Local vaginal flaps include Martius graft order discount suhagra on-line, gluteal skin flaps cheap suhagra, gracilis muscle flaps generic suhagra 100mg overnight delivery, peritoneal flaps (Figure 107 100 mg suhagra. The most commonly used vaginal flap is the Martius graft, a transposition of a labial fat pad with or without the bulbocavernosus muscle. It is a long band of adipose tissue from the labia majora and has excellent strength and vascularity. The lateral border is supplied by the obturator branch, and the inferior aspect of the graft is supplied by the inferior labial artery [45]. Typically, the graft is mobilized on each side and left intact at either the superior or inferior end. The vaginal epithelium is mobilized and a long curved clamp is passed through the vaginal incision to the mobilized fat pad. Grasping the free end of the graft, it is passed medially under the labia minora and attached with delayed absorbable suture to cover the fistula repair. Alternatively, for proximal fistula near the cuff, a peritoneal graft can be utilized by advancing the posterior peritoneum including the preperitoneal fat after mobilization by sharp dissection. The flap is advanced to cover this fistula closure and secured utilizing small absorbable sutures. Following this, the vaginal advancement flap is closed thus 1584 completing the repair. Early complications include hemorrhage, bladder spasms, bladder infections, vaginal infections, and intra- abdominal infections. Treatment of these early complications should be initiated as soon as complications present to prevent fistula recurrence. Postoperative antibiotics may be used in the cases of bladder, vaginal, and intraabdominal infections. Delayed complications include fistula recurrence, urinary incontinence, vaginal shortening, vaginal stenosis, and ureteral injury from the repair. It is not uncommon for patients to complain of dyspareunia from vaginal stenosis and/or from the Martius graft site [45]. Patients must have a realistic expectation of possible complications and outcomes related to fistula repair. It is equally important to counsel patients that urinary incontinence after successful repair can be as high as 12%. Waaldijk reported occurrence of urinary incontinence after repair of fistulas in 1% of cases without sphincter involvement, 13% with sphincter involvement with no additional tissue loss, and 16% with both sphincter and tissue loss [48]. In developed countries, urogenital fistulas are typically a result of a gynecological procedure, most commonly a hysterectomy. The literature on urogenital fistulas is mainly based on small case series and expert opinion. The tenants of fistula surgery are well established and include adequate exposure and visualization of the fistula tract, careful dissection of the surrounding tissues to allow a tension-free watertight closure, and use of well-vascularized flaps, nonoverlapping suture lines, and appropriate bladder drainage. Prevention is key and good surgical technique is mandatory in any surgical procedure but especially when operating deep 1585 in the pelvis. Even when injuries to the bladder do occur during a surgical procedure and are properly and promptly repaired, a fistula may still occur. Proper patient counseling is vitally important and may help mitigate medicolegal action. Success in management is dependent upon multiple factors including the individual patient, the fistula characteristics, and the surgeons’ experience. Each patient should undergo individualized management using the principles outlined throughout this chapter. Patients must undergo extensive counseling regarding what happened, the rationale in identifying the problem, and the appropriate steps to fix the problem as soon as technically feasible. In the vast majority of cases, early intervention via vaginal repair is associated with outstanding success rates. These patients should be reassured at frequent intervals throughout the process, and meticulous follow-up after surgery insuring adequate drainage and absence of other complications is critical to achieving surgical success. The risk of vesicovaginal and urethrovaginal fistula after hysterectomy performed in the English National Health service—A retrospective cohort study examining patterns of care between 2000–2008. Successful endoscopic closure of radiation induced vesicovaginal fistula with fibrin glue and bovine collagen. Fibrin sealant for the management of genitourinary injuries and surgical complications. Role of day care vesicovaginal fistula fulguration in small vesicovaginal fistula. Combined percutaneous antegrade and cystoscopic retrograde approach in the treatment of distal ureteric fistulae. Surgery for the obstetric vesicovaginal fistula: A review of 100 operations in 82 patients. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. Best Practice Policy Statement for the Prevention of Deep Vein Thrombosis in Patients Undergoing Urologic Surgery. Behandlung hochsitzender Blasen-und Mastdarmscheiden den Fisteln nach Uterusexstirpation mit hohem Scheidenverschluss. Large vesicovaginal fistula in women with pelvic organ prolapse: The role of colpocleisis revisited. Die operative Widerherstellung Der vollkommen fehlendden Harnohre und des Schiessmuckels derselben. Ten-year experience with transvaginal vesicovaginal fistula repair using tissue interposition. The surgeon who can cure someone of their leakage caused by vesicovaginal/uterine fistula can truly make a difference in the patient’s life. The best opportunity for success lies in the initial diagnosing and treating surgeon’s hands. While fistula repair can be approached in myriad ways, the most effective way of closure lies with the approach with which the surgeon is most comfortable. If there are any concerns about multiple abdominal adhesions due to prior surgeries or radiation, preoperative planning with colorectal surgery may be prudent. Perioperative antibiotics are administered within 30 minutes to 1 hour of incision time and are chosen to appropriately cover the skin and vaginal flora. If possible, the patient is positioned above the break in the bed to allow for exposure of the pelvis. Pneumatic compression devices are placed on the legs and per our protocol, subcutaneous heparin is administered prior to all our pelvic surgery cases. If there is concern for fistula proximity to the ureters, a cystoscopy can be performed prior to the procedure and ureteral stents placed for localization. During this time, the fistula tract can be cannulated to help with manipulation during the surgery. Cystoscopy can be deferred if a transvesical approach is planned and open-ended catheters or feeding tubes can be placed through the cystotomy under direct visualization of the ureteral orifices. The main benefit of an extraperitoneal approach is the avoidance of entering the peritoneum. Depending on the etiology of fistula, the intraperitoneal approach could be less desirable due to multiple adhesions. The drawback of an extraperitoneal approach is the inability to utilize different types of flaps, such as omentum, that are only available intraperitoneally. After a catheter has been inserted into the bladder, a Pfannenstiel or infraumbilical midline incision is made. If there is any difficulty locating the bladder due to prior surgical interventions in the retropubic space, the urethral catheter can be backfilled. Proper dissection and mobilization of the surrounding tissue allows for the placement of an interposition flap such as omentum or peritoneum. The benefit of bivalving the bladder is the ability to catheterize the ureteral orifices intraoperatively and increased exposure [4]. The alternative to minimize the potential complications of a large cystotomy is a transvesical approach [5]. Another option is to leave the fistula tract in situ and incorporate it into the repair. The bladder detrusor and mucosa are then closed separately using absorbable suture.

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Most intoxicated passengers on commercial air- liners have ingested alcohol purchase suhagra 100mg mastercard, opioids cheapest suhagra, or sedatives generic 100mg suhagra fast delivery. Passengers who appear to be grossly intoxicated are often not permitted to board the aircraft suhagra 100 mg online. Also, a potentially dangerous level of alcohol intake on aircraft is relatively rare. In 2009, Girasek and Olsen published the results of their survey of 1,548 airline passengers, intended to assess in-fight alcohol consumption. Ninety-fve percent of the study group reported that they would have less than 1 drink an hour during their upcoming fights [13]. The average level of consumption reported among those who said they intended to drink was about 1. Factors that increased the likelihood of passengers reporting they would drink were being on evening or long fights, sitting in frst or business class, traveling with friends, or having already consumed alcohol on the day of the fight. Air rage is defned as violent or disruptive behavior that affects the fight crew or passengers [14]. It has many potential associated causes, including departure delays, underlying psychiatric illness, stress, and frustration. Airline employees often attri- bute air rage to intoxication and sometimes the triggering event is the denial of alcohol service to a passenger. Other drugs, prescription or illegal, can also contrib- ute to disruptive behaviors during fights [13]. A healthcare provider who volunteers to intervene in an emergency involving a potentially intoxicated passenger should begin the evaluation as in any other sce- nario, with an introduction, an offer to help the person, and an assessment of his or her airway, breathing, and circulation. Two likely scenarios that the provider is likely to encounter are a person being disruptive or someone who is diffcult to arouse. For the disruptive person, several physical signs can suggest the intoxicating 120 C. Yelling with slurred speech, an ataxic gait, clumsiness, and constricted or normal pupils may indicate alcohol or benzodiazepine ingestion. Yelling with clear, pressured speech, dilated pupils, and sweaty, fushed skin are often associated with a sympathomimetic such as cocaine. For passengers who are diffcult to arouse, the provider should assess if the patient is protecting his or her airway adequately. If the onboard medical kit does not contain a glucometer, there is a high probability that another passenger on the plane will have one, though clinicians should be mindful that cleanliness of supplies cannot truly be ensured. Treatment for intoxication will vary according to the assessment of the affected individual and the suspected agent. For the disruptive patient, the primary action is an attempt to deescalate the situation [11]. If the patient cannot be redirected and is a danger to himself or herself or other people, the next option would be restraints— physical or chemical. Most in-fight medical kits do not contain controlled sub- stances such as benzodiazepines. If the person is believed to be intoxicated by alcohol or sedative medications, then the medical care provider should be careful to not overse- date, even if the passenger is yelling and aggressive during the initial evaluation [11]. For example, a disruptive patient can be tied to a seat with neckties and other soft materials available from the crew and passengers. A physically-restrained person should be monitored for signs of hypoxia or overexertion caused by fghting against restraints, which could lead to metabolic acidosis. In-fight medical kits carry equipment that can be used to support an obtunded person’s breathing, if necessary. Vital signs should be monitored frequently and the person should be observed until he or she becomes more alert. Overall, the number of in-fight medical emergencies caused by intoxicated pas- sengers is low. The evaluation of these patients should be focused on their safety and the safety of others. Most of these injuries are caused by objects falling from luggage com- partments (24%) and by hot liquid spills (24%) [15]. Passengers can also experience blunt-force injuries and lacerations resulting from turbulence [9]. When treating a passenger with any traumatic injury, the healthcare provider should be mindful of the mechanism of injury, as described by the patient, and of 12 Other Presentations 121 factors such as age, medical conditions, and use of anticoagulants. It is important to assess the patient’s airway, breathing, and circulation to determine if other injuries are present. The medical care pro- vider should obtain a history and perform a physical examination, with additional attention to a neurologic assessment. People who use anticoagulants or are intoxi- cated require close monitoring and reassessment. If intracranial injury is suspected, fight diversion should be strongly considered. Passengers with abrasions and lacerations can be treated by controlling the bleeding with direct pressure and bandaging. Suture material is not available in the medical kit, but initial frst-aid care is usually suffcient in the acute setting. If a fracture is suspected, the limb should be splinted with materials found in the frst-aid kit and placed in a non-weight-bearing position. Patients with extremity injuries and those requiring splinting should be reassessed frequently for worsening pain, which might signal early compartment syndrome or a worsening condition requiring diversion. The medical responder should note the degree and location of the burn(s) (especially to the face, hands, feet, genitalia, perineum, and major joints). Minor burns should be irrigated with clean water to remove debris and covered with bandages from the frst- aid kit. An initial evaluation will usually be suffcient until the passenger can receive additional care at the plane’s destination or diversion location (if warranted). Most airlines carry non-opiate anal- gesics, which may not provide suffcient relief but can be given in an attempt to address the patient’s pain. Conclusion The in-fight environment presents specifc challenges to medical care providers responding to emergencies and operating in a resource-limited, confned setting. Although it is impractical to prepare for every injury and illness that might occur during a fight, an awareness of the more common conditions that can affect airline passengers is benefcial. Knowledge of the medical supplies and manage- ment options that are available on most airlines helps healthcare providers have a level of preparedness to deliver care in this truly austere environment. Telemedical assistance for in-fight emergencies on intercontinental commercial aircraft. Preflight Medical Clearance: Nonurgent 13 Travel via Commercial Aircraft William Brady, Lauren B. The medical literature is quite robust in many areas of aviation medicine, including mili- tary applications and rotary-wing civilian aeromedical evacuations. Unfortunately, in this area of aviation medicine, the medical literature supporting this medical deci- sion making is surprisingly limited; consequently, nonevidence-based recommen- dations and expert opinion are commonly encountered and frequently used by patients, travel specialists, airlines, and physicians. It is estimated that 3 billion people fy commercially each year; on a daily basis, approximately 8 million people are fying commercially [1]. The majority of these trips occur for personal and/or leisure activities, followed by business-related excur- sions. Illness, whether a new event or exacerbation of existing syndrome, as well as traumatic injury can occur because of a range of issues, both related and unrelated to the travel. Medical care provided at the location of the event most often provides appropriate stabilization and treatment, allowing for ultimate discharge from inpa- tient management. In many such situations, the patient would like to return to their home region, not only for further medical care but also for the psychological and W. Certain medical and traumatic events do not require signifcant consideration with regard to the commercial fight to the home region; non-concerning chest pain presentations, uncomplicated urinary tract infections, simple soft-tissue injuries, and basic strains and sprains are examples of such medical entities in which commercial fight is likely quite safe from a medical perspective. Considerations which the physician must review, beyond those involving specifc medical factors related to the illness or injury, include the length of the anticipated trip, the presence of medical escort during fight, and the ability of the aircraft to divert in the event of an in-fight medical emergency. And, of course, common sense, employed by the clinician, the patient, and the airline, is a very important consider- ation. It must be remembered that a commercial aircraft is not a medical mission [2, 3]; thus, the expectation that trained personnel and appropriate equipment are present on such aircraft, allowing for the delivery of comprehensive medical care, is absurd. First of all, the “medical common sense” approach will provide the most use- ful information to the clinician, coupled with an awareness of the austere nature of a commercial aircraft from the medical perspective. In other words, is the patient able to tolerate physical exertion and physical stresses of travel considering basic medical principles and concepts?

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The impulse producing concealment may originate anywhere in the heart – in the sinus node order suhagra 100mg free shipping, an ectopic atrial 7 site buy suhagra 100mg cheap, the A-V junction order line suhagra, the fascicles order suhagra with amex, or the ventricles. The most common site manifesting the effects of concealed conduction is the A-V node. The effects of retrograde concealment in the A-V node under different circumstances are shown in Figures 6-1 through 6-4. The effect of His bundle, fascicular, or ventricular extrasystoles on subsequent A- V nodal conduction is inversely related to the coupling interval of the premature depolarization. Slow pathway can be maintained by retrograde invasion into the fast pathway (see Chapter 8). Retrograde concealment at multiple levels of the A-V conduction system may also occur (Fig. The levels of concealment depend on the relative timing of antegrade and retrograde impulses. The most frequent clinical circumstances in which concealed conduction is operative are: (a) atrial fibrillation during which the irregular ventricular response is due to the varying depth of penetration of the numerous 8 wavefronts bombarding the A-V node ; (b) prolongation of the P-R(A-H) interval or production of A-V nodal block by a premature depolarization of any origin; (c) reset of a junctional (His bundle) pacemaker by atrial or subjunctional premature depolarizations; and (d) perpetuation of aberrant conduction during tachyarrhythmias. In the latter circumstance, retrograde penetration of the blocked bundle branch subsequent to transeptal 12 13 conduction perpetuates aberration. His bundle depolarizations are frequently not recognized because they must conduct antegrade and/or retrograde to have any P. Incomplete penetration (concealment) of His bundle depolarizations in either direction, producing unexpected abnormalities of antegrade or retrograde conduction, may present a particularly 9 10 difficult diagnostic problem. The first beat is a conducted sinus beat, with an A-H = 100 msec, H-V = 80 msec, and a right bundle branch block configuration. Note that there is no manifest conduction above the atrioventricular (A-V) junction (i. Note, however, in the next sinus beat that the A-H interval is prolonged to 135 msec, indicating that the retrograde wavefront from the preceding beat partially penetrated (concealed) in the A-V node, rendering it relatively refractory to the next sinus impulse. A, atrial deflection; H, His bundle deflection; Hr, retrograde His deflection; V, ventricular deflection. A-V dissociation is present, and there is no retrograde activation of the atria by the His bundle escape rhythm. The A-V nodal block in the first beat and the A-V nodal delay in the third beat are due to concealed retrograde conduction of the His bundle beats into the A-V node. Thus, despite antegrade intra-His block, the distal His bundle escape rhythm can conduct retrogradely and affect antegrade conduction (i. The right panel represents ventricular tachycardia without manifest retrograde conduction. Block of the first and third sinus impulses in the atrioventricular (A-V) node results from retrograde concealed conduction of the ventricular beats into the A-V node, rendering it refractory. This results in concealed conduction so that the subsequent sinus complex is a block in the A-V node. The rhythm is sinus, with ventricular pacing at a cycle length of 1200 msec (S, arrow). Following the second stimulated complex, the sinus impulse blocks in the A-V node, indicating concealed conduction to that structure. Following the third stimulated complex, the sinus impulse blocks below the His bundle, indicating concealment into the His–Purkinje system, rendering it totally refractory to the antegrade impulse. Although interference with normal antegrade conduction or with a subsidiary pacemaker by a concealed premature depolarization may be easy to conceptualize, unexplained facilitation of conduction requires further explanation. Simultaneous shortening of refractoriness and providing more time to recover excitability is the most common mechanism. These and other mechanisms of facilitation explain some instances of pseudo-supernormal conduction. During atrial pacing at a cycle length of 440 msec, 2:1 block below the His bundle occurs. Gap Phenomenon 16 The term gap in A-V conduction was originally used by Moe et al. The gap phenomenon was attributed to functional differences of conduction and/or refractoriness in two or more regions of the conducting system. With earlier impulses, proximal delay is encountered, which allows the distal site of early block to recover excitability and resume conduction. A: Atrial pacing at a cycle length of 310 msec produces right bundle branch block aberration. B: Pacing at a longer cycle length of 350 msec produces left bundle branch block aberration. A and B: At the longer basic cycle length (S1-S1) of 700 msec and an S1-S2 of 400 msec, (A) the S2-H2 is 210 msec with standard stimulation (method I). All measurements are in milliseconds; pertinent deflections and intervals are labeled. Atrioventricular nodal conduction and refractoriness after intranodal collision from antegrade and retrograde impulses. The major significance of the gap phenomenon is its contribution to the understanding of conduction and refractoriness of the A-V conducting system. In particular, the resumption of conduction at shorter coupling intervals has frequently been interpreted as a form of “supernormal” conduction. In fact, the majority of cases of so-called supernormal conduction can be explained physiologically by the gap phenomenon. The common finding of all gaps already described has been that predicted by Moe; that block initially occurs distal to the stimulation site and that conduction resumes when earlier impulses result in proximal delay allowing the initial 16 site of block to recover. Any pair of structures in the A-V conduction system that have the appropriate physiologic relationship to one another can participate in gap phenomena. Six 18 19 20 different types of antegrade gap and two types of retrograde gap have been described (Table 6-1). These are, in descending order of frequency, by far the most common forms of antegrade gap. These three types, and all others in which the His–Purkinje system is the site of initial block, are most commonly observed during long drive cycle lengths, at which times His–Purkinje refractoriness is greatest. One such example is shown in Figure 6-13, in which distal block in the His–Purkinje system initially recovers because of delay in the proximal His–Purkinje system. Earlier coupling intervals again block, but dual A-V nodal pathways observed at even shorter coupling intervals (see Chapter 8) produce enough A-V nodal delay to allow the His–Purkinje system time to recover again. Retrograde gaps can manifest initial delay in the A- V node or in the His–Purkinje system, with proximal delay in the distal His–Purkinje system (Fig. Because the gap phenomenon depends on the relationship between the electrophysiologic properties of two sites, any interventions that alter these relationships (e. The basic atrial drive rate (A1-A1) in each panel is 700 msec, with the introduction of progressively premature atrial depolarization (A2). A: There is intact A-V conduction with a prolonged (120 msec) A2-H2 interval and an H1-H2 interval of 470 msec. C: Conduction resumes despite a still shorter A1-A2 (400 msec) and a shorter H1-H2 (430 msec). The conduction system of the heart: Structure, function and clinical implications. Supernormality Supernormal conduction implies conduction that is better than anticipated or conduction that occurs when block 22 23 24 is expected. When an alteration in conduction can be explained in terms of known 25 26 physiologic events, true supernormality need not be invoked. Physiologic mechanisms can be invoked to explain virtually all episodes of apparent supernormal conduction observed in humans. Physiologic mechanisms explaining apparent supernormal conduction include (a) the gap phenomenon, (b) peeling back refractoriness, (c) the shortening of refractoriness by changing the preceding cycle length, (d) the Wenckebach phenomenon in the bundle branches, (e) bradycardia-dependent blocks, (f) summation, and (g) dual A-V nodal pathways. Gap phenomena and changes in refractoriness, either directly by altering cycle length or by peeling back the refractory period by premature stimulation, are common mechanisms of apparent supernormal conduction. Each of these phenomena is not uncommonly seen at long basal cycle lengths, during which His–Purkinje refractoriness is prolonged and infra-His conduction disturbances are common. It should be emphasized that most of the cases of so-called supernormal conduction described in humans have been associated with baseline P. Therefore, the term supernormal has referred to improved conduction but not to 20 conduction that is better than normal. The gap phenomenon and all its variants are probably the most common mechanisms of pseudo-supernormality (Figs.

Side effects include histamine release and autonomic effects suhagra 100 mg cheap, depending on the drug buy discount suhagra 100 mg line. Renal excretion is significant in clearing doxacurium discount suhagra american express, pancuronium purchase genuine suhagra, vecuronium, and pipecuronium. Side effects: Histamine release (hypotension, tachycardia, bronchospasm), laudanosine toxicity (breakdown product of Hofmann elimination that can cause central nervous system excitation and is metabolized by liver), prolonged action (at abnormal pH and temperature). Cisatracurium (benzylisoquinoline; stereoisomer of atracurium) Metabolism and excretion: Same as atracurium. Side effects: Laudanosine toxicity (significantly lower levels than with atracurium), prolonged action (at abnormal pH and temperature). Vecuronium (steroidal) Metabolism and excretion: Excretion is primarily biliary and secondarily renal (25%); limited liver metabolism. Gantacurium (chlorofumarate) Metabolism and excretion: Cysteine adduction and ester hydrolysis. Nondepolarizing muscle relaxants: Neuromuscular transmission is blocked by nondepolarizing muscle relaxants that bind to postsynaptic nicotinic cholinergic receptors. Reversal of Nondepolarizing Muscle Relaxants Spontaneous reversal: Occurs with gradual diffusion, redistribution, metabolism, and excretion of nonde- polarizing muscle relaxants. Pharmacologic reversal: Occurs with the administration of specific reversal agents. Reversal with acetyl- cholinesterase inhibitors should be monitored with a peripheral nerve stimulator. Cardiovascular system: The predominant muscarinic effect on the heart is a vagal-like bradycardia that can progress to sinus arrest. Pulmonary receptors: Muscarinic stimulation can result in bronchospasm and increased respiratory secre- tions. Gastrointestinal receptors: Muscarinic stimulation increases peristaltic activity (esophageal, gastric, and intestinal) and glandular secretions (e. Perioperative bowel anastomotic leakage, nau- sea and vomiting, and fecal incontinence have been attributed to the use of cholinesterase inhibitors. Onset: Effects apparent in 5 to 10 minutes; peak at 10 minutes and last more than 1 hour. If used with glycopyrrolate, should be given several minutes after glycopyrrolate so that onset time matches. Clinical note: Can be used to treat central anticholinergic toxicity from scopolamine or atropine overdose. Clinical note: Because of concerns about hypersensitivity and allergic reactions, not yet approved by the U. Clinical pharmacology: Extent of anticholinergic effect depends on the degree of baseline vagal tone. Presynaptic muscarinic receptors on adrenergic nerve terminals are known to inhibit norepinephrine release, so antagonism may modestly enhance sympathetic activity. Inhibit the secretions of the respiratory tract mucosa Relaxation of the bronchial smooth muscle Reduces airway resistance Increases anatomic dead space Cerebral: Spectrum of effects depending on drug and dosage. Absorption by vessels in the conjunctival sac is similar to subcutaneous injection. Systemic manifestations include dry mouth, tachycardia, atropine flush, atropine fever, and impaired vision (although not in this case). What other drugs possess anticholinergic activity that could predispose to the central anticholinergic syn- drome? Tricyclic antidepressants, antihistamines, and antipsychotics have antimuscarinic properties that may potentiate the side effects of anticholinergic drugs. Cholinesterase inhibitors indirectly increase the amount of acetylcholine available to compete with anticho- linergic drugs at the muscarinic receptor. In contrast, physostigmine, a tertiary amine, is lipid soluble and effectively reverses central anticholinergic toxicity (an initial dose of 0. If the anticholinergic overdose were accompanied by tachycardia, fever, and so on, it would be prudent to postpone the surgery in this elderly patient. However, if the patient’s mental status responds to physostigmine and there are no other apparent anticholinergic side effects, it would be reasonable to proceed. These receptors are widely distributed throughout the body, and their effect depends on end-organ distribution. Alpha-2 adrenergic receptors: Principle function is as presynaptic autoreceptors, which decrease adenylate cyclase activity, thus decreasing calcium entry into neuronal terminal, limiting subsequent exocytosis of storage vesicles containing norepinephrine. This negative feedback mechanism reduces endogenous norepinephrine release from central nervous system neurons, causing sedation, decreased sympathetic outflow, and subsequent peripheral vasodi- lation with decreased systemic vascular resistance. They function to increase adenyl- ate cyclase activity, converting adenosine triphosphate to cyclic adenosine monophosphate, thus initiating a kinase phosphorylation cascade. Beta-1 agonists cause increased chronotropy, dromotropy (increased conduction velocity), and inotropy. Beta-2 adrenergic receptors: Mostly postsynaptic receptors located in smooth muscle and gland cells. Beta-2 agonists also cause glycogenolysis, lipolysis, gluconeogenesis, and insulin release. Beta-2 receptors activate the Na-K pump, driving potassium intracellularly, which can lead to hypokalemia and arrhythmias. Clinical Uses: Potent and reliable antihypertensive Diluted to a concentration of 100 µg/mL. In patients with renal failure, accumulation of large amounts of thiocyanate may result in thyroid dys- function, muscle weakness, nausea, hypoxia, and acute toxic psychosis. The last of the three cyanide reactions is respon- sible for the development of acute cyanide toxic- ity, which is characterized by metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (inability to utilize oxygen). Another early sign of cyanide toxicity is the acute resistance to the hypotensive effects of escalating doses of sodium nitroprusside (tachyphylaxis). Cyanide toxicity can usually be avoided if cumulative dose of sodium nitroprusside is less than 0. Pharmacologic treatment of cyanide toxicity: Aim to shunt cyanide away from cytochrome oxidase. Sodium thiosulfate (150 mg/kg over 15 min) 3% sodium nitrate (5 mg/kg over 5 min): Oxidizes hemoglobin to methemoglobin Hydroxocobalamin: Combines with cyanide to form cyanocobalamin (vitamin B ) 12 Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrate can be treated with methy- lene blue (1–2 mg/kg of a 1% solution over 5 min); reduces methemoglobin to hemoglobin. Reflex-mediated tachycardia and contractility (offset the favorable changes in myocardial oxygen requirements). Dilation of coronary arterioles by sodium nitroprusside may result in an intracoronary steal of blood away from ischemic areas that are already maximally dilated. Intracranial hypertension may be minimized by slow administration and hyperventilation or hypocapnia. Reductions in pulmonary artery pressure decrease perfusion to normally ventilated alveoli, thereby physiologic dead space = V/Q mismatch and arterial oxygenation. Inhibits hypoxic pulmonary vasoconstriction: V/Q mismatch and arterial oxygenation. Nitroglycerin: Effect on Organ Systems Cardiac: Preload (venous dilation) and afterload (arteriolar dilation); reduces myocardial oxygen demand, increases myocardial supply. Pooling of blood in large-capacitance vessels, venous return, preload, ventricular end-diastolic pres- sure = myocardial oxygen demand and endocardial perfusion. Reminder: A significant decrease in diastolic pressure may lower coronary perfusion and actually decrease myocardial oxygen supply. Nitroglycerin redistributes coronary blood flow to ischemic areas of subendocardium. Profound preload reduction is very useful in relieving cardiogenic pulmonary edema. Heart rate is largely unchanged; rebound hypertension less likely after discontinuation (in contrast with sodium nitroprusside). They are weak bases, usually with a positive charge at the tertiary amine group at physiological pH. Physicochemical properties are determined by linkage, substitutions in the aromatic ring, and alkyl groups attached to the amine nitrogen. Mechanism of Action Neurons have voltage-gated Na channels that can produce and transmit membrane depolarization along the nerve membrane after chemical, mechanical, or electrical stimuli. All local anesthetics bind the α subunit of the transmembrane Na channel on nerve fibers and inhibit the voltage-gated Na channels from activation and Na influx associated with membrane depolarization. At high enough local anesthetic concentrations and with a sufficient fraction of local anesthetic-bound Na channels, an action potential can no longer be generated because Na cannot cross the membrane, and impulse propagation is abolished.