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      Comparing the effect of pregabalin, gabapentin, and acetaminophen on post-dural puncture headache

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          Abstract

          Introduction:

          Post-dural puncture headache (PDPH) is a common complication of lumbar puncture for any purpose. To avoid the need for invasive methods of treating PDPH such as blood patch, the search for novel pharmacological agents to manage PDPH continues. The aim of this study was to compare the effects of acetaminophen, gabapentin and pregabalin in controlling PDPH in patients who underwent surgery under spinal anesthesia.

          Materials and Methods:

          A total of 90 patients who underwent elective orthopedic surgery under spinal anesthesia and suffered from PDPH consequently were enrolled in this randomized trial. Patients were categorized randomly into three groups. Group A, B and C have received Acetaminophen, Gabapentin and Pregabalin (3 times a day for 3 days), respectively. The effect of medications on the severity of PDPH was evaluated and compared using visual analog scale (VAS).

          Results:

          The mean VAS score was significantly lower in pregabalin group compared with others 24, 48 and 72 h after the onset of headache ( P = 0.001 for all of them) and lower in Gabapentin group compared with Acetaminophen group 24, 48 and 72 h after the onset of headache ( P = 0.001 for all analyses). No adverse outcome was reported in groups.

          Conclusion:

          Pregabalin and gabapentin are both useful and safe in management of PDPH, but pregabalin is more effective in this regard.

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          Most cited references21

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          A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin.

          Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium influx and subsequent release of excitatory neurotransmitters; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours. Orally administered gabapentin exhibits saturable absorption--a nonlinear (zero-order) process--making its pharmacokinetics less predictable. Plasma concentrations of gabapentin do not increase proportionally with increasing dose. In contrast, orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour. Absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage. Both drugs can be given without regard to meals. Neither drug binds to plasma proteins. Neither drug is metabolized by nor inhibits hepatic enzymes that are responsible for the metabolism of other drugs. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours. Pregabalin and gabapentin both show dose-response relationships in the treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a pregabalin dosage of 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be more effective than gabapentin, on the basis of the magnitude of the reduction in the seizure frequency. In conclusion, pregabalin appears to have some distinct pharmacokinetic advantages over gabapentin that may translate into an improved pharmacodynamic effect.
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            Post-dural (post-lumbar) puncture headache: risk factors and clinical features.

            This is an analytic, interventional, cross sectional study to evaluate the risk factors of post-dural (post-lumbar) puncture headache (PDPH) and the validity of the diagnostic criteria for PDPH from the ICHD II. Six-hundred-and-forty patients (332 non-pregnant women and 308 men) aged 8-65 years underwent spinal anesthesia with Quincke 25G or 27G needles in elective surgery. Forty-eight (7.5%) of the patients developed PDPH. The binary logistic regression analysis identified as risk factors: gender [11.1% female vs. 3.6% male, OR 2.25 (1.07-4.73); p = 0.03], age [11.0% 31-50 years of age vs. 4.2% others, OR 2.21 (1.12-4.36); p = 0.02], previous history of PDPH [26.4% positive vs. 6.2% negative, OR 4.30 (1.99-9.31); p < 0.01] and bevel orientation [16.1% perpendicular vs. 5.7% parallel, OR 2.16 (1.07-4.35); p = 0.03]. The period of latency between lumbar puncture and headache onset range from 6 to 72 hours and the duration from 3 to 15 days. In 34/48 (71%) patients with PDPH, at least one of the following was present: neck stiffness, tinnitus, hypoacusia, photophobia, or nausea. In conclusion, 14/48 patients (29%) suffered none of the above-mentioned symptoms, indicating that a significant number of patients may suffer from PDPH in the absence of any symptoms apart from the headache itself. This suggests that a further analyses of existing studies should be made to determine if a criteria change may need consideration.
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              Gabapentinoids: Gabapentin and Pregabalin for Postoperative Pain Management

              Editorial Postsurgical pain is normally perceived as nociceptive pain. Surgical trauma has been known to induce central and peripheral sensitization and hyperalgesia, which in untreated cases could lead to chronic postoperative pain after surgery. Indeed pain is one of the three most common medical causes of delayed discharge after ambulatory surgery, the other two being drowsiness and nausea/ vomiting. Antihyperalgesic drugs improve postoperative pain by preventing the development of central sensitization (1). The development of newer agents available for postoperative pain control create possibilities for better combinations in multimodal analgesia. The recent advances in postoperative pain management can be specifically grouped in the following areas: Finding exact molecular mechanisms, new pharmaceutical products and other routes and modes of analgesic delivery. For the years, opioids have been the mainstay of postoperative pain management but they have side effects. For this purpose the multimodal approach and non-opioid drugs have been suggested to improve postoperative analgesia and to reduce opioid related side effects (2). Gabapentinoids (gabapentin and pregabalin) were originally introduced as antiepileptics but have analgesic, anticonvulsant, and anxiolytic effects also. These easily tolerable drugs by patients have limited side-effects. Gabapentin an anti-epileptic drug binds to the alpha-2 delta subunit of the presynaptic voltage gated-calcium channels and inhibits calcium release so prevents the release of excitatory neurotransmitters involved in the pain pathways (2, 3). Gabapentin has demonstrated analgesic effect in diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain. Several meta-analyses reveal that perioperative gabapentin helps to produce a significant opioid-sparing effect and probably decreses postoperative pain score relative to the control group (4, 5). Pregabalin is a structural analog of gamma-aminobutyric acid (GABA). It acts by presynaptic binding to the α -2-λ subunit of voltage-gated calcium channels that are widely distributed in the spinal cord and brain6. By this mechanism, pregabalin modulates the release of several excitatory neurotransmitters, such as glutamate, norepinephrine, substance P, and calcitonin gene-related peptide. It leads to inhibitory modulation of “overexcited” neurons and returning them to a “normal” state. Centrally, pregabalin could reduce the hyperexcitability of dorsal horn neurons that is induced by tissue damage (6). To sum up, pregabalin has a more appropriate pharmacokinetic profile than gabapentin, including dose-independent absorption and far more potent than gabapentin while producing fewer adverse effects (7-9). Pregabalin has efficacy of varying degree in neuropathic pain conditions such as postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia. While some surveys do not demonstrate a significant analgesic effect in the acute, including postoperative pain control (9, 10), other studies suggest pregabalin to have effective sedative and opioid-sparing effects (11-13), and emphasize on its effectiveness in acute pain control. Since safe postoperative pain control is nessecary, established role of pregabalin as an analgesic adjuvant as a part of multimodal analgesia for acute pain control is in progress (7, 8, 14, 15). Its unique potency in reducing opioid requirements, prevention of opioid tolerance, enhancement the quality of opioid analgesia, decreased respiratory depression and anxiolysis, make it an attractive drug to consider for control of pain in the post-operative setting (15-17). Lots of meta-analyses and clinical trials show that perioperative pregabaline helps to produce a significant opioid-sparing effect and probably improves postoperative pain score relative to the control group (18-21). Having looked at these two drugs from different angles and aspects, one comes to this understanding that these multi-purpose drugs have found a strong and reliable place in acute pain service setting. So, Gabapentinoids are an effective tool in the treatment of postoperative pain.
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                Author and article information

                Journal
                Saudi J Anaesth
                Saudi J Anaesth
                SJA
                Saudi Journal of Anaesthesia
                Medknow Publications & Media Pvt Ltd (India )
                1658-354X
                0975-3125
                Jul-Sep 2014
                : 8
                : 3
                : 374-377
                Affiliations
                [1] Department of Anesthesiology and Pain Medicine, Imam Khomeini Training Hospital, Urmia University of Medical Sciences, Urmia, Iran
                Author notes
                Address for correspondence: Dr. Alireza Mahoori, Department of Anesthesiology, Imam Khomeini Training Hospital, Urmia University of Medical Sciences, Urmia, Iran. E-mail: ar_mahoori@ 123456yahoo.com
                Article
                SJA-8-374
                10.4103/1658-354X.136436
                4141388
                25191190
                704209a9-807a-42df-b1c1-80351e60c5eb
                Copyright: © Saudi Journal of Anaesthesia

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Original Article

                Anesthesiology & Pain management
                acetaminophen,gabapentin,post-dural puncture headache,pregabalin

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