This document summarizes information about the drug sodium valproate, including its chemical properties, history of use, indications, dosing, mechanisms of action, side effects, contraindications, and considerations for special populations. Some key points are:
- Sodium valproate is an anticonvulsant and mood stabilizer derived from valproic acid that is used to treat epilepsy and bipolar disorder.
- It was first isolated in 1882 and first used clinically in 1964, gaining approval in various countries in the late 1960s and 1970s.
- Its mechanisms of action involve increasing GABA transmission and blocking voltage-gated sodium channels.
- Common side effects include weight gain,
6. b
Valproic acid (VPA) is
an organic weak acid
The conjugate base is
valproate
The sodium salt of the acid is
sodium valproate
VPA looses proton H+ and form
9. • For 80 years valporic acid is used as solvent
•After 80 years
First clinical trial in 1964( sodium
valproate and valporic acid)
It was launched in france in 1967 as
DEPAKINE
Britain-1973
USFDA approval-1978
10. • In the United States, AbbVie Inc.
(formerly Abbott Laboratories)
manufactures Depakine, and Depacon.
• In Europe, however, the drug is called
Depakine and is manufactured by Sanofi.
11. Indications
All types of epilepsy
VPA is extensively used in the treatment of
bipolar disorders
Other neurological conditions such as
migraine and neuropathic pain
14. • VPA has been shown to reduce the
number of migraine attacks, as well
as their duration and intensity in 50
to 70% of patients for periods of
three months, up to one year or
longer
15. 750 mg/day PO in divided doses;
adjust dose as rapidly as possible to
desired therapeutic effect; not to
exceed 60 mg/kg/day
16. Acute mania or hypomania
• Step 1: Antipsychotic or valproate or lithium
• Step 2: add benzodiazepine
Prophylaxis bipolar
• First line : lithium
• Second line: valproate , antipsychotic
19. MOA
There is no single mechanism of action that can explain valproate’s broad
effects on neuronal tissue. Its pharmacological effects include:
increased gamma-aminobutyric acid transmission
(GABA Trasaminase inhibitor, stimulates GABA
secretion)
blockade of voltage-gated sodium channels
modulation of dopaminergic and serotonergic
transmission
20. S/E
• Weight gain, Sleepiness, Tremors, Liver
injury, Dizziness, Paresthesia (tingling or
pricking sensation), Hypersensitivity, Anemia
(low number of red blood cells), Deafness,
Urinary incontinence, Decreased sodium level
in blood, Pain during periods
21. S/E
• VPA can cause direct bone marrow
suppression leading to aplastic anemia
• Hepatotoxicity: Regarding possible
hepatotoxicity of VPA, transient elevations of
hepatic enzymes without clinical symptoms
are seen in 15 to 30% of patients
22. C/I
When used by pregnant women, it has the
potential to harm their unborn children by
causing
still births,
slowed neurological development,
and congenital birth defects.
24. Elderly
• Increased sleepiness.
• More people stopped the medication for this
reason. Additional side effects of weight loss
and decreased food intake were also
associated with one-half of people who
become sleepy
25. Polycystic ovary syndrome (PCOS) is a
condition in which the ovaries produce an
abnormal amount of androgens, male sex
hormones that are usually present in
women in small amounts.
26. PCOS
• PCOS regarded as a controversial issue in
women with epilepsy.
• The syndrome is characterized by endocrine
dysfunction such as irregular menstruation or
amenorrhoea, hirsutism and infertility, but its
pathogenesis and clinical symptoms are
heterogeneous, and the syndrome is also
related to obesity, regardless of drug treatment
27. • polycystic ovary syndrome appear
to be more common with VPA as
compared to other AEDs