Anti Epileptics

Question 1

AED decreases the —– and —– of seizures in people with epilepsy
They treat the ——
Minimze —– and ——

Answer 1

Severity and frequency
Symptoms and ot the cause
Seizures and adverse drug effects

Question 2

Mechanism of action categories:
1-
2-
3
4

Answer 2

1-promoting the inactivated state of voltage Na+ channels
2-enhanced GABA
3-limits activation of voltage Ca channels known as T current
4-inhibit glutamate receptors

Question 3

What are the 2 neurotransmitters that are inhibittory

Answer 3

GABA
Glycine

Question 4

AEDs with Na+ inactivation
1-
2-
3-
4-
5-
6-

Answer 4

Lamotrigine
Carbamazepine
Topiramate
Phenytoin
Valproate
Zonisamide

Question 5

AEDs with enhanced GABA
1-
2-
3-
4-
5-

Answer 5

Barbiturates
Benzodiazepine
Vigabatrin
Valproate
Tiagabine

Question 6

AEDs with decrease in Ca channels
1-
2-

Answer 6

Valproate
Ethosuximide

Question 7

Phenytoin
MOAction at low and high
Usages 3

Answer 7

-Blocks Na channels by binding to the inactivate state and slowing its recovery
- x5-10 will block the ca channels
-used for partial and generalized tonic clonic
Not for absenceeee
Primary tx for status epilepticus

Question 8

Pharmacokinetics
Moa:
Not given:
Prodrug
—- bound to serum proteins
—-metabolism
Inducer or inhibitor of drug metabolism
After hepatic hydroxylatiom system saturation——-

Answer 8

Orally
Muscular extremely painful and necrotic
Fosphenytoin
90%
Hepatic cyp2c9 or 2c19
Inducer
Adter saruration small increase in dose will lead to large increase in plasma conc which will lead to toxicity

Question 9

Adverse effects of phenytoin:
1-acute
2-chronic
3-allergic
4-teratogenic

Answer 9

Acute: cerebellaf atrophy ataxia nystagmus and diplopia
Chronic gingival hyperplasia metabolic bone disease and peripheral neuropathy
Allergic: stevens jhonsons syndrome, fever rash hepatic failure aplastic anemia and lymphadenopathy
Terato: fetal malformations and cardiac abnormalities

Question 10

Phenytoin DD
1-
2-
3-
4-

Answer 10

1-carbamazepine enhances metabolusm of phenytoin
2-valproate phenylhutazone and sulfonamides they displace phenytoin in plasma
3-phenytoin enhances oral contraceptives metabolism and lead to unplanned pregnancy
4-phenytoin enhances vit k and D metabolism which may lead to osteoporosis or hypoptothrombinemia

Question 11

Carbamazepine
Mechanism
Uses 3
Adverse 5

Answer 11

Blocking sodium channels
Partial tonic clonic seizures
Not in absence
Trigeminal neuralgia
Bipolar,mood stabilizer
1- increase frequency if given to absence
2- steven johnsons
3-water retention and hyponatremia
4-blood dyscarsia:aplastic anemia agranulocytosis
5-teratogenic : fetal malformations

Question 12

Carba
Pharmacokinetics
Moa:
Distribution
—- bound with/without displacement
Prodrug
Inducer or inhibitor of met
Metaboluzed by?

Answer 12

Orall with variable absorption
Low distrib
70% without dis
Oxcarbamazepine
Inducer
1a2 2c8 3a4 to one active (10-11 epoxide)

Question 13

Lamotrigine
Mode of action
Uses
Pharmacokinetics
Interactions
Adverse 4

Answer 13

Blocks sodium and calcium channels
Partial and generalized
Active against absence and myoclonic
Bipolar
Completely absorbed
55 protein absorbed
Glucorinidation
Half life 24 hr
Valproate increase drug half by inhibiting glucu
Inducers: phenytoin carbam or phenobarbital decrease half to 14 hr
Dizziness and ataxia
Blurred or diplopia
Nausea and vomitting
SJS

Question 14

Zonisamide
Moa
Derivative of?
Uses
Adverse

Answer 14

Prolongs inactivation of na
Inhibits ca
Sulfonamide derivative
Refractory partial
Somnolence
Ataxia
Anorexia
Nervousness
1% develop renal calculi
Oligohydrosis

Question 15

Enhanced GABA mechanisms:
1-
2-
3-

Answer 15

Inhibit GABA reuptake
GABA breakdown
Increase GABA release

Question 16

Phenobarbital
MOAction:
Uses:
——– is metabolized to phenobarbital

Answer 16

1-enhancement of inhibitory effects of GABA
2-at high concentration: suppresses repetitive firing in neurons through an action on Na conductance and block Ca
Primidone

Question 17

Uses of phenobarbital:
1-
2-
3-
4-
Adverse:
Inducer or inhibitors

Answer 17

1-status epilepticus
2-partial seizures
3-generalized tonic clonic
4-when the patient is refractory to many drugs (chronic therapy)
Sedation,cognitive impairment and potential for osteoporosis
Inducer

Question 18

Tiagabine
Mechanism
Uses
Contraindication
Adverse

Answer 18

Blocks GABA uptake into presynaptic neurons
Tx for partial seizures
Contraindicated absence seizure
Adverse: tiredness dizziness gastrointestinal

Question 19

Gabapentin
Mechanism of action
Uses
Pharmacokinetics
Andverse 4

Answer 19

Analog of GABA and promote release of GABA
Uses: partial seizures and neuropathic pain (diabetic perioheral neuropathy)
Nooooott bound to pp
Notttt metabolized and doesn’t induce hepatic enzymes (renal elimination unchanged)
T1/2 4.5 to 7 hrs
Somnolence
Dizziness
Ataxia
Headache

Question 20

Levetiracetam
Mechanism of action:
Uses:
Pharmacokinetics
Adverse

Answer 20

Binds to vesicular protein SV2A and modify synaptic release of glitamate and GABA
Partial and secondarily generalized tonic clonic
Myoclonic seizures
Dont interact with CYP or UTG
Minimal (dizziness headache weakness)

Question 21

Topiramate
Mech:
Used
Pharmacokinetics
Interactions
Adverse

Answer 21

Blocks voltage Na
Increase GABa frequency
Block calcium
Inhibing glutamate NMDA receptors

Partial and generalized tonic clonic
Migraines prophylaxis
80% bioavailable
Minimal (15%) ppbinding
Moderate metabolism (20-50%) half life 20-30 hr

Birth control pills may be less effective
Acute myopia
Parasthesia,renal stones weight loss headache and oligohydrosis

Question 22

Ethosuximide
Mech:
Uses:
Pharmaco:
Interactions:
Adverse:

Answer 22

Inhibiting ca channels
First choice for absence seizures
Absorption is complete, not pb, half life 40 hrs
Valproic acid inhibits the metabolism of etho
Gastric distress including pain nausea and vomiting

Question 23

Divalproex
Combination of:
Mechanism

Answer 23

Sodium valproate and valproic acid and is reduced to valproate when it reaches GI
Reduces the Ca current
Blockade sodium channel
Block NMDA
Increase level of GABA (facilitating GAD the enzyme responsible for GABA) inhibiting GABA transaminase

Allll type of epilepsy including status epilepticus

Question 24

Pharmakokinetics of divalproex
Adverse
DD interactions

Answer 24

Food will delay absorption
90% bound to pp
Half life 9-18 hr
Nausea vomiting hepatotoxicity
Teratogenic effects
Valproate displaces phenytoin
Valproate inhibits phenobabital phenytoin and carbamazepine metabolism

Question 25

Bezodiazepine
Mech
Uses
Adverse

Answer 25

Enhance effect of GABA at GABAA receptors
Clonic tonic seizures and status epilepticus and adjunctive for myoclonic seizures:
1- diazepam (IV or rectally)
2- lorazepam (more effective and long acting)
Absence clonazepam
Adverse: sedation and tolerance

Question 26

AED in absence
Non enzyme imducing AEDs

Answer 26

Lamotrigine,divaloproex ethosuximide clonazepam

Gabapentin
Lamotrigine
Levetiracetam
Second generation (lesser risk for DD interactions)

Question 27

Antiseizure therapy and pregnancy
Teratogenic effects:
Recommandations

Answer 27

Phenytoun, carbamazepine divalproex and phenobarbital

1-trial period without antiseizure medication
2- monotherapy with careful attention to drug level