ANTICONVULSANTS

Question 1

Define
1) Seizure
2) Fit / Convulsions
3) Epilepsy

Answer 1

1) A seizure is a sudden uncontrolled electrical disturbance that manifests either as motor , sensory or even psychic
2) Fit / convulsion - seizures that manifests as motor activity
3) Epilepsy - when seizure attacks are chronic

Question 2

Give the classification of anticonvulsants

Answer 2

Hydantoins
Iminostilbenes
Barbiturates
Benzodiazepines

Question 3

Give two examples of Iminostilbenes

Answer 3

Carbamazepine and Oxcarbazepine

Question 4

Give the structure of carabmazepine

Answer 4

It is a dibenzazepine - two benzene rings fused to an azepine group

Question 5

Give the moa of carbamazepine

Answer 5

It is a sodium channel blocker

Question 6

Sodium channels exist in which three states

Answer 6

Closed (resting)
Open
Inactivated

Question 7

Sodium chanels are multimeric complexes composed of which subunits

Answer 7

a - has four homologous repeats
b - two auxiliary units

Question 8

Carbamazepine blocks sodium channels during which state

Answer 8

The inactivated state

Question 9

Give two aspects of carbamazepine that enable it preferentially inhibit action potentials during seizure and less interfere with ordinary ongoing action potential

Answer 9

Use dependence and Voltage dependence

Question 10

Explain
1) use dependant blocking action
2) voltage dependant blocking action

Answer 10

Carbamezapine has use dependant blocking action as it effectively blocks high frequency action potentials than low frequency action potentials due to more accumulation of the action potentials during high frequency firing.

They are also voltage dependant as most sodium channels exist in the inactivated state thus alows for more blocking at this voltage

Question 11

Give and explain advantages of using carbamezapine in seizures

Answer 11

They are both voltage and use dependant thus prevent occurrence of seizures without causing unacceptable neurological impairment

Question 12

State the effects of carbamezapine and food.

Answer 12

Giving carbamezapine after meals slows its absorption and reduces peak levels thus enables patients to tolerate high doses

Question 13

State a unique feature in regards to carbamezapine and its metabolism

Answer 13

It is able to induce its own metabolism causing the serum concentrations to fall after a few weeks of trearment.

During the first week a half life of abput 36 hrs is seen but drops to about 8-12hrs in patients receiving continuous treatment

Dose adjusments are thus required during the first weeks of treatment

Question 14

Carbamezapine is metabolized in which organ and to what metabolite and by which enzyme(s)

Answer 14

Liver
carbamezapine -10,11- epoxide
Mainly CYP3A4 but CYP3A5 and CYP2C8 may assist

Question 15

Give PK of Carbamezapine

Answer 15

1) Volume of distribution is low at 1L/Kg
2) Plasma binding is ~ 70%
3) Metabolized in the liver by CYP3A4 and able to induce its own metabolism.
5) Only 5% is excreted unchanged

Question 16

Give the clinucal uses of Carbamezapine , atleast four

Answer 16

1) Treatment of focal seizures
2) Treatment of focal to bilateral tonic clonic seizures
3) Trigeminal and glossopharyngeal neuralgia
5) Mania in bipolar disorder
6) Treatment of GTCS but should be used with caution as it may exacerbate absence and myoclonuc seizures

Question 17

Give AEs of Carbamezapine

Answer 17

1) Diplopia - occurs first and may last less than an hour
2) Ataxia
3) Blurred vision
4) Git discomfort
5) Sedation at high doses
6) Benign leukopenia
7) SJS - especially wuth persons having HLA-B*1502 allele
8) Rash and hyponatremia - most common cause for dicontinuation

Question 18

Gice the C/I of Carbamezapine

Answer 18

Absence seizures as it may cause increase in seizures

Question 19

Give the structure of Oxcarbazepine

Answer 19

It is a 10 keto analogue of Carbamezapine

Question 20

Oxcarbazepine results in an epoxide metabolite , true or false

Answer 20

False

Question 21

The metabolites of Oxcarbazepine contribute to its activity and are termed as

Answer 21

Monohydroxy derivatives - MHDs

Question 22

Oxcarbamezapine MHDs undergo what type of metabolism to give Dihydroxy derivative (DHD)

Answer 22

glucoronide conjugation

Question 23

Between Carbamezapine and Oxcarbazepine which is less potent

Answer 23

Oxcarbazepine

Question 24

Eslicarbzepine is a prodrug of

Answer 24

S(+) - licarbazepine a metabolite of Oxcarbazepine

Question 25

Give the half life of S(+)- licarbazepine following oral administration of Eslicarbzepine

Answer 25

20-24hrs thus OD

Question 26

Lamotrigine is classified as what in terms of its srructure

Answer 26

Phenyltriazine

Question 27

Give the MOA of Lamitrogine

Answer 27

Block sodium channels

Question 28

Lamotrigine is prefeered due to

Answer 28

its high tolerability

Question 29

The main clinical use of Lamotrigine

Answer 29

Focal seizures

Question 30

As an A/E instead of sedation Lamotrigine paradoxically causes

Answer 30

insomnia

Question 31

Although well tolerated give A/ E of Lamotrigine that may occue

Answer 31

Dizziness , Diplopia , SJS , rash

Question 32

Ethosuximide is primarily used to treat which type of seizures?

Answer 32

Absence seizures

Question 33

Give the mechanism of action of ethosuximide as a succinimide

Answer 33

It is a T type calcium channel blocker in the thalamocortical neurons. It can also block other ion channels such as Voltage dependent Na channels and the Ca dependent K channels

Question 34

Ethosuximide is not protein bound , true or false

Answer 34

True

Question 35

Give the half-life of ethosuximide.

Answer 35

40 hours . Has low clearance

Question 36

Give the metabolism of ethosuximide

Answer 36

Metabolised by hydroxylation by CYP3A4 while 20% is excreted unchanged in urine

Question 37

Give the dosage of ethosuximide

Answer 37

Due to the long half life , the drug can allow for OD but to reduce adverse GI effects it is guven BD or TDS

Question 38

Give the DDI of ethosuximide and valproic acid

Answer 38

Administration of ethosuximide with valproic acid reduces the clearance due to inhibition of ethosuximide metabolism

Question 39

Valproic acid was initially used as a

Answer 39

Solvent mixture for other antiseizure drugs

Question 40

Give the stryctyre of valproic acid

Answer 40

simple branched chain carboxylic acid

Question 41

Give the MOA od Valproic acid

Answer 41

1) Sodium channel blockade 2) Blocks NMDA receptor ( glutamate receptor) 3) Increases GABA by stimulating Glutamic acid decraboxylase for GABA synthesis and inhibiting GABA transaminase for GABA degradation

Question 42

Give the effect pf absorption of Valproic acid and food

Answer 42

Absoption is slowed

Question 43

Give the PK of Valproic acid

Answer 43

1) Rapidly absorbed after oral administration 2) Protein bound 3) 90% protein bound 4) Metabolised by CYP2C9 5) May indrrgo carrier mediated transport into and out of CSF

Question 44

Give the most common A/ E of valproic acid

Answer 44

GIT symptoms such as nausea, vomiting, abdominal pain , heartburn

Question 45

Give other A/E of Valproic acid

Answer 45

Sedation , ataxia and tremor Acute pancreatitis Rash Weight hain and stimulation of appetite

Question 46

What mist be measured in valproic acid use

Answer 46

LFTS due to hepatotoxicity that is increased in children less than 2 and polypharmacy

Question 47

Use of valproic acid in 1st trimester can lead to

Answer 47

neural tube defects , CVS orofaciaal and digital abnormalities Cognitive impairment

Question 48

Valproic acid can lead to hyperammonia that presents as The hyperammonia is more common in patients with

Answer 48

lethargy Genetic defects of ammonia metabolism leading to fatal encephalopathy

Question 49

Valproic acid inhibits metabolism of

Answer 49

phenytoin phenobarbital ethosuximide lorazepam

Question 49

Valproic acid inhibits metabolism of

Answer 49

phenytoin phenobarbital ethosuximide lorazepam

Question 50

Valproic acid reduces the clearance of

Answer 50

Lamotrigine

Question 51

Valproic acid is termed as a broad spectrum antiseizure drug and is used in the treatment of

Answer 51

GTCs Absence and Myoclonic partial seizures Migraine prophylaxis and Bipolar disorder

Question 52

Give the structure of Topiramate

Answer 52

Substituted monosaccharide

Question 53

Give the MOA of Topiranate

Answer 53

1) Blocks sodium channels 2) Potentiates / increases the inhibitory effects of GABA

Question 54

Toxicity with Topiramate

Answer 54

Somnolence , fatigue , parasthesia , nervousness Urolithiasis Refuced verbal fluency , Conitive impairment Acute glaucoma - withdraw drug Congenital oral cleft formation Weight loss Oligohydrosis Reduced serum bicarbonate due to inhibition of carbonic anhydrase

Question 55

Give the oxazolidinediones

Answer 55

Trimetthadione Dimethadione Paramethadione

Question 56

Trimethadione was used in the treatment of absence seizudes before introduction of succinimides

Answer 56

True

Question 57

Give ghe Moa of dimethadione

Answer 57

inhibiton of T type calcium channels

Question 58

Trimethadione is not protein bound

Answer 58

True

Question 59

Trimethadione undergoes what type of metabolism

Answer 59

demethylation to dimethadione that has he major anticonvulsant activity

Question 60

Give the half life of dimethadione

Answer 60

240hrs

Question 61

Give the A/ E of oxazolidinediones

Answer 61

sedation day blindness