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Pharmacology
Systemic Pharmacotherapeutics of the Nervous System
Anticonvulsants
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Chapters in Pharmacology
  • Pharmacology Introduction
  • Systemic Pharmacotherapeutics of the Cardiovascular System
  • Systemic Pharmacotherapeutics of the Digestive System
  • Systemic Pharmacotherapeutics of the Eye
  • Systemic Pharmacotherapeutics of the Integumentary System
  • Systemic Pharmacotherapeutics of the Muscular System
  • Systemic Pharmacotherapeutics of the Nervous System
  • Systemic Pharmacotherapeutics of the Reproductive System
  • Systemic Pharmacotherapeutics of the Respiratory System
  • Systemic Pharmacotherapeutics of the Urinary System
  • Chemotherapeutics Introduction
  • Anthelmintics
  • Antibacterial Agents
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Topics in Systemic Pharmacotherapeutics of the Nervous System
  • Overview of Systemic Pharmacotherapeutics of the Nervous System
  • Anticonvulsants
  • Anticonvulsants Used to Stop Ongoing Seizure Activity
  • Maintenance Anticonvulsant Therapy
  • Tranquilizers, Sedatives, and Analgesics
  • Psychotropic Agents
     
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    Anticonvulsants

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    Anticonvulsants are used to stop an ongoing seizure or to decrease the frequency or severity of anticipated future seizures. During a seizure episode or status epilepticus, the route of administration for anticonvulsants is IV (see Systemic Pharmacotherapeutics of the Nervous System: Drugs Used for Treatment of Status EpilepticusTables). For longterm maintenance, the oral route is preferred, although absorption may be limited or variable depending on the drug used (see Systemic Pharmacotherapeutics of the Nervous System: Anticonvulsant DrugsTables). SC or IM injections are seldom used because of the variability in drug absorption.

    Table 1

    PrintOpen table in new window Open table in new window
    Drugs Used for Treatment of Status Epilepticus

    Drug

    Species and Dosage

    Diazepam

    Dogs, cats 0.5–2.0 mg/kg, IV bolus; can be repeated 2–3 times at intervals of 5–10 min; CRIa 0.5–2.0 mg/kg/hr

    Foals: 0.05–0.4 mg/kg, IV slowly

    Adult horses: 25–50 mg/horse, IV

    Ruminants: 0.5–1.5 mg/kg, IV or IM

    Phenobarbital

    Dogs, cats: 2–4 mg/kg/ IV bolus; can be repeated at 20- to 30-min intervals until a total dosage of 20 mg/kg is reached; CRI 3–10 mg/hr to effect

    Foals, adult horses: loading dose of 12–20 mg/kg, IV over 20 min, then 6.65–9 mg/kg, IV over 20 min every 8–12hr

    Sodium pentobarbital

    Dogs, cats: 2–15 mg/kg, IV, to effect to stop motor activity

    Foals, adult horses: 2–4 mg/kg, IV to effect

    Propofol

    Dogs, cats: 2.5–4.0 mg/kg, IV, to effect to stop motor activity; CRI: 0.1–0.3 mg/kg/min to effect

    Phenytoin

    Dogs 2–5 mg/kg as slow IV infusion

    Foals, adult horses: 5–10 mg/kg, IV followed by 1–5 mg/kg, IV, IM, or PO every 2–4 hr until seizures stop and maintenance dose started

    a CRI: constant rate infusion

    Drugs Used for Treatment of Status Epilepticus

    Drug

    Species and Dosage

    Diazepam

    Dogs, cats 0.5–2.0 mg/kg, IV bolus; can be repeated 2–3 times at intervals of 5–10 min; CRIa 0.5–2.0 mg/kg/hr

    Foals: 0.05–0.4 mg/kg, IV slowly

    Adult horses: 25–50 mg/horse, IV

    Ruminants: 0.5–1.5 mg/kg, IV or IM

    Phenobarbital

    Dogs, cats: 2–4 mg/kg/ IV bolus; can be repeated at 20- to 30-min intervals until a total dosage of 20 mg/kg is reached; CRI 3–10 mg/hr to effect

    Foals, adult horses: loading dose of 12–20 mg/kg, IV over 20 min, then 6.65–9 mg/kg, IV over 20 min every 8–12hr

    Sodium pentobarbital

    Dogs, cats: 2–15 mg/kg, IV, to effect to stop motor activity

    Foals, adult horses: 2–4 mg/kg, IV to effect

    Propofol

    Dogs, cats: 2.5–4.0 mg/kg, IV, to effect to stop motor activity; CRI: 0.1–0.3 mg/kg/min to effect

    Phenytoin

    Dogs 2–5 mg/kg as slow IV infusion

    Foals, adult horses: 5–10 mg/kg, IV followed by 1–5 mg/kg, IV, IM, or PO every 2–4 hr until seizures stop and maintenance dose started

    a CRI: constant rate infusion

    Table 2

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    Anticonvulsant Drugs

    Anticonvulsant Drug

    Dosage and Frequency

    Half-life

    Time to Steady State

    Therapeutic Level

    Adverse Effects/Comments

    First-Line Maintenance Anticonvulsant Drugs

    Phenobarbital

    Adjust dosage in all species by monitoring serum levels and seizure diary.

    Dogs: 2–4 mg/kg, PO, bid (starting dose); up to 10 mg/kg, bid

    40–90 hr (Beagles 25–38 hr)

    10–24 days

    15–45 μg/mL (66–200 μmol/L), preferably keep values within 20–35 μg/mL (85–150 μmol/L)

    Sedation, polydipsia, induces P450 system, increase in liver enzymes; liver failure is uncommon.

    Cats: 2–4 mg/kg, PO, bid (starting dose)

    34–43 hr

    10–30 μg/mL

    Liver enzymes do not typically increase in cats.

    Horses: 3–5 mg/kg, PO, sid as a starting dose; up to 11 mg/kg, PO, sid

    18 hr

    10–40 μg/ml (43–175 μmol/L)

    Foals: As above

    13 hr

    Ruminants: 11 mg/kg, PO sid

    Bromide (potassium salt)

    Dogs, cats: 20–40 mg/kg, PO, sid or divided bid if GI upset.

    Dogs: loading dose 400–600 mg/kg, PO divided into 4 doses, given over 1–4 days

    Horses: 90 mg/kg/day, PO

    Dogs: 20–46 days

    Cats: 10 days

    Horses: 5 days

    Dogs: 100–200 days

    Cats: 6 wk

    Bromide alone: 1–3 mg/mL (15–20 μmol/L)

    Bromide/phenobarbital combined: 1–2 mg/mL

    Sedation, weakness, polydipsia, vomiting, polyphagia, skin rash. Reduce dose with renal insufficiency. High chloride intake increases bromide elimination. Chloride content of diet should be stable. Use with extreme caution in cats and monitor with thoracic radiographs because bronchial/asthmatic signs may be fatal in cats.

    Bromide (sodium salt)

    17–30 mg/kg, PO, sid or divided bid if GI upset. The dose of sodium bromide is less than that of potassium bromide to account for the higher bromide content.

    See potassium bromide notes.

    Diazepam

    Dogs: 0.5–2 mg/kg per rectum at onset of seizure; repeat up to 3 times in 24 hr

    Cats: 0.25-0.5 mg/kg, PO, bid-tid

    Dogs: 2.5–3.2 hr

    Cats: 5.5 hr

    Horses: 7–22 hr

    While oral diazepam is not effective in dogs, rectal administration can be used to stop cluster seizures or status epilepticus. Oral diazepam can be used in cats as a maintenance drug; sedation, liver failure are potential problems in cats.

    Second-Line (Add-on) Anticonvulsant Drugs

    Clonazepam

    Dogs: 0.1–0.5 mg/kg, PO, bid-tid

    1.5–3 hr

    22–77 ng/mL

    Extremely potent benzodiazepine; sedation, withdrawal signs if drug stopped abruptly.

    Clorazepate

    Dogs: 2–6 mg/kg, PO, bid-tid

    5–6 hr

    1–2 days

    20–75 μg/L

    15 times less potent than clonazepam; sedation, withdrawal seizures.

    Felbamate

    Dogs: 15 mg/kg, PO, tid; increase by 15 mg/kg biweekly until seizures controlled; maximal (toxic) dosage 300 mg/kg

    5–6 hr

    1 day

    125–250 μmol/La

    Blood dyscrasia; induces P450 system, liver disease. Use with care with other potentially hepatotoxic drugs.

    Gabapentin

    Dogs: 10 mg/kg, PO, tid; up to 30–60 mg/kg, tid

    3–4 hr

    <24 hr

    4–16 mg/La (70–120 μmol/L)

    Sedation, dizziness, ataxia, fatigue, diarrhea; reduce dose with renal dysfunction.

    Levetiracetam

    Dogs: 20 mg/kg, PO, tid

    4–10 hr

    2–3 days

    35–120 μmol/La

    Restlessness, vomiting, ataxia at dosages >400 mg/kg/day.

    Topiramate

    Dogs: 5–10 mg/kg/day, PO, bid

    2–4 hr

    3–5 days

    2–25 mg/L (15–60 μmol/L)a

    GI upset, irritability

    Valproic acid

    Dogs: 10–60 mg/kg, PO, tid

    90–120 min

    <24 hr

    Probably ineffective due to very short half-life; liver toxicity and pancreatitis.

    Zonisamide

    Dogs: 4–8 mg/kg/day, PO, divided; up to 10 mg/kg, bida

    15–20 hr

    3–4 days

    10–40 mg/L (45–180 μmol/L)

    Sedation, ataxia, loss of appetite

    a Therapeutic range established for humans

    Anticonvulsant Drugs

    Anticonvulsant Drug

    Dosage and Frequency

    Half-life

    Time to Steady State

    Therapeutic Level

    Adverse Effects/Comments

    First-Line Maintenance Anticonvulsant Drugs

    Phenobarbital

    Adjust dosage in all species by monitoring serum levels and seizure diary.

    Dogs: 2–4 mg/kg, PO, bid (starting dose); up to 10 mg/kg, bid

    40–90 hr (Beagles 25–38 hr)

    10–24 days

    15–45 μg/mL (66–200 μmol/L), preferably keep values within 20–35 μg/mL (85–150 μmol/L)

    Sedation, polydipsia, induces P450 system, increase in liver enzymes; liver failure is uncommon.

    Cats: 2–4 mg/kg, PO, bid (starting dose)

    34–43 hr

    10–30 μg/mL

    Liver enzymes do not typically increase in cats.

    Horses: 3–5 mg/kg, PO, sid as a starting dose; up to 11 mg/kg, PO, sid

    18 hr

    10–40 μg/ml (43–175 μmol/L)

    Foals: As above

    13 hr

    Ruminants: 11 mg/kg, PO sid

    Bromide (potassium salt)

    Dogs, cats: 20–40 mg/kg, PO, sid or divided bid if GI upset.

    Dogs: loading dose 400–600 mg/kg, PO divided into 4 doses, given over 1–4 days

    Horses: 90 mg/kg/day, PO

    Dogs: 20–46 days

    Cats: 10 days

    Horses: 5 days

    Dogs: 100–200 days

    Cats: 6 wk

    Bromide alone: 1–3 mg/mL (15–20 μmol/L)

    Bromide/phenobarbital combined: 1–2 mg/mL

    Sedation, weakness, polydipsia, vomiting, polyphagia, skin rash. Reduce dose with renal insufficiency. High chloride intake increases bromide elimination. Chloride content of diet should be stable. Use with extreme caution in cats and monitor with thoracic radiographs because bronchial/asthmatic signs may be fatal in cats.

    Bromide (sodium salt)

    17–30 mg/kg, PO, sid or divided bid if GI upset. The dose of sodium bromide is less than that of potassium bromide to account for the higher bromide content.

    See potassium bromide notes.

    Diazepam

    Dogs: 0.5–2 mg/kg per rectum at onset of seizure; repeat up to 3 times in 24 hr

    Cats: 0.25-0.5 mg/kg, PO, bid-tid

    Dogs: 2.5–3.2 hr

    Cats: 5.5 hr

    Horses: 7–22 hr

    While oral diazepam is not effective in dogs, rectal administration can be used to stop cluster seizures or status epilepticus. Oral diazepam can be used in cats as a maintenance drug; sedation, liver failure are potential problems in cats.

    Second-Line (Add-on) Anticonvulsant Drugs

    Clonazepam

    Dogs: 0.1–0.5 mg/kg, PO, bid-tid

    1.5–3 hr

    22–77 ng/mL

    Extremely potent benzodiazepine; sedation, withdrawal signs if drug stopped abruptly.

    Clorazepate

    Dogs: 2–6 mg/kg, PO, bid-tid

    5–6 hr

    1–2 days

    20–75 μg/L

    15 times less potent than clonazepam; sedation, withdrawal seizures.

    Felbamate

    Dogs: 15 mg/kg, PO, tid; increase by 15 mg/kg biweekly until seizures controlled; maximal (toxic) dosage 300 mg/kg

    5–6 hr

    1 day

    125–250 μmol/La

    Blood dyscrasia; induces P450 system, liver disease. Use with care with other potentially hepatotoxic drugs.

    Gabapentin

    Dogs: 10 mg/kg, PO, tid; up to 30–60 mg/kg, tid

    3–4 hr

    <24 hr

    4–16 mg/La (70–120 μmol/L)

    Sedation, dizziness, ataxia, fatigue, diarrhea; reduce dose with renal dysfunction.

    Levetiracetam

    Dogs: 20 mg/kg, PO, tid

    4–10 hr

    2–3 days

    35–120 μmol/La

    Restlessness, vomiting, ataxia at dosages >400 mg/kg/day.

    Topiramate

    Dogs: 5–10 mg/kg/day, PO, bid

    2–4 hr

    3–5 days

    2–25 mg/L (15–60 μmol/L)a

    GI upset, irritability

    Valproic acid

    Dogs: 10–60 mg/kg, PO, tid

    90–120 min

    <24 hr

    Probably ineffective due to very short half-life; liver toxicity and pancreatitis.

    Zonisamide

    Dogs: 4–8 mg/kg/day, PO, divided; up to 10 mg/kg, bida

    15–20 hr

    3–4 days

    10–40 mg/L (45–180 μmol/L)

    Sedation, ataxia, loss of appetite

    a Therapeutic range established for humans

    Last full review/revision March 2012 by Linda Shell, DVM, DACVIM-Neurology

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