Need a Fix for That Fit? Feline Seizures

Total Page:16

File Type:pdf, Size:1020Kb

Need a Fix for That Fit? Feline Seizures Need a Fix for that Fit? Feline Seizures by James Lavely, DVM, DACViM-Neurology, VCA Animal Care Center of Sonoma County CVMA Spring Seminar in yosemite Speaker CV66_6.indb 20 11/2/12 11:43 AM eline seizures off er unique challenges treatment may lead to better seizure control. Patients compared to dogs. Both dogs and cats with cluster seizures, status epilepticus or secondary can have generalized or partial seizures. epilepsy should have anticonvulsant therapy started However, cats commonly present with without delay. Patients with an underlying etiology rather bizarre partial seizures. Complex other than idiopathic epilepsy may require medication Need a Fix for that Fit? partial seizures or psychomotor seizures in addition to anticonvulsant therapy. Anticonvulsant Fcan manifest with the cat acting aggressive for therapy is targeted to increase quality of life, decrease several minutes at a time, and may frighten their the frequency and severity of seizures with as few Feline Seizures caretakers. Symptomatic epilepsy or secondary adverse eff ects as possible. epilepsy is more common in cats and accounts for almost half of all seizure disorders in cats. Anticonvulsant therapy for cats is often frustrating Meningiomas are the most common brain tumor in when phenobarbital is unsuccessful. The use of cats, followed by lymphosarcoma. Cryptococcosis, potassium bromide is no longer recommended in FIP and toxoplasmosis are also potential causes of cats due to the potential for asthma secondary to feline seizures. Hypoglycemia should be considered bromide therapy. Signs may resolve once bromide in cats receiving insulin therapy. Idiopathic epilepsy therapy is discontinued. The longer half-life of represents 21% to 59% of feline seizure disorders. diazepam in cats makes them a possible candidate for Interictal neurological examination is normal in cats long term anticonvulsant therapy. However, the use with idiopathic epilepsy, whereas cats with secondary of oral diazepam is limited/not recommended due epilepsy can have a normal or abnormal examination. to the potential risk of severe and potentially fatal Unilateral defi cits identifi ed on examination suggest a hepatopathy in cats. Extensive studies regarding safety structural or vascular cause. and effi cacy of newer anticonvulsants in cats are lacking. Gabapentin 5-10 mg/kg PO BID to TID may Complex partial seizures or psychomotor seizures can manifest with the cat acting aggressive for several minutes at a time, and may frighten their caretakers. Symptomatic epilepsy or secondary epilepsy is more common in cats and accounts for almost half of all seizure disorders in cats. The increased incidence of secondary epilepsy in be used, however, it has not been highly effi cacious cats warrants further investigation for the cause, for seizures in small animals. Newer anticonvulsants even when the neurological examination is normal such as levetiracetam 20 mg/kg PO TID, zonisamide and signalment is consistent with idiopathic epilepsy. 5-10 mg/kg PO SID and pregabalin 1-2 mg/kg PO BID A thorough evaluation for the underlying cause for in cats appear promising. Due to the limited number seizures should be pursued to optimize anticonvulsant of studies and anecdotal experience (lower incidence therapy. CBC, chemistry, urinalysis, thoracic of seizures in cats compared to dogs) care should be radiographs and abdominal ultrasound should be used when prescribing these medications. Starting at done to rule out extracranial causes for seizures, while the lower end of the dose range may be of benefi t. MRI and CSF should be done to rule out intracranial Serial monitoring of the CBC and serum chemistry is causes. Results of diagnostic testing are normal in recommended when cats are receiving anticonvulsant idiopathic epileptics. Cats with idiopathic epilepsy medication. Therapeutic levels for levetiracetam, typically fi rst seizure between the ages of one and zonisamide and pregabalin are relatively unknown for fi ve. Generalized tonic clonic seizures are typically cats and dogs at this time. seen with idiopathic epilepsy, although focal seizures are also possible. Autosomal recessive inheritance is Phenobarbital most common in dogs, but has not been established Phenobarbital is typically dosed at about 2.5 mg/ in cats. Anticonvulsant therapy is typically started kg PO BID. Most cats are started at 8.1 mg PO BID, when seizure frequency increases, particularly when while small cats are started at four mg PO BID. two or more seizures occur within six months. A Phenobarbital increases the seizure threshold and baseline period is helpful to determine the natural decreases the spread to surrounding neurons. It seizure frequency and can help assess response enhances the inhibitory postsynaptic eff ects of GABA, to anticonvulsant therapy. However this baseline inhibits glutamate activity and decreases calcium fl ux period should not be too long, as earlier antiepileptic across neuronal membranes. Peak levels are achieved November/December 2012 | 21 CV66_6.indb 21 11/2/12 11:43 AM 4-6 hours post oral administration and its T ½ is 34- metabolism in the dog. The T ½ is 3-4 hours in dogs and 50 hours in cats. Phenobarbital metabolism increases about three hours in cats. Cats are given 5-10 mg/kg PO with chronic therapy in dogs, but less commonly in cats. BID to TID. Sedation and ataxia are the most common Adverse eff ects include sedation, ataxia, polyphagia, PU/ adverse eff ects. PD and liver disease. Pregabalin Levetiracetam Pregabalin is a GABA analog structurally similar to Levetiracetam binds synaptic vesicular protein SV2A. gabapentin. Pregabalin has a higher affi nity for the Levetiracetam may prevent hypersynchronization of α2δ subunit of neuronal voltage-gated calcium burst fi ring and seizure propagation. The T ½ is four channels than does gabapentin. The T ½ of pregabalin hours in dogs and three hours in cats. Peak plasma is 7 hours in dogs and 10.4 hours in cats. Pregabalin is concentration occurs two hours post administration administered 2 ‒ 4 mg/kg PO BID to TID in dogs and 1-2 in most cats with approximately 100% bioavailability. mg/kg PO BID in cats. Adverse eff ects include sedation Levetiracetam is started at 20 mg/kg PO TID. Adverse and ataxia and are not uncommon in dogs. Thus, starting eff ects appear minimal, with sedation, ataxia and dose at a lower dose and titrating the dose upward is decreased appetite occurring uncommonly. Food recommended. does not aff ect absorption of levetiracetam. Most of the drug is excreted unchanged through the kidneys. Conclusion The cytochrome P 450 system does not appear to A thorough evaluation is essential for the seizuring cat. be involved. However, concurrent phenobarbital Therapy should be directed at the underlying cause of administration has been shown to decrease seizures, with anticonvulsant therapy to control seizures levetiracetam T ½ and decreases levetiracetam blood and optimize quality of life. Phenobarbital has been the levels in dogs. Thus patients on both phenobarbital and mainstay of anticonvulsant therapy in cats. However, levetiracetam concurrently may require higher dosages when phenobarbital therapy is unsuccessful or if of levetiracetam. adverse eff ects occur the use of newer anticonvulsants can be helpful. Serial monitoring of the CBC and serum Zonisamide chemistry is recommended when cats are receiving Zonisamide is a sulfonamide-based anticonvulsant anticonvulsant medication. drug. Zonisamide blocks voltage-dependent sodium channels and T-type calcium channels. Its T ½ is about Suggested reading: 15 hours in the dog and 35 hours in cats. Zonisamide 1. Cautela MA, Dewey CW, Schwark WS, et al. is metabolized by hepatic microsomal enzymes and Pharmokinetics of oral pregabalin in cats after single is also renally excreted. Its T ½ is reduced with dose administration. In Proceedings ACVIM Forum. concurrent phenobarbital administration. Zonisamide Anaheim, CA: 2010, p 739. is administered 5-10 mg/kg PO BID in dogs, with the 2. Dewey CW, Cerda-Gonzalez S, Levine JM, et al. higher dose range for dogs also receiving phenobarbital. Pregabalin as an adjunct to phenobarbital, potassium Cats are given 5-10 mg/g PO q 24 hours, due to the bromide, or a combination of phenobarbital and longer T ½. Zonisamide is typically well tolerated, with potassium bromide for treatment of dogs with anorexia, sedation and ataxia being the most common suspected idiopathic epilepsy. J Am Vet Med Assoc adverse eff ects. Adverse eff ects are much more common 2009;235:1442‒1449. with increased dosing. About half of cats given 20 mg/ 3. Siao KT, Pypendop BH, Ilkiw JE. Pharmacokinetics of kg had adverse eff ects such as anorexia, vomiting, gabapentin in cats. Am J Vet Res 2010;71(7):817-21. diarrhea, sedation and ataxia. 4. Smith Bailey K, Dewey CW. The seizuring cat. Diagnostic work up and therapy. J Feline Med Surg Gabapentin 2009;11(5):385-94 Gabapentin binds voltage-gated calcium channels and 5. Thomas WB. Idiopathic epilepsy in dogs and cats. Vet decreases intracellular calcium infl ux. It is excreted Clin Small Anim Pract 2010;40:161-179. unchanged by the kidneys with about 30-40% hepatic Dr. James Lavely leads a team of four neurologists at VCA Animal Care Center of Sonoma. He earned his DVM degree from The Ohio State University in 1999. After completing an internship at Angell Memorial Animal Hospital he underwent his neurology and neurosurgery residency training at UC Davis. Dr. Lavely has published articles on CNS infections, pediatric neurology and seizures. He has also conducted research regarding the diagnosis of myasthenia gravis. Dr. Lavely will be speaking at the CVMA Spring Seminar in Yosemite March 8-10, 2013 (see page 23 ). 22 | California Veterinarian CV66_6.indb 22 11/2/12 11:43 AM.
Recommended publications
  • STATUS EPILEPTICUS in ADULTS (Convulsive Seizures in Patients Aged > 16 Years Old) Link Consultant: Dr Hannah Cock
    STATUS EPILEPTICUS IN ADULTS (Convulsive Seizures in patients aged > 16 years old) Link consultant: Dr Hannah Cock Status epilepticus (SE) is defined as continuous seizure activity which has failed to self- terminate leading to a risk of neurological damage. The risks are highest with generalised tonic/clonic (convulsive) seizures. Convulsive SE may present as either a run of discreet generalised tonic/clonic seizures without full recovery in between (ie without regaining consciousness), or continuous generalised tonic/clonic seizure activity. Most convulsive seizures terminate spontaneously within 3 minutes, and do NOT need emergency treatment. Convulsive seizures lasting longer than 5 minutes, or recurring without recovery should be managed as Convulsive SE, unless the patient is known to habitually have longer seizures with self-termination (eg information from relatives, friends, or the patient’s epilepsy card or diary). The mortality and morbidity of generalised status epilepticus is high, and it is important to control fits as soon as possible, to use adequate doses of 1st and 2nd line agents, but not to over-treat patients in whom seizures have terminated but are slow to recover. GENERAL MANAGEMENT 1st stage (0-10mins). Protect the patient e.g. padded bed rails. Do not restrain. Administer oxygen. During an inter-ictal period insert an airway and then administer oxygen. Do not attempt to insert anything in the patient’s mouth during a seizure, even if the tongue is injured. Place the patient in a semi-prone position with the head down to prevent aspiration. Establish iv access. Note the time. 2nd Stage (0-30mins). Institute regular monitoring (temperature, cardiac, respiration, BP).
    [Show full text]
  • Zonegran, INN-Zonisamide
    SCIENTIFIC DISCUSSION 1. Introduction Many patients (30 to 40% of the overall population with epilepsy) continue to have seizures in spite of receiving antiepileptic drug (AED) treatment. The prevalence of active epilepsy, 5-10/1000, is one of the highest among serious neurological disorders with more than 50 million people affected worldwide. Two peaks of incidence are observed, in early childhood and among elderly people. Some patients will have life-long epilepsy. International classifications, such as the International League Against Epilepsy (ILAE) classification recognise many epileptic diseases or syndromes and each of them can be expressed clinically by one or several seizure groupings. Partial epilepsies (localisation related) are the more frequent, accounting for more than 60% of the epilepsies, and they include most of the difficult-to-treat patients. In terms of seizure types, partial epilepsies include simple partial seizures (without impairment of consciousness), complex partial seizures (with impairment of consciousness and often more disabling) and secondarily generalized tonic-clonic seizures. The symptoms are a function of the localisation of the site of seizure onset in the brain (epileptogenic zone) and of the propagation pathways of the abnormal discharge. Therapeutic management usually follows a staged approach with newly diagnosed patients starting prophylactic treatment with a single drug, and several alternative drugs may be tried in the event of lack of efficacy or poor tolerability. For patients not responding to several attempts of monotherapy, combinations of antiepileptic drugs are generally employed early in the management process. Uncontrolled epilepsy is associated with cognitive deterioration, psychosocial dysfunction, dependent behaviour, restricted lifestyle, poor quality of life and excess mortality, in particular from sudden unexpected death in epilepsy patients (SUDEP).
    [Show full text]
  • Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy
    Original Article / Özgün Makale DODO I: 10.4274/ I: 10.4274/jtsm.xxxjtsm.69188 Journal of Turkish Sleep Medicine 2018;5:12-6 Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy Levetirasetam Monoterapisi Altında Epilepsi Hastalarında Huzursuz Bacak Sendromu Gülnihal Kutlu, Fatma Genç*, Yasemin Ünal, Dilek Aslan Öztürk, Abidin Erdal*, Yasemin Biçer Gömceli* Muğla Sıtkı Koçman University Faculty of Medicine, Department of Neurology, Muğla, Turkey *University of Health Sciences, Antalya Training and Research Hospital, Clinic of Neurology, Antalya, Turkey Abstract Öz Objective: Restless Legs syndrome (RLS) is a frequent neurological Amaç: Huzursuz Bacak sendromu (HBS) sık görülen bir nörolojik disease. Levetiracetam (LEV) is an effective and broad-spectrum hastalıktır. Levetirasetam (LEV) etkili ve geniş spektrumlu bir antiepileptik anticonvulsant drug. The aim of this study is to investigate the frequency ilaçtır. Bu çalışmanın amacı epilepsi tanısı ile LEV monoterapisi alan of RLS in patients diagnosed with epilepsy who took LEV monotherapy. hastalarda HBS sıklığını araştırmaktır. Materials and Methods: Two neurologists were reviewed the files of Gereç ve Yöntem: Epilepsi polikliniğinde takip edilen 1680 hastanın 1680 patients, who were followed in epilepsy outpatient clinic. One dosyası iki nörolog tarafından gözden geçirildi. En az 6 aydır LEV hundred seven patients under LEV monotherapy for at least six months monoterapisi alan 107 hasta ve 120 sağlıklı kontrol çalışmaya alındı. and 120 healthy controls were included in the study. The criteria for the International Restless Legs Syndrome Study Group were taken into HBS değerlendirmesi için Uluslararası Huzursuz Bacak Sendromu Çalışma consideration for the assessment of RLS. Grubu’nun kriterleri göz önüne alındı. Results: The mean age of patient group was 38.26±17.39 years, while Bulgular: Sağlıklı kontrollerin ortalama yaşı 39,17±16,12 yıl iken, the mean age of healthy controls was 39.17±16.12 years.
    [Show full text]
  • Epilepsy & Behavior
    Epilepsy & Behavior 80 (2018) 365–369 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh Brief Communication Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events Virupakshi Jalihal a, Rohit Shankar b,c,⁎, William Henley c, Mary Parrett d, Phil Tittensor e, Brendan N. McLean d, Ammad Ahmed f, Josemir W. Sander g,h,i a Ramaiah Medical College and Hospitals, Bengaluru, Karnataka 560054, India b Cornwall Partnership NHS Foundation Trust, Threemilestone Industrial Estate, Truro TR4 9LD, UK c Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK d Royal Cornwall Hospital, Truro, Cornwall TR1 3LJ, UK e Royal Wolverhampton NHS Trust, UK f Bial Pharma Ltd., Admiral House, Windsor SL4 3BL, UK g NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK h Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire SL9 0RJ, UK i Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, Netherlands article info abstract Article history: Background: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) Received 13 November 2017 withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized Revised 16 January 2018 with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly Accepted 17 January 2018 used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric Available online 5 February 2018 illnesses such as mood disorders, aggression, and anxiety.
    [Show full text]
  • Mechanisms of Action of Antiepileptic Drugs
    Review Mechanisms of action of antiepileptic drugs Epilepsy affects up to 1% of the general population and causes substantial disability. The management of seizures in patients with epilepsy relies heavily on antiepileptic drugs (AEDs). Phenobarbital, phenytoin, carbamazepine and valproic acid have been the primary medications used to treat epilepsy for several decades. Since 1993 several AEDs have been approved by the US FDA for use in epilepsy. The choice of the AED is based primarily on the seizure type, spectrum of clinical activity, side effect profile and patient characteristics such as age, comorbidities and concurrent medical treatments. Those AEDs with broad- spectrum activity are often found to exert an action at more than one molecular target. This article will review the proposed mechanisms of action of marketed AEDs in the US and discuss the future of AEDs in development. 1 KEYWORDS: AEDs anticonvulsant drugs antiepileptic drugs epilepsy Aaron M Cook mechanism of action seizures & Meriem K Bensalem-Owen† The therapeutic armamentarium for the treat- patients with refractory seizures. The aim of this 1UK HealthCare, 800 Rose St. H-109, ment of seizures has broadened significantly article is to discuss the past, present and future of Lexington, KY 40536-0293, USA †Author for correspondence: over the past decade [1]. Many of the newer AED pharmacology and mechanisms of action. College of Medicine, Department of anti epileptic drugs (AEDs) have clinical advan- Neurology, University of Kentucky, 800 Rose Street, Room L-455, tages over older, so-called ‘first-generation’ First-generation AEDs Lexington, KY 40536, USA AEDs in that they are more predictable in their Broadly, the mechanisms of action of AEDs can Tel.: +1 859 323 0229 Fax: +1 859 323 5943 dose–response profile and typically are associ- be categorized by their effects on the neuronal [email protected] ated with less drug–drug interactions.
    [Show full text]
  • Chapter 25 Mechanisms of Action of Antiepileptic Drugs
    Chapter 25 Mechanisms of action of antiepileptic drugs GRAEME J. SILLS Department of Molecular and Clinical Pharmacology, University of Liverpool _________________________________________________________________________ Introduction The serendipitous discovery of the anticonvulsant properties of phenobarbital in 1912 marked the foundation of the modern pharmacotherapy of epilepsy. The subsequent 70 years saw the introduction of phenytoin, ethosuximide, carbamazepine, sodium valproate and a range of benzodiazepines. Collectively, these compounds have come to be regarded as the ‘established’ antiepileptic drugs (AEDs). A concerted period of development of drugs for epilepsy throughout the 1980s and 1990s has resulted (to date) in 16 new agents being licensed as add-on treatment for difficult-to-control adult and/or paediatric epilepsy, with some becoming available as monotherapy for newly diagnosed patients. Together, these have become known as the ‘modern’ AEDs. Throughout this period of unprecedented drug development, there have also been considerable advances in our understanding of how antiepileptic agents exert their effects at the cellular level. AEDs are neither preventive nor curative and are employed solely as a means of controlling symptoms (i.e. suppression of seizures). Recurrent seizure activity is the manifestation of an intermittent and excessive hyperexcitability of the nervous system and, while the pharmacological minutiae of currently marketed AEDs remain to be completely unravelled, these agents essentially redress the balance between neuronal excitation and inhibition. Three major classes of mechanism are recognised: modulation of voltage-gated ion channels; enhancement of gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission; and attenuation of glutamate-mediated excitatory neurotransmission. The principal pharmacological targets of currently available AEDs are highlighted in Table 1 and discussed further below.
    [Show full text]
  • Mode of Seizure Inhibition by Sodium Channel Blockers, an SV2A Ligand
    Epilepsy Research 154 (2019) 42–49 Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Mode of seizure inhibition by sodium channel blockers, an SV2A ligand, and T an AMPA receptor antagonist in a rat amygdala kindling model ⁎ Ting Wua, Katsutoshi Idoa, Makoto Ohgoha, Takahisa Hanadab, a Neurology Tsukuba Research Department, Discovery, Medicine Creation, Neurology Business Group, Eisai Co., Ltd. Japan b Clinical Science Department, Medical Division, Eisai Co., Ltd. Nishigokencho 13-1, Shinjuku-ku, Tokyo 162-0812, Japan ARTICLE INFO ABSTRACT Keywords: Purpose: A number of antiepileptic drugs (AEDs) with a variety of modes of action, are effective in treating focal AMPA receptor antagonist seizures. Several AEDs, such as perampanel (PER), levetiracetam (LEV), lacosamide (LCM), lamotrigine (LTG), Antiepileptic drug and carbamazepine (CBZ), have been shown to elevate the seizure threshold in kindling models. These AEDs are Mode of seizure inhibition clinically effective, but differences exist in the anti-seizure profiles of drugs with similar modes ofaction. Focal seizure Therefore, we hypothesized that there are differences in how these AEDs affect seizures. Here, we evaluated the Perampanel effects of AEDs on various seizure parameters in a rat amygdala kindling model upon stimulation attheafter- Synaptic transmission discharge threshold (ADT) and at three-times the ADT (3xADT) to characterize the differences in the effects of these AEDs. Methods: PER, LEV, LCM, LTG, CBZ, or vehicle was administered intraperitoneally to fully kindled rats. Changes in Racine seizure score, after-discharge duration (ADD), and latency to Racine score 4 generalized seizure (S4L) were measured to assess differences in the modes of seizure inhibition among the AEDs.
    [Show full text]
  • Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva
    REVIEW ARTICLE Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva Philip N. Patsalos, FRCPath, PhD*† and Dave J. Berry, FRCPath, PhD† INTRODUCTION Abstract: Blood (serum/plasma) antiepileptic drug (AED) therapeu- Measuring antiepileptic drugs (AEDs) in serum or tic drug monitoring (TDM) has proven to be an invaluable surrogate plasma as an aid to personalizing drug therapy is now a well- marker for individualizing and optimizing the drug management of established practice in the treatment of epilepsy, and guidelines patients with epilepsy. Since 1989, there has been an exponential are published that indicate the particular features of epilepsy and increase in AEDs with 23 currently licensed for clinical use, and the properties of AEDs that make the practice so beneficial.1 recently, there has been renewed and extensive interest in the use of The goal of AED therapeutic drug monitoring (TDM) is to saliva as an alternative matrix for AED TDM. The advantages of saliva ’ fl optimize a patient s clinical outcome by supporting the man- include the fact that for many AEDs it re ects the free (pharmacolog- agement of their medication regimen with the assistance of ically active) concentration in serum; it is readily sampled, can be measured drug concentrations/levels. The reason why TDM sampled repetitively, and sampling is noninvasive; does not require the has emerged as an important adjunct to treatment with the expertise of a phlebotomist; and is preferred by many patients, AEDs arises from the fact that for an individual patient
    [Show full text]
  • Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review
    Current Pain and Headache Reports (2019) 23: 37 https://doi.org/10.1007/s11916-019-0774-0 OTHER PAIN (A KAYE AND N VADIVELU, SECTION EDITORS) Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review Omar Viswanath1,2,3 & Ivan Urits4 & Mark R. Jones4 & Jacqueline M. Peck5 & Justin Kochanski6 & Morgan Hasegawa6 & Best Anyama7 & Alan D. Kaye7 Published online: 1 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. Recent Findings Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Summary Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain. Keywords Neuropathic pain . Chronic pain . Ion Channel blockers . Anticonvulsants . Membrane stabilizers Introduction Neuropathic pain, which is a result of nervous system injury or lives of patients who are affected. Frequently, it is difficult to dysfunction, is often debilitating, severely limiting the daily manage and as a result leads to the progression of a chronic condition that is, in many instances, refractory to medical This article is part of the Topical Collection on Other Pain management.
    [Show full text]
  • Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats
    [Downloaded free from http://www.amhsr.org] Original Article Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats Goyal S, Singla S, Kumar D, Menaria G Department of Pharmacology, Pacific College of Pharmacy, Pacific University, Udaipur, Rajasthan, India Address for correspondence: Dr. Sachin Goyal, Abstract Department of Pharmacology, Background: Evidence has been generated that various anticonvulsant agents provide relief Pacific College of Pharmacy, Pacific University, of several chronic pain syndromes and therefore as an alternative to opioids, nonsteroidal Udaipur ‑ 313 024, Rajasthan, India. anti‑inflammatory, and tricyclic antidepressant drugs in the treatment of neuropathic pain. The E‑mail: [email protected] results of these studies thus raise the question of whether all anticonvulsant drugs or particular mechanistic classes may be efficacious in the treatment of neuropathic pain syndromes. Aim: The aim was to compare the clinically used anticonvulsant drugs which are differ in their mechanism of action in a chronic pain model, the chronic constriction injury, in order to determine if all anticonvulsants or only particular mechanistic classes of anticonvulsants are analgesic. Materials and Methods: The study included zonisamide, ethosuximide and pregabalin. All compounds were anticonvulsant with diverse mechanism of actions. The peripheral neuropathic pain was induced by chronic constriction injury of the sciatic nerve in male Sprague‑Dawley rats. Zonisamide (80 and 40 mg/kg), ethosuximide (300 and 100 mg/kg), pregabalin (50 and 20 mg/kg), and saline was administered intraperitoneally in respective groups in a blinded, randomized manner from postoperative day (POD) 7‑13. Paw withdrawal duration to spontaneous pain, chemical allodynia and mechanical hyperalgesia and paw withdrawal latency to mechanical allodynia and thermal hyperalgesia were tested before drug administration on POD7 and after administration on POD 7, 9, 11 and 13.
    [Show full text]
  • Current Status of Antiepileptic Drugs As Preventive Migraine Therapy Simy K
    Curr Treat Options Neurol (2019) 21: 16 DOI 10.1007/s11940-019-0558-1 Headache (JR Couch, Section Editor) Current Status of Antiepileptic Drugs as Preventive Migraine Therapy Simy K. Parikh, MD Stephen D. Silberstein, MD* Address *Jefferson Headache Center, Thomas Jefferson University, Suite 200, Philadel- phia, PA, 19107, USA Email: [email protected] Published online: 18 March 2019 * Springer Science+Business Media, LLC, part of Springer Nature 2019 This article is part of the Topical Collection on Headache Keywords Migraine I Headache I Preventive therapy I Pharmacology I Antiepileptic drugs I Anticonvulsants Abstract Background Antiepileptic drugs (AEDs) are an important class of agents used in the treatment of migraine, a neurological disorder that imparts significant socioeconomic burden. It is important for neurologists to understand the rationale for AEDs in migraine- preventive treatment, as well as each agent’s efficacy and tolerability profile, in order to best determine clinical care. Purpose of this review This article specifically provides the following: (1) a review of the mechanism of action, efficacy, and tolerability of topiramate and divalproex sodium/ sodium valproate, the most widely used AEDs for migraine prevention, (2) a discussion on emerging evidence regarding the efficacy of zonisamide and levetiracetam, and (3) comments on gabapentin, pregabalin, carbamazepine, oxcarbazepine, and lamotrigine, AEDs which have insufficient evidence for use in migraine prevention. Recent findings The potential role for new extended-release formulations of topiramate in migraine prevention is discussed. Summary There is substantial evidence supporting the use of AEDs in migraine prevention. Specific agents should be chosen based on their efficacy and tolerability profiles.
    [Show full text]
  • UNDERSTANDING PHARMACOLOGY of ANTIEPILEPTIC DRUGS: Content
    UNDERSTANDING PHARMACOLOGY OF ANTIEPILEPTIC DRUGS: PK/PD, SIDE EFFECTS, DRUG INTERACTION THANARAT SUANSANAE, BPharm, BCPP, BCGP Assistance Professor of Clinical Pharmacy Faculty of Pharmacy, Mahidol University Content Mechanism of action Pharmacokinetic Adverse effects Drug interaction 1 Epileptogenesis Neuronal Network Synaptic Transmission Stafstrom CE. Pediatr Rev 1998;19:342‐51. 2 Two opposing signaling pathways for modulating GABAA receptor positioning and thus the excitatory/inhibitory balance within the brain Bannai H, et al. Cell Rep 2015. doi: 10.1016/j.celrep.2015.12.002 Introduction of AEDs in the World (US FDA Registration) Mechanism of action Pharmacokinetic properties Adverse effects Potential to develop drug interaction Formulation and administration Rudzinski LA, et al. J Investig Med 2016;64:1087‐101. 3 Importance of PK/PD of AEDs in Clinical Practice Spectrum of actions Match with seizure type Combination regimen Dosage regimen Absorption Distribution Metabolism Elimination Drug interactions ADR (contraindications, cautions) Mechanisms of Neuronal Excitability Voltage sensitive Na+ channels Voltage sensitive Ca2+ channels Voltage sensitive K+ channel Receptor‐ion channel complex Excitatory amino acid receptor‐cation channel complexes • Glutamate • Aspartate GABA‐Cl‐ channel complex 4 Mechanism of action of clinically approved anti‐seizure drugs Loscher W, et al. CNS Drugs 2016;30:1055‐77. Summarize Mechanisms of Action of AEDs AED Inhibition of Increase in Affinity to Blockade of Blockade of Activation of Other glutamate GABA level GABAA sodium calcium potassium excitation receptor channels channels channels Benzodiazepines + Brivaracetam + + Carbamazepine + + (L) Eslicarbazepine + Ethosuximide + (T) Felbamate +(NMDA) + + + + (L) + Gabapentin + (N, P/Q) Ganaxolone + Lacosamide + Lamotrigine + + + + (N, P/Q, R, T) + inh. GSK3 Levetiracetam + + (N) SV2A, inh.
    [Show full text]