Antiseizure drug Pharmacology Dr. Pond Flashcards
(55 cards)
What are the possible causes of seizures?
-disturbed levels of body water/electrolytes
-disturbed level of blood glucose
-altered blood gases
-raised body temperature
-altered sleep patterns
-hormonal changes
-Toxicity
excess excitation
lack of inhibition
Where in the brain are seizures thought to arise?
Cerebral cortex (outermost part of the brain)
partial seizures
generalized seizures
What is the difference between partial and generalized seizures?
-partial seizures: start a specific locus in the cerebral cortex
-generalized seizures: both hemispheres are involved in the onset
What differentiates a simple partial seizure from a complex partial seizure?
simple: consciousness is not impaired
complex: consciousness is impaired -> may have a simple partial-onset where patients are aware -> followed by loss of consciousness OR they are unconscious right away
Secondarily generalized seizures
-simple partial to generalized (start at on area and spread to both hemispheres)
-complex partial to generalized
-simple partial to complex partial to generalized
What is a synonym for secondarily generalized seizures?
tonic-clonic seizure?
What is the gyrus (bump) before the central sulcus called?
-precentral gyrus
-> Primary motor cortex Homunculus, frontal lobe
-> collateral control: left control right sight of the body
seizures in the left side of the motor cortex will affect the right sight of the body
Which structure is found behind the central sulcus?
Postcenter gyrus
-> Primary somatosensory cortex Homunculus
collateral: sensation on the right side of the body are received on the left side of the brain
seizures in this area can sometimes be perceived as a tingeling
In which lobe is the Primary somatosensory cortex Homunculus located?
Parietal lobe
How long does a simple partial seizure last?
20-60 seconds
consciousness is not impaired
What symptoms are expected when seizures occur in the motor cortex?
Tonic-clonic movements of the upper or lower limb
Other symptoms - seizure
Occipital lobe (eye): flashing lights
Temporal lobe (auditory): ringing, noises
Autonomic: sweating, flushing, pallor, or epigastric sensation
How long does a complex partial seizure last?
-30 seconds to 2 minutes
impairment of consciousness
Features of complex partial seizures
-blank stare
-funny face, grimaces
-chewing movements of the mouth
-bad or unusual smell before the seizure
-dysphasia (unable to speak)
-auditory hallucination
-visual hallucination
Symptoms of Generalized seizures: Absence
last less than 30 sec
-vacant stare
-eyes rolled upwards
-eyelids flutter
-cessation of activity
-lack of responses
-patients may be unaware that they are having a seizure and move on with what they have been doing before the seizure
How are muscles affected by seizures?
Myoclonic: sudden, shock-like contraction (<1sec)
-> often occur falling asleep or shortly after waking up
Tonic: muscle stiffening -> person falls to the ground
Clonic: repetitive muscle jerking and short post-ictal phase
Atonic: sudden loss of muscle tone, dropping of head or limb, possible fall to the ground
Characteristics Tonic-clonic seizure
Tonic phase: stiffening, epileptic cry, cyanosis, incontinence
Clonic phase: clonic jerks of limbs, body and head, salivary frothing (foam), eyes blinking, cyanosis
Post-ictal (time after the seizure): confusion, fatigue, drowsiness, hypotension, confusion, headache, nausea
Antiseizure drug MOA
-Sodium channel modulation (fast inactivation)
-Sodium channel modulation (slow inactivation)
-K+ channel opener
-Blockade of voltage-gated calcium channels
-> getting back to resting potential
What is the MOA of Levetiracetam/brivaracetam?
-Synaptic vesicle protein 2A modulation
hinder vesicle formation
What are MOAs that involve GABA?
-Prolongs chloride channel opening: GABA binds to Cl(-) channels -> inhibitory (IPSP): barbiturates and stiripentol
-Increased frequency of chloride channel opening: benzodiazepines, ganaxolone
-Inhibits GABA-transaminase
-Blocks synaptic GABA reuptake
-increases GABA: Valproate
-Glutamate antagonist (Glutamate is an excitatory NT -> blocking will have an inhibitory effect):
->AMPA/kainate: phenobarbital, lamotrigine, perampanel, topiramate
->NMDA: carbamazepine, valproate, felbamate, lamotrigine, oxcarbazepine,
eslicarbazepine
Which channels are affected by Phenytoin?
-blocking voltage-gated Na-channels (presynaptic - preventing action potential, postsynaptic)
-blocking Ca2+ channels -> prevent Glutamate (excitatory NT) release
Kinetic features of Phenytoin
-Elimination of phenytoin is dose-dependent (1st order), -> metabolism is saturable - changes to 0 order when accumulating
-Fosphenytoin: prodrug, more soluble, less alkaline -> less skin irritation
Phenytoin: Adverse Effects
-Drowsiness
-Involuntary movement of the eyes, double vision
-Loss of muscle coordination (ataxia)
-Gingival hyperplasia (20% of chronic therapy)
-Hirsutism
-Pregnancy risk !!!
-Stevens-Johnson Syndrome (SJS)/Toxic epidermal
necrolysis (TEN)
-> Immune-complex–mediated hypersensitivity complex
-Purple Glove Syndrome (IV) – must be
administered slowly
What is a common Phenytoin IV complication?
-Purple Glove Syndrome
Skin necrosis and gangrene may develop
