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Pharmacology 1 choefsho > Antiepileptic drugs (AEDs) > Flashcards

Antiepileptic drugs (AEDs) Flashcards

1
Q

A clinical manifestation of abnormal electrical activity in the brain.

  1. Cluster seizures
  2. Status epilepticus (SE)
  3. Epilepsy
  4. Seizure (convulsion)
A
  1. Seizure (convulsion)
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2
Q

1 seizure lasting 5 minutes or longer.

  1. Cluster seizures
  2. Status epilepticus (SE)
  3. Epilepsy
  4. Seizure (convulsion)
A
  1. Status epilepticus (SE)
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3
Q

2 or more seizures over minutes to hours with full recovery of consciousness in-between.

  1. Cluster seizures
  2. Status epilepticus (SE)
  3. Epilepsy
  4. Seizure (convulsion)
A
  1. Cluster seizures
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4
Q

Seizures that occur intermittently over months to years.

  1. Cluster seizures
  2. Status epilepticus (SE)
  3. Epilepsy
  4. Seizure (convulsion)
A
  1. Epilepsy
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5
Q

2 or more discrete seizures without full recovery of consciousness in-between.

  1. Cluster seizures
  2. Status epilepticus (SE)
  3. Epilepsy
  4. Seizure (convulsion)
A
  1. Status epilepticus (SE)
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6
Q

T or F. An antiepileptic (anticonvulsant, antiseizure) drug is used to stop a seizure in progress and to prevent further seizures from occurring.

A

True

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7
Q

Antiepileptic drugs limit initialization of seizures or limit the spread of seizure focus. Which of the following is NOT a mechanism of action of most AEDs?

  1. Block voltage-gated inward positive currents: Na+ or Ca++
  2. Decrease inhibitory neurotransmitters: GABA
  3. Decrease excitatory neurotransmitters: glutamate
  4. Increase outward positive current: K+
  5. All of the above are correct
A
  1. Decrease inhibitory neurotransmitters: GABA
  • It INCREASES inhibitory NT GABA
  • All of these mechanisms will hyperpolarize the cell and make it less likely to initiate an action potential
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8
Q

What is the first line agent for stopping a seizure in progress?

  1. Benzodiazepines
  2. Phenobarbital
  3. Bromide
  4. Zonisamide
  5. Levetiracetam
A
  1. Benzodiazepines (Diazepam/Valium, Midazolam, Lorazepam)
  • Why? Because it has high lipophilicity and rapid brain penetration; the brain has lots of benzodiazepine receptor sites that are part of the GABA receptor complex.
  • Effective in wide variety of experimental seizure models: decreased duration of seizure discharge and limited spread of seizure discharge
  • Very fast, IV, give higher dose than you would for pre-med
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9
Q

What is the major inhibitory neurotransmitter in the CNS?

A

GABA! 2 types:

  • GABA-A: post-synaptic, linked to Cl- channel
  • GABA-B: pre-synaptic, mediated by K+ currents
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10
Q

What antiepileptic drug would you use to stop a seizure in progress in your clinic (EMERGENCY!)?

  1. Diazepam/Valium
  2. Midazolam
  3. Lorazepam
A
  1. Diazepam/Valium
  • IV
  • If you can’t hit the vein, give the same dose rectally (via teat cannula or rubber catheter) or intranasally (squirt into nares)
  • If the seizures continue, it is most likely status epilepticus now
    • Give Diazepam dose 3x and if seizures continue, follow SE protocol
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11
Q

What antiepileptic drug would you use to stop a seizure in progress at home on a dog that is a known epileptic with history of status epilepticus or cluster seizures (likely already on maintenance anitepileptic drugs)?

  1. Diazepam/Valium
  2. Midazolam
  3. Lorazepam
A
  1. Diazepam/Valium
  • Dispense Diazepam for owner to give to dog via rectum (teat cannula or rubber catheter)
    • Legalities must be considered (controlled substance IV)
    • Diazepam binds to plastic in most syringes; rate and amount of binding depends on time, temperature, light exposure, concentration, surface area, etc.; the amount of drug in solution gradually declines, so DON’T STORE DIAZEPAM IN A PLASTIC SYRINGE
    • Same dose as IV, but if a dog is already on maintenance phenobarbital, higher dose is used (2mg/kg)
    • Owner can give up to 3x within a 24 hour period
    • Suppositories, gell formulations available, but $$$
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12
Q

What antiepileptic drugs would you use to stop seizures on a patient with status epilepticus?

A
  • Diazepam CRI (if no response after 3 doses, use something else)
  • Mix with 5% dextrose or 0.9% saline; avoid LRS because calcium in LRS causes diazepam to precipitate
  • Lorazepam IV slowly q 4-6 hours (longer duration of action than diazepam)
  • Midazolam IV or IM or CRI (does not adhere to plastic)
  • Levetiracetam (Keppra) IV
  • Phenobarbital IV and repeated to effect up to maximum dose
  • Propofol IV 1/4th dose every 30 seconds until desired effect > can move to CRI; MUST INTUBATE!
  • Inhalation general anesthesia
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13
Q

What antiepileptic drugs would you use to prevent additional seizures from occurring on a patient with status epilepticus?

A
  • Begin maintenance antiepileptic drugs orally if dog is conscious (IV if not)
  • Choose maintenance AED that rapidly enters CNS and has a short half-life (oral zonisamide or levetiracetam) or one that can be ‘loaded’ (phenobarbital or levetiracetam)
    • Loading dose to acheive a therapeutic concentration in the body quickly
    • Phenobarbital loading dose IV and repeated effect up to maximum dose; slowly, diluted 1:1 in saline
    • Levetiracetam: IV bolus
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14
Q

When would you start giving an epileptic dog maintenance AEDs to reduce the frequency and severity of seizures?

A
  • Varies with patient, owner, history
  • Consideration starts after the 2nd or 3rd documented single seizure occurring within a 6-12 month period
  • Usually 3-4 seizures/year are enough to start, but we decide when based on interval between the seizures, how severe the seizures are, how easy/difficult it may be to medicate the patient
  • ANY status epilepticus case
  • After ANY cluster seizures in which cause is untreatable or not identified/preventable
  • After seizures that occur within one week of head injury
  • Old rule of thumb: more than 1 seizure per month
  • Be careful because syncopy (fainting) can look like a seizure!
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15
Q

You prescribe maintenance AEDs to your epileptic patient and the owner asks you how effective it will be, what is your answer?

A
  • Effective in about 33%
  • Some control in about 33%
  • Ineffective in the rest
    • We now have to start thinking about quality of life
    • Make sure to tell the owner that the goal of the drug is to reduce the frequency and severity while avoiding serious side effects and not completely curing it
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16
Q

What kind of pharmacokinetics do you have to consider when using antiepileptic drugs?

A
  • Bioavailability: How well absorbed is AED after oral dosing
  • How rapidly does it get into the CNS?
  • When do peak levels occur?
  • Half-life? Changes in half-life?
  • Will elimination half-life decrease over time?
  • How is it metabolized? Liver? Kidney?
  • Will changes in diet, weight, body composition alter the PK?
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17
Q

What do you have to consider before selecting an antiepileptic drug?

A
  • Species
    • Diazepam can be used in cats as maintenance AED (NOT ORALLY), but not in the dog because of very short half-life in dog
    • Bromide is used in dogs but about 1/3rd of cats on bromide develop asthma/pneumonitis; not worth the risk
  • Efficacy
  • Safety
  • Price and affordability for client
  • Pharmacological information
  • Client compliance: how often can clients give AED?
  • Interaction with other drugs, conditions
  • Your clinical experience
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18
Q

When prescribing maintenance AEDs to your patient, what kind of client/owner education should you discuss?

A
  • Goals of therapy: don’t expect ‘cure’; expect decrease in severity and/or frequency of seizures
  • Potential side effects
  • Client compliance: don’t skip doses! Missed doses can cause withdrawal seizures; if a barbiturate (phenobarbital) is used and a dose is missed, the patient can get barbiturate withdrawal seizures and status epilepticus can occur
  • Data log/diary/calendar of seizures is a must
  • Most animals on AEDs will require meds for life; dose adjustments or changes in drugs may be necessary as tolerance or side effects develop
  • Periodic (usually q 6-12 months) therapeutic drug monitoring (TDM) and bloodwork (CBC, chemistry)
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19
Q

Which of the following is not a commonly used antiepileptic drug in dogs and cats?

  1. Phenytoin
  2. Phenobarbital
  3. Bromide
  4. Zonisamide
  5. Levetiracetam
  6. Gabapentin
  7. Pregabalin
A
  1. Phenytoin; also, Felbamate, Valproate, and Primidone
    * MOST COMMON ARE PHENOBARBITAL, BROMIDE (not used in cats unless no other choice), ZONISAMIDE, AND LEVETIRACETAM
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20
Q

Which of the following AEDs is a long-acting (long half-life) barbiturate and is also a controlled drug?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital; DRUG OF CHOICE IN BOTH DOGS AND CATS
  • Potentiates GABA-A receptor activity
  • High efficacy; enters CNS readily
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21
Q

Which AED can be given orally twice a day?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital and 3. Zonisamide
  • Phenobarbital has variable oral absorption (does not work as rapidly); steady state in 10-14 days; IV loading dose for emergencies; elixirs available
  • Zonisamide requires double the dose BID if concurrently on phenobarbital; therapeutic range for humans is currently used
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22
Q

Which AED has high efficacy, but develops tolerance because it is an enzyme inducer?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital
  • Cytochrome P450 induction
  • Half-life can go from 100 hours in a dog to 24 hours with enzyme induction
  • Increase in alkaline phosphatase common
  • Interactions with other drugs
  • Zonisamide also develops tolerance
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23
Q

Which AED is the best choice for cats?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital
  • Long record of safety and efficacy
  • Can be loaded to achieve rapid blood levels
  • Also CHEAP!
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24
Q

Which AED can cause PUPD, sedation or hyperexcitability, hepatotoxicity, tolerance, and addiction?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital
  • Because it is a narcotic, there are rules and it can cause addiction (so can’t miss a dose!)
  • Chronic phenobarb users > fat dog
25
Q

What is the protocol for phenobarbital therapeutic monitoring?

A

On the basis of history of seizure control and serum level

  • If seizures are well controlled and dose is not excessive, check serum levels every 12 months in conjunction with hemogram and biochemistries
    • Some clinicians check serum levesl 2 weeks after starting if owner CAN afford it
    • Some clinicians check serum levels 2 weeks after any increase in dose
  • Do not use serum separator gell tubes: falsely lowers results
  • For routine monitoring, it probably doesn’t matter if you take sample during trough or peak because steady state should have been reached
  • For cases that are difficult to control, taking sample at trough tells you the lowest possible level of the drug (trough level: lowest concentration of a drug; an hour just before the next does)
26
Q

Which AED is a salt/chemical available as a powder from chemical suppliers which can be compounded into pills or liquid?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide; KBr more commonly used
    * MOA unknown; it raises seizure threshold by competing with Cl- transport across cell membranes resulting in membrane hyperpolarization
27
Q

Is potassium bromide used as the primary AED or as an add on?

A

Either

28
Q

Which AEDs are metabolized in the liver?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Phenobarbital and 3. Zonisamide
29
Q

Which AED has a long half-life (24 days) and is eliminated by the kidneys?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide
  • 4 months to get to steady state (check bloodwork at this time) > really long time!
  • Good for long term
  • Efficacy not as high as phenobarbital
  • Good for patients with hepatopathies
30
Q

Which AED, if not loaded, will take over 9 weeks before levels are high enough to prevent seizures?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide
  • May be better to add on to phenobarbital
  • Oral loading dose divided over 4 days, give with food or it can cause vomiting or sedation
  • Regular oral dose can be given once a day or divided
  • Serum concentrations can be measured to check bromide dosing, but chemistry can’t tell between chloride and bromide
    • Serum Cl- values may be reported as falsely high in dogs on bromide
31
Q

Dogs on what kind of diet require higher doses of bromide to maintain serum concentrations?

A

High salt diet because high Cl- intake increases Br loss in the urine and lowers serum Br concentrations

32
Q

Which AED causes asthma in cats and should be avoided?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide
33
Q

Which AED causes PUPD, sedation, pancreatitis, ataxia, rear limb weakness, and toxicosis?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide
  • Toxicosis (bromism) can cause blindness, paresis, altered behavior or coma, dysphagia, megaesophagus
    • Reduce/stop Br and use a diuretic (IV NaCl fluids, fuorsemide) > EMERGENCY!
34
Q

Which AED is a pyrrolidine derivative (amine that forms basis of many other compounds)?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam (Keppra)
    * MOA unknown; synaptic vesicle protein, GABA and glycine gate currents, voltage-dependent K+ currents
35
Q

Is Levetiracetam (Keppra) used as a primary AED or as an add-on to other AEDs?

A

Either

36
Q

Which AED is mostly excreted unchanged in the urine?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam (70-90% excreted unchanged, the remainder is hydrolyzed in serum and other tissues)
    * Not metabolized by liver
37
Q

T or F. Levetiracetam (Keppra) has a faster onset than phenobarbital and bromide.

A

True; half life is 3-4 hours in dogs, and 3 hours in cats

  • Compare to 100 hour half-life in phenobarbital and 24 day half-life in bromide
38
Q

Which AED rarely causes sedation, does NOT cause PUPD, but causes a decrease in appetite?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam
  • Few side effects (salivation, vomiting, ataxia)
  • Zonisamde also has minimal, yet similar side effects
39
Q

Which AED is given orally TID or QID?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam (2nd shortest half-life), 5. Gabapentin (shortest half-life), and 6. Pregabalin (Lyrica)
  • Levetiracetam dose can be increased in increments
  • Compare to BID for phenobarbital and SID for bromide
  • Extended release tablets are available for Keppra but cannot be halved because of the non-digestible coating with a small pore that allows the drug inside the tablet to gradually leak out; $$$
  • Levetiracetam IV form for status epilepticus use
  • Gabapetin start low and increase dose over 1-2 weeks
  • Pregabalin TID for dogs, but BID anecdotal for cats
40
Q

Which AED requires little to no therapeutic monitoring?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam (Keppra)
41
Q

Which AED causes the “Honeymoon” effect so may not be good for long term?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Levetiracetam
42
Q

Which AED is sulfonamide-based (antibiotic related)?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Zonisamide
    * MOA not completely understood; potentiates GABA receptors, affects Na and Ca channels
43
Q

Is Zonisamide used as a primary AED or as an add-on?

A

Either

44
Q

Which AED has a half life of 15 hours in dogs and 35 hours in cats (once a day dosing possible in cats) and reaches steady state at 48 hours?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Zonisamide
45
Q

T or F. Dogs receiving other drugs known to induce hepatic microsomal enzymes (ex. phenobarbital) require nearly twice the dosage of zonisamide to achieve and maintain serum concentrations.

A

True! It is metabolized by P450 so a higher dose is required if on phenobarbital

46
Q

Which AED has the fastest onset of action?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Gabapentin (2-4 hours in dogs)
  • Levetiracetam is fast with a half life of 3-4 hours in dogs, 3 hours in cats
  • Pregabalin is fast with a half life of 6 hours in dogs
  • Zonisamide is also quick 15 hours in dogs, 35 hours in cats
  • Phenobarbital is slow (ORALLY) at half-life of 100 hours (~4 days)
  • Bromide is slow at half-life of 24 days
47
Q

Which AED is not significantly metabolized by the liver?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Zonisamide
48
Q

T or F. Phenobarbital and zonisamide can develop tolerance.

A

True

49
Q

Which AED causes dry eye, blood dyscrasias, hypothyroidism with long term use, and vasculitis?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Zonisamide (sulfa side effects)
    * Also expensive and low availability (fairly new drug)
50
Q

Which AED is a synthetic analog of GABA that has multiple mechanisms, such as blocking neuronal Na+ channels and potentiating the release and actions of GABA?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin (Lyrica)
A
  1. Gabapentin and 6. Pregabalin (Lyrica)
51
Q

Is Gabapentin and Pregabalin (Lyrica) used as primary AEDs or as add-ons?

A

Usually as an add-on

52
Q

Which AED has a short half-life (2-4 hours in the dog), is well absorbed (dog) after oral dosing, but is metabolized in both the liver and kidney?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Gabapentin
53
Q

Which AED has minimal side effect, no drug interactions, and requires no therapeutic monitoring?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Gabapentin
54
Q

Which AED contains xylitol in oral solutions, which is toxic in dogs?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Gabapentin
    * Xylitol causes massive insulin release and then the patient becomes hypoglycemic
55
Q

Which AED causes sedation and ataxia?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Gabapentin (at higher doses) and 6. Pregabalin (Lyrica)
56
Q

Which AEDs are eliminated by the kidneys?

  1. Phenobarbital
  2. Bromide
  3. Zonisamide
  4. Levetiracetam
  5. Gabapentin
  6. Pregabalin
A
  1. Bromide and 6. Pregabalin
57
Q

What should you do if AEDs aren’t working?

A

Evaluate case

  • Wrong diagnosis
  • Disease may be getting worse
  • Client compliance may be poor (drug monitoring)
  • Drug dose may be too low (drug monitoring)
  • Tolerance may have developed (increase in dose will fix problem for a while)
  • May need to add on another AED
  • Look for and avoid precipitating factors if they exist
  • Referral to a neurologist
58
Q

Can a patient just stop using AEDs?

A

Not usually; most primary epileptics can’t ever be weaned from AED

  • Exceptions:
    • Cause of seizures disappears (secondary epileptics) and seizure focus isn’t present any longer (if underlying cause is resolved ex. liver shunt)
      • Ex. a dog with acute onset status epilepticus due to vasculitis caused by Ehrlichia canis needed AEDs; E. canis treated successfully, dog is on AEDs for 6 months without seizures; try weaning if case has been seizure-free those last 6 months
      • Dose tapered slowly over 2-6 months
      • Decrease by 1/8-1/4 every few weeks; warm owner of risk of return of seizures
      • Re-start at prior dosing if seizures return

Pharmacology 1 choefsho (13 decks)

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