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House Pharmacology > Pharmacotherapy of epilepsy > Flashcards

Pharmacotherapy of epilepsy Flashcards

1
Q

Epilepsy –

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

A

hypersynchronous discharge of neurons

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2
Q

Epilepsy

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

A

abnormally with excitatory neurotransmission

inhibitory neurotransmission.

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3
Q

Epilepsy

Features could be motor or non-motor

T/F

A

T

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4
Q

Classification of seizures – seizures are classified into two broad group

Generalized – implies that seizure foci occur ———————

Focal – Implies that seizure focus occur __________________

A

on both sides of the brain

on one side of the brain

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5
Q

Seizure classification

•Generalized:

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

•focal

A

Grand mal

petite mal

Tonic
Clonic
Atonic
Myoclonic

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6
Q

Classification of antiepileptic drugs

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

A

chemical structure

generation

mechanism of action

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7
Q

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

A

phenobarbitone

primidone

phenytoin, fosphenytoin

carbamazepine, oxcarbazepine

ethosuximide; valproic acid

clonazepam, diazepam, lorazepam,

lamotrigine; Gabapentin

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8
Q

Classification based on generation

First generation antiepileptic drugs – ______,_______,_______,________, and _____

Second generation – ———,———-,———-,———,————,———-

Third generation – _______,________,_____,_______,_______,_____

A

phenobarbitone, phenytoin, carbamazepine, valproate and
Ethosuximide

levetiracetam , lamotrigine, oxcarbazepine, gabapentin, zonisamide, pregabalin,

retigabine, bivaracetam, lacosamide, lasigamine, carabersat, carisbamate.

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9
Q

_________ 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.

A

Second; first

Poorly

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10
Q

Classification of antiepileptic drugs – MOA

________ channel blockers
Facilitators of _______ neurotransmission

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

A

Sodium

GABAergic

Glutamate; Calcium

potassium

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11
Q

Sodium channel blockers

Include _____,_____,___,______,_______

A

phenytoin, carbamazepine, oxcarbazepine, zonisamide, lamotrigine

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12
Q

Sodium channel blockers

They act by ___________________

This prevents the ______________

A

preventing the entry of Na into the neurons.

generation of action potentials.

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13
Q

Sodium channel blockers

The sodium channel exists in 3 stages –

_______ stage – ________________ sodium passes into the cell

_______ phase –__________________ into the cells

_________ phase – ______________,__________

A

resting; sodium potassium ATPASE

Active ; increased infux of sodium

Inactive; channels are closed. POTASSIUM EFFLUX

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14
Q

Sodium channel blockers

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

A

inactive stage.

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15
Q

GABAERGIC FACILITATION

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

A

benzodiazepines, barbiturates

chloride influx

hyper

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16
Q

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 – ______,______

A

tiagabine; vigabatrine

valproate

Gabapentin, valproate

pregabalin, gabapentin

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17
Q

Glutamate receptor antagonists

Glutamate is the main _______ neurotransmitter in the brain

Blockade of its action will inhibit the generation of _____ .

A

excitatory

seizures

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18
Q

Glutamate receptor antagonists

AMPA /Kainate – _____,______

NMDA-__________ , probably levetiracetam

A

topiramate, perampanel

felbamate

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19
Q

Calcium channel blockers

Important in ______ seizure

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

A

absence

thalamic T type

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20
Q

Calcium channel blockers

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

A

T

thalamic neurons

thalamocortical

ethosuximide

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21
Q

Carbamazepine

An ______________

First line agent for ________________________________ seizures

A

iminostilbene

focal and generalized tonic-clonic

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22
Q

Carbamazepine

Contraindicated in _____________________________ seizures

A

myoclonic, atonic, tonic and absence

23
Q

Carbamazepine

Orally, ____% plasma protein bound

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

A

75

carbamazepine 10-11 epoxide

carbamazepine-10,11- diol

24
Q

Carbamazepine

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

A

20-40 hours

10-20 hours

25
Q

Adverse effects of carbamazepine

Sedation, dizziness, vertigo, diplopia and ataxia. _________ and _____ seen with higher doses.

Hypersensitivity reactions ————,______,_______ . Life threatening. This necessitates drug withdrawal.

A

Vomiting diarrhoea and worsening of seizures

rashes, photosensitivity, hepatitis

26
Q

Drug interactions

Carbamazepine is an enzyme (inducer or inhibitor?) –(reducing or increasing ?) the levels of ________,_______,________,________ and other AEDs.

Other drugs induce its metabolism – ______,______, and ________

A

inducer

reducing

haloperidol, oral contraceptives, lamotrigine , topiramate

phenobarbitone, phenytoin and valproate.

27
Q

Carbamazepine

Other uses
__________ ————-

________ illness and acute ——— as a ________

A

Trigeminal neuralgia

Manic depressive; mania

mood stabilizer

28
Q

Valproic acid

Useful in ———— seizures and _____ seizures

A _______________________________ acid

(Single or Multiple?) mechanism of action

A

generalized; focal

Branched chain aliphatic carboxylic acid

Multiple

29
Q

Valproic acid

Gabamimetic action

inhibition of ____________
upregulation of ————-

A

GABA transaminase

GABA synthesis

30
Q

Valproic acid

__________ action

———— dependent ______ of Na channel activation

__________ of Ca mediated T current

A

Gabamimetic

Frequency; prolongation

Weak attenuation

31
Q

Valproic acid

Pharmacokinetics

Orally or IV?
Bound to plasma protein ____%

A

Orally

90

32
Q

VALPROIC ACID

Pharmacokinetics

(Completely or Incompletely?) metabolized in the _____

Excreted in urine after ________ conjugation

Half life -_________

A

Completely ; liver

glucuronide conjugation

-10-15hours

33
Q

Adverse effects of valproic acid

(Low or High?) toxicity

Hepatotoxic –in children below age _______
.
Weight _____.

Cognitive and behavioural effect not prominent

In pregnancy –_______ and ________

A

Low

3years.

gain.

spinal bifida and neural tube defects

34
Q

Other uses of VALPROIC acid

List 3

A

Mood stabilizers

Panic attack

Migraine prophylaxis

35
Q

Drug interactions of valproic acid

Enzyme (inducer or inhibitor ?)

Displaces _______ from binding sites

A

inhibitor

phenytoin

36
Q

Seizures

A seizure is a state of abnormal excessive or ______________________activity that manifest physically as _______ with or without ________________

A

synchronous electrical brain

convulsions

loss of consciousness

37
Q

Seizures cAn be be provoked or unprovoked

T/F

A

T

38
Q

Epilepsy is a (acute or chronic?) neurologic syndrome characterized by a predisposition to ____________ (provoked or unprovoked?) ____________

Affects about _____% of the general population

A

Chronic

two or more unprovoked seizures

5-10

39
Q

Causes of Epilepsy??

A

V accular(stroke)
I inflammatory or infectious disease
T Raumatic /toxic
A nomalous
M etabolic
I diopathic
Neoplasms
D egenerative

40
Q

SEIZURES: TRIGGERS

Excessive ________
______ consumption
Fever
Sleep _______
___________
_______
__________ changes

A

physical exertion

Alcohol; deprivation

Flashing lights; Music

Hormonal

41
Q

Inhibitory neurotransmitters includes
-_______

Excitatory neurotransmitters includes
–_________
–__________

A

GABA

Glutamate

Aspartate

42
Q

Types of seizures

Focal/ Partial
– ______
– _________

Generalized
–_______
–_________

A

Simple; Complex

Primary; Secondary

43
Q

In tonic phase, there is ___________ of body and limbs

In clonic phase, there is ______ of body,limbs, head

A

Straightening

Clonic jerks

44
Q

CLASSIFICATION of anti-seizure drugs

First generation
List 6

Second generation
List 6

A

-Phenytoin
– Carbamazepine
– Phenobarbital
– Valproate
– Ethosuximide
– Benzodiazepine

– Lamotrigine
– Topiramate
– Gabapentin
– Tiagabine
– Levitiracetam – Oxcarbazepine – Zonisamide

45
Q

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

A

Enhance; receptors; degradation; reuptake

Inhibit; Na+ ; Ca2+

46
Q

MECHANISM OF ACTION

First Generation
– Phenytoin: _______ ______ ______
– Carbamazepine: _______ ______ ______
– Ethosuximide: _______ ______ ______
– Valproate: _______ ______ ______ & _______________
– Phenobarbital: _____________
– Benzodiazepine: ____________________

A

Inactivates Na+ channels

Inactivates Na+ channels

Inactivates Ca2+ channels

Inactivates Ca2+ channels; Inhibits GABA transaminase

Stimulates GABA receptors

Stimulates GABA receptors

47
Q

MECHANISM OF ACTION

Second generation

– Oxcarbazepine:________ _______ ______
– Vigabatrin: ________ _______ ______
– Pregabalin: ________ _______ ______
– Tiagabine: _____________
– Lamotrigine: ________ _______ ______ & _________
– Topiramate: ________ _______ ______ &________
– Gabapentin: ________ _______ ______ &________

– Levitiracetam: ________ _______ ______ &________

A

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

48
Q

ADVERSE EFFECT

Carbamazepine
–__________ & Diplopia
– Dizziness & Ataxia
– Depression of AV conduction
–________/________ syndrome
– Hepatotoxicity
– Nephrotoxicity
–___________
– (Induce or inhibit?) cytochrome P-450

A

Blurred vision

Skin rashes; Steven Johnson’s

Teratogenicity

Induce

49
Q

ADVERSE EFFECT

Phenytoin
– _________
– ________
– __________/ ___________ syndrome
– _________ ————-
– Hyperglycemia
– Megaloblastic anemia
– Osteomalacia.
–(induce or inhibit?) cytochrome P-450

A

Sedation Hirsutism

Skin rashes/ Steven Johnson’s syndrome

Gingiva hyperplasia

Induce

50
Q

ADVERSE EFFECT

Valproate
– Weight _____
–___________
–______________ syndrome
–______
–(induce or inhibits?) cytochrome P-450

A

gain

Teratogenicity

Polycystic ovary

Alopecia; Inhibits

51
Q

ADVERSE EFFECT

Phenobarbital
–_______________ depression
–_________
–___________
– Sedation
–(induce or inhibit?) cytochrome P-450

A

Cardiorespiratory

Tolerance; Dependence

Induce

52
Q

ADVERSE EFFECT

Benzodiazepine
– Sedation
– Hallucination
–___________
–__________
–___________ depression
–(induce or inhibit?) cytochrome P-450

A

Dependence

Tolerance

Respiratory

Induce

53
Q

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 _______

A

sharp objects

ABCs; resuscitation

recovery position; self-limiting

pharmacological treatment.

5 minutes; Anti-seizure

54
Q

Anti-seizure Drug of Choice

– Tonic-Clonic Seizures/ Grand mal
_________,__________

– Absence Seizure/Petite mal
_________,__________

– Partial seizures
__________,___________

– Status epilepticus
___________/____________

A

VALPORATE LAMOTRIGINE

ETHOSUXIMIDE VALPORATE

CARBAMEZEPINE VALPORATE

BARBITUATE/ BENZODIAZEPINE

House Pharmacology (50 decks)

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