Heat stroke in schizophrenia during clozapine treatment: rapid recognition and management.

Section of Clinical Neuropharmacology, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London. A case of heatstroke is reported in a 32-year-old man diagnosed with schizophrenia and on clozapine monotherapy. The importance of the need to avoid misdiagnosing heat stroke as neuroleptic malignant syndrome is reviewed.

Calcium release from sarcoplasmic reticulum is facilitated in human myotubes

Malignant hyperthermia (MH) is caused by increased calcium release from sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle relaxants. Numerous mutations associated with MH have been detected in the skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated calcium release has only been demonstrated for a few of them. This is a prerequisite for confirming the causative role of an RyR1 mutation for MH. Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC), caffeine, and halothane was determined in human myotubes by calcium imaging. The RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in individuals susceptible to MH. In myotubes of individuals carrying the RyR1 Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced, all consistent with facilitated calcium release from the sarcoplasmic reticulum. From these data we conclude that both mutations are pathogenic for MH.

Mydocalm causing anaphylaxis

The case of anaphylactic shock due to Mydocalm administration is presented. 49-year-old woman suffered from spinal osteoarthritis and she was treated with NSAIDs and Mydocalm for many years. 6 weeks before admission to hospital the first anaphylactic shock was developed with loss of consciousness after oral administration of Mydocalm. Then she was admitted to the hospital in order to diagnose and verify the suspicion whether Mydocalm caused this reaction. Percutaneous test with Mydocalm was performed and it caused anaphylactic shock. Only thirteen cases like this one have been documented in the world literature. It is the first case reported in Poland.

Treatment of fibromyalgia with Cyclobenzaprine, Flexeril: A meta-analysis.

OBJECTIVE: To systematically review the effectiveness of Cyclobenzaprine, Flexeril in the treatment of fibromyalgia. METHODS: Articles describing randomized, placebo-controlled trials of Cyclobenzaprine, Flexeril in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted. RESULTS: Five randomized, placebo-controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6-5.6) with a pooled risk difference of 0.21 (95% CI 0.09-0.34), which calculates to 4.8 (95% CI 3.0-11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time. CONCLUSION: Cyclobenzaprine, Flexeril-treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

GW280430A: pharmacodynamics and potential adverse effects.
Lien CA, Belmont MR, Heerdt PM.


Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound.

Low and medium potency benzodiazepines were initially introduced for the treatment of insomnia and anxiety. Their therapeutic actions as anxiolytics, sedative hypnotics, anticonvulsants, and muscle relaxants / relaxant (with their low toxicity) have led to their use as first-line treatments, and they have become one of the most prescribed classes of drugs. Novel therapeutic uses of benzodiazepines were discovered with the introduction of the high-potency benzodiazepines (e.g., alprazolam, clonazepam, and lorazepam). They were found to be effective in treating panic disorder and panic attacks with or without agoraphobia, as add-on therapy to selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder and panic disorders, and as adjunctive therapy in treating patients with acute mania or acute agitation. High-potency benzodiazepines have replaced low and medium potency benzodiazepines in all benzodiazepine clinical indications due to their greater therapeutic effects and rapid onset of action. Differences in distribution, elimination half-life, and rate of absorption are important considerations when choosing a high-potency benzodiazepine. Typically, a benzodiazepine with long distribution and elimination half-lives is preferred. A maximum dose of 2 mg/day of any of the high-potency benzodiazepines when given for more than 1 week is recommended. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.

Anesthetic management of three patients with myotonic dystrophy in a family

Case-1: A 24-year-old woman was admitted because of pressing hydramnion. She was treated by ritodrine hydrochlorides leading to rhabdomyolysis, and she was diagnosed as myotonic dystrophy. She underwent cesarean section because of urgent premature birth. The surgery was performed with spinal anesthesia using tetracaine. Case-2: A 1-year-old boy, the son of Case 1, underwent orchiopexy. He showed respiratory distress at birth and needed respiratory support for 140 days. The surgery was performed under general anesthesia combined with caudal anesthesia. Anesthesia was induced with nitrous oxide-oxygen-sevoflurane. He was intubated without muscle relaxants. Since he recovered consciousness soon after the surgery, he was extubated and returned to the ward. Case-3: A 30-year-old woman, the sister of Case 1, underwent tonsillectomy. At the age of 27 she underwent salpingectomy under general anesthesia with nitrous oxide-oxygen-halothane, after which she was diagnosed as myotonic dystrophy. She was anesthetized with propofol and fentanyl. Because severity of the myotonic dystrophy varies among the patients, the strategy for anesthesia should be planned on each patient. Generally speaking, regional anesthesia including spinal and epidural anesthesia is preferable.

Patterns of potentially inappropriate medication use across three cohorts of older medicaid recipients.
Rigler SK, Jachna CM, Perera S, Shireman TI, Eng ML.
Department of Medicine, Research Faculty, Landon Center on Aging, School of Medicine, University of Kansas, Kansas City, KS.
BACKGROUND: Potentially inappropriate medication use is a serious quality concern, especially when it occurs in more vulnerable older adults or for extended durations. OBJECTIVE: To characterize patterns of inappropriate medication use and duration among 3 cohorts with differing health status. METHODS: We identified unconditionally inappropriate drug use, using Beers 1997 criteria, among 3185 older Kansas Medicaid beneficiaries. Claims from May 2000 to April 2001 provided data for 3 cohorts: nursing facility (NF) residents, recipients of home- and community-based services through the Frail Elderly (FE) program, and persons with neither NF/FE care (Ambulatory). Duration, categorized as short-term (1-9 mo), or chronic (>9-12 mo), was determined for each drug and cohort. Drug-disease associations were explored. RESULTS: Any inappropriate medication use occurred in 21%, 48%, and 38% of Ambulatory, FE, and NF cohorts, respectively. Inappropriate analgesics, antihistamines, antidepressants, muscle relaxants, and oxybutynin were most common, but prevalence and duration varied by cohort. Short-term analgesic and antihistamine use was common. FE cohort members had the highest use rates for all drugs. The NF cohort had less antidepressant and muscle relaxant / relaxants use. Drug-disease associations were noted for amitriptyline use in diabetes mellitus, propoxyphene use in musculoskeletal and upper gastrointestinal conditions, and muscle relaxant / relaxants use in musculoskeletal conditions. CONCLUSIONS: Cross-sectional, one-year prevalence figures are comprised of both short- and long-term use that varies by drug and cohort. NF residence is associated with reduced use of drugs scrutinized during mandated medication review. Relevant diseases are associated with specific inappropriate prescribing. Future efforts should target extended and chronic duration of use and persons at highest risk for adverse effects, including recipients of home- and community-based care.


Anesthesia for ambulatory anorectal surgery.

The prevalence of minor anorectal diseases is 4-5% of adult Western population. Operations are performed on ambulatory or 24-hour stay basis. Requirements for ambulatory anesthesia are: rapid onset and recovery, ability to provide quick adjustments during maintenance, lack of intraoperative and postoperative side effects, and cost-effectiveness. Anorectal surgery requires deep levels of anesthesia. The aim is achieved with 1) regional blocks alone or in combination with monitored anesthesia care or 2) deep general anesthesia, usually with muscle relaxants / relaxant and tracheal intubation. Modern general anesthetics provide smooth, quickly adjustable anesthesia and are a good choice for ambulatory surgery. Popular regional methods are: spinal anesthesia, caudal blockade, posterior perineal blockade and local anesthesia. The trend in regional anesthesia is lowering the dose of local anesthetic, providing selective segmental block. Adjuvants potentiating analgesia are recommended. Postoperative period may be complicated by: 1) severe pain, 2) urinary retention due to common nerve supply, and 3) surgical bleeding. Complications may lead to hospital admission. In conclusion, novel general anesthetics are recommended for ambulatory anorectal surgery. Further studies to determine an optimal dose and method are needed in the group of regional anesthesia.

Intrathecal drug therapy using the Codman Model 3000 Constant Flow Implantable Infusion Pumps: experience with 17 cases.

OBJECTIVES: The objective of this study was to evaluate the accuracy, reliability, safety, and efficacy of the Codman Model 3000 Constant Flow Implantable Infusion Pump for intrathecal baclofen delivery as a therapeutic option for the treatment of severe spasticity. The distinctive features of this pump include a raised, easily palpable septum, a safety valve protecting the bolus pathway, no programmer needed, and no battery to fail. DESIGN: A total of 17 patients with spinal cord injury, multiple sclerosis, or cerebral palsy were implanted with this pump. The accuracy of the pump and drug treatment efficacy was determined at each visit and adjustments to the dosages were made as required. All the intrathecal drug delivery system complications were reviewed. RESULTS: The expected efficacy was achieved. The accuracy of the implanted pumps ranged from 90-97% (average 94%). There were no complications due to primary pump problems. The complications reported are similar to other implantable infusion devices and include dehiscence of the suture line, pressure ulcer development, formation of seroma, inversion of the pump, baclofen overdose, and catheter failures. CONCLUSION: The Codman Model 3000 Constant Flow Implantable Infusion Pump is an accurate, reliable, and convenient option for patients needing intrathecal baclofen therapy, with complications similar to other available pumps.