Gene/Protein Disease Symptom Drug Enzyme Compound
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Pentazocine (Talwin) originally was believed to be a safe, nonaddictive analgesic, but further experience has shown that severe mental and emotional disturbance, as well as addiction, may occur. This survey documents the experience in the Texas Medical Center and elsewhere. The accumulated data show the following: (1) Depressive states are reported most frequently, while toxic psychoses, hallucinogenic reactions with panic, and paranoid states on withdrawal of the drug are less frequent. (2) Of the 197 cases of addiction reported to date, only six were related to oral use of the drug. The abstinence syndrome is mild, consisting usually of restlessness, nausea, cramps, and insomnia. (3) Convulsions have been reported on four occasions. Euphoria and psychotomimetic effects may relate to rapid release of noradrenaline and dopamine. Oral use of the drug is advised to avoid euphoriant effects and addiction, and physicians should alert patients to report unusual visual phenomena. Tranquilizers are of value in cases of severe reactions.
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PMID:Mental and emotional disturbance with pentazocine (Talwin) use. 115 70

Pain management, nutritional support, and psychosocial support are fundamental services that enhance patients' ability to cope with their cancer and its therapy. The common goal of symptom prevention mandates that each of these supportive services be provided to all patients throughout their cancer experience. Comprehensive cancer pain management begins with identifying the origin of all of the patient's pains and treating each one specifically. Pain prevention can be achieved through around-the-clock opioid administration with as-needed supplements for breakthrough pain and dose titration. Common narcotic side effects such as constipation and nausea also must be prevented. Successful opioid analgesia requires that patient and family concerns regarding addiction and tolerance be dispelled at the outset. Cancer pain prevention can be further optimized with the use of appropriate coanalgesics in response to the pathophysiology of the patient's pains. Cognitive and behavioral therapies may also be useful adjuncts to reduce both pain and suffering. Procedure-oriented pain control should be considered when systemic pharmacologic therapy does not provide adequate pain relief or is associated with intolerable side effects. The only absolute contraindications for pain-relieving procedures are untreatable coagulopathy and a decrease in mental status not related to medical pain management. Useful neurodestructive techniques include radiofrequency lesioning, cryoanalgesia, and chemical neurolysis with agents such as phenol, alcohol, and hypertonic saline. The most beneficial pain-relieving procedures and percutaneous cordotomy, spinal narcotics, celiac and hypogastric plexus ablation, spinal neurolysis, and epidural injection of steroids and hypertonic saline. Procedure selection depends on the cause of the pain and the patient's prognosis. Common indications for pain-relieving procedures include unilateral pain below the shoulder, upper abdominal visceral pains, pelvic visceral pain, perineal pain, vertebral body metastasis, discogenic pain, and spinal stenosis. As results of well-conducted scientific trials begin to appear in the literature, the indications for these procedures will be better understood, resulting in their more appropriate use. Principles of nutritional support in patients with cancer include an awareness of the problem of malnutrition and its impact on performance status, quality of life, prognosis, and treatment; identification of those patients at risk; prophylactic versus therapeutic intervention; and analysis and management of the specific impediment(s) to adequate nutrient intake and absorption. The primary goals for nutritional support in cancer patients are prevention of weight loss and maintenance of adequate protein status. Appreciation of practical issues of nutritional support will enable the practicing physician to achieve these goals using primarily oral nutrition options.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Supportive care in oncology. 128 50

In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain.
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PMID:Long-term oral opioid therapy in patients with chronic nonmalignant pain. 157 87

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.
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PMID:A long-term survey of morphine in cancer pain patients. 162 12

More than 135 different strategies for medical treatment have been described for the treatment of alcohol withdrawal syndromes. The substances used most frequently (benzodiazepines, barbiturates, or clomethiazol) themselves pose some risk for abuse or addiction. Anticonvulsants, especially carbamazepine (CBZ), have been discussed for the treatment of alcohol withdrawal since the early seventies. Various studies report favourable results with CBZ, usually combined with sedative agents. Nineteen out-patients and 19 in-patients took part in an open study of CBZ in alcohol withdrawal. The dose of CBZ was adjusted individually and ranged from a mean dose of 761 mg on day 1 to 616 mg on day 3 and to 388 mg on day 7 in the group of out-patients, and from 789 mg on day 1, 694 mg on day 3 to 562 mg on day 7 in the sample of in-patients. The "Objective Clinical Scale in Assessment and Measurement of Alcohol Withdrawal" (OCSAMAW) was used for treatment evaluation. Statistical analysis showed a significant improvement on the 5%-level in both groups; four in-patients needed concomitant treatment with oxazepam. Nausea and pruritus were the most common side-effects of CBZ treatment.
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PMID:Carbamazepine monotherapy in the treatment of alcohol withdrawal. 208 98

Identification of 5-HT receptor subtypes--5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 (possibly A and B), 5-HT3 subtypes, and possibly 5-HT4--has encouraged the manufacture of 5-HT receptor inhibitors with greater subtype specificity. However, it appears that the receptors interact, and drugs initially thought to be specific may have multiple actions. For some conditions such as anxiety/depression, almost all receptors are implicated. Clinical studies provide clear evidence that manipulation of the 5-HT system has a role in treating depression, anxiety, obsessional illness, migraine, and eating disorders. Interactions between the various receptor subtypes make it difficult to identify specific clinical functions. The 5-HT1A receptors may be involved in aggression, anorexia, and hypotension. The 5-HT1B receptors may be involved in aggression, while the 5-HT1C receptors may play a role in central aversion systems and anxiety/depression. The role of the 5-HT1D receptors remains speculative; 5-HT2 receptors appear to be involved in depression, anxiety, appetite, sleep, vasoconstriction, and hypertension. Many drugs that are effective in treating migraine are potent 5-HT2 antagonists. 5-HT3 antagonists at high doses are effective in treating nausea and at low doses in treating anxiety. Treatment of aggression, suicidal behaviour, addiction behaviour, memory impairment, dementia, and schizophrenia with 5-HT inhibitors requires further testing.
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PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41

The potential role of nicotine in tobacco dependence was investigated using the strategies of abuse liability assessment. Eight male volunteer cigarette smokers with histories of drug abuse resided on a research ward for the duration of the study. Each subject was tested with three doses of i.v. nicotine (0.75, 1.5 and 3.0 mg/10-sec infusion) and placebo each test day, and with three doses of inhaled nicotine, in the form of research cigarette smoke (0.4, 1.4 and 2.9 mg estimated yield) and placebo (sham-smoking), given on alternate test days. Each subject was tested on 4 days with both routes of administration, according to identical experimental protocols. Physiologic, subjective and observer data were collected at intervals ranging from 15 sec to 10 min beginning 10 min before drug administration and continuing for 30 min after administration. Both i.v. and inhaled nicotine produced dose-related increases in heart rate and blood pressure, and i.v. nicotine produced a transient bradycardia in four subjects during the first 30 sec after drug administration. Skin temperature was decreased by nicotine and pupil diameter was not consistently changed. Ratings of drug dose "strength" and drug "liking" were directly related to dose level whereas "desire to smoke cigarettes" was inversely related. Scores on the Morphine-Benzedrine Group (or Euphoria) scale of the Addiction Research Center Inventory were elevated by nicotine, and i.v. doses were identified frequently as cocaine. Signs and symptoms were similar for nicotine across the two routes of administration and included coughing, dizziness, nausea and relaxed feelings. Nicotine shared the pharmacologic profile of prototypic drugs of abuse. The study supports the hypothesis that the role of nicotine in tobacco dependence is equivalent to the role of other psychoactive drugs in substance abuse, e.g., to the role of cocaine in coca leaf use.
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PMID:Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine. 400 94

Children who were born in the early 1980s in the Stockholm suburb that was studied had a home environment that may be described as follows. The material standards in the area were good, the dwellings were spacious and modern, the outdoor environment was pleasant for children and the municipal service facilities were well developed. The transport services to the city are frequent, comfortable and convenient. In a typical case, the parents are about 30 years old, they are of old Swedish stock and are living together, married or unmarried. They received a good education and usually also occupational training. Generally, both parents have a job outside the home. In quite a few such cases the mother has shift- or nightwork. Although both parents have jobs, the family surprisingly often has financial problems. Thus more than one family in five needed financial assistance from the authorities. The financial difficulties may be due to illness and addiction in the parents. About one in ten of the mothers has been hospitalised for a chronic somatic disease and about one in ten of the fathers is in the records for alcoholism. Criminality is also common, every sixth or seventh father having a police record. About every fourth child born in this suburb will grow up in a home where either the father or the mother is known for an addiction and/or criminality, and/or has been treated for mental illness. To conjure up and describe the atmosphere in a home in this suburb is not easy but in the present study information was obtained supporting the suspicion that many homes are characterised by insecurity, isolation and hopelessness and a serious unsatisfied need for help. Many of the mothers have grown up in rather special social conditions--for instance, in "broken homes", or with an alcoholic father or a mentally ill mother. As a result, nearly every tenth mother had been placed outside the home at an early age (in a foster-home or suchlike). In later years also, many of the mothers have had the burden of sick, malformed or mentally retarded children in their home, or have experienced the serious illness or death of some person close to them. Particularly in the period before their child's birth many women have had reason to feel anxious. About one woman in three has already had a miscarriage and/or abortion, and during pregnancy she may have suffered from serious nausea or depression. Quite a few also needed to take medicines during that time. In many families, it is reported, the man and woman have had trouble in living together, with resultant divorce situations, quarrels and assaults.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Home environment of children in a new Stockholm suburb. A prospective longitudinal study. 658 82

Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan, is the main ingredient in a number of widely available, over-the-counter antitussives. Initial studies (Bornstein 1968) showed that it possessed no respiratory suppressant effects and no addiction liability. Subsequently, however, several articles reporting abuse of this drug have appeared in the literature. The drug is known to cause a variety of acute toxic effects, ranging from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood changes, perceptual alterations, inattention, disorientation and aggressive behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953; Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand et al 1989). There have also been two reported fatalities from DM overdoses (Fleming 1986). However, there are no reports describing the effects of chronic abuse. This report describes a case of cognitive deterioration resulting from prolonged use of DM.
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PMID:Cognitive deterioration from long-term abuse of dextromethorphan: a case report. 780 71

Physiological dependence on benzodiazepines is accompanied by a withdrawal syndrome which is typically characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, sweating, difficulty in concentration, dry wretching and nausea, some weight loss, palpitations, headache, muscular pain and stiffness and a host of perceptual changes. Instances are also reported within the high-dosage category of more serious developments such as seizures and psychotic reactions. Withdrawal from normal dosage benzodiazepine treatment can result in a number of symptomatic patterns. The most common is a short-lived "rebound" anxiety and insomnia, coming on within 1-4 days of discontinuation, depending on the half-life of the particular drug. The second pattern is the full-blown withdrawal syndrome, usually lasting 10-14 days; finally, a third pattern may represent the return of anxiety symptoms which then persist until some form of treatment is instituted. Physiological dependence on benzodiazepines can occur following prolonged treatment with therapeutic doses, but it is not clear what proportion of patients are likely to experience a withdrawal syndrome. It is also unknown to what extent the risk of physiological dependence is dependent upon a minimum duration of exposure or dosage of these drugs. Withdrawal phenomena appear to be more severe following withdrawal from high doses or short-acting benzodiazepines. Dependence on alcohol or other sedatives may increase the risk of benzodiazepine dependence, but it has proved difficult to demonstrate unequivocally differences in the relative abuse potential of individual benzodiazepines.
Addiction 1994 Nov
PMID:The benzodiazepine withdrawal syndrome. 784 56


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