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The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
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PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun
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PMID:[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning]. 1050 96

The present article summarizes the main results of the cross-sectional part of the 'Munich Vulnerability Study' in which healthy first-degree relatives of patients with an affective disorder were investigated by assessing their neuroendocrine, polysomnographic and psychometric status. As patients with an acute episode of a major depression, the group of the healthy relatives exhibited signs of a hyperactive hypothalamic-pituitary-adrenocortical system verified by the combined dexamethasone corticotropin-releasing hormone (DEX/CRH) test, as well as a slow wave sleep deficit in the first sleep cycle and an increased amount of rapid eye movements during REM sleep. The psychometric profile of the healthy relatives was characterised by elevated scores on the scales measuring 'Rigidity' and 'Autonomic Lability'. On a single-case level, 32% of the healthy first-degree relatives of patients with an affective disorder exhibited 'depression-like' features or conspicuous findings in at least two of the three (i.e. neuroendocrine, polysomnographic, psychometric) areas assessed. Whether the relatives with the neurobiological and psychometric abnormalities we identified have a higher risk for developing an affective disorder than those without has to be answered by the still ongoing prospective part of the study.
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PMID:Neuroendocrine, polysomnographic and psychometric observations in healthy subjects at high familial risk for affective disorders: the current state of the 'Munich vulnerability study'. 1117 71

Dexmedetomidine is a relatively new, highly selective, short-acting central alpha 2 agonist. Although not yet officially introduced for clinical use in Israel, it has become increasingly popular among anesthesiologists and intensive care physicians abroad when used as an adjuvant to the classical regimen of anesthesia techniques. Its administration potentiates the effect of other sedative and hypnotic agents while causing minimal respiratory depression. It also blunts the sympathetic response--thus minimizing changes in blood pressure and heart rate--during critical moments such as laryngoscopy and intubation. However, bradycardia and hypotension may ensue. DXM minimizes opioid-induced muscle rigidity and attenuates postoperative shivering. These pro-anesthesia effects are attributed to the capability of DXM to reduce central adrenergic outflow. Although its precise mechanism(s) of action are still debatable, DXM will undoubtedly find an increasing role in clinical peri-operative anesthesia.
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PMID:Dexmedetomidine: a promising agent for anesthesia and perioperative care. 1134 41

Most traditional opioids and non-steroidal anti-inflammatory drugs that are used to control perioperative pain have substantial side effects. The number of choices in clinical use was recently increased by two promising groups of drugs: N-methyl-D-aspartate receptor antagonists and central alpha2 agonists. One N-methyl-D-aspartate antagonist, dextromethorphan, blocks the generation of central pain sensation that arise from peripheral nociceptive stimuli by moderating the activity of N-methyl-D-aspartate. It pre-empts the sensation of acute pain at doses of 30-90 mg without serious side effects, while reducing the amount of analgesics required perioperatively by 50%. It is available in oral form and has a confirmed lack of effect on haemodynamics and respiration. Dexmedetomidine is a relatively new, highly selective central alpha2 agonist. Its sedative, pro-anaesthetic and pro-analgesic effects at 0.5-2 microg/kg given intravenously stem mainly from its ability to blunt the central sympathetic response by as yet unknown mechanism(s) of action. It also minimises opioid-induced muscle rigidity, lessens postoperative shivering, causes minimal respiratory depression, and has haemodynamic stabilising effects.
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PMID:Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. 1171 40

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32-50 years of age (mean +/- SD, 39.7 +/- 7.6 years) and they had a mean disease duration of 5.4 +/- 2.1 years (range, 2-9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.
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PMID:Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation. 1221 Aug 94

A 59-year-old man, who was diagnosed as having Parkinson's disease and depression seven years ago and was on oral antiparkinsonian agents, antianxiety agents, and antidepressants, developed a high fever, disturbed consciousness, and marked muscle rigidity after discontinuation of etizolam and amitriptyline. He was admitted to a nearby hospital. Hypothyroidism had been noted two months before admission. Marked muscle rigidity and increased serum CK were observed. Since discontinuation of benzodiazepine has been known to rarely trigger a neuroleptic malignant syndrome (NMS), he was diagnosed as having NMS. After receiving dantrolene and bromocriptine, these symptoms temporarily improved but he again developed consciousness disturbance, and convulsive seizures associated with an elevated serum CK. He was transferred to our hospital. On admission, the CK level was normal at 168 IU/l, while free T4 was 0.6 ng/dl (normal range, 0.9-2.3) and TSH was 108.7 mU/ml (normal range, 0.2-4.2) in serum, indicating the presence of primary hypothyroidism. As an increase in thyroid hormone dosage improved the thyroid function to normal level, his disturbed consciousness and muscle rigidity gradually improved. Convulsive seizure and recurrence of NMS in a short interval are unusual in neuroleptic malignant syndrome. In this patient, hypothyroidism may have contributed to the development of malignant syndrome through metabolic changes of the central dopaminergic system, and discontinuation of etizolam, a kind of benzodiazepine, may have triggered NMS, since there has not been reported that discontinuation of antidepressants including amitriptyline triggers NMS.
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PMID:[A patient with Parkinson's disease complicated by hypothyroidism who developed malignant syndrome after discontinuation of etizolam]. 1242 63

Three women in labor for whom epidural analgesia was contraindicated--2 with sepsis (pylonephritis and chorioamnionitis) and 1 with sacral agenesia--were provided intravenous analgesia with propofol (0.4-1.2 mg/kg/h) and remifentanil (0.033-0.1 microgram/kg/min plus boluses of 20 micrograms controlled by the patient) with oxygen supplementation. Heart rate, noninvasive blood pressure, maternal oxygen saturation and fetal heart rate were monitored. Maternal satisfaction, quality of analgesia, maternal side effects (sedation, depression, breathing, muscle rigidity, nausea, and vomiting) and fetal side effects (heart rate variability and Apgar score) were evaluated. We conclude that in cases where epidural analgesia is contraindicated, intravenous perfusion of low doses of propofol and remifentanil can provide a valid alternative for analgesia during labor.
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PMID:[3 cases of sedation and analgesia using propofol and remifentanil for labor]. 1460 71

The purpose of this study was to investigate the state of wakefulness during the induction of anesthesia with high-dose fentanyl using the isolated forearm technique. Ten patients scheduled for elective cardiovascular surgery were premedicated with morphine (0.15 mg/kg) and scoploamine (0.3-0.4 mg) intramuscularly one hour before induction. The induction of anesthesia was performed by intravenous administration of 100 micro g/kg of fentanyl in 15 min or over. The pneumatic tourniquet applied on the left upper arm was inflated to 220-240 mmHg after 10 micro g/kg of fentanyl was given and then pancuronium was administered. Verbal commands were given to the patient after 25, 50, 75 and 100 micro g/kg of fentanyl was administered. Eight patients out of 10 responded to the verbal commands after administration of 25 micro g/kg of fentanyl. Six patients also responded after administration of 100 micro g/kg of fentanyl and diazepam 5 mg was given to prevent tachycardia and rigidity during endotracheal intubation. Muscle rigidity and tachycardia were noticed in three and four patients respectively. These complications disappeared by diazepam administration. It was noted that wakefulness frequently occurred during the induction by high-dose fentanyl and oxygen anesthesia. To prevent such wakefulness therefore, it is necessary to use anesthetic supplements which do not cause cardiovascular depression.
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PMID:Wakefulness during the induction with high-dose fentanyl and oxygen anesthesia. 1523 75

Hyponatremia is a significant complication of treatment with serotonin selective reuptake inhibitors (SSRI). We describe a case of a 53-year-old woman that was started on fluoxetine 20 mg/day for depression. Nine days later, the patient started with weakness, nausea, progressing to confusion, inappetence and vomit. Three hours later she became unresponsive and had a generalized seizure. She was brought to our emergency service. On admission, the patient was normovolemic, without focal motor deficits, but had mild generalized muscle rigidity and Babinski's sign bilaterally. Serum sodium was 105 mmol/L, serum osmolality, 220 mmol/L, and urinary osmolality, 400 mmol/L. The other laboratory exams, chest X-ray, cerebrospinal fluid and cranium tomography were normal. She was found to have fluoxetine-induced SIADH and it was discontinued. We started the hyponatremia correction and, in 5 days, the mental status of the patient gradually returned to a normal baseline, paralleling the resolution of her hyponatremia, without recurrence. Hyponatremia and SIADH should be considered if a patient experiences deterioration in his or her clinical condition while taking SSRI. The use of SSRI antidepressants should be remembered in the differential diagnosis of drug-induced hyponatremia.
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PMID:Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report. 1662 73


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