Pharmacotherapy of epilepsy Flashcards
Epilepsy –
The occurrence of signs and symptoms as a result of abnormal excessive ______________ of ________ in select brain areas .
hypersynchronous discharge of neurons
Epilepsy
The features of epilepsy occur when some neurons in the brain discharge ____________________________ predominating over ___________
abnormally with excitatory neurotransmission
inhibitory neurotransmission.
Epilepsy
Features could be motor or non-motor
T/F
T
Classification of seizures – seizures are classified into two broad group
Generalized – implies that seizure foci occur ———————
Focal – Implies that seizure focus occur __________________
on both sides of the brain
on one side of the brain
Seizure classification
•Generalized:
Generalized tonic clonic seizures –____
Absence seizures -__________
______
_______
______
————
•focal
Grand mal
petite mal
Tonic
Clonic
Atonic
Myoclonic
Classification of antiepileptic drugs
Based on the _____________
Based on the —————
Based on the __________
chemical structure
generation
mechanism of action
Classification based on chemical structure
Barbiturates - ______________
Deoxybarbiturate – _________
Hydantoin – ______,________
Iminostilbene –________,__________
Succinimide – ____________
Aliphatic carboxylic acid –________, Na valproate, divalproex
Benzodiazepines –_____,_____,________
Phenyltriazine –___________
Cyclic GABA analogue – ________
Newer drugs – Vigabatrin, topiramate, tiagabine, zonisamide, levetiracetam
phenobarbitone
primidone
phenytoin, fosphenytoin
carbamazepine, oxcarbazepine
ethosuximide; valproic acid
clonazepam, diazepam, lorazepam,
lamotrigine; Gabapentin
Classification based on generation
First generation antiepileptic drugs – ______,_______,_______,________, and _____
Second generation – ———,———-,———-,———,————,———-
Third generation – _______,________,_____,_______,_______,_____
phenobarbitone, phenytoin, carbamazepine, valproate and
Ethosuximide
levetiracetam , lamotrigine, oxcarbazepine, gabapentin, zonisamide, pregabalin,
retigabine, bivaracetam, lacosamide, lasigamine, carabersat, carisbamate.
_________ generation antiepileptic drugs have better tolerability but are not superior in efficacy to _______ generation antiepileptic drugs.
Their teratogenic potentials are also (poorly or well?) defined.
Second; first
Poorly
Classification of antiepileptic drugs – MOA
________ channel blockers
Facilitators of _______ neurotransmission
________ receptor blockade
________ channel blockers
Neuronal _______ channel opener
Others -
Sodium
GABAergic
Glutamate; Calcium
potassium
Sodium channel blockers
Include _____,_____,___,______,_______
phenytoin, carbamazepine, oxcarbazepine, zonisamide, lamotrigine
Sodium channel blockers
They act by ___________________
This prevents the ______________
preventing the entry of Na into the neurons.
generation of action potentials.
Sodium channel blockers
The sodium channel exists in 3 stages –
_______ stage – ________________ sodium passes into the cell
_______ phase –__________________ into the cells
_________ phase – ______________,__________
resting; sodium potassium ATPASE
Active ; increased infux of sodium
Inactive; channels are closed. POTASSIUM EFFLUX
Sodium channel blockers
Sodium channel blockers bind to the sodium channels and keeps them in the ____________
inactive stage.
GABAERGIC FACILITATION
GABAa agonist – _________,___________. Bind to GABAa receptors thereby increasing __________ into the cell leading to _____polarization.
benzodiazepines, barbiturates
chloride influx
hyper
GABAERGIC FACILITATION
Increase in concentration of GABA
GABA uptake inhibitors-________.
GABA transaminase inhibitor – _______ . I THINK VALPROATE TOO
Succinic semialdehyde dehydrogenase - _______
GAD modulation – ______ ,_______.
Facilitation of GABAergic transmission – ______,______
tiagabine; vigabatrine
valproate
Gabapentin, valproate
pregabalin, gabapentin
Glutamate receptor antagonists
Glutamate is the main _______ neurotransmitter in the brain
Blockade of its action will inhibit the generation of _____ .
excitatory
seizures
Glutamate receptor antagonists
AMPA /Kainate – _____,______
NMDA-__________ , probably levetiracetam
topiramate, perampanel
felbamate
Calcium channel blockers
Important in ______ seizure
Hyperactivity of _________ calcium channel are implicated in the pathophysiology of epilepsy.
absence
thalamic T type
Calcium channel blockers
Blockade of the ____ type calcium channels of _________ projecting to the cortex ( ________ circuits ) controls absence seizures – _______
T
thalamic neurons
thalamocortical
ethosuximide
Carbamazepine
An ______________
First line agent for ________________________________ seizures
iminostilbene
focal and generalized tonic-clonic
Carbamazepine
Contraindicated in _____________________________ seizures
myoclonic, atonic, tonic and absence
Carbamazepine
Orally, ____% plasma protein bound
Metabolized in the liver to _________________ an active metabolite, and finally to _____________ an inactive metabolite.
75
carbamazepine 10-11 epoxide
carbamazepine-10,11- diol
Carbamazepine
Half live initially ______ but falls to _________ with prolonged use because of autoinduction
20-40 hours
10-20 hours
Adverse effects of carbamazepine
Sedation, dizziness, vertigo, diplopia and ataxia. _________ and _____ seen with higher doses.
Hypersensitivity reactions ————,______,_______ . Life threatening. This necessitates drug withdrawal.
Vomiting diarrhoea and worsening of seizures
rashes, photosensitivity, hepatitis
Drug interactions
Carbamazepine is an enzyme (inducer or inhibitor?) –(reducing or increasing ?) the levels of ________,_______,________,________ and other AEDs.
Other drugs induce its metabolism – ______,______, and ________
inducer
reducing
haloperidol, oral contraceptives, lamotrigine , topiramate
phenobarbitone, phenytoin and valproate.
Carbamazepine
Other uses
__________ ————-
________ illness and acute ——— as a ________
Trigeminal neuralgia
Manic depressive; mania
mood stabilizer
Valproic acid
Useful in ———— seizures and _____ seizures
A _______________________________ acid
(Single or Multiple?) mechanism of action
generalized; focal
Branched chain aliphatic carboxylic acid
Multiple
Valproic acid
Gabamimetic action
inhibition of ____________
upregulation of ————-
GABA transaminase
GABA synthesis
Valproic acid
__________ action
———— dependent ______ of Na channel activation
__________ of Ca mediated T current
Gabamimetic
Frequency; prolongation
Weak attenuation
Valproic acid
Pharmacokinetics
Orally or IV?
Bound to plasma protein ____%
Orally
90
VALPROIC ACID
Pharmacokinetics
(Completely or Incompletely?) metabolized in the _____
Excreted in urine after ________ conjugation
Half life -_________
Completely ; liver
glucuronide conjugation
-10-15hours
Adverse effects of valproic acid
(Low or High?) toxicity
Hepatotoxic –in children below age _______
.
Weight _____.
Cognitive and behavioural effect not prominent
In pregnancy –_______ and ________
Low
3years.
gain.
spinal bifida and neural tube defects
Other uses of VALPROIC acid
List 3
Mood stabilizers
Panic attack
Migraine prophylaxis
Drug interactions of valproic acid
Enzyme (inducer or inhibitor ?)
Displaces _______ from binding sites
inhibitor
phenytoin
Seizures
A seizure is a state of abnormal excessive or ______________________activity that manifest physically as _______ with or without ________________
synchronous electrical brain
convulsions
loss of consciousness
Seizures cAn be be provoked or unprovoked
T/F
T
Epilepsy is a (acute or chronic?) neurologic syndrome characterized by a predisposition to ____________ (provoked or unprovoked?) ____________
Affects about _____% of the general population
Chronic
two or more unprovoked seizures
5-10
Causes of Epilepsy??
V accular(stroke)
I inflammatory or infectious disease
T Raumatic /toxic
A nomalous
M etabolic
I diopathic
Neoplasms
D egenerative
SEIZURES: TRIGGERS
Excessive ________
______ consumption
Fever
Sleep _______
___________
_______
__________ changes
physical exertion
Alcohol; deprivation
Flashing lights; Music
Hormonal
Inhibitory neurotransmitters includes
-_______
Excitatory neurotransmitters includes
–_________
–__________
GABA
Glutamate
Aspartate
Types of seizures
Focal/ Partial
– ______
– _________
Generalized
–_______
–_________
Simple; Complex
Primary; Secondary
In tonic phase, there is ___________ of body and limbs
In clonic phase, there is ______ of body,limbs, head
Straightening
Clonic jerks
CLASSIFICATION of anti-seizure drugs
First generation
List 6
Second generation
List 6
-Phenytoin
– Carbamazepine
– Phenobarbital
– Valproate
– Ethosuximide
– Benzodiazepine
– Lamotrigine
– Topiramate
– Gabapentin
– Tiagabine
– Levitiracetam – Oxcarbazepine – Zonisamide
MECHANISM OF ACTION
Increase inhibitory activity
–_____ GABA synaptic transmission
•Stimulate GABA ———
•Inhibit GABA ______
•Inhibit GABA _______
Reduce excitatory activity
–______ Glutamate synaptic transmission
– Inactivate ____ channels
– Inactivate _____ channel
Enhance; receptors; degradation; reuptake
Inhibit; Na+ ; Ca2+
MECHANISM OF ACTION
First Generation
– Phenytoin: _______ ______ ______
– Carbamazepine: _______ ______ ______
– Ethosuximide: _______ ______ ______
– Valproate: _______ ______ ______ & _______________
– Phenobarbital: _____________
– Benzodiazepine: ____________________
Inactivates Na+ channels
Inactivates Na+ channels
Inactivates Ca2+ channels
Inactivates Ca2+ channels; Inhibits GABA transaminase
Stimulates GABA receptors
Stimulates GABA receptors
MECHANISM OF ACTION
Second generation
– Oxcarbazepine:________ _______ ______
– Vigabatrin: ________ _______ ______
– Pregabalin: ________ _______ ______
– Tiagabine: _____________
– Lamotrigine: ________ _______ ______ & _________
– Topiramate: ________ _______ ______ &________
– Gabapentin: ________ _______ ______ &________
– Levitiracetam: ________ _______ ______ &________
Inactivate Na+ channel
Inactivate Na+ channel
Inactivate Ca2+ channel
Inhibits GABA reuptake
Inactivate Na+ channel & ↓ Glutamate
Inactivate Na+ channel and ↑ GABA
Inactivate Ca2+ channels & ↑GABA
Inactivate Ca2+ channels & ↑GABA
ADVERSE EFFECT
Carbamazepine
–__________ & Diplopia
– Dizziness & Ataxia
– Depression of AV conduction
–________/________ syndrome
– Hepatotoxicity
– Nephrotoxicity
–___________
– (Induce or inhibit?) cytochrome P-450
Blurred vision
Skin rashes; Steven Johnson’s
Teratogenicity
Induce
ADVERSE EFFECT
Phenytoin
– _________
– ________
– __________/ ___________ syndrome
– _________ ————-
– Hyperglycemia
– Megaloblastic anemia
– Osteomalacia.
–(induce or inhibit?) cytochrome P-450
Sedation Hirsutism
Skin rashes/ Steven Johnson’s syndrome
Gingiva hyperplasia
Induce
ADVERSE EFFECT
Valproate
– Weight _____
–___________
–______________ syndrome
–______
–(induce or inhibits?) cytochrome P-450
gain
Teratogenicity
Polycystic ovary
Alopecia; Inhibits
ADVERSE EFFECT
Phenobarbital
–_______________ depression
–_________
–___________
– Sedation
–(induce or inhibit?) cytochrome P-450
Cardiorespiratory
Tolerance; Dependence
Induce
ADVERSE EFFECT
Benzodiazepine
– Sedation
– Hallucination
–___________
–__________
–___________ depression
–(induce or inhibit?) cytochrome P-450
Dependence
Tolerance
Respiratory
Induce
MANAGEMENT of seizures
Principle of Managing Seizures
– Remove or control hazards (e.g. remove _______ in the patient’s vicinity)
– Check _____; if needed, perform cardiopulmonary _________
– Place the patient in the ________ to prevent injury.
– Acute seizures are usually _________ and do not require _________
– But If a seizure has not ceased after ________ then give _______
sharp objects
ABCs; resuscitation
recovery position; self-limiting
pharmacological treatment.
5 minutes; Anti-seizure
Anti-seizure Drug of Choice
– Tonic-Clonic Seizures/ Grand mal
_________,__________
– Absence Seizure/Petite mal
_________,__________
– Partial seizures
__________,___________
– Status epilepticus
___________/____________
VALPORATE LAMOTRIGINE
ETHOSUXIMIDE VALPORATE
CARBAMEZEPINE VALPORATE
BARBITUATE/ BENZODIAZEPINE
