Pharmacotherapy of epilepsy Flashcards by Iseoluwa Ojo

Epilepsy –

The occurrence of signs and symptoms as a result of abnormal excessive ______________ of ________ in select brain areas .

hypersynchronous discharge of neurons

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Epilepsy

The features of epilepsy occur when some neurons in the brain discharge ____________________________ predominating over ___________

abnormally with excitatory neurotransmission

inhibitory neurotransmission.

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Epilepsy

Features could be motor or non-motor

T/F

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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

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Seizure classification

•Generalized:

Generalized tonic clonic seizures –____
Absence seizures -__________
______
_______
______
————

•focal

Grand mal

petite mal

Tonic
Clonic
Atonic
Myoclonic

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Classification of antiepileptic drugs

Based on the _____________
Based on the —————
Based on the __________

chemical structure

generation

mechanism of action

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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

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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.

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_________ 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

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Classification of antiepileptic drugs – MOA

________ channel blockers
Facilitators of _______ neurotransmission

________ receptor blockade
________ channel blockers
Neuronal _______ channel opener
Others -

Sodium

GABAergic

Glutamate; Calcium

potassium

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Sodium channel blockers

Include _____,_____,___,______,_______

phenytoin, carbamazepine, oxcarbazepine, zonisamide, lamotrigine

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Sodium channel blockers

They act by ___________________

This prevents the ______________

preventing the entry of Na into the neurons.

generation of action potentials.

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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

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Sodium channel blockers

Sodium channel blockers bind to the sodium channels and keeps them in the ____________

inactive stage.

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GABAERGIC FACILITATION

GABAa agonist – _________,___________. Bind to GABAa receptors thereby increasing __________ into the cell leading to _____polarization.

benzodiazepines, barbiturates

chloride influx

hyper

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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

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Glutamate receptor antagonists

Glutamate is the main _______ neurotransmitter in the brain

Blockade of its action will inhibit the generation of _____ .

excitatory

seizures

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Glutamate receptor antagonists

AMPA /Kainate – _____,______

NMDA-__________ , probably levetiracetam

topiramate, perampanel

felbamate

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Calcium channel blockers

Important in ______ seizure

Hyperactivity of _________ calcium channel are implicated in the pathophysiology of epilepsy.

absence

thalamic T type

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Calcium channel blockers

Blockade of the ____ type calcium channels of _________ projecting to the cortex ( ________ circuits ) controls absence seizures – _______

thalamic neurons

thalamocortical

ethosuximide

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Carbamazepine

An ______________

First line agent for ________________________________ seizures

iminostilbene

focal and generalized tonic-clonic

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Carbamazepine

Contraindicated in _____________________________ seizures

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myoclonic, atonic, tonic and absence

Carbamazepine

Orally, ____% plasma protein bound

Metabolized in the liver to _________________ an active metabolite, and finally to _____________ an inactive metabolite.

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carbamazepine 10-11 epoxide

carbamazepine-10,11- diol

Carbamazepine

Half live initially ______ but falls to _________ with prolonged use because of autoinduction

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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

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

Pharmacotherapy of epilepsy Flashcards

(54 cards)