Seizures

Question 1

Etiology of Seizures : Single seizure causes
1. C,A,T,M,M,M,M

2. Meds associated with seizures?

Answer 1

1. CNS depressant withdrawal
   ◦ Acute illness
   ◦ Toxicity
   ◦ Medical conditions
   ◦ Metabolic disturbances
   ◦ Medical procedures
   ◦ Medications
2. Anticholinergics
   -Anticholinesterases
   -Antidepress
   -Antiemetics
   -Antiseizure meds
   -Antihistamines
   -Antimalarials
   -Antimicrobials
   -Antineoplastics
   -Antipsychotics
   -Contrast agents
   -Baclofen
   -Beta blockers
   -CNS stims
   -Oxytocin
   -Estrogen
   -Lithium
   -Anesthetics
   -Opioids
   -Sympathomimetics

Question 2

Etiology
1.Chronic seizure disorders :
-S, I, N, Other such as ? (4)

2. Other etiology such as ___

Risk factors
1. Congenital : ___ during gestation/early life, abnormal ___ at birth, and abnormal ____/___, cerebral palsy
2. Childhood/devel : seizures in ___, serious __ or ___, intellectual ___, intractable ___
3. Illness/Trauma such as?

Answer 2

1. Stroke, other vascular abnorms
   -Intellectual disability
   -Neurodevel/birth injury
   -CNS neoplasms, Cerebral palsy, genetic predisposition, head trauma
2. Genetics
3. Underweight, brain structure, blood vessel structure/function in brain
4. 1st month of life, brain injury , lack of oxygen to brain , disability , febrile seizures
5. brain tumors, infections of brain, encephalitis, stroke, seizures within days after head injury, family history of epilepsy or fever-related seizures,
   advanced Alzheimer’s disease

Question 3

Focal Seizures :
1. Formerly known as?
2. Focal Motor - sx’s ?
3. Focal Non motor -Sx’s?
4. A__

Answer 3

1. partial
2. involuntary body movement (twitching, jerking, stiffening) or automatisms (automatic movements such as lip smacking, rubbing hands, walking, running)
3. other symptoms occur before seizure, such as somatic (paresthesia), sensory (visual, auditory, olfactory, gustatory hallucinations), psychological symptoms (detachment, déjàvu, fears, illusions)
4. Auras

Question 4

Generalized Motor :
1. Formerly known as?
2. Tonic refers to , clonic refers to
3. Prodromal sx’s in some patients such as?
4. Postictal phase ?
5. EEG will show what ?

Answer 4

1. Tonic clonic or grand mal
2. Stiffening, jerking
3. Irritability , decr concentration
4. Unarousable at first, then lethargic, confused, sleepy
5. generlized spike and wave discharges, generalized poly-spike discharges

Question 5

Generalized Non-Motor
1. Formerly known as
2. Ages ?
3. Momentary lapse in awareness lasting ?
4. Sx’s?
5. No ____
6. Atypical non motor has __ and __ components
7. EEG will show?

Answer 5

1. Absence or Petit mal
2. 5-15 yrs, first peak 6-7 yrs, second peak ~12 yrs
3. 10-30 secs
4. motionless staring, arrest of any activity , mild motor facial jerks, automatisms, rapid blinking
5. postictal period
6. tonic, autonomic
7. 2-3 Hertz Spike and wave discharge on EEG

Question 6

Generalized Other motor
1. Myoclonic : sx’s?
2. Atonic (Akinetic) sx’s?

Answer 6

1. Rapid, lightning -like jerk movements of entire body
   - can affect small, isolated muscle groups of face, arms or may involve larger areas of head, limbs, trunk
2. Drop attacks, sudden loss of muscle tone
   -fragmentary (head drop) or generalized (usually resulting in fall)

Question 7

Treatment :
1. Initiate ASM therapy if your pt at incr risk of ? Such as ?

2. TX goal?
3. Non pharm tx options ?

Answer 7

1. Recurrent seizures (Sleep deprivation, fever, substance use)
2. Seizure free without AE’s, monotherapy desirable
3. Vagus nerve stim, responsive neurostim, surgery , ketogenic diet in pt’s w/refractory epilepsy who have failed >=2ASMs

Question 8

Carbamazepine (Tegretol)
1. Indications ? (5)

2. Metabolism with enzyme? (DDI)
3. Autoinduction will complete when ?
4. BBW? (3)
5. 10 fold incr risk of TEN/SJS in which individuals?
6. ADRs?
   -CNS such as
   GI such as
   __ and __ deficiency –> incr osteoporosis risk
   Dose related such as (4)
   Idiosyncratic such as ?
7. RIsk of hypersensitivity rxn may be INCR with variant ___
8. Monitor ?? (3)
9. Discontinue if?
10. What do u have to repeat every 3 months for 6 months and then annually? (4)

Answer 8

1. Focal onset, gen tonic clonic, mixed seizures, trigeminal neuralgia, bipolar disorder
2. CYP3A4
3. 20-30 days, max 4 weeks
4. aplastic anemia and agranulocytosis
   - SJS, TEN
5. Asian descent , test for HLA-B*1502 Allele and avoid use if positive
6. Dizzi, drowsiness, HA, fatigue
   - N/V
   - Vitamin D, Calcium
   - Diplopia, drowsy, nausea, sedation
   -Rash, SJS, aplastic anemia, anemia, leukopenia, SIADH, Cholestatic jaundice
7. HLA-A*3101 allele
8. LFTs, CBC, CMP
9. WBC or ANC < 3000/mm^3 or 1500 /mm^3
10. LFTS, CBC, Carbam levels, CMP

Question 9

Oxcarbazepine (Trileptal)
1. Monotherapy or adjunctive in what types of seizures and for what ages?

2. CYP interactions?
3. Warnings : cog/neuropsych rxns such as?
4. Avoid use if positive for HLA-B*1502 because of?
5. Cross hypersensitivity rxn to ___
6. AE’s ? CNS, Dose related, Idiosyncratic
7. Need to Monitor ?

Answer 9

1. Monother or adjunctive in focal onset seizure in adults. Mono for 4-16, Adjunct for 2-16
2. Strong CYP3A4 inducer
3. concentration difficulties, speech/language problems, and psychomotor slowing, somnolence or fatigue, coordination problems such as ataxia and gait disturbances
4. SJS, TEN
5. Carbamazepine (25-30%)
6. Drowsy, ataxia , diplopia
   -N/HA
   -Hyponatremia!, Blood dyscrasias
7. CBC , CMP every 3 months then annually

Question 10

Comparing Carbamazepine Vs Oxcarbazepine

1. Autoinduction ?
2. Hyponatremia?
3. DDI’s?
4. Better tolerated due to NO metabolism to epoxide?
5. Measure drug levels?
6. Dosage of oxcarb compared to carb ?

Answer 10

1. Carb
2. Low risk with carb, high risk with oxcarb
3. Carb has more DDI’s
4. Oxcarb
5. Carb = measure levels , Oxcarb = measure MHD levels! (its metabolite)
6. oxcarb = 1.2-1.5x daily dose of carbam

Question 11

Ethosuximide (Zarontin) :
1. Indicated for ?
2. Metabolized by ?
3. Warnings for ? (4)
4. AE’s CNS, Dose related, Idiosyncratic
5. Monitoring Baseline , every 3 months then annually? (3)

Answer 11

1. Gen non-motor (absence) seizures
2. CYP 3A4 (CYP3A4 substrate)
3. Blood dyscrasias
   * Avoid in renal AND hepatic dysfunction
   * Systemic lupus erythematosus (SLE)
   * Dermatologic reactions, including SJS and TEN
4. CNS : Drowsy, fatigue
   DR : Anorexia, weight loss, GI upset, AB cramps
   Idio : Leukopenia, eosinophilia, Psych disturbances, sleep disturbances, aggression, hiccups
5. CBC, CMP, Ethosuximide levels

Question 12

Gabapentin (Neurontin)
1. Indications: ADJUNCTIVE for ___ +/- secondary generlization in >=3yrs, postherpetic neuralgia

2. Warnings such as :
   - Neuropsych ae’s in ____ w/ seizures ages __
   -T ___ potential
   -Sudden, unexplained ___ in pt’s w/epilepsy
   -_____ including serious, life threatening, fatal
   -Concomitant use with ___
3. AE”s : CNS, Other, Concentration related ?
4. What needs to be monitored q3months + annually?

Answer 12

1. Focal onset seizures
2. pediatric pt’s, 3-12 yrs

• Tumorigenic
• death
  -Respiratory depression
  -Opioids

3. Dizzy!, somnolence, ataxia!
   - Peripheral edema!, weight gain!
   - Drowsy, sedation!
4. baseline CBC , CMP

Question 13

Lacosamide (Vimpat)
1. Indications : adjunctive therapy for?
2. metabolized by ? (3 enzymes)
3. Warnings for ___ and ___, including dose dependent prolonged ___, Atrial __ and ___
-S__

4. AE’s CNS, GI, Other, Idiosyncratic
5. Need to monitor ___ at baseline and steady state maintenance dose recc if underlying ___, severe ___ or taking concomitant meds that affect conduction

Answer 13

1. Focal onset seizures in >17 yrs
2. CYP3A4, 2C9, 2c19
3. cardiac rhythm, conduction abnorms, PR interval, fib, flutter
   -syncope
4. CNS : Dizzi, HA, Somnolence, ataxia/shakiness
   -Nausea
   -Diplopia
   -Hepatic impairment, 1st degree AV Block
5. ECG at baseline, proarrhythmic conditions, cardiac disease

Question 14

Lamotrigine (Lamictal) :
1. Indications for adjunctive therapy in >= 2 yrs with ____, primary ____, generalized seizures of ___, and ___ (>=18yrs)

2. Boxed warnings?
3. Increased risk of boxed warning with concomitant use of ___, initial doses exceeding __, and dose escalations exceeding recc’s
4. What should we do at first sign of rash ?
5. When should you re-titrate the medication?
6. WHich drugs affect the dosing titration of Lamictal?
7. Warnings for ? (2)
8. AE”s : CNS, DR, Idiosyncratic
9. Monitoring for ? (3)

Answer 14

1. focal onset seizures, gen tonic clonic seizures, LGS, bipolar
2. serious skin rashes, including SJS, TEN
3. Valproate !!
   - recommendations
4. DISCONTINUE unless its clearly not medication related
5. If medication missed for > 5 half lives
6. Valproate, Carb, Phenytoin, Phenobarb, Primidone
7. Cardiac rhythm and conduction abnorms
   - Concomitant use w/oral contraceptives (They incr clearance of drug, lower lamictal)
8. Dizzy, ataxia, blurred vision
   -Rash, N/V
   -Life threatening rash, hepatic failure, hemophagocytic lymphohistiocytosis
9. Baseline CBC, CMP, and rash q3months then annually

Question 15

Levetiracetam (Keppra) :
1. Indications : Mono or adjunctive for ___ in >=1 month, adjunctive for ___ in >=12yrs w/juvenile ___, adjunctive for primary ___ in >=6yrs w/idiopathic epilepsy

2. Warnings for :
   Behavioral abnorms such as ?
   -CNS depression including ? (3)
   -Derm rxns such as ?
   -C___ difficulties
   -Blood ___
   -Incr in ___
   -Seizure control during ___
3. AE’s : CNS, DR, Idiosyncratic
4. Monitoring baseline, q3months, annually

Answer 15

1. focal onset seizures, myoclonic seizures , myoclonic epilepsy, gen tonic-clonic seizures
2. psychotic sx’s (psychosis, aggression,anger)
   - somnolence, fatigue, ataxia
   - SJS, TEN
   -Coordination
   -Dyscrasias
   -BP
   -Pregnancy
3. CNS : Drowsiness, ataxia
   DR: Nausea /HA
   Idio: Cog and mood changes, depression!, irritablity
4. CBC, CMP

Question 16

Phenytoin (Dilantin) :
1. Indicated for ?

2. Metabolism by which enzymes?
3. BOXED WARNINGS for ?
4. WARNINGS : S,T, B,H,B,A,Exacerbation of P__ , R or H impairment, Hypo__, Hyper___
5. Chronic use associated with ?
6. T___
7. Sustained phenytoin serum levels above thera range may produce ?
8. AE”s : CNS , DR, Idisocyncratic
9. AE’s IV related ?
10. Monitoring baseline, q3months, annually
11. Does what to oral contraceptives?

Answer 16

1. Gen tonic clonic seizures, prevention and tx post neurosurgery, status epilepticus
2. CYP 2C9, 2C19, 3A4–> CYP inducer !!!
3. Cardiovasc events w/IV infusion >50mg/min
   -Peds should not exceed 1-3mg/kg/min to decr risk of severe hypotension, cardiac arrhythmias (or just avoid in children)
4. SJS, TEN (Test for HLAB*1502 allele , avoid if possitive) , Blood dyscrasias, hepatic injury, bradycardia/cardiac arrest, angioedema, porphyria, renal , hepatic, albuminemia, glycemia
5. Decr bone mineral density , fractures
6. Teratogenicity
7. Confusional states including delirium, psychosis, enceph, or rarely , irreversible cerebellar dysfunction and or cerebellar atrophy
8. CNS : Nystagmus, ataxia, diplopia, cerebral atrophy (chornic use)
   DR : N/V/C
   Idio : Blood dyscrasias, hepatotoxic, hirutism, gingival hyperplasia, acne, arrhythmias, SJS, alt of Vitamin D metab, folate deficiency
9. Phlebitis, seevre soft tissue damage (purple glove syndrome), hypotension and bradycardia related to propylene glycol
10. CBC, CMP, PHENYTOIN LEVELS
11. Decr their levels

Question 17

Fosphenytoin (Cerebyx)
1. Indications for?
2. metab?
3. Boxed warning : rate of admin should not exceed ?
-Whats associated w/RAPID INFUSION?

4. Warnings: B, D, D, Local toxicty such as __. S, H, A,P, R or H or H, Exacerbation of __, Hyper ___
5. AE’s such as ? (2)

Answer 17

1. Gen tonic clonic status epilepticus, prevention and tx of seizures during neurosurgery
2. Rapidly via hydrolysis to PHENYTOIN –> CYP 2c9, 2c19, 3a4
3. 150mg PE/min in adults, 2mgPE/kg/min in peds
   -Cardiovasc events
4. Blood dyscrasias, dosing errors, derm rxns (SJS and TEN) , Pruple glove syndrome (Less common than phenytoin) , Sensory disturbances (burning, itching paresthesia), hepatic injury, angioedema, phosphate load (caution w/severe renal impairment), renal, hepatic disease, hypoalbum, porphyria , Glycemia
5. Hypotension, Perianal pruritus

Question 18

See chart on Phenytoin vs Fosphenytoin

Answer 18

See chart

Question 19

Phenobarbital (Luminal ) :
1. Indications?
2. Metabolism by ?
3. Warnings :
__ and __depression
-Derm rxns such as ?
-___ stim response
-may reduce potency of __ and other __

4. AE’s ? CNS,DR, ___ in children, Decr ___ w/chronic use
5. Monitoring at baseline, q3months, annually? (3)

Answer 19

1. Gen seizures, focal onset, status epilepticus
2. CYP 2C19, 2C9, 2E1 –> its an enzyme inducer
3. CNS, respiratory
   SJS , TEN
   Paradoxical
   -Warfarin, anticoags
4. CNS : somnolence, confusion, cog impair
   DR : HTN, respiratory depression, coma
   Hyperactivity
   - Bone mineral density
5. CBC, cmp, phenobarb levels!

Question 20

Valproate (Depakote )
1. Indications for mono and adjunctive in ___? (4)
2. Metabolism by which enzymes?
3. Boxed warnings for ? (3)
4. Warning for
-Hyper ___ , incr risk with concomitant ___
-___ disorders
-Hypo___
-DR ____
-Use in women of ___
-False positive for ____ and altered ___
-Reduced ___ w/concomitant ___ abx
-Medication residue in __

5. AE’s : CNS, Dose related, Idiosyncratic
6. Monitoring baseline, q3months, annually?
7. VALPLATE ?

Answer 20

1. Focal onset impaired awareness seizures, gen non motor (absence) seizures in >10yrs, mania, migraine prophylaxis
2. CYP 2A6, 2B6, 2C9 –> CYP inhibitor !!!
3. Hepatic failure, Pancreatitis, Structural birth defects
4. Ammonemia, topiramate use
   -urea cycle
   -thermia
   -thrombocytopenia
   -childbearing age
   -urine ketone test, thyroid function test
   -Valproate serum concentrations , carbapenem
   -Stool
5. tremor, somnolence, reversible and irreversible
   cerebral and cerebellar atrophy
   - N/V/weight gain, reversible thrombocytopenia, alopecia
   -Hepatotoxic, Idiopathic thrombocytopenia, rash
6. CBC, CMP, Valproic acid levels !!!!
7. Vomiting (N/D) , Alopecia, Levels, Pancreatitis, liver toxic, albumin/ammonia levels , thrombocytopenia/tremor, enzyme inhibition

Question 21

Topiramate (Topamax)

1. Indications for ? (5)
2. Inducer of __ which may cause interactions with ?
3. Warnings for Cog effects such as ?
4. Acute __ and secondary ___ . Visual ____.
5. Metabolic ___, Oligo___ and hyper____
6. Fetal ___, serious skin rxns including ___ (2)
7. N
8. Hyper ___ and E___
9. Hypothermia with concomitant ___
10. AE’s : CNS, DR
11. Monitoring of baseline __ ,___, ___ every 3months then annually

Answer 21

1. Focal onset or primary gen tonic clonic seizures in >2yrs, adjunctive for focal seizures, primary gen tonic clonic, seizures associated with LGS in >2yrs, migraine prophylaxis in >12 yrs
2. Enzymes , birth control
3. confusion, psychomotor slowing, difficulty with concentration, word-finding difficulties, neuropsychiatric effects –depression, mood swings, fatigue, somnolence
4. Myopia, angle close glaucoma. Field defects
5. ACidosis, oligohidrosis, hyperthermia
6. Toxicity , SJS, TEN
7. Nephrolithiasis
8. Hyperammonemia, enceph
9. Valproic acid use
10. Cog impairment, psychomotor slowing, somnolence and fatigue
    - N/Dyspepsia, weight LOSS, hyperchloremic non anion gap metab acidosis, neprholithiasis
11. CBC, CMP, urinalysis

Question 22

Zonisamide (Zonegran)
1. Indications such as adjunctive therapy in ?
2. Metabolism by?
3. Warnings for C/N, M,N,Serious ___, Serious ___
4. O__, hyperthermia in peds
5. Acute __ and secondary ___
6. Increased ___
7. Hyper__ and E___
8. S____!!!!!!
9. T____

10. AE’s such as CNS and Dose related ?
11. Monitoring baseline , q3months, annually?

Answer 22

1. focal onset seizures in adults
2. CYP3A4 –> lots of DDI’s
3. Cog/neuropsych effects (Confusion, psychomotor slowing, depression psychosis, somnolence , fatigue)
   -metab acidossis
   -Nephrolithiasis
   -serious hematologic events
   -Skin rashes (SJS and TENS)
4. Oligohidrosis
5. Myopia, angle closure glaucoma
6. renal dsyfunction
7. Ammonemia, encephalopathy
8. Sulfonamide rxns
9. Teratogenicity
10. Drowsy, dizzy, confusion, tremor, cog dulling
    - N/V/WEIGHT LOSS, paresthesias
11. CBC, CMP

Question 23

Status Epilepticus -Initial ASM TX : Diazepam

1. what form of diazepam?
2. What other formulations could you use of Diazepam if IV is not available, and IV Loraz/IM Midaz is not available either?
3. COnsiderations for the drug ?

Answer 23

1. IV
2. Rectal Diazepam (Level B evidence)
3. has active metabolite, short duration, IV contains propylene glycol

Question 24

Status Epilepticus - Initial ASM TX Lorazepam and Midazolam

1. What form of lorazepam?
2. COnsiderations?
3. What form of Midazolam is 1st line?
4. What 2 other forms are level B evidence ?
5. Considerations?

Answer 24

1. IV, IV push
2. IV contains propylene glycol
3. IM
4. Intranasal and Buccal
5. Active metab, short duration , renal elim

Question 25

Enzyme Inducing ASMS : 1. List the 5 drugs For each of the affected drug classes, give examples : 2. ASMs 3. ANticoags 4. Antipsychs 5. BZD's 6. Steroids 7. Antidepress

Answer 25

1. Carbamazepine, Cenobamate (mod dose), Phenobarb, Phenytoin, Primidone 2. CArbamazepine, felbamate, lamotrigine, Oxcarb, Tiagabine, Topiramate , Valproate, Zonisamide 3. warfarin (reduced inr) 4. Chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone 5. Alpraz, CLobaz, Clonaz, Diaz, midaz 6. Dexameth, hydrocort, methylpred, pred , prednisolone 7. Wellbutrin, citalopram, paroxetine, TCA's, mirtazapine

Question 26

Which Enzyme inducing ASMs have an interaction with oral contraceptives? (7)

Answer 26

1. Carbamazepine 2. Cenobamate (moderate) 3. Oxcarbazepine 4. Phenobarb 5. Phenytoin 6. Primidone 7. Topiramate with >=200 mg/day

Question 27

ASM Enzyme Inhibition 1. Valproic acid can increase plasma levels of? 2. Valproic acids inhibition of glucoronidation is associated with ? 3. May potentiate ____ 4. Oxcarb can incr ___ at doses of ___

Answer 27

1. Phenobarb, phentoin, carbamazepine 10,11-epoxide 2. incr risk of derm ae's in combination with lamictal 3. CNS effects of BZD's 4. Phenytoin plasma levels at doses >1200 mg/day