Anticonvulsants Flashcards
seizures typically originate in what part of the brain
cerebral cortex
differentiate between partial and generalized seizures
- Partial: begin in focused area in the cortex that may spread throughout the brain. Partial seizures often develop years after head injury or stroke
- Generalized: generally involve both hemispheres from the outset
List the three types of partial seizures
- Simple partial: jerking, lasting about 60 sec, preservation of consciousness, minimal spread
- Complex partial: impairment of consciousness <2 min, automatic movements such as lip smacking or hand wringing; originates from the temporal lobe, often involves the limbic system
- Partial with secondary generalized tonic-clonic: originates as a partial seizure and develops into tonic-clonic; loss of consciousness, muscle contractions alternating with relaxation
Describe simple partial seizures
- focal
- brief (< 90 sec)
- no loss of consciousness
Describe complex partial seizures
- last < 2 min
- altered or loss of consciousness; hallucination
- begin in temporal lobe
Describe partial with secondary generalized tonic-clonic
- originates as a partial seizure and develops into tonic-clonic;
- loss of consciousness
- muscle contractions alternating with relaxation
List the four types of generalized seizures
- Tonic-clonic (grand mal)
- Absence (petit mal)
- Myoclonic
- Atonic
describe a Tonic-clonic (grand mal) seizure
- loss of consciousness
- muscle contractions, urinary incontinence
- Tonic rigidity followed by tremor followed by clonic violent jerking of body
describe a absence generalized seizure
- 10-30 sec
- loss of awareness but not consciousness
- staring, cease activity; may be some mild clonic movements
describe a myoclonic generalized seizure
- brief shock-like muscle contraction, may be part of one extremity or general
describe an atonic generalized seizure
- sudden loss of postural tone
- patient can fall down
Anticonvulsants act on GABA to
- goal is to increase GABA inhibitory activity
- protects against both generalized and partial seizures
- experimental blockade of GABA receptors causes seizures
MOA (4) of drugs that affect GABA neurotransmission and act as anticonvulsants
- block GABA re-uptake
- Inhibit GABA metabolism
- Stimulate GABAA receptors
- binds synaptic vesicular protein; SV2A
Goal of drugs that affect Glutamate and act as anticonvulsants.
- activation of glutamate receptors (NMDA) causes seizures
- goal is to decrease excitatory glutamate activity
common targets of drugs that inhibit glutamate activity
-
voltage gated Na+ channels
- targets rapidly firing neurons
-
thalamic Ca2+ channels
- T-type Ca2+ channels are overactive in absence seizure
-
SV2A
- increase GABA release
Which 3 anti seizure drugs induce CYP450s
- Phenytoin
- Carbamazepine
- Phenobarbital
MOA of Phenytoin (Dilantin)
- Prolongs inactivation of Na+ channels
Phenytoin (Dilantin) and Fosphenytoin (Cerebyx) treats what type of seizures
- partial and generalized tonic-clonic seizures
- not effective for absence seizures
MOA of Fosphenytoin
- prolongs inactivation of Na+ channels
- Blocks high-frequency repetitive firing
route of administration of Fosphenytoin
injectable
Elimination of Phenytoin and Fosphenytoin is
-
Dose dependent
- first order metabolism occurs at low doses
- therapeutic range and higher doses, liver reaches maximum capacity, and metabolism becomes zero-order.
Side effects of Phenytoin (dilantin)
- gingival hyperplasia
- risk of stevens johnson syndrome
- pregnancy-category D
DOC for parital seizures
Carbamazepine
MOA of Carbamazepine
- inhibits Na+ channels and decreases transmitter release
side effects of Carbamazepine
- diplopia
- ataxia
- stevens johnson syndrome
- pregnancy category D
MOA of Phenobarbital
- Prolongs opening of chloride channel at GABA receptor
Phenobarbital is used in treatment of what type of seizures
- parital seizures
- generalized tonic-clonic seizures
MOA of Gabapentin
-
GABA analog
- but does not act on GABA receptor
- may increase GABA release
Uses of Gabapentin
- adjunct for partial and generalized tonic-clonic seizures
- neuropathic pain
drug interactions with Gabapentin
Negligible
Levetiracetam (Keppra) is used to treat what type of seizures
- Partial
- myoclonic
- tonic-clonic
MOA of Levetiracetam (Keppra)
- binds to synaptic vesicular protein (SV2A)
- decreases glutamate and increases GABA release
MOA of Lamotrigine (Lamictal)
- voltage dependent inactivation of Na+ channels
Lamotrigine (Lamictal) is used to treat what type of seizures
- Partial seizures
side effects of Lamotrigine (Lamictal)
- skin rash and stevens-johnson syndrome
Topiramate (Topamax) is commonly used to treat what type of seizure disorder
- partial and generalized tonic-clonic seizures
MOA of Topiramate (Topamax)
- Blocks Na+ channels
side effects of Topiramate (Topamax)
- acute myopia/glaucoma
Tiagabine is used to treat what type of seizures
- adjunct treatment for partial seizures
MOA of Tiagabine
- inhibits reuptake of GABA (GAT-1)
- enhances GABA activity
Vigabatrin is used to treat what type of seizures
-
refractory complex partial seizures
- infantile spasm (west’s syndrome)
MOA of Vigabatrin
- irreversibly inhibits GABA transaminase
- decreases GABA metabolism and enhances activity
side effects of Vigabatrin
- visual field problems/ retinal damage
DOC for absence seizures
Ethosuximide
MOA of Ethosuximide
- inhibits T-type Ca2+ channels
side effects of Ethosuximide
- hiccup
- stevens johnsons syndrome
second choice for absence seizures
Valproic acid
Valproic acid is used to treat what type of seizures
- absence seizures
- myoclonic seizures
- mixed sz
MOA of Valproic acid
- blocks Ca2+ channels and Na+ channels
side effects of Valproic acid
- hepatotoxicity
- pregnancy category D
- alopecia
Clonazepam is a BZ that is used to treat what types of seizures
- absence seizures
adverse effects of Clonazepam
- sedation
- tolerance for anti-sz effect may occur
DOC status epilepticus
Diazepam
MOA of Diazepam and Lorazepam
- Benzodiazepines
- stimulate GABA channel
adverse effects of Diazepam and Lorazepam
pregnancy category D
What anti-seizure medications have the highest risk to produce stevens johnson syndrome
- phenytoin
- Lamotrigine
- Carbamezapine
- Valproate
what is stevens johnson syndrome
- toxic epidermal necrolysis
which Drugs are used in absence seizures
- Ethosuximide (Zarontin®)
- Valproic acid (Depakene®)
- Clonazepam (Klonopin®)
