To investigate the biochemical and cellular basis for the rise in polymorphonuclear leukocyte (PMN) count during epinephrine administration, PMN from subjects receiving epinephrine were studied for their capacity to adhere to nylon wool fibers and endothelial cell monolayers. After administration of epinephrine, the PMN count increased by 80% at 5 min, and isolated PMN adherence to nylon fibers fell from a base line of 44±2-18±3%. In contrast, when subjects were infused with the β-antagonist propanolol before receiving epinephrine, the PMN count failed to rise and PMN adherence was normal. Exposure of PMN endothelial cell monolayers to 0.1 μM epinephrine led to diminished PMN adherence that could be blocked by 10 μM propanolol but not by 10 μM phentolamine. Sera obtained from subjects 5 min after receiving epinephrine or from supernates derived from endothelial cell monolayers exposed to 90 nM epinephrine inhibited PMN adherence to nylon fibers. Addition of anticyclic AMP antisera but not anticyclic guanosine monophosphate antisera to the postepinephrine sera or to the postepinephrine supernate derived from the endothelial cell monolayers abolished their inhibitory effect of PMN adherence to nylon fibers. In contrast, direct exposure of PMN to epinephrine failed to affect their adherent properties. Because it has been previously shown that endothelial cells contain β-receptors and respond to catecholamines by raising their intracellular concentrations of cyclic AMP, and that PMN adherence is attenuated by cyclic AMP, it would appear that diminished PMN adherence after epinephrine administration is mediated through endothelial cell β-receptor activity, which in turn impairs PMN margination in vivo and could account for the rise in circulating PMN.
Several therapeutic approaches have been developed to treat choroidal hemangioma. However, all these therapies are associated with a potential risk of damaging the overlying retina.
We report a case of circumscribed choroidal hemangioma (CCH) in a 59-year-old man refractory to laser treatment. Visual acuity was 20/200 and a serous macular detachment was present. The CCH was treated with oral propanolol, whereupon visual acuity improved to 20/20 and the macular detachment resolved without systemic or local adverse effects.
Propanolol is a β-blocker commonly used in cardiology that may induce endothelium vasoconstriction and inhibit endothelial proliferation. It has been shown to be effective in infantile facial hemangiomas, and proved safe and effective for the CCH in our patient. Further studies are needed to confirm our observation.
Circumscribed choroidal hemangioma; Propanolol; β-Blocker
Previous studies using a mixed β1 and β2 adrenergic antagonist, propanolol, have indicated that β adrenoceptors have little effect on the cognitive functioning of the prefrontal cortex. However, recent studies have suggested that endogenous stimulation of β1 adrenoceptors impairs working memory in both rats and monkeys. Since propanolol has no effect on cognition, we hypothesized that activation of β2 adrenoceptors might improve performance in a working memory task. We tested this hypothesis by observing the effects of the β2 agonist, clenbuterol, on spatial working memory performance. Clenbuterol was either infused directly into the prefrontal cortex (rats) or administered systemically (monkeys). Results demonstrated that clenbuterol improved performance in many young and aged rats and monkeys who performed poorly under control conditions. Actions at β2 adrenoceptors were confirmed by challenging the clenbuterol response with the β2 adrenergic antagonist, ICI 118,551. The effects of clenbuterol were not universal and depended on the cognitive status of the animal: the drug moderately improved only a subset of animals with working memory impairment.
Clenbuterol; ICI 118,551; Beta-2; Norepinephrine; Working memory; Aging; Prefrontal cortex
The aim of the present study was to compare the responses of blood pressure, heart rate, and rate-pressure product of hypertensive women using beta-blockers with healthy controls during resistance exercise (by the end of the concentric phase of the contractions) and in the postexercise period (5 and 30 minutes after). Ten untrained normotensive women (N) and 10 mildly hypertensive females receiving 40 mg/day of propanolol (H) were selected. Three sets of 10 repetitions at 80% of 10 repetitions maximum with 30 s rest interval were performed on the leg press exercise. The H group exhibited lower systolic blood pressure after the second set compared with N. Heart rate and rate-pressure product were lower in H in all analyzed periods compared with N. Propanolol attenuates the cardiovascular response to a leg press resistance exercise in mildly hypertensive women.
Iron deficiency (ID) results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1) intravenous norepinephrine would alter heart rate (HR) and contractility, 2) abdominal aorta would be larger and more distensible, and 3) the beta-blocker propanolol would reduce hypertrophy.
1) 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2) Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3) An additional 10 rats (5 ID, 5 control) were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed.
Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio.
ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.
Two investigations have been carried out. The first studied the effects of autonomic blockade on the cardiovascular response to a step test, a 50% maximum isometric grip test and a Valsalva manoeuvre: the step test was of 5 minutes duration and the other two for as long as possible. beta adrenergic blockade by propanolol diminished the blood pressure and pulse rate response to both the step test and isometric grip. The pulse rate response to the step test was also affected by cholinergic blockade with atropine. The response to the Valsalva test showed a cholinergic blockade effect of pulse rate alone and a blood pressure response alone on alpha adrenergic blockade by phenoxybenzamine. The second studied psychological stressing on physical and mental ability. A potential 'punishment' situation increased the blood pressure and pulse rate response to isometric grip while decreasing the time for which it could be maintained. A potential 'reward' situation increased both the maximum grip and the time for which 50% grip could be maintained. It is concluded that psychological factors can affect performance dependant on whether the situation is perceived as one of 'reward' or 'punishment'. A factor in the mediation of the adverse response is an inappropriate response of the autonomic nervous system.
Following an initial dose response study, metoprolol, a selective beta1-receptor blocking agent, was compared with equipotent dosages of propanolol in a double blind cross-over study, including exercise tolerance tests, on fourteen patients with angina pectoris. Long term therapy with metoprolol then followed until the seventy-second week. Patients performed 8% more total work on metoprolol with 15% more work recorded up to the onset of S-T depression, in comparison with propranolol. In the long term, ther was no significant difference in work performed when the daily dosage of metoprolol was changed from a q.i.d. to a b.d. regime. Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment.
To further our understanding of the functional role of catecholaminergic systems in regulating hypothalamic corticotropin-releasing hormone (CRH) secretion, we assessed the direct effects of a multiplicity of catecholamine agonists and antagonists on hypothalamic CRH secretion. To accomplish this, we used an in vitro rat hypothalamic organ culture system in which CRH secretion from single explants was evaluated by a specific RIA (IR-rCRH). Norepinephrine (NE) stimulated IR-rCRH secretion dose dependently, with peak effects in the nanomolar range. The effect of NE was antagonized by the mixed alpha antagonist phentolamine, the alpha 1 antagonist prazosin, and the alpha 2 antagonist yohimbine, but not by the beta blocker, L-propanolol. Compatible with these data were the findings that the alpha 1 agonist phenylephrine and the alpha 2 agonist clonidine both stimulated IR-rCRH secretion in a dose-dependent fashion. On the other hand, whereas the beta agonist, isoproterenol, caused a weak, non-dose-dependent increase in IR-rCRH secretion, this effect could not be antagonized by L-propanolol. Despite pretreatment with serotonin and acetylcholine antagonists, the effect of NE upon IR-rCRH secretion was undiminished, suggesting that NE-induced CRH secretion is not mediated by either neurotransmitter. On the other hand, pretreatment with gamma-aminobutyric acid (GABA) attenuated NE-induced IR-rCRH secretion. Whereas epinephrine (E) stimulated IR-rCRH secretion, this occurred only at higher concentrations, and was antagonized by phentolamine, but not by L-propanolol. Dopamine (DA) had a weak stimulatory effect that could be antagonized by the DA1 receptor antagonist, SCH 23390, but not by phentolamine. We conclude that NE and E stimulate hypothalamic IR-rCRH secretion via alpha 1 and alpha 2 receptors. The effect of NE upon IR-rCRH secretion is not apparently mediated by serotonergic or cholinergic interneurons, but is modulated by the inhibitory neurotransmitter, GABA. These data support the idea that the central catecholaminergic systems are excitatory rather than inhibitory upon CRH secretion when acting directly at the hypothalamic level.
Degranulation of lysosomes is one of the consequences of neutrophil activation. Regulatory mechanisms of lysosomal secretion are thought to be localized largely in the plasma membrane and cytosol, with the lysosome playing a passive role in secretion. Recent evidence indicates that the intralysosomal pH is highly acidic (pH congruent to 5.5) and is maintained by active transport of H+. We investigated whether changes in the intralysosomal pH altered the availability of lysosomes for exocytosis. Intralysosomal pH in intact neutrophils was monitored with the weakly basic fluorescent probe, 9-aminoacridine (9AA). The weak bases, methylamine, chloroquine, clindamycin, propanolol, and ammonium chloride (0.1-50 mM), caused an alkalinization of the intralysosomal pH as determined by reversal of quenching of 9AA fluorescence. Similarly, each of the weak bases, including ammonium chloride, methylamine, chloroquine, ethylamine, propylamine, propanolol, clindamycin, and dansylcadaverine, inhibited neutrophil degranulation in response to the calcium ionophore A23187, phorbol myristate acetate, or the chemotactic peptide, formyl-methionine-leucine-phenylalanine plus cytochalasin B. These studies indicate that an acid intralysosomal pH is important to the neutrophil secretory response and suggest that the lysosome may play an active part in control of degranulation.
Bleeding from the edge of an ileostomy site is a common problem. In those who have undergone a proctocolectomy with ileostomy formation in conjunction with a risk of chronic liver disease (even with normal liver function tests), this may be due to peristomal varices. If this is the case, significant, difficult-to-control and potentially life-threatening bleeding is likely in the future and may require transfusion. Improvements in radiological imaging techniques can give quick, sensitive and specific information to diagnose and guide management in this group. In those patients with major bleeding episodes, an initial conservative management policy should be adopted with the knowledge that, if bleeding persists, propanolol therapy, portosystemic shunt insertion or even liver transplantation may be indicated.
Peristomal varices; Major bleeding; Propanolol therapy; Portosystemic shunt
The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics.
Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three-dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx® system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10054 at baseline and 10059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length.
Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6±20.3% vs. 57.9±23.7%, p=0.027. This was true/significant for paroxysmal AF (47±23% vs. 40±22%, p=0.003), but not for persistent AF (65±22% vs. 62±25% respectively, p=0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170±33 ms to. 180±40 ms (p=0.001). Fractionation decreases only in the 14/27 patients with a significant (>6ms) prolongation of the AF cycle length (64±20% vs. 59±24%, p=0.027), while fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58±21% vs. 56±25%, p=0.419).
Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length.
Complex fractionated atrial electrograms; autonomic nervous system; ganglionated plexus; atrial fibrillation; catheter ablation; cycle length
Vestibular migraine is considered to be the second most common cause of vertigo and the most common cause of spontaneous episodic vertigo. The duration of attacks varies from seconds to days, usually lasting minutes to hours, and they mostly occur independently of headaches. Long-lasting individual attacks are treated with generic antivertiginous and antiemetic drugs. Specific antimigraine drugs are unlikely to be very effective for rescue. The mainstay of the management of vestibular migraine is prophylactic medication. To date, there are no controlled trials available; the body of knowledge builds on case series and retrospective or observational studies. Most drugs are also used for the prevention of migraine headaches. The choice of medication should be guided by its side effect profile and the comorbidities of patients. Betablockers such as propanolol or metoprolol are preferred in patients with hypertension but in the absence of asthma. Anticonvulsants include topiramate when patients are obese, valproic acid and lamotrigine. Lamotrigine is preferred if vertigo is more frequent than headaches. Calcium antagonists include verapamil and flunarizine. If patients have anxiety, tricyclic antidepressants such as amitryptiline or nortryptiline or SSRIs and benzodiazepines such as clonazepam are recommended. Acetazolamide is effective in rare genetic disorders related to migraine-like episodic ataxia; however, its place in vestibular migraine is still to be established. Nonpharmacological measures such as diet, sleep, hygiene and avoidance of triggers are recommended as they are for migraine. Vestibular rehabilitation might be useful when there are complications such as loss of confidence in balance or visual dependence.
migraine; vestibular; prophylaxis; beta-blockers; anti-convulsants
Recombinant interferon α (IFN α), alone or in combination, is used extensively in the treatment of hepatitis C infection. IFN therapy is not free of side-effects and autoimmune thyroiditis is one of its rare side-effects. We present here a case of a patient with hepatitis C virus–human immunodeficiency virus coinfection on interferon therapy who presented with significant weight loss. He was found to have IFN-related autoimmune thyrotoxicosis and responded to antithyroid drugs and propanolol. Therefore, this case highlights that IFN-induced thyroiditis is an unusual side-effect and that during treatment, a thyroid-stimulating hormone assay should be performed at regular intervals (every 8–12 weeks).
HIV; interferon α; thyroiditis; weight loss
We present a case of a 42-year-old male, an old case of deep vein thrombosis on warfarin and other drugs like quetiapine, aspirin, diclofenac sodium, fenofibrate, atorvastatin, propanolol and citalopram for concurrent illnesses, who presented with widespread mucocutaneous bleeding and epidural spinal hematoma. The epidural bleed presented clinically as a nontraumatic, rapidly improving myeloradiculopathy. Magnetic resonance imaging (MRI) of the spine revealed an epidural hematoma at D12-L1 level. The case was managed conservatively due lack of neurosurgical facilities. The patient gained full neurological recovery on conservative management alone. This case highlights the problem of drug interaction on warfarin therapy and also an unusual spontaneous recovery of spinal hematoma. Our case was anticoagulated in the recommended therapeutic INR range of 2.2 to 2.4. Most of the similar cases reported in literature were also anticoagulated in the therapeutic range. Thus intraspinal hemorrhage is a rare but dangerous complication of anticoagulant therapy. It must be suspected in any patient on anticoagulant agents who complains of local or referred spinal pain associated with neurological deficits. Drug interactions with warfarin are common. High suspicion and immediate intervention are essential to prevent complications from intraspinal hemorrhage.
Anticoagulant; spinal epidural hematoma; warfarin
This study give a preliminary survey of pharmaceutical contamination and accumulation in surface waters and sediments along the river Po basin (74,000 km2, the largest in Italy), a strategic region for the Italian economy: it collects sewage from a vast industrialized area of Italy (Autorità di Baciono del fiume Po, 2006, 2009). 10 pharmaceuticals (atenolol, propanolol, metoprolol, nimesulide, furosemide, carbamazepine, ranitidine, metronidazole, paracetamol, and atorvastatin) from several therapeutic classes were searched in 54 sampling points along the river Po from the source to the delta, and at the mouth of its major effluents. In water samples were found pharmaceuticals in the range of 0.38–0.001 μg/L, except for furosemide (max conc. 0.605 μg/L), paracetamol (max conc. 3.59 μg/L), metoprolol (never detected) and for atenolol (not analysed). In sediment samples, only paracetamol was not detected, while the others were generally found in the range of 0.4–0.02 μg/kg ww with high concentrations for atenolol (max conc. 284 μg/kg ww) and furosemide (max conc. 98.4 μg/kg ww). The findings confirm also STPs as point sources of contamination. Despite of the much evidence for the adverse effects of pharmaceuticals in the aquatic environment, the observed low levels cannot be considered to pose a serious risk to human health; further studies are necessary for a comprehensive risk assessment.
Infantile haemangioma (IH) frequently requires no intervention. Eighty percent of IHs are focal and solitary. Fifteen percent of cutaneous haemangiomas occur on the extremities. A large size or a specific location or both may carry complications such as ulceration which is one of the main complications, and active treatment is usually required to manage pain, potential scarring, and occasionally, bleeding and infection. Oral propanolol is used in the treatment of IH and is found to be an effective treatment for complicated IH, replacing systemic corticosteroids as first-line therapy. Recommendations for instituting treatment with propranolol in infants differ among different specialties and academic centres. We report an infant with ulcerated IH of leg who responded dramatically to treatment with propranolol in 4 months.
Haemangioma; infancy; propranolol; ulcerated infantile haemangioma
Stimuli that are paired with opioid withdrawal can themselves produce effects similar to withdrawal that might promote relapse.
This study compared precipitated and conditioned withdrawal, and tested whether withdrawal is modified by clonidine or morphine.
Morphine-treated rats (10 mg/kg/12 h) received naloxone (3.2 mg/kg) in a novel environment (conditioned stimuli=CS). Other rats received naloxone in the absence of the CS. Body weight and observable signs were used to measure withdrawal.
Naloxone produced weight loss and withdrawal signs in morphine-treated rats. Following pairings of the CS and naloxone, the CS alone had effects similar to naloxone; conditioned withdrawal was greater after three naloxone/CS pairings, as compared to one, and with longer morphine treatment. Antagonist-precipitated withdrawal was greater in rats that previously were physically dependent on morphine, as compared to withdrawal in rats that were never dependent; however, conditioned withdrawal did not differ between groups. When administered concurrently with naloxone, clonidine (0.1 mg/kg) attenuated some precipitated withdrawal signs, although conditioned withdrawal was largely unchanged. Administration of 10 mg/kg of morphine before the CS alone attenuated all conditioned withdrawal signs, whereas 0.1 mg/kg of clonidine before the CS alone reduced some directly observable signs and not weight loss.
Conditioned withdrawal occurs rapidly and is greater with longer periods of morphine treatment or more pairings of naloxone and the CS; however, a history of physical dependence does not increase conditioned withdrawal. Modification of conditioned withdrawal by drugs might be a useful approach for treating relapse.
morphine; conditioned withdrawal; naloxone; clonidine; rats
Repeated withdrawals from chronic ethanol induce a persistent adaptive change. Further, stress substitutes for the initial two withdrawals of a multiple-withdrawal protocol to sensitize rats to withdrawal-induced anxiety-like behavior (‘anxiety’). Therefore, it was tested whether the persistent adaptation induced by multiple-withdrawal exposures allows stress to elicit anxiety after a period of abstinence. Social interaction was used to assess the degree of anxiety induced by 45 min of restraint stress 3, 7, or 14 days after rats were exposed to multiple withdrawals from a chronic 4.5% ethanol diet. Restraint stress reduced social interaction (ie anxiety-like behavior) at 3, but not at 7 or 14 days, after the multiple withdrawals. No anxiety response was observed in animals that received multiple withdrawals without stress or in animals that received stress when exposed only to control liquid diet. Drugs (ie a CRF1-receptor antagonist, a benzodiazepine receptor antagonist, and a 5-HT1A-receptor agonist) previously demonstrated to block the cumulative adaptation, when administered during repeated withdrawals, prevented stress-induced anxiety-like behavior during abstinence. Additionally, these drugs applied prior to stress in the rats previously exposed to the repeated withdrawal protocol, likewise, minimized stress-induced anxiety. The anxiety following stress during abstinence from previous chronic ethanol exposure is indicative of an interaction of stress with the persistent adaptive change caused by repeated withdrawals. Stress eliciting anxiety-like behavior during abstinence from previous ethanol exposures in rats is consistent with stress inducing anxiety during recovery (sobriety) in the alcoholic, a circumstance that can facilitate craving and relapse.
anxiety; social interaction; chronic ethanol; stress; multiple withdrawals; abstinence; buspirone; flumazenil; CP154,526
The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure. The acoustic startle reflex—a measure of anxiety induced by opiate withdrawal—was used to resolve and quantify discrete withdrawal episodes, and pharmacological interventions were used to manipulate withdrawal severity. Startle potentiation was observed during spontaneous withdrawal from a single morphine exposure, and individual differences in initial withdrawal severity positively predicted the subsequent development of sensitization. Manipulations that reduce or exacerbate withdrawal severity also produced parallel changes in the degree of sensitization. These results demonstrate that the episodic experience of withdrawal during daily drug exposure has a novel role in promoting the development of psychomotor sensitization—a prominent model of drug-induced neurobehavioral plasticity. Episodic withdrawal may have a pervasive role in many effects of intermittent drug exposure and contribute to the development of addiction.
addiction; morphine; withdrawal; acoustic startle; individual differences; sensitization; addiction and substance abuse; opioids; psychopharmacology; mood/anxiety/stress disorders; morphine; withdrawal; acoustic; startle; individual differences; sensitization
The management of medication overuse headache (MOH) is based essentially on the withdrawal of the overused drug(s). Drug withdrawal is performed according to widely differing protocols, both within and across countries; therefore, therapeutic recommendations for the acute phase of detoxification vary considerably among studies. Basically, the aims of MOH management are: (a) to withdraw the overused drug(s); (b) to alleviate withdrawal symptoms by means of a bridge therapy, which includes pharmacological and non-pharmacological support, designed to help the patient to tolerate the withdrawal process; (c) to prevent relapse. Today, there is extensive debate over the best strategies for achieving these goals and the different aspects of this debate are discussed in this review. The authors searched for the best available evidence relating to the following questions: should medication withdrawal be abrupt or gradual? Should patients receive replacement therapy? What are the most effective therapeutic programmes for controlling withdrawal symptoms? Should replacement therapy be administered routinely or as rescue therapy? Should preventive treatment be started before, during or after withdrawal? What are the most effective preventive treatments? Should patients be managed through inpatient or outpatient withdrawal programmes? What is the best approach to adopt in preventing relapses? Treatment of MOH is a difficult challenge, but may be very rewarding. Although there is still a lack of high-quality studies providing evidence-based answers to the many specific questions it raises, neurologists need to know that the combination of education with a rational use of selected therapeutic strategies may be beneficial to people with chronic headache and help to relieve their suffering.
Medication overuse headache; Therapy; Management; MOH; Review
Nicotine withdrawal symptoms are related to smoking cessation. A Rasch model has been used to develop a unidimensional sensitivity score representing multiple correlated measures of nicotine withdrawal. A previous autosome-wide screen identified a nonparametric linkage (NPL) log-likelihood ratio (LOD) score of 2.7 on chromosome 6q26 for the sum of nine withdrawal symptoms.
The objectives of these analyses are: a) to assess the influence of nicotine withdrawal sensitivity on relapse, b) conduct autosome-wide NPL analysis of nicotine withdrawal sensitivity among 158 pedigrees with 432 individuals with microsatellite genotypes and nicotine withdrawal scores, and c) explore family-based association of single nucleotide polymorphism (SNPs) at the mu opioid receptor (MOR) candidate gene (OPRM1) to nicotine withdrawal sensitivity in 172 nuclear pedigrees with 419 individuals with both SNP genotypes and nicotine withdrawal scores.
An increased risk for relapse was associated with nicotine withdrawal sensitivity score (odds ratio, OR=1.25, 95% confidence interval, 95%CI=1.10,1.42). A maximal NPL LOD score of 3.15, suggestive of significant linkage, was identified at chr6q26 for nicotine withdrawal sensitivity. Evaluation of 18 OPRM1 SNPs via the family based association test (FBAT) with the nicotine withdrawal sensitivity score identified eight tagging SNPs with global P-values<0.05 and false discovery rate Q-values<0.06.
An increased risk of relapse, suggestive linkage at chr6q26, and nominally significant association with multiple OPRM1 SNPs was found with Rasch modeled nicotine withdrawal sensitivity score in a multiplex smoking pedigree sample. Future studies should attempt to replicate these findings and investigate the relationship between nicotine withdrawal symptoms and variation at OPRM1.
Tramadol is a centrally acting opioid analgesic used to treat moderate to sever pain. It has more advantage and less opioid adverse effects than conventional opioid analgesia.
This article reports a patient with tramadol dependency that had psychosis after tramadol withdrawal.
By the increase of tramadol usage for relief of chronic pain, tramadol abuse and dependency is increased. Some of tramadol withdrawal symptoms are not related to opioid, for example when the effectiveness is not only on opioid receptors, but on catecholamine and serotonin receptors. So, together with typical symptoms of withdrawal, atypical symptomes had been reported. Psychosis is one of tramadol atypical withdrawal symptoms which subsided a few days after suppression of withdrawal symptoms. In such cases, the diagnosis is substance withdrawal instead of psychotic disorder due to substance withdrawal and treatment is based on this diagnosis.
Tramadol; Psychosis; Atypical withdrawal
A cannabis withdrawal syndrome has been characterized, but its clinical significance remains uncertain. One method of assessing the significance of cannabis withdrawal is to compare it directly to an established withdrawal syndrome. The present study was a within-subject comparison of cannabis, tobacco, and combined cannabis and tobacco withdrawal among users of both substances. Participants (N=12) completed three 5-day periods of abstinence in a randomized order, separated by 9-day periods of usual substance use. Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted. These results are consistent with other evidence suggesting cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11. Additional research is needed to replicate these findings and to further investigate the effects of abstaining from multiple drugs simultaneously.
cannabis; marijuana; tobacco; nicotine; withdrawal; dependence
To develop and test the validity and reliability of the Withdrawal Assessment Tool - Version 1 (WAT-1) for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients.
Prospective psychometric evaluation. Pediatric critical care nurses assessed eligible at-risk pediatric patients for the presence of 19 withdrawal symptoms and rated the patient’s overall withdrawal intensity using a numeric rating scale (NRS) where 0 indicated no withdrawal and 10 indicated worst possible withdrawal. The 19 symptoms were derived from the Opioid and Benzodiazepine Withdrawal Score (OBWS), the literature and expert opinion. Setting: Two Pediatric Intensive Care Units (PICU) in university-affiliated academic children’s hospitals.
83 pediatric patients, median age 35 months (IQR: 7months -10 years), recovering from acute respiratory failure who were weaning from more than 5 days of continuous infusion or round-the-clock opioid and benzodiazepine administration.
Repeated observations during analgesia and sedative weaning. A total of 1040 withdrawal symptom assessments were completed, with a median (IQR) of 11 (6-16) per patient over 6.6 (4.8-11) days.
Measurements and Main Results
Generalized linear modeling was used to analyze each symptom in relation to withdrawal intensity ratings, adjusted for site, subject and age group. Symptoms with high redundancy or low levels of association with withdrawal intensity ratings were dropped, resulting in an 11-item (12-point) scale. Concurrent validity was indicated by high sensitivity (.872) and specificity (.880) (WAT-1 ≥3 predicting NRS ≥4). Construct validity was supported by significant differences in drug exposure, length of treatment and weaning from sedation, length of mechanical ventilation and intensive care unit stay for patients with WAT-1 scores ≥3 compared to those with lower scores.
The WAT-1 shows excellent preliminary psychometric performance when used to assess clinically important withdrawal symptoms in the PICU setting. Further psychometric evaluation in diverse at-risk groups is needed.
drug withdrawal symptoms; opioid analgesia; benzodiazepine; sedation
Both heroin-addicted individuals and methadone maintenance patients are likely to face untreated opioid withdrawal while incarcerated. Limited research exists concerning the withdrawal experiences of addicted inmates and their impact on individuals’ attitudes and plans concerning drug abuse treatment. In the present study, 53 opioid dependent adults (32 in methadone treatment and 21 out-of-treatment) were interviewed in an ethnographic investigation of withdrawal experiences during incarceration. When treatment for opioid withdrawal was unavailable, detoxification experiences were usually described as negative and were often associated with a variety of unhealthy behaviors designed to relieve withdrawal symptoms. Negative methadone withdrawal experiences also negatively influenced participants’ receptivity to seeking methadone treatment upon release. A minority of participants took a positive view of their withdrawal experience and saw it as an opportunity to detox from heroin or discontinue methadone. Findings support the importance of providing appropriate opioid detoxification and/or maintenance therapy to opioid dependent inmates.
Opioid addiction; Incarceration; Withdrawal; Methadone; Ethnography