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Antiepileptic Medications

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Antiepileptic Medications Antiepileptic Medications When to measure Peak levels and monitor Factors that affect Drug Dose MOA Metabolism Bioavailability Half Life Steady state Therapeutic range Other factors Side effects concentration absorption bloodwork Phenobarbital MAINTENANCE Dog: Barbituate - Increases 90% (absorbed 4-8 hours 7-20 days 15-35 mg/dL (don't Levels 2 weeks and 6 low protein diet may eliminate Collect blood in a non Common: Sedation (especially with hepatic (1/3 goes 32-89 hours 2.2-4.4 mg/kg PO q12h neuronal responsivity to within 2 hours) (Dog) 8-10 go above 35 mg/dL) weeks after starting or Pb more rapidly; alkalinizing serum separator tube; secondary brain disease), elevation in unchanged in (40-90 in (can be given IV) GABA; prolongs opening days (Cat) dose change and then the urine may result in hypertriglyceridemia liver enzmyes Rare: hepatotoxicity, urine) dog; 40-50 Cat:2.2-4.4 mg/kg PO of the chloride channel at every 6 months; general enhanced renal elimination; may falsely elevate Pb cytopenias, superficial necrolytic in cat) q12h (can be given IV ) GABA a receptor health panel every 6 drug is a potent inducer of measurements; will dermatitis, changes in thyroid tests, Some anti-glutamate hepatic enzyme LOADING: Dog months artifically lower T4 and facial pruritis (in cats) effects activity and can induce and cat 16-20 mg/kg IV increase TSH Inhibits calcium uptake toxicity more often at high or PO over 24 hours into neurons doses or when other potential hepatotoxic drugs are used Binds to synaptic vesicle Kidney (1/3 via 2.3-4 hours 5-45 ug/mL (human) Levels not Phenobaribal lowers the half Neuroprotective Rare: Sedation; at doses >400 Levetriacetam MAINTAINENCE: 20- 100% 2 hours 17 hours 40 protein A (SVA2) involved glomerular (dog); 3 (seldom performed recommended; general life to 1.5 hours, therefore use properties that may mg/kg/d see ataxia, vomiting, filtration) hours (cat) due to expense and health panel every 6 decrease seizure salivation, and restlessness mg/kg PO q8h (can be in modulation of NT higher dose or increased given IV, IM, and SQ); release, reuptake and high safety margin) months frequency in patients already induced brain good for use in recycling on phenobarbital damage; "anti-kindling emergency situation; effect"; Possible LOADING: 20-60 "honeymoon effect"; brivaracetam and mg/kg every 2-8 hours seletracetam are being evaluted in human medicine Levetriacetam Binds to synaptic vesicle 100% 3-7 hours 5 hours 28 hours Neuroprotective Rare: Sedation; at doses >400 20-30mg/kg PO q12h 5-45 ug/mL (human) Levels not Phenobaribal lowers the half Extended protein A (SVA2) involved Kidney (1/3 via (dog) properties that may mg/kg/d see ataxia, vomiting, (cannot break tablet); (seldom performed recommended; general life to 1.5 hours, therefore use Release in modulation of NT glomerular decrease seizure salivation, restlessness and "ghost some patients require filtration) due to expense and health panel every 6 higher dose in patients release, reuptake and induced brain damage; capsules" (patient's feces may contain q8h dosing high safety margin) months already on phenobarbital recycling "anti-kindling effect"; part of the outer capsule) Possible "honeymoon effect"; brivaracetam and seletracetam are being evaluted in human medicine Salt - Bromide ion thought minimal, not 60-100% - 15-45 days 80-120 days 100-300 mg/dL Levels at 4-6 weeks and IVF with non physiologic Bromide MAINTENANCE: 20-40 monitor levels q 6mo to Common: Nausea (give with food and to hyperpolarize neuronal protein bound; then 12 weeks after sodium content, Na in diet mg/kg PO q24h; DO prevent toxicity; BID), PU, PD, polyphagia, bromidism, membranes after excretion via starting or dose change (increased intake, increases NOT USE IN CATS; pseudo- pancreatitis, megaesophagus, traversing neuronal kidneys and then every 6 the rate of elimination) LOADING: 100mg/kg/d hypercholermia on pneumonitis in cats; Rare: behavioral chloride channels months; general health PO for 5 days laboratory testing changes (i.e. aggression), coughing (competes with chloride), panel every 6 months thereby raising seizure threshold; primarily at GABA receptors 5-10 mg/kg PO q12h Sulfonamide-like: hepatic 68% 3-4 hours 15-17 h 4-7 days 10-40 ug/mL (human); Levels not typically Do not use in Ataxia, lethargy, KCS, inappetance, Zonisamide phenobarbital decreases (dog); 10-20mg/kg PO blockade of T-type Ca+ metabolism via (dog); 34.5h check trough level performed, though Dobermans or other idiosyncractic hepatotoxicity serum concentration (start at q24h (cat) channels and voltage microsomal (cat) ACVIM consensus patients sensitive to 10mg/kg PO q12h if patient is gated Na+ channels, enzmyes (10% statement recommends sulfonamides on phenobarbital), enhancement of GABA, excreted level at 2 weeks after phenobarbital shortens the modulates other NTs; unchanged in starting and then every 6 half life and less bioavailable may provide kidneys) months; general health neuroprotective effects panel every 6 months 30-40% Gabapentin 20-30 mg/kg PO q8h blockade and preventing 80% 1 hour 3-4 hours 16.5-22 h 4-16 mg/mL (seldom Levels not None Good analgesic, not Ataxia and sedation metabolized by synaptogenesis of the performed due to recommended; general typically effective as liver and 60-70% alpha-2-delta subunit of expense and high health panel every 6 an anticonvulsant; no excreted the voltage gated T-type safety margin) months good studies in cats unchanged in the calcium channel kidney Pregabalin 2-4 mg/kg PO q8h; may blockade and preventing Unknown, likely 2.8-8.2 ug/mL (seldom Levels not Good analgesic - 6-7 hours 1.5 hours 33-40 h None Sedation (usually transient) be possible to dose synaptogenesis of the same to performed due to recommended; general medication; possible alpha-2-delta subunit of q12h; start at low end of gabapentin expense and high health panel every 6 anxiolytic dose and go up the voltage gated T-type safety margin) months calcium channel; decreases glutamate, NE and substance P Felbamate 30% hepatic 20-100 ug/mL (seldom Levels not Synergistic hepatotoxicity, EXPENSIVE; may offer At high doses: nervousness, - 3-7 hours 4-8 hours 20-30 h 15-20 mg/kg PO q8h enhances sodium metabolism; performed due to recommended; general especially if on other some protection of hyperexcitability, and decreased (can be increased in 15 channel inactivation, Excreted expense and high health panel every 6 potentially hepatotoxic drugs, neurons from appetite; Rare: blood dyscrasias, KCS, mg/kg increments q2 enhances GABA, and unchanged in the safety margin) months so monitor liver values/CBC ischemic or hypoxic hepatotoxicity, generalized tremors (in weeks up to 70mg/kg). reduces glutamate urine q6 month; can damage; toxic dose is small breed dogs) No information about excitation (via NMDA increase Pb levels (due to 300 mg/kg/day; dosing in cats receptors) P450) Flurofelbamate is being investigated in people and may be a less toxic option in the future May be more effective Topiramate Renal 30 minutes - 4 2-3.8 h 11-20 hours - Levels not recommended; None Sedation, ataxia, weight loss 2-10 mg/kg PO 8-12h. Sulphamate-substituted as a TID dose, due to hours general health panel monosaccaride. Enhaces short half life; May be Start at low dose and every 6 months titrate up as needed. No GABAergic activity and helpful as an add-on for information about inhibits voltage-gated refractory epileptics; dosing in cats sodium and calcium exteneded release version available in channels human medicine in liver to several Diazepam 0.5 mg/kg IV or IN; 1 Benzodiazepam enhance 90% 30 minutes - 2 2.5-3.2 14-16 h - N/A - ER use only None Can develop tolerance Idiosyncratic hepatopathy in cats; metabolites, mg/kg rectally the activity of GABA intravenously; hours in dogs contradictory CNS excitement glucuronic 50% rectally; conjugation, 80% intranasally highly protein bound Lorazepram Benzodiazepam enhance May be more effective 0.2 mg/kg IV (dog only) hepatic - - short - - N/A - ER use only None Sedation the activity of GABA than diazepam Midazolam 0.066-0.22 mg/kg IV, Benzodiazepam enhance hepatic, safer May be more effective - - short - - N/A - ER use only None Sedation IN, or IM the activity of GABA than diazepam than diazepam Levels not patients may develop a Chlorazepate Hepatic - - 3-6 hours 16.5-33 h - potential for hepatotoxicity initially 0.5-1 mg/kg Benzodiazepam enhance recommended; general Concurrent phenobarbital; tolerance; possible use (can go up to 2-4 health panel every 3-6 drug may increase Pb for at home use for the activity of GABA mg/kg) PO q12h months concentration after 1 month cluster patients Levels not Can be helpful in Clonazepam 0.5 mg/kg PO q12h Hepatic - - - - - - Benzodiazepam enhance recommended; general refractory seizures; Hepatotoxicity if used for more than a health panel every 3-6 mainly used in the activity of GABA few months months hypertonicity diseases Anticonconvulsants NOT recommended in dogs and cats, due to toxicity and/or short half life: Primidone, phenytoin (Dilantin), carbamazepine, valproic acid, ethosuximide, vigabatrin, lamotrigine, oxcarbazepine, triagabi ne Anticonconvulsants available in the EU for dogs and cats: Pexion (Imepitoin) .
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  • With LAMOTRIGINE IN
    were independent of seizure type. Cardiac abnormalities occurring in epilepsy with GTCS may potentially facilitate sudden cardiac death (SUDEP). ETHOSUXIMIDE, VALPROIC ACID, AND LAMOTRIGINE IN CHILDHOOD ABSENCE EPILEPSY Efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy were compared in a double-blind, randomized, controlled clinical trial performed at six centers in the US and organized as a Study Group. Drug doses were incrementally increased until freedom from seizures or highest tolerable dose was reached, Primary outcome was freedom from treatment failure after 16 weeks therapy, and secondary outcome was attentional dysfunction. In a total of 453 children, the freedom-from-failure rates after 16 weeks were similar for ethosuximide (53%) and valproic acid (58%), and higher than the rate for lamotrigine (29%) (P<0.001). Attentional dysfunction was more common with valproic acid (49%) than with ethosuximide (33%) (P=0.03). (Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med March 4 2010;362:790-799). (Reprints: Dr Tracy A Glauser, Cincinnati Children's Hospital, 3333 Burnett Ave, MLC 2015, Cincinnati, OH 45229. E- mail: [email protected]). COMMENT. "Older is better," is the conclusion of Vining EPG, in an editorial (N Engl J Med 2010;362:843-845). As generally accepted in US practice and confirmed by the above controlled trial, ethosuximide from the 1950s is the optimal initial therapy for childhood absence epilepsy without GTCS. Ethosuximide is equal to valproic acid in seizure control and superior in effects on attention.
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  • Pexion, Imepitoin
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  • Evaluation of Pexion® (Imepitoin) for Treatment of Storm Anxiety in Dogs: a Randomised, Double-Blind, Placebo-Controlled Trial
    Received: 20 July 2020 Revised: 7 October 2020 Accepted: 3 December 2020 DOI: 10.1002/vetr.18 ORIGINAL RESEARCH Evaluation of Pexion® (imepitoin) for treatment of storm anxiety in dogs: A randomised, double-blind, placebo-controlled trial Irina Perdew1 Carrie Emke1 Brianna Johnson1 Vaidehi Dixit2 Yukun Song2 Emily H. Griffith2 Philip Watson3 Margaret E. Gruen1 1 Department of Clinical Sciences, North Abstract Carolina State University College of Background: While often grouped with other noise aversions, fearful Veterinary Medicine, Raleigh, North Carolina, USA behaviour during storms is considered more complex than noise aversion 2 Department of Statistics, North Carolina alone. The objective here was to assess the effect of imepitoin for the treat- State University College of Sciences, Raleigh, ment of storm anxiety in dogs. North Carolina, USA Methods: In this double-blind, placebo-controlled randomised study, eligible 3 Ingelheim am Rhein, Boehringer-Ingelheim dogs completed a baseline then were randomised to receive either imepitoin Vetmedica GmbH, Ludwigshafen am Rhein, (n = 30; 30 mg/kg BID) or placebo (n = 15) for 28 days. During storms, owners Germany rated their dog’s intensity for 16 behaviours using a Likert scale. Weekly, own- Correspondence ers rated intensity and frequency of these behaviours. Summary scores were Margaret E. Gruen, Department of Clinical compared to baseline and between groups. Sciences, North Carolina State University Results and Conclusions: Imepitoin was significantly superior to placebo in College of Veterinary Medicine, 1060 William Moore Drive, Raleigh NC 27607, USA. storm logs and weekly surveys for weeks 2 and 4, and in the end-of-study sur- Email: [email protected] vey.
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  • Pentobarbital Sodium
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  • 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.
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  • Idiopathic Epilepsy in Dogs – Part One: Patient Approach
    Vet Times The website for the veterinary profession https://www.vettimes.co.uk Idiopathic epilepsy in dogs – part one: patient approach Author : Jacques Penderis, Holger Volk Categories : Vets Date : February 9, 2015 Dogs with recurrent epileptic seizures, and where no interictal neurological deficits or abnormalities on routine diagnostic tests are evident, have traditionally been defined as having “idiopathic epilepsy”. Rather than being a specific, single diagnosis, it is probable idiopathic epilepsy represents a complex interplay between genetic predisposition and intrinsic and extrinsic environmental factors, and the term “presumed genetic” has also been suggested to define these patients. A genetic basis for idiopathic epilepsy has been proposed in a number of breeds, including the golden retriever, Labrador retriever, Bernese mountain dog, Irish wolfhound, English springer spaniel, Keeshond, Hungarian vizsla, standard poodle, border collie and Finnish spitz (Viitmaa et al, 2013) and a possible susceptibility locus for epileptic seizures has been characterised in the Belgian shepherd dog (Seppälä et al, 2012). Reflecting its importance in veterinary medicine, idiopathic epilepsy is reported as the most common chronic neurological disease in dogs, with a prevalence of around 0.6 per cent in first opinion practice. Generalised seizures (where there is impairment of consciousness) are the most common type of epileptic seizure in dogs, while partial seizures appear to be relatively more common in cats; this, in part, represents the tendency for dogs with idiopathic epilepsy to have generalised seizures, or focal seizures with rapid secondary generalisation. The accurate description of generalised seizures in a patient with suspected idiopathic epilepsy is important, firstly to differentiate the episodes from other causes of collapse (for example, syncope) and secondly because the presence of generalised seizures is one of the criteria for making a diagnosis of idiopathic epilepsy.
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