‫بسم هللا الرحمن الرحيم‬

Tiratam Basic Training

NEURON ANATOMY

 Extensions
outside the cell
body
 Dendrites –
conduct
impulses toward
the cell body
 Axons – conduct
impulses away
from the cell
body (only 1!)
Tiratam Basic Training
AXONS AND NERVE IMPULSES

 Axons end in axonal terminals

 Axonal terminals contain vesicles with
neurotransmitters
 Axonal terminals are separated from the
next neuron by a gap
 Synaptic cleft – gap between adjacent
neurons
 Synapse – junction between nerves
Tiratam Basic Training
Tiratam Basic Training
CONTINUATION OF THE NERVE IMPULSE BETWEEN
NEURONS

 Impulses are able to cross the synapse

to another nerve
 Neurotransmitter is released from a nerve’s
axon terminal
 The dendrite of the next neuron has
receptors that are stimulated by the
neurotransmitter
 An action potential is started in the dendrite
Tiratam Basic Training
Epilepsy
 Definition
“Recurrent, paroxysmal (convulsive)
disorder of cerebral function
characterized by sudden, brief attacks
of disturbance of consciousness, motor
activity, sensations, emotions or
behavior, caused by abnormal
excessive discharge of cerebral
neurons”
Tiratam Basic Training
 Etiology
• Epilepsy may be: idiopathic (> 70% of cases)
or symptomatic (< 30% of cases)

• Idiopathic indicates that no obvious cause can be

found. Genetic factors probably have a role.
• Symptomatic indicates that a cause exists.

• In symptomatic cases, therapy for the cause is

indicated, together with treatment of the epileptic
fits.
Tiratam Basic Training
 Examples of focal causes
• Brain tumors
e.g. glioma (1ry CNS tumors arises from glial cells)
meningioma common brain Tumor arise from the arachnoidal cap cells
of the meninges
• Head trauma e.g. birth injury, skull fracture
• Infections e.g. encephalitis, brain abscess, AIDS
• Cerebrovascular disease e.g. embolic cerebral infarction,
intra-cerebral haematoma
• Vascular malformations
• Congenital or developmental abnormalities e.g. lipid
storage diseases

Tiratam Basic Training

Examples of generalized causes
• Fevers e.g. febrile convulsions, heatstroke
• Hypoxia e.g. at birth, post-operative
• Hypoglycemia, ketoacidosis
• Electrolyte disturbances e.g. Hypocalcemia,
hyponatremia
• Drugs and toxins e.g. antibiotics e.g. quinolones ,
antidepressants e.g. buprobion, antipsychotics e.g.
clozapine, aminophylline, cocaine, strychnine
• Drug withdrawal e.g. alcohol, barbiturates,
benzodiazepines
Tiratam Basic Training
Classification

Tiratam Basic Training

 ILAE Classification 2010
• Partial seizures:
1. Simple (consciousness not impaired)
2. Complex (with impairment of consciousness)
3. With secondary generalization
• Generalized seizures:
1. Tonic-clonic seizures
2. Tonic seizures
3. Atonic seizures
4. Myoclonic seizures
5. Absence ( simple and complex)
6. Clonic
• Unclassified seizuresTiratam Basic Training
Clinical Picture

Tiratam Basic Training

• About 70% of patients have only one type of
seizure; about 30% have two or more types.
• Generalized tonic-clonic seizures occur in about
80%. Absence seizures occur in about 20%.
Complex partial seizures occur in about 40%.
• Idiopathic epilepsy generally begins in the young
before 15 years of age, but may occur at any age.
• Seizures before age 2 are usually caused by
developmental defects, birth injuries, or a
metabolic disease.
• Those beginning after age 25 (late onset epilepsy)
are more likely to be symptomatic than early onset
cases.

Tiratam Basic Training

 Status Epilepticus
• In status epilepticus, seizures follow one
another with no intervening periods of
normal neurologic function.
• Generalized convulsive status epilepticus
may be fatal. It may result from rapid
withdrawal of anticonvulsants.
• Confusion may be the only manifestation of
complex partial or absence status epilepticus,
and an EEG may be needed to diagnose
seizure activity.
Tiratam Basic Training
 Prognosis
• About 80% of patients will achieve complete
control with long-term remission more than 2
years while receiving drugs.

• About 70% of patients with well-controlled

seizures can eventually discontinue drugs without
relapse. This is done very gradually after at least 2
years of freedom from fits.

• About 20% of patients are never fit free for long

periods (i.e. never completely controlled).
Tiratam Basic Training
 Presented By Mohamed Saleh

Tiratam Medical Knowledge

 Levetiracetam
• Tiratam is AED that induces a decrease in the
number of the frequent epileptic discharges.
• Tiratam is a Pyrollidine derivative.
• It is structurally similar to piracetam.
• It is structurally unrelated to any of the existing
AED.

Tiratam Basic Training

 Mechanism of action
• Levetiracetam has a specific brain binding site (SV2A)
which is a presynaptic protein located on the
synaptic vesicles.

• The mechanism of action of Levetiracetam does not

seem to involve any conventional modulation of the
three main mechanisms relevant for the action of
classic antiepileptic drugs.

Tiratam Basic Training

 Pharmacokinetics
Absorption Rapid and complete 1 hour The extent is not affected by food
The rate is affected minimally by food
Bioavailability 100%
Protein binding <10%
½ life 6-8 hours elderly 2.5 hrs longer
Pharmacokinetis Linear up to a dose of 5000 mg and time-invarient
Excretion 66% of the dose is renally excreted as unchanged drug
Metabolism No Hepatic metabolism & LEV is neither inducing nor inhibiting
a) CYT P450 b)Epoxide hydrolase C)UDP glucuronosyl transferase
•Rest of the dose are subjected to enzymatic hydrolysis of the acetamide
group
Metabolite Inactive
Tablet & syrup Are Bioequivalent
Pharmacokinetic profile make it easy to start easy to manage
Tiratam Basic Training
 Drug-Drug interaction
• No drug-drug interactions with other AEDs
(Phenytoin - valproate - Carbamazepine -
Phenobarbital - primidone - gabapentin -
Lamotrigine)

• Other drug interactions:

No drug interactions with
- oral contraceptives.

- digoxin.
- warfarin.
Tiratam Basic Training
Special patient groups

Tiratam Basic Training

 Renal patient

Total body mL/min Patients’ Dosage Frequency

clearance of group Mg/day
Levetiracetam

>80 Normal 500-1500 Every

12 hours
40% 50-80 Mild 500-1000

50% 30-50 Moderate 250-750

60% <30 Severe 250-500

70% _ *End stage 500-1000 Every

renal disease 24 hours
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• *Following dialysis a supplemental dose of
levetiracetam is given (250- 500 mg).

• A 4-hour dialysis procedure reduces 50% of total

body levetiracetam.

Tiratam Basic Training

 Pregnancy & Breast feeding

-Pregnancy category C drug.

Animal studies
-Minor fetal skeletal abnormalities.
-Retarded offspring growth.
•Nursing mothers
Excreted in the breast milk and due to potential
risks a decision has to be made weather to
continue medication or nursing.
Tiratam Basic Training
 Dose
Tiratam TM

500mg &1000mg tablets

100mg/ml Oral Solution

Adults: 1000mg/day (500mg bid)

Daily dose of 1000,2000,3000mg given as twice daily dosing have
been shown to be effective

Children: 20-60mg/kg/day given as twice daily doses.

Dose increase when needed should be made by increments of 20
mg/kg/day every 2 weeks up to the dose of 60 mg/kg/day
(Age from one month to 6 months 14 mg-42 mg/kg/day given as
twice daily doses

Tiratam Basic Training

 Presented By Moh Saleh

Competitor knowledge
 Classification of AED
Chronological Mechanism of action Seizure type
Partial seizures
1st generation Na Channel Blocker
1st line 2nd line
•Bromide •Valproate •Phenytoin Carbamazepine Benzodiazepine
•Barbiturates •Clonazepam •Carbamazepine Phenobarbitone Valproate
•Carbamazepine •Phenytoin •Primidone(mysoline) Primidone Lamotrigine
•Lamotrigine Phenytoin Oxcarbazepine
•Oxcarbazepine
Tonic-Clonic seizures
2nd generation GABA enhancing
1st line 2nd line
•Oxcarbazepine •Vegabatrin •Valproate Sodium Carbamazepine Benzodaiazepine
•Lamotrigine •Pergablin (Transaminase inhibitor) Phenobarbitone Lamotrigine
•Gabapentin •Levetiracetam •Clonazepam phenytoin Oxcarbazepine
•Topiramate •Gabapentin Valproate

Absence Seizures
Ca channel blocker
1st line 2nd line
Ethosuxemide Valproate Bezodiazepine
Ethosuximide Valproate
Tiratam Basic Training
 Oxcarbazepine
Brand Trileptal
Generic Oxcarbazepine
Mode of Action Na channel blocker
Indications •All types of seizures (partial or generalized) except absence
(Monotherapy & add on)
•Mood stabilizer
Dose 600-2400 mg/day B.I.D
Side effects •Hyponatraemia
•Nausea
•Skin rash (Milder than with Carbamazepine)
Comments It is a derivative of Carbamazepine; structure modification helped
to:
•decrease the effect of hepatic metabolism of the drug.
•Prevent serious forms of anemia associated with CBZ
Tiratam Basic Training
Tiratam competitive advantages
• Rapid titration Early clinical response.
• No drug-drug interactions.

Tiratam Basic Training

 Carbamazepine
Brand Tegretol
Generic Carbamazepine
Mode of Action Na channel blocker
Indications •All types of seizures (partial or generalized) except absence
(Monotherapy & add on)
•Mood stabilizer
•Trigeminal neuralgia

Dose 400-1800 mg/day B.I.D Adult dose

10-30 mg/kg/body weight
Side effects •Drowsiness •Hyponatraemia
•Agitation •Nausea
•Benign leukopenia •Skin rash
•Hepatic faliure
Comments It is an enzyme inducer
It interacts with other AED lowering their concentrations along
with WarfarinTiratam
& Oral Contraceptives
Basic Training
Tiratam competitive advantages
• Rapid titration Early clinical response.
• No drug-drug interactions.
• No Rash
• Cognition friendly profile.
• Flexible dosing options.

Tiratam Basic Training

 Sodium Valproate
Brand Depakine
Generic Sodium Valproate
Mode of Action GABA transaminase inhibitor
Indications •All types of seizures (partial or generalized)
•Lennox Gastaut Syndrome
•Mood stabilizer
Dose 500-3000 mg/day B.I.D Adult dose
10-40 mg/kg/day
Side effects •Hepatotoxicity •Weight gain
•Pancriatitis •Alopecia
•Thrombocyotpenia •GIT disturbances
•Rash •Tremors
Comments It is an enzyme inhibitor

Tiratam Basic Training

Tiratam competitive advantages
• No hepatotoxicity
• No drug-drug interactions.
• Rapid titration Early clinical response.
• Flexible dosing options.
• No cosmetic side effects.

Tiratam Basic Training

 Phenytoin (Diphenylhydantoin)
Brand Epanutin
Phenytin
Generic Phenytoin
Mode of Action Na channel blocker
Indications •All types of seizures (partial or generalized) except absence

Dose 200-500 mg/day B.I.D

Side effects •Gingival hyperplasia •Ataxia
•Hypocalcaemia •Anaemia
•Hormonal dysfunction •Sedation,lethergy
•Thyroid dysfunction •Mood changes
•Intellectual blunting
Comments It is a potent enzyme inducer

Tiratam Basic Training

Tiratam competitive advantages
• Rapid titration Early clinical response.
• No drug-drug interactions.
• No cosmetic side effects.
• Patient friendly side effect profile.

Tiratam Basic Training

 Common drawbacks of AED
• Drug-Drug interactions.
• Most of them need Serum level monitoring.
• Tedious titration at the introduction of the
treatment.
• Very bad effect on cognitive functions.
• Drop outs related to adverse events are more
frequent.

Tiratam Basic Training

Tiratam Basic Training