4. What is epilepsy?
Epilepsy “seizure disorder” is a
syndromic disease characterized by
disorder of the brain's electrical
system. Abnormal electrical impulses
cause brief changes in
movement, behaviour, sensation, or
awareness. These interruptions, known
as seizures, may last from a few
seconds to a few minutes. People who
have had two or more seizures are
considered to have epilepsy.
5. What is seizure?
Time-limited paroxysmal events
that result from
abnormal, involuntary, rhythmic
neuronal discharges in the brain
Seizures are usually unpredictable
and brief ( < 5 minutes) and stop
spontaneously
6. Etiology of epilepsy
Any process that alters the structure or the
function of the brain neurons can cause epilepsy
Processes that lead to structural alteration
include;
Congenital malformation
Degenerative disease
Infectious disease
Trauma
Tumors
Vascular process
In majority of patients, the etiology is proposed
but not found
8. Classification of Seizures
• Traditionally divided into “ grand mal” and “petit mal”
seizures
• ILAE classification of epileptic seizures in 1981 based on
clinical observation and EEG findings
• Seizures were divided into partial and generalized seizures
based on loss of consciousness
• Partial seizures were divided into simple partial and complex
partial based on alteration of consciousness
9. Observe seizure type
Generalized
seizures
Loss of consciousness?
Complex partial
Partial
seizures
Altered consciousness? Simple partial
11. Partial seizures (focal or
localized)
• In partial seizures just one side of the brain is affected. Simple partial seizures may cause
jerking motions or hallucinations, but the person often remains aware of what is happening.
• Simple Partial Seizure
• No loss of awareness
• With sensory, motor, autonomic, or psychic signs
• Complex Partial Seizure
• Impaired consciousness. (patient is conscious but unaware of what he’s doing)
• Duration (typically 30 seconds to 3 minutes)
• Partial Seizure with Secondary Generalization
• Begins focally, with or without focal neurological symptoms
• Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases
• Typical duration 1-3 minutes
• Postictal confusion, and somnolence.
13. Absence seizures
Brief staring spells (“petit mal”) with
impairment of awareness
3-20 seconds
Sudden onset and sudden resolution
Often provoked by hyperventilation
Onset typically between 4 and 14
years of age.
Often resolve by 18 years of age.
Some children experience up to 100
absence seizures in a day
14. Myoclonic seizures
Brief, shock-like muscle contractions
Typically bilaterally synchronous
Impairment of consciousness difficult to assess
(seizures <1 second)
May progress into clonic or tonic-clonic seizure
May be associated with a progressive neurologic
deterioration
16. Atonic seizures
Sudden loss of postural muscle tone
When severe often results in falls
When milder produces head nods or
jaw drops.
Consciousness usually impaired
Duration - usually seconds, rarely more
than 1 minute
17. Tonic-Clonic
Seizures
Associated with loss of consciousness
and post-ictal confusion/lethargy
Duration 30-120 seconds
Tonic phase
Stiffening and fall
Often associated with ictal cry
Clonic Phase
Rhythmic extremity jerking
18. Treatment of epilepsy
First Line
Approved Anti-Epileptic Drugs (AEDs)
Second Line (intractable epilepsy)
Epilepsy Surgery
Vagus Nerve Stimulation Therapy
Experimental Therapy
AEDs
Implanted Devices
19. Treatment: Medication
Most common drugs for epilepsy are the
group called (Anti-epileptics) or (Anti-
convulsants).
Most anti-epileptic agents act either by
blockade of depolarisation channels
(Na+ and Ca++)
OR
Enhancing the activity of GABA
(neurotransmission inhibition)
21. Tegretol (Carbamazepine)
(CBZ)
Carbamazepine was discovered by chemist Walter Schindler
at J.R. Geigy AG (now part of Novartis) in
Basel, Switzerland, in 1953. Schindler then synthesized the
drug in 1960, before its anti-epileptic properties had been
discovered.
Carbamazepine was first marketed as a drug to treat
trigeminal neuralgia (formerly known as tic douloureux) in
1962. It has been used as an anticonvulsant and antiepileptic
in the UK since 1965, and has been approved in the U.S. since
1974.
It was first used to control mania at 1971.
22. Indications
It’s used primarily in the treatment of epilepsy and bipolar disorder, as well as
trigeminal neuralgia.
It is also used off-label for a variety of indications, including
Attention-deficit hyperactivity disorder (ADHD),
Schizophrenia, phantom limb syndrome,
Complex regional pain syndrome,
Paroxysmal extreme pain disorder,
Neuromyotonia,
intermittent explosive disorder,
borderline personality disorder,
post-traumatic stress disorder.
23. Pharmacokinetics
Bioavailability 80 % (CR tab is less by 15% than other forms)
Protein binding 76 %
Hepatic by CYP3A4 to active epoxide
Metabolism from (10,11 epoxide)
Half-life (25-65) hours
72 % in urine (2-3) % unchanged
Excretion 28 % in feces
Therapeutic range (17-50) ngm/ml
Saliva conc. (20-30) %
(Compared with plasma conc.)
Breast milk conc. (25-60) %
(Compared with plasma conc.)
Placental barriers Cross
Syrup 2 hours
PPC
Reached Conv. tab 12 hours
after
CR tab 24 hours (CR is less by 25% than conv. tabs).
Single dose 36 hours
T1/2
Multiple doses 16-24 hours
24. Tegretol precautions
Do not start taking Tegretol without telling
your doctor if you are pregnant or planning
to become pregnant. Seizure control is very
important during pregnancy. The benefit of
preventing seizures may outweigh any risks
posed by taking Tegretol, do not stop taking
it without your doctor's advice
DO NOT take Tegretol if you have:
• a history of boneif you are allergic to
carbamazepine or an antidepressant such
as imipramine marrow suppression
• (Tofranil).
25. Tegretol in Novartis sales (2007)
Sales
Name Indication(s)
(US$millions)
Diovan Hypertension 5000
Gleevec Chronic myelogenous leukemia 3100
Zometa Cancer complications 1300
Sandostatin Acromegaly 1000
Sandimmune and Neoral Organ transplantation 944
Femara Breast cancer 937
Trileptal
Lotrel Hypertension 748
Voltaren
Trileptal
anti-inflammatory
Epilepsy
747
692
9th
Lescol hypercholesterolemia 665
Exelon Alzheimer's disease 632
Comtan Parkinson's disease 420
Tegretol Epilepsy 413
Lucentis
Age-related macular
393 Tegretol
degeneration
Ritalin
Exjade
AD/HD
Iron chelator
375
357
13th
Tobramycin Cystic fibrosis 273
26. Mechanism of action
The mechanism of action of carbamazepine and its
derivatives is relatively well understood.
Carbamazepine stabilizes the inactivated state of
Voltage-gated sodium channels, making fewer of
these channels available to subsequently open. This
leaves the affected cells less excitable until the drug
dissociates. Carbamazepine has also been shown to
potentiate GABA receptors made up of
alpha1, beta2, gamma2 subunits
28. • Kwan and Brodie. NEJM 2000; 342: 314-319.
• Mohanraj and Brodie. Epil Behav 2005; 6: 382-387
29. Tegretol provides excellent sensory
symptomes relief in diabetic neuropathy
patients
Patients with diabetic
neuropathy after six
weeks of treatment of
CBZ with daily dose of
600mg.
An update on the pharmacological
management of post-herpetic
neuralgia and painful diabetic
neuropathy . CNS drugs.
2008;22(5) :417-42
30. Carbamazepine and phenytoin. Comparison of
cognitive side-effects in epileptic patients
during monotherapy and withdrawal.
We compared the cognitive effects of carbamazepine and phenytoin with
neuropsychological tests exploring
intelligence, vigilance, attention, memory, and visuomotor performances
in 25 epileptics (13 receiving carbamazepine and 12 receiving phenytoin)
and 26 matched normal controls. Patients were seizure free for at least
two years and taking prolonged monotherapy. We also evaluated the
effects of drug withdrawal by retesting patients three months after
reduction at half drug dose and three months and one year after
complete withdrawal. Our findings suggest that phenytoin affects the
cognitive functions more than carbamazepine does, although the negative
effects of both drugs are reversible by complete therapy withdrawal.
Arch Neurol. 1988 Aug;45(8):892-4.
http://www.ncbi.nlm.nih.gov/pubmed/3395263
32. References
1. www.Wikipedia.com
2. www.Drugs.com
3. www.Rxlist.com
4. http://www.ncbi.nlm.nih.gov/pubmed
5. Other presentations by some neurologists.
6. Recreation of some data.