Seizures Flashcards
Define seizure
- Paroxysmal event caused by excessive electrical discharge of neurons
- May disturb consciousness, sensory or motor systems
- Discharges seen as spikes on EEG
Define epilepsy
Group of chronic neuro disorders characterized by unprovoked recurrent seizures (usually idiopathic)
Define status epilepticus
Prolonged seizures without recovery in between
Describe simple partial seizures
NO LOC
Describe complex partial seizures
With LOC, may prgoress to GTC
Describe secondarily generalized partial seizure
Begins as partial and has LOC
Describe absence seizures
- Sudden onset, blank stare
- Typically young children
- LOC but returns instantly
Describe generalized tonic-clonic seizures
- Muscle rigidity followed by sharp contractions
- LOC and confusion upon return to consciousness
Describe myoclonic seizures
- Generalized
- Brief sudden muscle contractions
- Face, trunk, extremities
Describe atonic seizures
- Generalized
- Complete loss of muscle tone
Describe tonic seizures
Uncontrolled extension of muscle groups
Describe clonic seizures
Repeated rhythmic jerking of arms and legs
Indications of phenytoin
Primary generalized
Partial
Advantages of phenytoin
- Well studied
- Many dosage forms
Disadvantages of phenytoin
- Challenging to dose (PK)
- DIs (CYP inducer, highly protein bound)
- Close monitoring required
- Extensive SE profile
Which formulation of phenytoin results in more active drug in the body?
Phenytoin ACID
Monitoring of phenytoin
- Risk of suicidal ideation
- CBC, LFTs, albumin
- Serum concentration due to narrow TI
Pregnancy category of phenytoin
D
Notable ADRs of phenytoin
- Gingival hyperplasia
- Hirsutism
- Osteomalacia
Why does phenytoin interact with other drugs?
Highly protein bound - other highly protein bound drugs can displace phenytoin
Drugs that increase phenytoin levels
- Acute ETOH intake
- Salicylates
- Estrogens
- H2 blockers
Drugs that decrease phenytoin levels
- Carbamazepine
- Chronic ETOH abuse
- Antacids w/Ca
- Phenobarbital
- Rifampin
How does phenytoin initially interact with warfarin?
Immediately, phenytoin can displace warfarin which may INCREASE INR
How does phenytoin interact with warfarin after prolonged administration?
CYP2C9 induction - phenytoin induces the metabolism of warfarin which may DECREASE INR
Phenytoin and warfarin are both ___ for CYP2C9
Substrates
How are Vit K dependent clotting factors affected by phenytoin and warfarin interacting? How is INR affected?
- Warfarin inhibits synthesis of clotting factors
- Phenytoin may also deplete them
- INR INCREASES
Main factors of phenytoin and warfarin interactions
- Protein binding
- CYP2C9 induction
- Competitive inhibition
- Depletion of Vit K clotting factors
Indications for carbamazepine
- Primary generalized (non-emergent)
- Partial seizures (newly diagnosed)
Advantages of carbamazepine
Well studied
Disadvantages of carbamazepine
- Active metabolite
- Auto-inducer (DIs)
- CNS side effects
What should be monitored when using carbamazepine?
WBC and ANC
- Idiopathic blood dyscrasias
- Mild persistent leukopenia
Contraindications to carbamazepine
- Hypersensitivity to TCAs
- BM suppression
Black box warning of carbamazepine
Blood dyscrasias
-Asians should be screened for HLA-B*1502 beforehand
Pregnancy category of Carbamazepine
D
Oxcarbazepine indications
- Partial (mono or adjunct)
- GTC
Advantages of oxcarbazepine
Comparable efficacy to phenytoin, valproic acid and CBZ but may be better tolerated
Disadvantages of oxcarbazepine
- Hyponatremia
- DIs
Dosing of oxcarbazepine compared to CBZ
Oxcarbazepine doses may need to be 50% higher in order to obtain equivalent seizure control
Pregnancy category of oxcarbazepine
C
Eslicarbazepine acetate indications
Partial (mono or adjunct)
Metabolism of eslicarbazepine acetate
Metabolized to eslicarbazepine (active metabolite of oxcarbazepine)
What is the significance of eslicarbazepine acetate metabolism?
Converted to active metabolite of oxcarbazepine (better tolerated bc more exposure to active vs. inactive metabolites)
When should eslicarbazepine acetate be avoided?
Severe hepatic dysfunction
Topiramate indications
- Partial
- GTC
Advantages of topiramate
- Few DIs
- Wt loss?
Disadvantages of topiramate
- Cognitive functioning impairment
- Kidney stones
- Wt loss?
How should dosing of topiramate be adjusted?
50% dose reduction in CrCl less than 50
Common ADRs of topiramate
- Poor concentration, confusion, word finding difficulties
- Somnolence
- Wt loss
DIs of topiramate
- OCPs
- Digoxin
- Valproic acid
- Phenytoin, CBZ, barbiturates
- CNS depressants
How are OCPs affected by topiramate?
May be less effective (higher estrogen doses may be required)
How is digoxin affected by topiramate?
Decreased concentration
How does topiramate interact with valproic acid?
Increased risk of hyperammonemia
Lamotrigine indications
- Partial (mono or adjunct)
- GTC
- Absence
Advantages of Lamotrigine
- Not highly protein bound
- Does not cause wt gain
Disadvantages of Lamotrigine
- Rash
- DIs
Dosing of Lamotrigine
Varies based on other meds
Major ADR of Lamotrigine
Hypersensitivity reaction presenting as rash can lead to SJS
Which AED can cause a hypersensitivity rash leading to SJS?
Lamotrigine
DIs of Lamotrigine
- Anticonvulsants
- OCPs
Drugs that cause visual abnormalities
- CBZ
- Eslicarbazepine
- Oxcarbazepine
- Lamotrigine
- Phenytoin
- Pregabalin
Anticonvulsants that cause weight loss?
- Ethosuximide
- Felbamate
- Topiramate
- Zonisamide
Anticonvulsants that cause weight gain?
- Gabapentin
- Pregabalin
- Valproic acid
- Vigabatrin
Indications for valproic acid
- Primary generalized (myoclonic, atonic, absence)
- Partial
- Mixed disorders
Advantages of valproic acid
- Well studied
- Multiple dosage forms
Disadvantages of valproic acid
- Side effect profile
- DIs (enzyme inhibitor)
What is the active form of valproic acid?
Valproate ion
Half life of valproic acid?
9-18 hours
PK of valproic acid
- 90% protein bound
- Undergoes glucuronidation (inhibits glucuronidation of other agents)
Pregnancy category of valproic acid
D
Notable ADRs of valproic acid
- Sedation, fine hand tremor
- Hair loss, hepatotoxicity
- Thrombocytopenia
Indications for gabapentin
Partial (with or w/o secondary generalization)
Advantages of gabapentin
No known DIs
Which AEDs have no known drug interactions?
Gabapentin
Levetiracetam (Keppra)
Pregabalin
Disadvantages of gabapentin
- Very high doses required for seizure control
- Increased frequency of dosing
PK of gabapentin
- Not metabolized (renally excreted unchanged)
- Does NOT induce hepatic enzymes
Half life of gabapentin
5-8 hours
Pregnancy category of gabapentin
C
ADRs of gabapentin
- Somnolence
- Ataxia
- Tremor
- Dizzy
- HA
Indications for Levetiracetam (Keppra)?
- Partial (with or w/o secondary generalization)
- Adjunctive for myoclonic or primarily generalized
Advantages of Levetiracetam (Keppra)?
- No known DIs
- Various dosage forms
- Pediatric use
Disadvantages of Levetiracetam (Keppra)?
Limited indications
Pregnancy category of Levetiracetam (Keppra)
C
ADRs of Levetiracetam (Keppra)
- Somnolence
- Asthenia
- Dizzy
- Vertigo
- HA
- Not dependent on dose or titration
Indications for pregabalin
Partial (with or w/o secondary generalization)
Advantages of pregabalin
No known DIs
Disadvantages of pregabalin
- Brand name only (expensive)
- Schedule V
Which AED is expensive because it is available brand only?
Pregabalin
Pregnancy category of pregabalin
C
Common ADRs of pregabalin
- Dizzy
- Ataxia
- Somnolence
- Peripheral edema
- HA
Indications for tiagabine
Partial (adjunct)
PK (half life and metabolism) of tiagabine
6.7 hours
CYP3A4 metabolism
Drug interactions of Tiagabine
Highly protein bound but NO significant displacement of other protein bound agents
Pregnancy category of Tiagabine
C
Notable ADRs of tiagabine
- Generalized muscle weakness
- Depression
- Aphasia
- Encephalopathy
Indications for Zonisamide
Partial (adjunct)
Drug interactions of Zonisamide
CYP3A4
Pregnancy category of Zonisamide
C
Indications for phenobarbital
All seizure disorders
Advantages of phenobarbital
- Oldest anti-epileptic drug
- Broad spectrum
Disadvantages of phenobarbital
- Pan-inducer
- Toxicity
What does acute intoxication of phenobarbital cause?
- Unsteady gait
- Slurred speech
- Sustained nystagmus
Signs of chronic intoxication of phenobarbital?
- Confusion
- Poor judgment
- Irritability
- Insomnia
- Somatic complaints
Phenobarbital and ETOH interaction?
Lethal dose is LESS if taken with ETOH (circulatory collapse and respiratory depression)
ADRs of phenobarbital
- Dependence
- CNS depression
Use phenobarbital with caution in which patients?
Renal OR hepatic dysfunction
What are the withdrawal symptoms of phenobarbital?
Convulsions and delirium
DIs of phenobarbital
- Pan inducer of CYP450
- Increases Vit D metabolism (osteomalacia)
- CNS depressants (additive effect)
Pregnancy category of phenobarbital
D
Describe primidone
Converted to phenobarbital via hepatic oxidation
Pregnancy category of primidone
D
Indications for ethosuximide
Absence seizures
DIs of ethosuximide
Clearance is decreased by valproic acid
Indications for felbamate
Partial seizures (reserved for refractory cases)
ADRs of felbamate
Aplastic anemia
Severe hepatitis
When can AED therapy be discontinued?
Once a patient has been seizure free for 2-4 years
Treatments of status epilepticus
- 0-10 mins: IV lorazepam
- 10-30 mins: IV phenytoin or fosphenytoin
- 30-60 mins: additional dose of hydantoin, IV phenobarbital
Which GCSE treatment contains propylene glycol?
- IV Phenytoin (40%, can cause hypotension and cardiac arrhythmias)
- Fosphenytoin does NOT have propylene glycol
How should fosphenytoin be prepared?
Diluted in 5% dextrose or NS
Side effects of fosphenytoin
Paresthesia and pruritus of face and groin
Nonpharm therapy of GCSE
- IV thiamine
- IV glucose
- Vital signs
- Airway, ventilation
Describe midazolam
- Diffuses rapidly into brain
- Extremely short half life (give via continuous infusion)
