiting coronary artery stenoses. Phentolamine is occasionally used as a local vasodilator to prevent tissue necrosis when iatrogenic extravasation of a vasoconstrictor (e. The α- adrenoceptor antagonist may also be effective when treating refractory hypertension associated with clonidine withdrawal or tyramine exposure in patients receiving a monoamine oxidase inhibitor. Unlike phenoxybenzamine and phentolamine, prazosin is a relatively selective antagonist of α -adrenoceptors (α to α ratio of approximately1 1 2 1,000:1) that causes arterial and venous vasodilation. As a result, baroreceptor reflex-mediated tachycardia is substantially attenuated after administration of prazosin. Nevertheless, orthostatic hypotension is an important clinical side effect of prazosin when the drug is used for the treatment of hypertension. Patients who are treated with these medications occasionally58 present for surgery, and anesthesiologists should be aware that anesthetic- induced vasodilation might be exacerbated in the presence of these urologic α -adrenoceptor antagonists. Clonidine is a partial α -adrenoceptor agonist with relative selectivity for α -2 2 versus α -receptors of approximately 200:1. Because of its sympatholytic1 effects, clonidine was originally used for the treatment of hypertension. Activation of α -adrenoceptors in the vasomotor center, attenuation of2 peripheral norepinephrine release from postganglionic sympathetic neurons, and stimulation of central nervous system imidazoline receptors are postulated mechanisms for the antihypertensive effect of clonidine. In addition, clonidine stimulates parasympathetic nervous system activity, which, when combined with withdrawal of sympathetic tone, produces bradycardia. Unlike other antihypertensive medications, clonidine does not affect baroreceptor- mediated reflex control of heart rate. Nevertheless,1 hypotension and bradycardia may occur when large doses of the drug are administered. Clonidine continues to be used as an antihypertensive medication, but the drug also reduces volatile and intravenous anesthetic requirements, blunts the hemodynamic responses to laryngoscopy and endotracheal intubation, promotes intraoperative cardiovascular stability, partially attenuates the sympathetic stress response associated with surgery, and decreases postoperative tissue oxygen requirements. These anti-ischemic actions were presumably related to the drug’s67 sympatholytic effects, which reduce myocardial oxygen consumption. Clonidine augments the effects of local anesthetics and opioids and increases their duration of action when used for neuraxial and regional anesthesia. As68 831 a result, clonidine decreases the incidence and severity of side effects associated with local anesthetics and opioids because the quantities of these latter drugs required for anesthesia and analgesia are reduced. Clonidine is effective as a postoperative analgesic and also has well-documented utility in the treatment of chronic regional pain syndrome and neuropathic pain. The sedative and anxiolytic effects of clonidine are attributed to activation of α -2 adrenoceptors in the locus coeruleus. Notably, clonidine does not substantially inhibit respiratory drive in the presence or absence of opioids despite the α -2 adrenoceptor agonist’s sedative effect.