Anticonvulsants Flashcards
Levetiracetam
Anticonvulsant; affects release of neurotransmitters in the CNS by binding to the presynaptic protein SV2A on synaptic vesicles, and it may prevent hypersynchronization of epileptiform burst-firing and propagation of seizure activity; does not affect normal neuronal excitability
Injectable forms are useful for status epilepticus; may be used as adjunct therapy for canine epilepsy
Has been used to treat seizures caused by 5-FU neurotoxicosis
in cats - may be more effective than phenobarbital for myoclonic seizures
May have reduced efficacy in dogs over time
AE: sedation, ataxia in dogs; reduced appetite, ataxia, hypersalivation, lethargy in cats; may be transient; changes in behavior and GI effects can occur
Bromides
Anti seizure activity from generalized depressant effects on neuronal excitability and activity; bromide ions compete with chloride for transport access across cell membranes resulting in membrane hyperpolarization, raising seizure threshold and limiting spread of epileptic discharges
NO IV administration ofr potassium bromide - potentially fatal cardiotoxicity; sodium bromide can be given IV if necessary
AE: sedation, polyphagia, PU/PD, ataxia, hyperactivity, vomiting, increased ALP/ALT; less common - GI, aggression, tetraparesis, skin conditions (pustular dermatitis, ulcerative neutrophilic dermatitis, nodular panniculitis, white macules with scales), euthyroid sick syndrome, anisocoria, hepatotoxicity, pancreatitis, repetitive myoclonus, neuromyopathy, hyperchloremia; persistent cough in dogs
Cats - high incidence of adverse pulmonary effects - use rarely recommended; peribronchial infiltrates, can be fatal, but are reversible once d/c’d
changes in sodium intake and/or administration of sodium chloride containing IV fluids may decrease efficacy OR increase risk for toxicity
Dosages for sodium bromide are not the same as potassium bromide
Clonazepam
Benzodiazepine; depresses CNS subcortical levels (primarily limbic, thalamic, hypothalamic); exact mechanism unknown, but it may antagonize serotonin and/or facilitate GABA activity, and diminished release or turnover of acetylcholine in the CNS; receptors are lacking in white matter
contraindicated with narrow angle glaucoma, significant liver disease; may exacerbate myasthenia gravis; use with caution with those with renal impairment, use cautiously in aggressive patients
adjunct therapy for short term treatment of epilepsy in dogs and long term adjunctive treatment in cats; may also act as anxiolytic
tolerance has been reported, tablets may contain xylitol; taper off when treated chronically as abrupt discontinuation could result in status epilepticus or GI signs
AE: sedation and ataxia may occur; acute hepatic necrosis has been documented when given orally to cats; limited information on AE profile; humans - sedation, hypotonia, ataxia, increased salivation, hypersecretion in upper respiratory, GI, transient liver value elevation, hematologic effects
Clorazepate
Benzodiazepine as anxiolytic, sedative-hypnotic, anticonvulsant
The subcortical levels (primarily limbic, thalamic, and hypothalamic) of the CNS are depressed by clorazepate and other benzodiazepines, thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is unknown, but postulated mechanisms include antagonism of serotonin, increased release of and/or facilitation of γ-aminobutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS.
Contraindication: closed angle glaucoma, significant liver disease; use with caution in aggressive animals
Most prevalent AE is sedation and ataxia
Diazepam
Benzodiazepine used as anxiolytic, muscle relaxant, sedative, anti convulsant, anesthetic adjunct, behavior modifier
depresses CNS subcortical levels (primarily limbic, thalamic, hypothalamic); exact mechanism unknown, but it may antagonize serotonin and/or facilitate GABA activity, and diminished release or turnover of acetylcholine in the CNS; receptors are lacking in white matter
Contraindications: liver disease (especially in cats), cats exposed to chlorpyrifos; oral use should be avoided in cats; caution with renal and hepatic disease, aggressive behavior, debilitated, geriatric patients, those with significant respiratory depression, may be teratogenic; withdraw slowly with chronic dosing
AE: sedation, ataxia; dogs - CNS excitement, increased appetite; cats - hepatic failure with PO or behavior changes; rapid IV administration - hypotension, phlebitis if not flushed with fluids
slow biotransformation and inhibition of the efflux of bile, resulting in accumulation of bile acids in hepatocytes might contribute to feline hepatic liver injury after repeated doses
reversal: flumazenil
Felbamate
Second or third line antiepileptic medication for dogs
Anticonvulsant activity thought to be due to ability to reduce excitatory neurotransmission; believed to increase activation of sodium channels, thereby decreasing sustained high frequency firing of action potentials
use with caution in hepatic disease and those with blood dyscrasias
AE: KCS, liver enzyme induction, tremors, limb rigidity, salivation, restlessness, agitation, blood dyscrasias
Gabapentin
Anticonvulsant, anxiolytic, neuropathic pain analgesic
NOT a GABA agonist
Gabapentin binds to presynaptic alpha2delta subunits of voltage gated calcium channels which decrease calcium influx, inhibiting release of excitatory neurotransmitters (substance P, glutamate, Norep). for chronic pain - analgesic efffects may be mediated by voltage gated calcium channel induced modulation of noradrenergic transmission; can prevent allodynia and hyperalgesia
may be useful as adjunctive therapy for refractory complex partial seizures and chronic pain; ineffective for acute pain; beneficial for reducing fear responses associated with transportation, handling, examination, storm phobia
Use in caution with renal patients
avoid xylitol containing oral liquid in dogs
AE: sedation, ataxia; cats - hypersalivation, vomiting
Phenobarbital
Long acting Barbituate; used primarily as an antiseizure medication
prolong opening time of chloride ion channels in postsynaptic neuronal membranes, causing membrane hyperpolarization and impairing nerve impulse propagation; decreases intraneuronal sodium concentration, inhibits calcium influx into depolarized synaptosomes, raises brain serotonin levels, inhibits noradrenaline reuptake into synaptosomes; also exhibits GABA like effects and reversibly depresses activity of all excitable tissue
contraindications: severe cardiac, hepatic, renal disease; caution with hypovolemia, anemia, borderline hypoadrenal function, severe respiratory disease
AE: anxiety/agitation, lethargy, profound depression, ataxia, sedation, PU/PD, polyphagia, increase in ALP and ALT (more so in ALP); anemia, thrombocytopenia, pancytopenia - reversible once phenobarbital is d/c’d; increased triglycerides, increased pancreatic lipase; can alter thyroid function; superficial necrolytic dermatitis associated with changes in hepatocytes has been reported
May increase metabolism of cortisol and has been implicated in contributing to relative adrenal insufficiency; pseudolymphoma has been described in 1 dog and 2 cats
Cats are more sensitive to respiratory depression; additional AEs - facial pruritis, anorexia, pancytopenia, presumed case of pheno induced fever, high doses have resulted in coagulopathies in cats; rarely causes increase in liver enzymes in cats
Barbiturates relax skeletal muscle
Slow IV, severe irritation perivascularly
Topiramate
Exact mechanism unknown, blocks action potentials elicited repetitively by a sustained depolarization of neurons, it increases frequency that GABA activates GABAa receptors, and it antagonizes the kainite/AMPA receptors without affecting the NMDA receptor subtype; concentration dependent
weak inhibitor of carbonic anhydrase isoenzymes CAII and CAIV
May be useful for refractory seizures, particularly for partial seizure activity; may be of benefit in cats, but little info
Adverse effects may include GI distress, sedation, ataxia, inappetence, weight loss, and irritability in dogs; in cats, sedation and inappetence have been noted, a case of renal tubular acidosis was seen in a cat.; limited reports
Zonisamide
Add on oral drug for refractory epilepsy
Postulated to produce anti seizure activity at sodium and T type calcium channels which reduces transient inward currents and stabilizes neuronal membranes and suppresses neuronal hypersynchonization; may potentiate serotoninergic and dopaminergic neurotransmission but does not appear to potentiate GABA; has carbonic anhydrase inhibitory activity and can scavenge free radicals in the brain
Contraindicated if hypersensitivity to sulfonamides; Can be given once daily in cats
Known teratogen in dogs
AE: inappetence, sedation, ataxia, vomiting, rare - hepatopathy (even rarer to be life threatening), urinary calculi, metabolic and acute tubular acidosis, pseudolymphoma, febrile neutropenia, erythema multiforme, IMPA, anterior uveitis, abnormal behavior
Decreases total T4 levels
Zonisamide related hypersensitivity syndrome in a cat has been reported
Pregabalin
Anticonvulsant, neuropathic pain agent; approved for use in cats for alleviation of acute anxiety and fear associated with transportation and vet visits
structural analogue of the inhibitor neurotransmitter GABA. binds to CaVa2-d (alpha2delta subunit of voltage gated calcium channels), decreasing calcium influx and inhibiting the release of excitatory neurotransmitters
Use in caution with renal insufficiency
as an analgesic, pregabalin is 5 times more potent than gabapentin
AE: increased appetite, ataxia, sedation, weakness, disorientation, increased liver enzymes, reduced activity level; additional adverse effects in cats - emesis, proprioception abnormality, muscle tremors, anorexia, superficial dermatitis of the face reported in one cat
