Valproic acid (Sodium Valproate)

Valproic acid (Sodium Valproate)

Q. 1

A 26-year old lady has just recovered from acute manic episode. She has a diagnosis of bipolar affective disorder. Which one of the following is not used for the prophylaxis of the condition?

 A

Carbamazepine

 B

Lithium

 C

Semisodium Valproate

 D

Chlorpromazine

Q. 1

A 26-year old lady has just recovered from acute manic episode. She has a diagnosis of bipolar affective disorder. Which one of the following is not used for the prophylaxis of the condition?

 A

Carbamazepine

 B

Lithium

 C

Semisodium Valproate

 D

Chlorpromazine

Ans. D

Explanation:

Lithium, Semi Sodium Valproate (Depakote) and Carbamazepine are used in prophylaxis of Bipolar disorder.

Lithium is the drug of choice but it will require frequent blood level montoring due to it’s narrow therapeutic index.

Sodium valproate cannot be used in women of child bearing age due to possible teratogenicity to the foetus.

All mood stabilisers work by preventing manic episodes.

They have very little effcet on the depression. However, if mania is controlled the episodes of depression are likely to be insignificant. Chlorpromazine is an old generation anti-psychotic.


Q. 2

Which of the following teratogenic effects in incorrectly matched?

 A

Phenytoin – Cleft lip / palate

 B

Zidovudine – Skull defects

 C

Valproate – Neural tube defects

 D

Warfarin – Nasal Bone Dysplasia

Q. 2

Which of the following teratogenic effects in incorrectly matched?

 A

Phenytoin – Cleft lip / palate

 B

Zidovudine – Skull defects

 C

Valproate – Neural tube defects

 D

Warfarin – Nasal Bone Dysplasia

Ans. B

Explanation:

Zidovudine is an antiretroviral drug which inhibits viral reverse transcriptase(RNA dependent DNA polymerase).
It is not a teratogenic drug.
It does not cause any skull defects. Anemia and neutropenia are the most important side effects.
Myopathy, lactic acidosis, hepatomegaly, convulsions are infrequent side effects.
 
Ref: Essentials of Medical Pharmacology By KD Tripathi, 5th Edition, Page 372, 374, 566, 729

Q. 3

A mother with 10 weeks pregnancy and who had previously delivered a baby with open neural tube defect which statement is true :

 A

Sodium valproate causes open neural tube de­fect

 B

Risk of recurrence is 10%

 C

Amniocentesis should be done

 D

Give multivitamin

Q. 3

A mother with 10 weeks pregnancy and who had previously delivered a baby with open neural tube defect which statement is true :

 A

Sodium valproate causes open neural tube de­fect

 B

Risk of recurrence is 10%

 C

Amniocentesis should be done

 D

Give multivitamin

Ans. A

Explanation:

Ans. is a i.e Sodium valproate causes open neural tube defect

Sodium valproate “used during pregnancy. has produced neural tube defects in the offspring; therefore should be avoided”.

Therefore option “a” is correct

“The risk of recurrence of anencephaly is 5% after one affected child and 13% after two affected children.°

Therefore option “b” is incorrect.

Diagnostic protocol in case of patients who have had a child with neural tube defect :

In such patients At 16 weeks of gestation –                                                                        

  • Level II ultrasound
  • Maternal serum alpha feto protein (MSAFP).

Based on the results of these two investigations : the need for amniocentesis is decided.


Q. 4

Use of Valproate during pregnancy may cause :

 A

Neural tube defect

 B

Hydantoin syndrome

 C

Respiratory depression

 D

Mental retardation

Q. 4

Use of Valproate during pregnancy may cause :

 A

Neural tube defect

 B

Hydantoin syndrome

 C

Respiratory depression

 D

Mental retardation

Ans. A

Explanation:

Neural tube defect


Q. 5

Drug(s) used in bipolar disorder is/are.

 A

LiCO3

 B

Na valproate

 C

Phenytoin

 D

All

Q. 5

Drug(s) used in bipolar disorder is/are.

 A

LiCO3

 B

Na valproate

 C

Phenytoin

 D

All

Ans. D

Explanation:

A i.e. LiCO3; B i.e. Na valproate; C i.e. Phenytoin


Q. 6

Drug of choice for tonic-clonic seizures is ‑

 A

Sodium valproate

 B

Carbemazepine

 C

Phenobarbitone

 D

Felbamate

Q. 6

Drug of choice for tonic-clonic seizures is ‑

 A

Sodium valproate

 B

Carbemazepine

 C

Phenobarbitone

 D

Felbamate

Ans. A

Explanation:

Ans. is ‘a’ i.e., Sodium valproate


Q. 7

Drugs which increase GABA level in brains-

 A

Diazepam

 B

Phenobarbitone

 C

Sodium valproate

 D

Carbamazepine

Q. 7

Drugs which increase GABA level in brains-

 A

Diazepam

 B

Phenobarbitone

 C

Sodium valproate

 D

Carbamazepine

Ans. C

Explanation:

Ans. is ‘c’ i.e., Sodium valproate

GABA level is increased by

  1. Valproate and vigabatrine        —> by inhibiting GABA transaminase
  2. Gabapentin                            —> by increasing synaptic vesicle release of GABA.

Q. 8

Hepatotoxicity caused by valproate can be prevented by-

 A

Zinc

 B

Carnitine

 C

Pyridoxine

 D

Vit K

Q. 8

Hepatotoxicity caused by valproate can be prevented by-

 A

Zinc

 B

Carnitine

 C

Pyridoxine

 D

Vit K

Ans. B

Explanation:

Ans. is ‘b’ i.e., Carnitine

o Valprate is a hepatotoxic drug.

o Hepatotoxicity is due to its metabolite 4-pantenoic acid.

o Valprate hepatotoxicity is more common in persons with mitochondrial enzyme deficiency and may be ameliorated by administration of Carnitine, which valproate therapy can deplete.


Q. 9

The antiepileptic drug which does not produce enzyme induction is –

 A

Phenobarbitone

 B

Sodium valproate

 C

Phenytoin

 D

Primidone

Q. 9

The antiepileptic drug which does not produce enzyme induction is –

 A

Phenobarbitone

 B

Sodium valproate

 C

Phenytoin

 D

Primidone

Ans. B

Explanation:

Ans. is ‘b’ i.e., Sodium valproate

o Most of the anticonvulsants are enzyme inducers except valproate which is an inhibitor. Note : Valprate is an enzyme inhibitor overall but it induces metabolism of carbamazepine: “Valproate and carbamazepine induce each other;s metabolism”


Q. 10

The drug of choice in petit seizures is –

 A

Clonazepam

 B

Ethosuximide

 C

Diazepam

 D

Sodium Valproate

Q. 10

The drug of choice in petit seizures is –

 A

Clonazepam

 B

Ethosuximide

 C

Diazepam

 D

Sodium Valproate

Ans. D

Explanation:

Ans. is ‘d’ i.e., Sodium valproate

Petit mal seizures are synonymous with Absence seizure

Now DOC for absence seizure is valproate (previously it was Ethosuxamide).


Q. 11

A 15 year old boy with epilepsy on treatment with combination of valproate and phenytoin has good control of seizures. Levels of both drugs are in the therapeutic range. All of the following adverse effects can be attributed to valproate except :

 A

Weight gain of 5 kg

 B

Serum alanine aminotransaminase 150 IU/L

 C

Rise in serum ammonia level by 201.tg/dL

 D

Lymphadenopathy

Q. 11

A 15 year old boy with epilepsy on treatment with combination of valproate and phenytoin has good control of seizures. Levels of both drugs are in the therapeutic range. All of the following adverse effects can be attributed to valproate except :

 A

Weight gain of 5 kg

 B

Serum alanine aminotransaminase 150 IU/L

 C

Rise in serum ammonia level by 201.tg/dL

 D

Lymphadenopathy

Ans. D

Explanation:

Answer is D (Lymphadenopathy):

Lymphadenopathy ‘Pseudolymphoma’ is a complication associated with use of phenytoin and is not seen with valproate.

Side Effects of Valproate

Side effects of phenytoin:

1.

Hepatotoxicity :

1.

Hyperplasia of gums

 

– asymptomatic rise in serum transaminases is seen-KDT

2.

Hyperglycemia

 

– Fulminant hepatitis may be seen

3.

Hirsutism

2.

Weight gain

4.

Hypersensitivity reaction

3.

Hyper ammonemia

5.

Hydantoin syndrome is foetus : during pregnancy

4.

Gastric Irritation : Anorexia, vomiting

6.

Megaloblastic anemia

5.

Thrombocytopenia

7.

Osteomalacia

6.

Transient alopecia

8.

Lymphadenopathy – (Harrison 15th /2364)

7.

Ataxia, tremors and sedation may be seen

 

(Pseudolymphoma)

8.

Use during pregnancy may cause neural tube defects

9.

Neurological symptoms like dizziness, ataxia, incordination,

confusion, diplopia

Drugs causing Lymphadenopathy –Harrison

  • PhenytoinQ
  • PrimidoneQ



Q. 12

Patient of juvenile myoclonic epilepsy on valproate comes to you at 5 months of pregnancy with level H scan normal what will you advise‑

 A

Change the drug

 B

Continue the drug in same dose

 C

Decrease the dose of drug

 D

Increase the dose of drug

Q. 12

Patient of juvenile myoclonic epilepsy on valproate comes to you at 5 months of pregnancy with level H scan normal what will you advise‑

 A

Change the drug

 B

Continue the drug in same dose

 C

Decrease the dose of drug

 D

Increase the dose of drug

Ans. B

Explanation:

Ans. is ‘b’ i.e., Continue the drug in same dose

Valproic acid has the risk of fetal malformations during the first trimester of pregnancy.

This patient has normal level II scan at 5 months of pregnancy so the risk period of valproate is already over and valproate is the drug of choice in juvenile myoclonic epilepsy.

Thus the drug shoud be continued in the same doses.


Q. 13

Most serious side effect of valproate is

 A

Fulminant hepatits

 B

Spina bifida

 C

Weight gain

 D

Thrombocytopenia

Q. 13

Most serious side effect of valproate is

 A

Fulminant hepatits

 B

Spina bifida

 C

Weight gain

 D

Thrombocytopenia

Ans. A

Explanation:

Ans. is ‘a’ i.e., Fulminant hepatits

Valproate

  • Valproate acts by multiple mechanism :
  1. Prolongation of inactivated Na* channel.
  2. Inhibition of T type Ca’ current.
  3. Inhibition of degradation of GABA by GABA transminase → facilitation of GABA mediated Cl- channel opening.
  • Its most serious adverse effect is fulminant hepatitis especially in children below 3 years.
  • Used during pregnancy, it has produced spina bifida and other neural tube defects.
  • Uses (other than epilepsy) –> mania & bipolar illness, prophylaxis of migraine, trigeminal neuralgia, tardive dyskinesia.

Adverse effect of Valproate

  • Neurological – Ataxia, sedation,tremor
  • Systemic- Hepatotoxicity, thromobocytopenia,GI irritation, weight gain, transient alopecia, hyperammonemia, pancreatitis,coagulation disorder.


This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
Malcare WordPress Security