The medical complications of heroin use

PURPOSE OF REVIEW: Heroin use is associated with numerous adverse sequelae. As clinical services develop, addiction psychiatrists will increasingly be called upon to help identify and manage the complications of heroin use. This review focuses on recent research into the medical complications of heroin use and looks at strategies to minimize harm associated with this practice. RECENT FINDINGS: Mortality associated with heroin overdose has increased substantially in many countries. Parenteral use of opioid drugs is a central factor and other risk factors include polydrug use, particularly benzodiazepines and alcohol, mental health issues and environmental factors not conducive to resuscitation. Unravelling the determinants of blood-borne virus transmission continues, the focus shifting from needle sharing to inadvertent sharing of other injecting equipment. Trials addressing the challenges of antiviral therapy in injecting drug users are emerging. A greater understanding of the effects of opioids on immune functioning complements our knowledge of infection in the heroin-using group as well as possibly explaining the reduced response to vaccination in this group. SUMMARY: Medical complications of heroin affect a number of different organ systems. The role of the addiction specialist is to be aware of these so that early diagnosis and appropriate management is instituted. The latter will generally be done in collaboration with other specialists. The addictions specialist can play a significant role in the development of clinical systems to minimize these complications.     

氯氮平治疗海洛因戒毒后心理渴求疗效观察

目的：对戒毒后的海洛因依赖患者进行氯氮平治疗,观察其对心理渴求的效果。方法：43例自愿戒毒海洛因依赖患者,脱毒后由患者自愿选择氯氮平或纳曲酮治疗,使用自拟的心理渴求量表评定患者治疗前后渴求程度变化。结果：经氯氮平治疗3月后,患者心理渴求评分较疗前有明显降低,有效率65．2％;而纳曲酮组治疗前后改变不明显,有效率为20．0％。结论：氯氮平对海洛因依赖患者的心理渴求可能是具有较好的疗效。     

Mu阿片受体多态性与海洛因依赖的关联研究

目的：探讨上海汉族人群中Mu阿片受体（OPRMI）基因A118G位点、C1031G位点多态性与海洛因依赖关联性。方法：采用病例对照研究,分别检测201名海洛因依赖者（依赖组）和249名健康对照（对照组）OPRMI基因A118G和C1031G位点基因型及等位基因频率,分析海洛因依赖者OPRMI受体基因多态与物质依赖的相关性。结果：A118G和C1031G位点多态性在依赖组和对照组间的分布差异无显著性;单体型分析两位点4种单体型均与海洛因依赖间无关联。结论：OPRMI基因A118G和C1031G位点与海洛因依赖无显著相关性。     

Acute plexus lesions in heroin dependence]

A wide spectrum of acute and chronic neurological syndromes are associated with heroin addiction. We report two cases with acute brachial/lumbar plexus lesions, with details of the clinical findings, diagnostic procedures and therapy. Possible causes are allergic or toxic reactions to heroin or added substances, as well as nerve compression due to local muscle swelling in connection with rhabdomyolysis. The extent of paresis which occurs is also determined by this compression.     

双侧伏隔核立体定向射频毁损或DBS治疗海洛因精神依赖

目的 探讨外科手术治疗戒除海洛因药物成瘾所致精神依赖的有效性。方法 通过立体定向手术，对27例药物成瘾患者的双侧伏隔核进行射频毁损，1例患者双侧伏隔核行脑深部电刺激仪（DBS）植入术。结果 所有患者平均随访8个月，失随访2例，总随访数26例，其中优效者18例（69.2％），良好者4例（15.3％），一般者2例（7．7％），差效者2例（7．7％）。结论 立体定向引导下行双侧扣带回和（或）伏隔核射频热凝毁损或高频电刺激，戒除海洛因药物成瘾所致精神依赖是一种有效、可行的方法。     

海洛因依赖者的人格障碍及性别差异分析

目的了解海洛因依赖者的人格障碍及其性别差异。方法用DSM-Ⅲ-R人格障碍用定式临床检查手册,调查了93名自愿戒毒的海洛因依赖者DSM-Ⅲ-R轴Ⅱ人格障碍的诊断情况并对其进行不同性别间比较。结果轴Ⅱ人格障碍发生率达到89．2％。边缘型人格障碍(62．4％)和强迫型人格障碍(59．1％)最常见,其次是偏执型人格障碍(52．7％)。除反社会型人格障碍外,其它类型人格障碍不同性别间未发现显著性差异。结论海洛因依赖者存在各种类型的人格障碍。反社会型人格障碍更多见于男性患者。为了加强治疗效果预防复吸应针对不同性别个体采取个性化的治疗方法。     

Association between heroin dependence and prodynorphin gene polymorphisms

Dynorphin peptides and k-opioid receptor are important in the rewarding effects of drugs of abuse such as heroin. This study examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of prodynorphin (PDYN) gene (rs35286281 in promoter region and rs1022563, rs2235749, rs910080 in 3'UTR). Participants included 304 heroin-dependent subjects and 300 healthy controls. Genotype, allele frequencies and difference between groups were analyzed by HaploView 4.0 and SPSS 11.5 software. The analysis indicated a significant higher frequency of the PDYN 68bp VNTR (rs35286281) H allele in heroin-dependent subjects than in controls (p=0.002 after Bonferroni correction). Strong linkage disequilibrium was observed between rs1022563, rs2235749 and rs910080 polymorphism (D'>0.9). Significantly more TCT haplotypes were found in heroin-dependent patients than in the controls (p=0.006 after Bonferroni correction). We found significant pointwise correlation of these three variants (rs1022563, rs2235749 and rs910080) with heroin dependence. These findings support the important role of PDYN polymorphism in heroin dependence, and may guide future studies to identify genetic risk factors for heroin dependence.     

The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence

Recent clinical observations and psychiatric diagnostic findings of drug-dependent individuals suggest that they are predisposed to addiction because they suffer with painful affect states and related psychiatric disorders. The drugs that addicts select are not chosen randomly. Their drug of choice is the result of an interaction between the psychopharmacologic action of the drug and the dominant painful feelings with which they struggle. Narcotic addicts prefer opiates because of their powerful muting action on the disorganizing and threatening affects of rage and aggression. Cocaine has its appeal because of its ability to relieve distress associated with depression, hypomania, and hyperactivity.     

多巴胺D4受体基因多态性与海洛因依赖及渴求程度的关系

目的 探讨DRD4 exon Ⅲ 48bp可变串连重复序列（VNTR）与海洛因成瘾及线索诱发海洛因渴求程度的关系。方法 采用美国ABI公司3100基因分析仪对380名海洛因依赖者（依赖组）和275名健康对照者（对照组）的DRD4 exon Ⅲ 48bpVNTR基因多态进行检测,并给予依赖组实施线索诱发海洛因渴求实验。比较依赖组和对照组的DRD4 exon Ⅲ 48bpVNTR多态的基因型及等位基因频率是否有差异,分析不同基因型与线索诱发海洛因渴求程度的关系。结果 （1）依赖组与对照组相比．DRD4exon Ⅲ 48bpVNTR多态的基因型和等位基因频率差异均无显著性（P〉0．05）。（2）依赖组中,DRD4 exon Ⅲ 48bpVNTR长重复基因型诱发的渴求高于短重复基因型（P〈0．05）。结论 未发现DRD4 exon Ⅲ 48bpVNTR基因多态与海洛因成瘾有关,但该基因多态与线索诱发海洛因的渴求程度有关,长重复基因型线索诱发的海洛因渴求程度明显高于短重复基因型。     

海洛因依赖者伪装和制造疾病临床研究(附221例分析)

目的：了解海洛因依赖者在脱毒过程中伪装和制造疾病的原因和临床表现。方法：对符合中国精神疾病分类方案与诊断标准第2版修订本有关诈病诊断标准的海洛因依赖者进行回顾性研究。结果：发现22l例诈病，发生率4．6％，以青年男性、未婚、初中以下文化、无业占多数，吸毒时间长、多药滥用、涉嫌违法犯罪问题者较多。其动机依次是企图逃避法律惩罚、企图提前解除强戒．骗取成瘾药物、受人唆使胁迫等。方式有说谎、伪装、造伤等。结论：海洛因依赖诈病者较多，应引起注意。     

海洛因依赖对血浆抗氧化类维生素水平的影响

目的 探讨海洛因依赖对血浆抗氧化类维生素含量的影响。方法 采用分光光度比色分析法检测７４例海洛因依赖者（海洛因依赖组）和８０名健康人（对照组）血浆中的维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素含量并作对照比较。     

Safety of injectable opioid maintenance treatment for heroin dependence.

BACKGROUND: There is a growing debate about injectable opioid treatment programs in many Western countries. This is the first placebo-controlled study of the safety of injectable opioids in a controlled treatment setting. METHODS: Twenty-five opioid-dependent patients on intravenous (IV) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo. Acute drug effects were recorded, focusing on electrocardiography, respiratory movements, arterial blood oxygen saturation, and electroencephalography (EEG). RESULTS: After heroin injection, marked respiratory depression progressing to a Cheyne-Stokes pattern occurred. Peripheral arterial blood oxygenation decreased to 78.9 +/- 8.7% (mean +/- SD) ranging from 52%-90%. During hypoxia, 7 of the 16 subjects experienced intermittent and somewhat severe bradycardia. Five subjects exhibited paroxysmal EEG patterns. After methadone injection, respiratory depression was less pronounced than after heroin injection. No relevant bradycardia was noted. CONCLUSIONS: Opioid doses commonly prescribed in IV opioid treatment induce marked respiratory and circulatory depression, as well as occasionally irregular paroxysmal EEG activity. Further studies are needed to optimize the clinical practice of IV opioid treatment to prevent serious complications. Moreover, the extent of the observed effects raises questions about the appropriateness of IV opioid treatment in the present form.     

立体定向手术治疗海洛因依赖的远期随访分析

目的评估立体定向毁损术治疗海洛因依赖的手术疗效,分析术后复吸原因。方法回顾性分析接受脑立体定向术的154例海洛因成瘾者的临床资料,采用症状自评量表对病人精神卫生状况进行调查随访。结果随访154例,时间5~6年,其中复吸52例(33.8%,复吸组),未复吸102例(66.2%,未复吸组)。复吸组术后躯体化、强迫症状、敌对、偏执、精神病性等因子明显高于未复吸组和国内常模(均P<0.05)。结论立体定向手术是海洛因依赖的安全有效的治疗方法。强迫症状和人格障碍的改善是消除心理依赖的基础及手术戒毒治疗成功的重要因素;精神病性和躯体化是复吸的主要原因。     

Differential role of serotonergic polymorphisms in alcohol and heroin dependence

Background

Twin studies suggest that genetic factors account for 40–60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence.

Methods

165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of −1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI) = 1.98 (1.13–3.45) and 1.92 (1.07–3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df) = 10.21 (4), p = 0.037). The association of −1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups.

Conclusions

Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.     

The medical management of spasticity

When spasticity produces a clinical disability by interfering with posture, motor capacity, nursing or daily living activities, medical treatment is recommended. It is mainly indicated when the muscle overactivity is diffusely distributed and should be implemented early, to prevent permanent musculoskeletal deformities or contractures. A pharmacological approach relies on the use of drugs which modulate neurotransmitters acting at the cortico-spinal level (GABA, glycine, glutamate, noradrenaline, serotonin). The aim of this treatment is to decrease spinal reflex excitability by reducing the release of excitatory neurotransmitters, or by potentiating the activity of inhibitory inputs. Evaluation of the efficacy of these drugs is determined by the therapeutic objectives which may be biomechanical, or functional. Diazepam increases presynaptic inhibition by stimulating GABA_A receptors in the brainstem and spinal cord. In double-blind studies of patients with spinal cord lesions, antispastic efficacy has been shown, but side-effects are common. Baclofen stimulates GABA_B receptors inducing a suppression of excitatory neurotransmitter release. Antispastic efficacy is sufficiently documented, but no definite effects on ambulation or activities of daily living have been proved. Tizanidine has an α₂-agonist activity (at spinal and supraspinal level) and decreases the presynaptic activity of excitatory interneurones. The main clinical effects are a reduction in tonic stretch, polysynaptic reflexes, and co-contraction, with fewer side-effects but no definite functional change. The efficacy of several other antispastic drugs is documented in a few controlled studies, but the majority of information arises from open trials or anecdotal observations.     

The diagnosis and management of benzodiazepine dependence

PURPOSE OF REVIEW: Despite repeated recommendations to limit benzodiazepines to short-term use (2-4 weeks), doctors worldwide are still prescribing them for months or years. This over-prescribing has resulted in large populations of long-term users who have become dependent on benzodiazepines and has also led to leakage of benzodiazepines into the illicit drug market. This review outlines the risks of long-term benzodiazepine use, gives guidelines on the management of benzodiazepine withdrawal and suggests ways in which dependence can be prevented. RECENT FINDINGS: Recent literature shows that benzodiazepines have all the characteristics of drugs of dependence and that they are inappropriately prescribed for many patients, including those with physical and psychiatric problems, elderly residents of care homes and those with comorbid alcohol and substance abuse. Many trials have investigated methods of benzodiazepine withdrawal, of which the keystones are gradual dosage tapering and psychological support when necessary. Several studies have shown that mental and physical health and cognitive performance improve after withdrawal, especially in elderly patients taking benzodiazepine hypnotics, who comprise a large proportion of the dependent population. SUMMARY: Benzodiazepine dependence could be prevented by adherence to recommendations for short-term prescribing (2-4 weeks only when possible). Withdrawal of benzodiazepines from dependent patients is feasible and need not be traumatic if judiciously, and often individually, managed.