Epilepsy/ Seizures Flashcards
Name the 2 basic grps that seizures are gen classified into.
Partial seizures
Generalized seizures
What’s epilepsy?
Unprovoked seizures or abnormal “electrical storms” in the brain
What’s a partial seizure? Diff btw simple partial and complex partial seizures?
Starts in 1 part of the brain where the pt is either conscious or unconscious.
Simple partial= if there’s NO loss of consciousness
Complex partial = if there’s loss of consciousness
Are partial seizures (PS) only confirmed to 1 part of the brain?
No!
PS can spread to the other hemisphere of the brain resulting in “secondarily generalized tonic-sonic seizures”
Note: simple and complex PS stays in the hemisphere where the seizures start
What’s generalized seizures (GS)?
GS begins in BOTH hemispheres of the brain where consciousness is impaired
What’s the difference btw Secondarily generalized tonic-clonic seizures and Generalized seizures
Secondarily generalized tonic-clonic seizures = starts in 1 hemisphere and spreads to another hemisphere
Generalized seizures = starts in both hemisphere at the same time
What’s a status epilepticus?
Seizures that last longer than 5 minutes
OR
> = 2 seizures btw which the pt doesn’t regain consciousness
Which type of seizure/epilepsy is a medical emergency?
Status Epilepticus
List anticonvulsants/antiepileptic drugs/AEDs that are category D?
Carbamazepine
Clonazepam
Phenobarbital/Primidone
Phenytoin/Fosphenytoin
Topiramate
Valproate
All others are pregnancy category C
Which AEDs is assigned cat. X? Why?
Valproate used in migraine prophylaxis
Which AEDs is thot to have the highest risk of fetal harm?
Valproate
Whats the most common types of SE AEDs users experience?
CNS SEs e.g. Dizziness, somnolence and cognitive dysfunction (not surprising as AEDs penetrate CNS to work)
Most AEDs are strong inducers/ inhibitors/ substrates?
Most AEDs are strong INDUCERS
List the main AEDs that are strong inducers
Carbamazepine
Oxcarbazepine
Fosphenytoin
Phenytoin
Phenobarbital
Primidone
Topiramate (>= 200mg/d)
Effects of strong inducers (most AEDs)?
They can lower the blood conc of many drugs, as they increase their metabolism, so the other drugs are removed quickly from the body
What supplement should all pts on enzyme-inducing AEDs be on? Why?
Vit. D and Calcium
Bcuz bone loss can occur as soon as 2 yrs after starting AEDs, making pts prone to osteoporosis
Do all AEDs require MedGuide?
Yes.
All AEDs require a MedGuide due to risk of suicidality
How should seizure meds be d/c?
Taper off med slowly
Never d/c seizure meds abruptly due to seizure risk
When do u call 911 if u witness seizure?
Time seizure with ur watch, if longer than 5 mins without signs of slowing down, or
if person has trouble breathing afterwards, or
Appears to be inured, in pain, or
Recovery is unusual in some way
How can u keep the airway of the person experiencing seizures clear?
Turn the person gently onto 1 side
What’s the tx of status epilepticus?
Rapid-acting BZD first e.g. Lorazepam (BZD of choice in status)
Followed by AED therapy (LD followed by MD)
List BZD used to treat Status Epilepticus. Which is drug of choice?
Lorazepam (Ativan) - drug of choic
Diazepam
Rectal diazepam (Diastat Acudial)
What’s the dose of lorazepam used in status epilepticus?
Lorazepam (Ativan): 4mg given by slow IV (adult)
Max rate - 2mg/min
May repeat in 5-10 minutes, if no response
What’s the 2nd line tx in status epilecticus?
AEDs
List 1st line tx in Partial, including secondarily generalized
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
List 1st line tx in Primarily Generalized Tonic-Clonic ONLY (type of partial seizure)
Lamotrigine
Levetiracetam
Valproate
List 1st line tx in Absence seizures
Ethosuximide
Valproate
List 1st line tx in Atypical Absence, Myoclonic, Atonic seizures
Ethosuximde
Lamotrigine
Levetiracetam
Valproate
List 1st gen AEDs
Benzodiazepines (BZD)
Carbamazepine (CBZ)
Ethosuximide
Phenobarbital/Primidone
Phenytoin/Fosphenytoin
Valproic acid/Valproate
MOA of BZD (1st generation AED)
BZDs enhance the activity of gamma-aminobutyric acid (GABA)
GABA is an inhibitory neurotransmitter
List agents under BZDs (1st generation AED)
Clonazepam (Klonopin)
Clobazam (Onfi)
SEs of BZDs (1st generation AED)
Drowsiness
Ataxia
Behavior disorder
Dizziness
Lethargy
Cognitive impairment (limit other CNS depressants)
Depression
Physiological dependence
Tolerance
Retrograde amnesia
Which BZD used as aces is pregnancy cat. C? D?
Preg cat. C = Clobazam (Onfi)
Preg cat. D = Clonazepam (Klonopin)
Is Clonazepam a major 3A4 inducer, inhibitor or substrate?
Clonazepam is a major 3A4 substrate
MOA of carbamazepine? (1st generation AED)
Fast Na channel blocker
Stimulates release of anti diuretic hormone (ADH) => reabsorption of water
What’s the brand name of Carbamazepine? (1st generation AED)
Tegretol; Tegretol XR
Carbatrol
Epitol - used for Bipolar
What’s the therapeutic range of CBZ (Tegretol, Tegretol XR, carbatrol) (1st generation AED)?
4-12 mcg/mL
What’s the black box warning of CBZ (Tegretol; XR, Carbatrol) (1st generation AED)?
Serious skin rxns, including SJS and TEN
Fatal blood cell abnormalities (including aplastic anemia and agranulocytosis)
What MUST be done b4 a pt of Asian descent use CBZ (Tegretol; XR, Carbatol) (1st generation AED)?
Must be tested for HLA-B*1502 allele PRIOR to therapy
If positive CBZ can’t be used
If a pt of Asian descent tests positive for HLA-B*1502, can they still use CBZ (Tegretol; XR, Carbatrol) (1st generation AED)?
No!
Unless benefit clearly outweighs the risk
What’s the warning associated with CBZ (Tegretol; XR, Carbatrol) (1st generation AED) use?
Serious skin rxns (onset usually 2-8 wks after initiation)
SEs of CBZ (Tegretol; XR, Carbatrol) (1st generation AED)?
Nausea
Vomiting
Dizziness
Drowsiness
Headache
Ataxia
Fatigue
Vit. D and Calcium deficiency (bone loss)
SIADH/hyponatremia
Hepatotoxicity
Is CBZ an inhibitor, substrate/ inducer?
Potent CYP 450 INDUCER and autoinducer of many enzymes (1A2, 2C19, 2C8/9, 3A4)
T4 LOWERS the level of many drugs and of itself
And a major 3A4 Substrate (t4 inh will increase its level)
What supplementation is req with the use of carbamazepine (Tegretol; XR, Carbatrol) (1st generation AED)?
Calcium and Vit. D
Generally, should OCPs be used concurrently with AEDs?
No!
Use alternative, nonhormonal contraceptive
What seizure type is CBZ (Tegretol; XR, Carbatrol) (1st gen AEDs) used for?
Partial (simple and complex), including secondarily generalized
MOA of Ethosuximide?
T-type Ca channel blocker that increase seizures threshold and suppresses paroxysmal spike-and-wave pattern in absence seizures
What’s the brand name of Ethosuximide (1st gen AEDs)?
Zarontin
SEs of Ethosuximide (1st gen AEDs)?
GI upset (weight loss, abdominal pain, nausea & vomiting)
Hiccups
Types of seizure Ethosuximide (1st gen AEDs) is used for?
Absence seizure
Atypical Absence, Myoclonic, Atonic seizures
Is Ethosuximide a substrate, inducer/ inhibitor?
Major 3A4 substrate
T4 strong inducers like CBZ, Fosphenytoin, phenytoin, phenobarbital, Primidone may LOWER Ethosuximide levels
Which AEDs may INCREASE the level of Ethosuximide (1st gen AEDs)? (Most other AEDs lowers it’s level)
Valproic acid
MOA of phenobarbital/Primidone? (1st gen AEDs)
Enhance gamma-aminobutyric acid (GABA)- mediated chloride influx
What’s the brand name of phenobarbital?
Luminal
What’s Primidone (Mysoline)?
Prodrug of phenobarbital and phenylethylmalonamide (PEMA)
What’s the therapeutic range of phenobarbital (Luminal) and Primidone (Mysoline) in adults? (1st gen AEDs)
20-40 mcg/mL
What’s the therapeutic range of phenobarbital (Luminal) and Primidone (Mysoline) in children? (1st gen AEDs)
15-30 mcg/mL
SEs of phenobarbital (luminal) / Primidone? (1st gen AEDs)
Drowsiness
Cognitive impairment (limit other CNS depressants)
Dizziness/ataxia
Physiological dependence
Tolerance
Hang-over effect
Depression
Vit. D and calcium bone deficiency (bone loss)
Hepatotoxicity (rare)
How do u d/c phenobarbital (luminal) / Primidone? (1st gen AEDs). True for all AEDs also.
Taper slowly
Supplement with phenobarbital (luminal) / Primidone? (1st gen AEDs)? True for all AEDs.
Calcium and Vit. D
Are phenobarbital (luminal) / Primidone (1st gen AEDs), inhibitors, substrate, inducers?
Strong CYP 450 enzyme inducer
MOA of phenytoin/Fosphenytoin? (1st gen AEDs)
Fast Na channel blockers
What’s the brand name of Phenytoin (1st gen AEDs)?
Dilantin
Phenytek
What’s Fosphenytoin? (1st gen AEDs)
Prodrug of phenytoin
IV/IM Injection only
What’s the max rate for Phenytoin (Dilantin, Phenytek) infusion? (1st gen AEDs)
50 mg/min
What’s the max rate for Fosphenytoin infusion? (1st gen AEDs)
150 mg PE/min
How’s Fosphenytoin dosed?
In Phenytoin Equivalents (PE)
1mg PE = 1mg phenytoin
Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs) exhibits Michaelis-Menten kinetics. What does that mean?
They exhibit saturable
That means a small change in dose can cause a big change in serum level
What’s the relationship btw low albumin and phenytoin levels?
Low albumin (< 3.5g/dL) results in a false low phenytoin level (t4, PHT will appear artificially LOW)
T4 it’s corrected using this formula
PHT measure
Divided by
(0.2 x albumin) + 0.1
Or
Can measure a fre PHT level
What’s the value deemed to be low albumin?
Low albumin < 3.5g/dL
Since low albumin (< 3.5 g/dL) results in a false LOW PHT levels, whats the formula used to correct PHT?
PHT correction = PHT measured
Divided by
(0.2 x alb) + 0.1
What’s the therapeutic range of total PHT level measured?
Total PHT: 10-20 mcg/mL
T/F? PHT ER caps contains 8% less drug than chewable and suspension?
True!
T4 adjust dose if changing formulations
What’s the black box warning associated with Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs)?
PHT admin: NOT to exceed 50mg/minute
FosPHT admin: NOT to exceed 150mg PE/min
To avoid hypotension and cardiac arrhythmias
What’s the warning associated with IV PHT?
Vesicant: can cause venous irritation and
Purple glove syndrome (discoloration with edema & pain of distal limb)
Inject into large vein slowly & follow with saline flush
Dose-related SEs of Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs)?
Dose-related toxicity
- Ataxia
- Dizziness
- Drowsiness
- HA
- Nystagmus
- Slurred speech
Chronic SEs of Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs)?
Skin thickening (children)
Gingival hyperplasia
Hirsutism
Vit. D and Calcium deficiency (bone loss)
Connective tissue changes
Coarsening of facial features
Folate deficiency
Hepatoxicity
What’s unique about the supplementation of Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs)?
In addition to Vit. D and calcium,
Folic acid and Vit. B12 are also used?
What’s PHT compatible with only during IV?
NS only
Req a filter and is stable for 4 hrs only
Enteral feedings and PHT?
Enteral feedings may LOWER PHT absorption
T4 must separate!
Protein binding and Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs)?
Phenytoin (Dilantin, Phenytek) and Fosphenytoin (1st gen AEDs) are HIGH protein binding activity
PHT: 90-95%
FosPHT: 95-99%
Can displace other highly-protein bound drugs
What’s the brand name of Valproate/Valproic acid? (1st gen. AEDs)
Depakene - capsule, solution, syrup
Stavzor - delayed-release capsule
Depacon - IV
What’s the brand name of Divalproex? (1st gen. AEDs)
Depakote - delayed release tablet
Depakote ER - ext-release tablet
Depakote Sprinkle
What’s the usual therapeutic range of Valproic acid/Valproate?
50-100 mcg/ml
Some pts req higher levels
Effect of low albumin (< 3.5 g/dL) on valproate levels?
Same as PHT (results in a false LOW valproate levels) .
T4 low albumin = low PHT and valproate levels
Adjust using the same formula
Valproate correction formula =
Valproate measured
Divided by
(0.2 x albumin) + 0.1
Black box warnings of Valproate/Valproic acid and Divalproex? (1st gen. AEDs)
Hepatic failure
Teratogenicity
Pancreatitis
Who’s at the highest risk of hepatic failure as a result of Valproate/Valproic acid and Divalproex use? (1st gen. AEDs)
During 1st 6 months of use
Pts with mitochondrial disorders (at highest risk)
Children under the age of 2 yrs
What’s the sx of teratogenicity that occurs in Valproate/Valproic acid and Divalproex use? (1st gen. AEDs)
Neural tube defects e.g. Spina bifida
SEs of Valproate/Valproic acid and Divalproex use? (1st gen. AEDs)
GI upset (n/v)
Abdominal pain
Dizziness
Asthenia
Tremor
Alopecia (treat with a multivitamin containing selenium and zinc)
Somnolence
Weight gain
Polycystic ovary syndrome (PCOS)
Vit. D and calcium deficiency (bone loss)
Pancreatitis
Lower IQ in children if exposed in-utero
Dose-related SEs of Valproate/Valproic acid and Divalproex use? (1st gen. AEDs)
Thrombocytopenia
What may alleviate stomach ache?
Switch from Valproic acid to delayed-release Divalproex may reduce stomach upset
What’s unique about the role of Valproic acid (1st gen. AEDs)
Inhibitor of 2C9
Most AEDs are inducers
List 2nd generation anticonvulsants
Lamotrigine
Levetiracetam
Oxcarbazepine
Pregabalin/Gabapentin
Topiramate
Zonisamide
What’s the brand name of Lamotrigine (2nd generation AEDs)?
Lamictal
Black box warning of Lamotrigine (Lamictal) (2nd generation AEDs)
Serious skin rxn: including SJS and TENS
What’s the titration schedule of Lamotrigine (Lamictal) (2nd generation AEDs) based on?
It’s based on whether pt is:
On valproate (inhibitor)
On Inducer AEDs
Or, no concomitant AEDs
SEs of Lamotrigine (Lamictal) (2nd generation AEDs)?
Nausea
Insomnia
Drowsiness
Rash
What’s the brand name of Levetiracetam (2nd generation AEDs)?
Keppra
Keppra XR
SEs of Levetiracetam (Keppra) (2nd generation AEDs)?
Somnolence
Dizziness
What’s unique about Levetiracetam (Keppra), Pregabalin (Lyrica), Gabapentin (Neurotin) (2nd generation AEDs) and Rufinamide use?
No significant drug interactions
What’s the brand name of Oxcarbazepine (2nd generation AEDs)?
Trileptal
Oxtellar XR
Warnings associated with Oxcarbazepine (Trileptal, Oxtellar XR) (2nd generation AEDs) use?
Serious skin rxns
SEs of Oxcarbazepine (Trileptal, Oxtellar XR) (2nd generation AEDs)?
Somnolence
Dizziness
HA
GI effects (n/v/ abdominal pain)
Diplopia
Nystagmus
Abnormal vision
Ataxia
Tremor
Vit. D and Ca deficiency (bone loss)
Which SE should be monitored, esp in the 1st 3 months of Oxcarbazepine (Trileptal, Oxtellar XR) use?
Hyponatremia
Monitor serum Na levels esp during the first 3 months (more common than with CBZ)
What’s the same as all other AEDs?
Strong inducer
Supplement with Vit. D and Ca
MOA of pregabalin/Gabapentin
Bind to the alpha-2-delta subunit of voltage-dependent Ca channels within CNS
What’s the brand name of Pregabalin (2nd generation AEDs)?
Lyrica
SEs of Pregabalin (Lyrica) and Gabapentin (Neurotin) (2nd generation AEDs) use?
Dizziness
Somnolence
Peripheral edema
Weight gain
Ataxia
Diplopia
Blurred vision
Xerostomia
Whats the brand name of Gabapentin (2nd generation AEDs)?
Neurotin
Brand name of Topiramate (2nd generation AEDs)?
Topamax
Warning associated with Topiramate (Topamax) (2nd generation AEDs) use?
Metabolic acidosis
Oligohydrosis (reduced perspiration)/ Hyperthermia - mostly in kids
Neohrolithiasis - keep hydrated
What’s different in the SE of Topiramate (Topamax), compared to other AEDs?
Weight loss
What can be caused in newborn, if mother uses Topiramate (Topamax) while pregnant?
Cleft lip and/or palate in newborn
What’s the CI to Zonisamide (Zonegran) (2nd generation AEDs) use?
Hypersensitivity to Sulfonamides
What AEDs cause weight loss?
Topiramate (Topamax)
Zonisamide (Zonegran)
What’s warning associated with Zonisamide (2nd generation AEDs) use?
Serious skin rxns, including SJS/TEN
Oligohydrosis (reduced perspiration)/ hyperthermia - mostly in kids - try to limit sun and hydrate
Nephrolithiasis (kidney stones) - keep hydrated
Metabolic acidosis
SEs of Zonisamide use?
Drowsiness
Dizziness
Weight loss
Vit. D & Ca deficiency (bone loss)
List other AEDs
Eslicarbazepine Acetate (Aptiom)
Ezogabine (Potiga)
Felbamate (Felbatol)
Lacosamide (Vimpat)
Rufinamide (Banzel)
Tiagabine (Gabitril)
Vigabatrin (Sabril)
Perampanel (Fycompa)
Which AEDs has Retinal abnormalities and Blue skin discoloration as SEs (unique)?
Ezogabine (Potiga)
Unique SEs of Ezogabine (Potiga)?
Retinal abnormalities
Skin discoloration - typically blue
Urine to turn orangish/reddish/brown
Black box warnings of Felbamate (Felbatol)?
Hepatic Failure
And
Aplastic Anemia
What do I look out for if I see Felbamate being used in a case in exam?
There’s likely a reason why it should NOT be used.
T4 use at LFTs, other concomitant drugs that are hepatotoxic and the CBC
What’s unique SE of Rufinamide (Banzel) use?
QT shortening
What’s AEDs cause Teratogenicity?
CBZ, Clonazepam
Phenobarbital, PHT
Topiramate
Valproic acid
What’s AEDs cause Hepatoxicity?
CBZ
Felbamate
Phenobarbital/Primidone, PHT
Valproic acid
What’s AEDs cause decreased effects of OCPs?
CBZ, Clobazam
Oxcarbazepine
Perampanel, Phenobarbital, PHT, Primidone
Topiramate (>= 200mg/day)
What’s AEDs cause Fatal Pancreatitis?
Valproic acid
What’s AEDs cause Aplastic Anemia?
CBZ (also cuz Agranulocytosis)
Felbamate
What’s AEDs cause Skin rash (SJS)?
CBZ
Lamotrigine
Oxcarbazepine
Phenobarbital, PHT/Fosphenytoin
Tiagabine
Zonisamide
What’s AEDs cause:
Oligohydrosis - inability to sweat, risk of heat stroke - highest risk in kids
Nephrolithiasis (kidney stones)
Topiramate
Zonisamide
What’s AEDs cause weight gain?
Valproic acid
Gabapentin
Pregabalin
What’s AEDs cause Weight loss?
Felbamate
Ethosuximide
Topiramate
Zonisamide
What’s AEDs cause Hyponatremia?
CBZ
Oxcarbazepine (more common)
What should women in Teratogenic causing AEDs be encouraged to do, once they’re pregnant and still in med?
Enrol in North American Antiepileptic Drug (NAAED) pregnancy registry
What natural pdt should be avoided with AEDs?
St. John’s wort
List drugs/conditions that may lower the seizure threshold
Antipsychotics e.g, clozapine, phenothiazines, butyrophenones
Antivirals e.g, Amantadine, Rimantadine, Foscarnet, Ganciclovir, and
Acyclovir IV
Bupropion
Carbapenems (in poor renal fxn, esp. Imipenem)
Cephalosporin
Fluoroquinolones
Lindane
Lithium and Theophylline (in toxicity)
Mefloquine
Meperidine (in poor renal fxn)
Metoclopramide
Natural pdts such as dendrobium, evening primrose oil, gingko, melatonin, St. John’s wort
Penicillins
Sleep deprivation, alcohol intoxication, menstruation, infection, and fever (esp, in children) can worsen seizure
Look at pt counseling pts on pg 934-938
Look!
List sx PHT toxicity
Shakiness/walking unsteady
Double vision
Nystagmus
If PHT is used long-term, what can occur without proper supplementation?
Osteoporosis
Anemia
List some of the steps that can be taken if pt is found having seizures
Turn pt on their side
Remove sharp or hard objects away from the pt seizing and support their head
Loosen pts clothes
Time seizure