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- Is opiate action in cough due to sedation? [Journal Article]
- Ther Adv Chronic Dis 2014 Sep; 5(5):200-5.
Opiates have been used for cough suppression for centuries. It is unclear whether this antitussive action is due to their known sedative effects. We aimed to assess correlation between cough suppression and opiate usage.We performed a post hoc analysis of two published trials with three opioids. In study one, patients with chronic cough were treated with 4 weeks of modified release morphine sulphate (5 mg twice daily) or placebo in a double-blinded placebo-controlled fashion. Cough suppression was assessed subjectively by the Leicester Cough Questionnaire and objectively by citric acid aerosol (CAA) induced cough challenge. In study 2, normal volunteers were given single doses of placebo, codeine 30 mg or dextromethorphan 50 mg and cough suppression assessed using the CAA-induced cough challenge. Sedation was contemporaneously assessed by direct questioning.There were 14 episodes of patient-reported sedation; 2 with modified release morphine sulphate, 9 with codeine and 3 with dextromethorphan. There was no correlation between change in the Leicester Cough Questionnaire or the CAA-induced cough challenge and reported sedation.This observational study suggests that sedation is unlikely to underlie the antitussive properties of these opioids. Eliciting the mechanism of these medications in cough may be a target for future tailored drug development.
- The effects of gabapentin on severity of post spinal anesthesia headache. [JOURNAL ARTICLE]
- Pak J Pharm Sci 2014 Sep; 27(5):1203-1207.
Spinal anesthesia is a common anesthesia method and post dural puncture headache (PDPH) is one of its most common adverse effects. Gabapentin is a popular anticonvulsant drug that has been used as an oral nonopioid analgesic in recent years. In this placebo-controlled double-blind study, 120 patients were randomized in two equal groups (Placebo or gabapentin). The patients in the gabapentin group received gabapentin 300 mg orally one hour before the surgery and then every 12 hours for the first 24 hours after the surgery while the placebo group received placebos in the same way. Severity of headache and postoperative pain assessed by verbal rating score for pain (VRSP), morphine consumption, nausea, vomiting, somnolence, pruritus, dizziness in the first 48 hours, hypertension, hypotension, bradycardia and tachycardia in the first 24 hours after the surgery were recorded. In first 48 hour after surgery the mean of severity of headache in the gabapentin group was 0.20±0.05, and in the placebo group it was 0.93±0.01. The mean of postoperative pain in the gabapentin group was2.25±0.793, and in the placebo group it was3.77±0.813. In the first 24 hours post operative the mean of morphine consumptions were 0.20±0.030 and 0.32±0.0 30 mg in gabapentin and placebo groups. No significant differences were found between the two groups regarding incidence rate of the adverse effects. In this study, administration of gabapentin decreased the incidence and severity of post spinal anesthesia headache, postoperative pain and morphine consumption, without any significant differences in serious adverse effects.
- NeuroHIV and Use of Addictive Substances. [JOURNAL ARTICLE]
- Int Rev Neurobiol 2014.:403-440.
In the past three decades, substance abuse has been identified as a key comorbidity of human immunodeficiency virus-1 (HIV-1) infection. Many studies have found that the use and abuse of addictive substances hastens the progression of HIV-1 infection and HIV-associated neurocognitive disorders. Advances in highly active antiretroviral therapy (HAART) in the mid-1990s have been successful in limiting the HIV-1 viral load and maintaining a relatively healthy immune response, allowing the life expectancy of patients infected with HIV to approach that of the general population. However, even with HAART, HIV-1 viral proteins are still expressed and eradication of the virus, particularly in the brain, the key reservoir organ, does not occur. In the post-HAART era, the clinical challenge in the treatment of HIV infection is inflammation of the central nervous system (CNS) and its subsequent neurological disorders. To date, various explicit and implicit connections have been identified between the neuronal circuitry involved in immune responses and brain regions affected by and implicated in substance abuse. This chapter discusses past and current medical uses of prototypical substances of abuse, including morphine, alcohol, cocaine, methamphetamine, marijuana, and nicotine, and the evidence that systemic infections, particularly HIV-1 infection, cause neurological dysfunction as a result of inflammation in the CNS, which can increase the risk of substance abuse.
- A Common Molecular Motif Characterizes Extracellular Allosteric Enhancers of GPCR Aminergic Receptors and Suggests Enhancer Mechanism of Action. [JOURNAL ARTICLE]
- Curr Med Chem 2014 Aug 26.
Several classes of compounds that have no intrinsic activity on aminergic systems nonetheless enhance the potency of aminergic receptor ligands three-fold or more while significantly increasing their duration of activity, preventing tachyphylaxis and reversing fade. Enhancer compounds include ascorbic acid, ethylenediaminetetraacetic acid, corticosteroids, opioid peptides, opiates and opiate antagonists. This paper provides the first review of aminergic enhancement, demonstrating that all enhancers have a common, in obvious molecular motif and work through a common mechanism that is manifested by three common characteristics. First, aminergic enhancers bind directly to the amines they enhance, suggesting that the common structural motif is reflected in common binding targets. Second, one common target is the first extracellular loop of aminergic receptors. Third, at least some enhancers are antiphosphodiesterases. These observations suggest that aminergic enhancers act on the extracellular surface of aminergic receptors to keep the receptor in its high affinity state, trapping the ligand inside the receptor. Enhancer binding produces allosteric modifications of the receptor structure that interfere with phosphorylation of the receptor, thereby inhibiting down-regulation of the receptor. The mechanism explains how enhancers potentiate aminergic activity and increase duration of activity and makes testable predictions about additional compounds that should act as aminergic enhancers. Key words: GPCR, epinephrine, norepinephrine, dopamine, histamine, serotonin, EDTA, vitamin C, ascorbic acid, opiate, opioid, morphine, naloxone, naltrexone, aldosterone, corticosteroid, allostery, allosteric, antiphosphodiesterase, phosphodiesterase inhibitors, down-regulation, potentiates, increased potency, potentiation, enhances, enhancement, supersensitivity, molecular complementarity.
- Caudal Blockade for Children Undergoing Infra-abdominal Surgery. [Journal Article]
- AORN J 2014 Sep; 100(3):306-22.
The assessment and management of pain in children can be complicated by their inability to communicate effectively; therefore, it is important that every attempt be made to circumvent the undertreatment of pain. Caudal blockade is associated with excellent pain relief and minimal side effects, and it is an established technique used in conjunction with general anesthesia for children undergoing infra-abdominal surgery. Available local anesthetic agents have a relatively short analgesic duration period, so anesthesia professionals often combine their use with adjuvant medications (eg, epinephrine, clonidine, fentanyl, morphine, preservative-free ketamine, neostigmine). Additional consideration should be given to intraoperative care, postoperative observation (eg, measuring sedation, motor blockade, postoperative nausea and vomiting, pain), and discharge instructions for the patient's caregiver.
- Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial. [JOURNAL ARTICLE]
- Braz J Anesthesiol 2014 September - October; 64(5):343-349.
Esmolol is known to have no analgesic activity and no anaesthetic properties; however, it could potentiate the reduction in anaesthetic requirements and reduce postoperative analgesic use. The objective of this study is to evaluate the effect of intravenous esmolol infusion on intraoperative and postoperative analgesic consumptions as well as its effect on depth of anaesthesia.This randomized-controlled double blind study was conducted in a tertiary care hospital between March and June 2010. Sixty patients undergoing septorhinoplasty were randomized into two groups. History of allergy to drugs used in the study, ischaemic heart disease, heart block, bronchial asthma, hepatic or renal dysfunction, obesity and a history of chronic use of analgesic or β-blockers were considered cause for exclusion from the study. Thirty patients received esmolol and remifentanil (esmolol group) and 30 patients received normal saline and remifentanil (control group) as an intravenous infusion during the procedure. Mean arterial pressure, heart rate, and bispectral index values were recorded every 10min. Total remifentanil consumption, visual analogue scale scores, time to first analgesia and total postoperative morphine consumption were recorded.The total remifentanil consumption, visual analogue scale scores at 0, 20 and 60min, total morphine consumption, time to first analgesia and the number of patients who needed an intravenous morphine were lower in the esmolol group.Intravenous infusion of esmolol reduced the intraoperative and postoperative analgesic consumption, reduced visual analogue scale scores in the early postoperative period and prolonged the time to first analgesia; however it did not influence the depth of anaesthesia.
- Adding 75mg pregabalin to analgesic regimen reduces pain scores and opioid consumption in adults following percutaneous nephrolithotomy. [JOURNAL ARTICLE]
- Braz J Anesthesiol 2014 September - October; 64(5):335-342.
Adding novel adjunctive drugs like gabapentinoids to multimodal analgesic regimen might be reasonable for lessening postoperative pain scores, total opioid consumption and side effects after percutaneous nephrolithotomy. We aimed to evaluate the effect of pregabalin on postoperative pain scores, analgesic consumption and renal functions expressed by creatinine clearance (CrCl) and blood neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys C) levels in patients undergoing percutaneous nephrolithotomy (PCNL).60 patients undergoing elective PCNL were enrolled in the study. Patients were randomized to oral single dose 75mg pregabalin group and a control group. Visual Analog Scale pain scores (VAS), postoperative intravenous morphine consumption during the first 24 postoperative hours, serum NGAL, Cys C levels and creatinine clearance (CrCl) was measured preoperatively and post-operatively at 2nd and 24th hour.Postoperative VAS scores were significantly decreased in the pregabalin group at the postoperative 30th min, 1st, and 2nd hour (p=0.002, p=0.001 and p=0.027, respectively). Postoperative mean morphine consumption was statistically significantly decreased for all time intervals in the pregabalin group (p=0.002, p=0.001, p=0.001, p=0.001, p<0.001, respectively). No statistically significant differences were found between the two groups with regard to CrCl, or Cys C at preoperative and postoperative 2nd and 24th hour. Postoperative 24th hour NGAL levels were significantly decreased in the pregabalin group (p=0.027).Oral single-dose preemptive 75mg pregabalin was effective in reducing early postoperative pain scores and total analgesic consumption in patients undergoing PCNL without leading to hemodynamic instability and side effects.
- Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain. [Journal Article, Review]
- J Pain Res 2014.:495-503.
Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient's self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient's medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1-110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75-100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain.
- Pharmacogenomic study of the role of the nociceptin/orphanin FQ receptor and opioid receptors in diabetic hyperalgesia. [JOURNAL ARTICLE]
- Eur J Pharmacol 2014 Aug 25.
Targeting functionally independent receptors may provide synergistic analgesic effects in neuropathic pain. To examine the interdependency between different opioid receptors (µ-opioid peptide [MOP], δ-opioid peptide [DOP] and κ-opioid peptide [KOP]) and the nociceptin/orphanin FQ peptide (NOP) receptor in streptozotocin (STZ)-induced diabetic polyneuropathy, nocifensive activity was measured using a hot plate test in wild-type and NOP, MOP, DOP and KOP receptor knockout mice in response to the selective receptor agonists Ro65-6570, morphine, SNC-80 and U50488H, or vehicle. Nocifensive activity was similar in non-diabetic wild-type and knockout mice at baseline, before agonist or vehicle administration. STZ-induced diabetes significantly increased heat sensitivity in all mouse strains, but MOP, DOP and KOP receptor knockouts showed a smaller degree of hyperalgesia than wild-type mice and NOP receptor knockouts. For each agonist, a significant antihyperalgesic effect was observed in wild-type diabetic mice (all P<0.05 versus vehicle); the effect was markedly attenuated in diabetic mice lacking the cognate receptor compared with wild-type diabetic mice. Morphine was the only agonist that demonstrated near-full antihyperalgesic efficacy across all non-cognate receptor knockouts. Partial or near-complete reductions in efficacy were observed with Ro65-6570 in DOP and KOP receptor knockouts, with SNC-80 in NOP, MOP and KOP receptor knockouts, and with U50488H in NOP and DOP receptor knockouts. There was no evidence of NOP and MOP receptor interdependency in response to selective agonists for these receptors. These findings suggest that concurrent activation of NOP and MOP receptors, which showed functional independence, may yield an effective and favourable therapeutic analgesic profile.
- Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements? [JOURNAL ARTICLE]
- Support Care Cancer 2014 Aug 29.
Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing.In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected.Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS).This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice. Larger prospective studies are needed to define the opioid-sparing effects of adjuvants.Adjuvant agents are used in over 80 % of those treated for cancer pain.