Clinical pharmacy
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The pharmacology and history of development of nondepolarizing neuromuscular blocking agents are presented, and the pharmacokinetics and pharmacodynamics of these agents, administration guidelines for mechanically ventilated patients, adverse effects, factors affecting paralysis, and methods for blockade reversal are reviewed. Nondepolarizing neuromuscular blocking agents (tubocurarine, metocurine, pancuronium, vecuronium, and atracurium) are frequently used to induce prolonged pharmacologic paralysis in patients in the intensive-care unit (ICU). These agents are poorly absorbed after oral administration and must be administered by injection, preferably by the i.v. route. ⋯ Generally, patients no longer requiring paralysis in the ICU will be allowed to spontaneously regain muscle function after drug therapy has been discontinued. If the effects of the nondepolarizing neuromuscular blocking agents must be reversed more rapidly, acetylcholinesterase-inhibiting agents such as physostigmine, neostigmine, pyridostigmine, and edrophonium can be used. Nondepolarizing neuromuscular blocking agents can be used to paralyze mechanically ventilated patients, facilitating optimal oxygenation and ventilation.
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The pathogenesis and clinical manifestations of herpes zoster and postherpetic neuralgia and the use of nontraditional analgesics in the management of postherpetic neuralgia are reviewed. Herpes zoster represents the reactivation in an immunocompromised host of dormant varicella-zoster virus (Herpesvirus varicellae) contracted during a previous episode of chickenpox. Fever, neuralgia, and paresthesia occur four to five days before skin lesions develop. ⋯ Positive results have been reported with levodopa, amantadine, and interferon, but the role of these agents in the prevention of postherpetic neuralgia remains unclear. Nontraditional analgesic agents are useful in the management of postherpetic neuralgia, but patients must be selected and monitored appropriately. A tricyclic antidepressant (especially amitriptyline) is a reasonable first choice.
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The pharmacokinetics, pharmacodynamics, and clinical uses of fentanyl, sufentanil, and alfentanil are reviewed. The fentanyl derivatives have reduced or eliminated many of the disadvantages of opioid anesthetics, such as incomplete amnesia and undesirable hemodynamic responses to surgery. Fentanyl is 50-100 times as potent as morphine and was the first of the three to be marketed. ⋯ Fentanyl has been formulated as a transdermal patch that seems to provide the same degree of analgesia as a continuous i.v. infusion. Fentanyl has also been formulated as an investigational lozenge that has shown advantages as a preoperative sedative in children. As more is learned about these agents, their perioperative uses for anesthesia, analgesia, and sedation will continue to be refined.
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Current knowledge about the pathophysiology of septic shock is reviewed, and biotechnology-based therapies under development are discussed. Patients with septic shock begin their clinical course with leukocytosis, fever, tachycardia, tachypnea, and organ hypoperfusion; shock ensues as immunologic and vasoactive mediators produce hypotension. There are many metabolic and cardiovascular responses, and single- or multiple-organ failure is common. ⋯ Successful treatment of septic shock will probably require a combination of agents, including antimicrobials. An ideal goal for biotechnology in the area of septic shock is to prevent invading pathogens from overstimulating the host's immune system and to systematically eliminate those pathogens. Biotechnology is opening new avenues to the treatment of septic shock.
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Clinical studies of the injectable nonsteroidal anti-inflammatory agent (NSAIA) ketorolac tromethamine are reviewed, and the chemistry, pharmacology, pharmacokinetics, drug interactions, and adverse effects of ketorolac are described. Ketorolac exhibits anti-inflammatory, analgesic, and antipyretic activity. Although the exact mechanisms of action have not been determined, its effects appear to be associated principally with the inhibition of prostaglandin synthesis. ⋯ For short-term pain management, an initial i.m. ketorolac tromethamine loading dose of 30 or 60 mg is recommended. Ketorolac tromethamine appears to be as effective as morphine or meperidine for short-term management of moderate to severe postoperative pain. It lacks the respiratory depressant effects of opiate analgesics but shares the toxic potentials of other NSAIAs.