Anti-Epileptic Drugs for Pharm-D Students,, Pharmacy Practice

1. PATIENT PROFILE & PATIENT COUNSELING
C. DRUG PROFILE OF ATLEAST 25 IMPORTANT
MEDICATIONS
ANTIEPILEPTIC DRUGS
CLINICAL PHARMACY
BY
Zul Kamal
DEPARTMENT OF PHARMACY
SHAHEED BENAZIR BHUTTO UNIVERSITY,
SHERINGAL

2. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
EPILEPSY
Epilepsy is one of the chronic neurological
disorders characterized by recurrent seizures
which is relatively a common condition.
A seizure happens when abnormal electrical
activity in the brain causes an involuntary
change in body movement or function,
sensation, awareness, or behavior.
These seizures can vary from a temporary
disruption of the senses, to short periods of
unconsciousness or staring spells to convulsions.

3. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
NATURE OF EPILEPSY
Epilepsy affects about 0.5% of the population.
Worldwide at least 50 million people have
epilepsy and approximately 85% of these live in
developing countries.
The seizure is caused by an abnormal high-
frequency discharge of a group of neurons,
starting locally and spreading to a varying extent
to affect other parts of the brain.

4. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
TYPES OF EPILEPSY
 Seizures may be partial or generalized
depending on the location and spread of the
abnormal neuronal discharge.
The attack may involve mainly motor, sensory or
behavioral phenomena.
Unconsciousness occurs when the reticular
formation is involved.

5. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
TYPES OF EPILEPSY
 Partial seizures: The discharge begins locally,
and often remains localized. Produce relatively
simple symptoms without loss of consciousness.
 Generalised seizures: Involve the whole brain,
including the reticular system, thus producing
abnormal electrical activity throughout both
hemispheres. Immediate loss of consciousness.
Status epilepticus is a life- threatening condition
in which seizure activity is uninterrupted.

6. Nature of Epilepsy

7. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
TYPES OF EPILEPSY

8. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
CAUSES OF EPILEPSY
Mostly caused by many different conditions that affect a
person s brain like;
Stroke,
Head trauma,
Brain tumors,
Chemical abnormalities,
Alcohol or drug effects, 4
Complications during childbirth,
 Infections such as meningitis,
Encephalitis, cysticercosis, or brain abscess, and
Certain genetic or inherited disorders.
NOTE: Frequently, no definite cause can be found

9. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
NEUROPHYSIOLOGY OF EPILEPSY
The neurochemical basis of the abnormal
discharge is not well understood.
 It may be associated with enhanced excitatory
amino acid transmission, impaired inhibitory
transmission, or abnormal electrical properties
of the affected cells.
The glutamate content in areas surrounding an
epileptic focus is often raised.

10. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
COMPLICATONS OF EPILEPSY
Repeated epileptic discharge can cause
neuronal death (excitotoxicity).

11. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
TREATMENT AND MANAGEMENT OF EPILEPSY
 Mostly treated by the use of Antiepileptic drugs (AED); which is
effective in 70-80% of patients.
 Current antiepileptic drugs are thought to act mainly by two
main mechanisms;
1-Reducing electrical excitability of cell membranes, possibly
through inhibition of sodium channel.
2-Enhancing GABA-mediated synaptic inhibition. This may be
achieved by an enhanced pre- or post- synaptic action of
GABA, by inhibiting GABA-transaminase, or by drugs with
direct GABA-agonist properties.

12. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
ANTIEPILEPTIC DRUGS
The main drugs in current use are: Phenytoin,
Carbamazepine, Valproate and Ethosuximide.
Secondary drugs include:Phenobarbitone:
(highly sedative), various Benzodiazepines (e.g.
Clonazepam); Diazepam used in treating status
epilepticus.

13. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
ANTIEPILEPTIC DRUGS
1. VOLPOIC ACID (1978)
PHARMACOKINETICS
 Administered Orally.
 Metabolized in Liver by Glucoronoid Conjugation as well as
Beta-Oxidation.
 Protein Binding Capacity is 80-90%.
 Excreted via Urine.

14. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
1. VOLPOIC ACID
PHARMACODYNAMICS
MECHANISM O ACTION
 Volporic acid inhibits an enzyme GABA transaminase which is
responsible for metabolism of GABA (Gamma amino butyric
acid) in brain.
 Increases level of GABA in brain is responsible for inhibition of
abnormal impulses.
 GABA causes openings of Chloride channels which causes
Hyperpolarization and thus inhibition of abnormal channels.
 It is also supp(when the body produce too much acid or when
the kidney is not removing enough acid from the body)osed
that Volporic acid causes metabolic acidosis which prevents
abnormal excitation of impulses in brain.

15. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
1. VOLPOIC ACID
INDICATIONS
 Absence Seizure
 Myoclonic Seizure
 Tonic-Clonic Seizure
 Migraine
CONTRAINDICATION
 Pregnancy
 Hepatic Dysfunction
 Hypersensitivity patients to Volporic acid

16. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
1. VOLPOIC ACID
ADVERSE EFFECTS
 Dizziness
 Alopecia
 Skin Rashes
 Insomnia
 Dyspepsia
 Hepatitis
 Anorexia
 Nausea
 Vomiting etc

17. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
1. VOLPOIC ACID
DRUG INTERACTIONS
 Volporic acid displaces Phenytoin from its binding sites and
thus causes toxicity of Phenytoin.
 Barbiturates interacts with Volporic acid and increases its half
life.
DOSAGE FORM
 Tablets,
 Syrups,
 Injection

18. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
1. VOLPOIC ACID
BRAND NAMES
 Epival (Abbott), Tab, 250, 500 mg, Control release Tabs of 500
mg, 60 mL Syrup, Injection of 500 mg
 Epilim (Aventis), Tab, 200 mg, Syrup 250 mL/mL
 Valep (Geofman), Tab, 500 mg, Syrup 250 mg/mL
DOSE
 500 mg-1000 mg, OD

19. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN (1937)
PHARMACOKINETICS
ADMINISTRATION
 Orally
 IV (Emergency condition like in status epilepticus)
NOTE: It should not be given through IM because its crystallization
occur in muscles and cause tissue damage.
 Phenytoin is a weak acid, its intestinal absorption is variable
and plasma concentration can vary widely. Monitoring is
therefore needed.
METABOLISM

20. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
METABOLISM
 Metabolized in Liver into Parahydroxy Phenetoin by hydroxylation
reaction
NOTE:
 At LOW DOSES Phenytoin follows 1st Order Kinetics; i.e the rate
of drug metabolism is directly proportional to the
concentration of free drug and follow the 1st order kinetics (the
enzyme will available freely at low doses so when we increase
the drug conc. more enzyme will be available for it and will be
metabolized.
 At HIGH DOSES Phenytoin follows Zero-Order Kinetics in which
all the enzymes bond with drug molecule and if we further
increases the drug conc. Then enzyme will not be available for it
and its increase conc will produce toxicity in patients.

21. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
MECHANISM OF ACTION
acts by stabilizing membranes
 Blocking voltage-dependence Na+ channel (which is responsible
for depolarization of cell )
 Blocking voltage-dependence Ca2+ channel (Inhibiting calcium-
induced secretary processes, including release of hormones and
neurotransmitters).
 Increase GABA concentration in brain and thus causes of
inhibition of repetitive impulses.

22. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
INDICATIONS
 Generalized and Partial Seizure
 Status Epilepticus (Severe condition of epilepsy, Pt loss his conscious
for long time, IV administered Phenytoin)
 Ventricular Arrhythmia (especially those which are induced by
Digoxin toxicity).
 It is used in pain of trigeminal neuralgia (intense pain along a nerve).
CONTRAINDICATIONS
 Pregnancy (because of its teratogenic effects it may cause cleft
palate, retard growth and mental retardation).
 Seizures which are induced by hypoglycemia.
NOTE: 1st Trimester (organogenesis of fetus----All drugs should be banned)

23. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
ADVERSE EFFECTS
DOSE RELATED ADRS
 Diplopia (Double Vision)
 Ataxia (Jerky movements)
 Nystagmus (Rolling of eyeball which is involuntary)
ADRS RELATED TO LONG-TERM THERAPY
 Gum hypertrophy
 Changes in facial features (collagen thickness)
It also causes;
 Hirsutism (hairy face)
 Acne (red pimples)
 Megablastic anemia (RBC enlarges due to decrease folic acid)

24. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
DRUG INTERACTIONS
 Oral Anti-Coagulants , Sulfonamides, Phenylbutazone, Valporic
acid displaces Phenytoin from its binding sites and thus
produces its toxicity.
 Enzyme inducers like Carbamezaphines and Phenobarbitone
when given with Phenytoin it will increase its metabolism.
 Similarly Enzyme inhibitors like Cimitidine, Clarithromycin and
INH will decrease its effects due to decreased metabolism.

25. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
2. PHENYTOIN
DOSAGE FORM
 Capsule (Oral)
 Injectables
BRAND NAMES
 Epitoin (Dosaco Pharmaceutical), Cap, 100 mg
 Epigran (Atco Pharmaceutical), Inj, 250 mg/5 mL
DOSE
 150-300 mg , OD or BD
 The maximum allowed dose is 600 mg daily

26. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
3. CARBAMAZEPINE (1974)
 Derivative of tricyclic antidepressants
 Similar profile to that of phenytoin, but with fewer unwanted
effects
 Effective in most forms of epilepsy (except absence seizures);
particularly effective in psychomotor epilepsy.
 Also useful in trigeminal neuralgia and mania.
 Strong inducing agent; therefore many drug interactions
 Low incidence of unwanted effects; principally sedation, ataxia,
mental disturbances, water retention

27. C. DRUG PROFILE OF ATLEAST 25 IMPORTANT MEDICATIONS
POTENTIAL TARGET RANGE OF AED SERUM CONCENTRATIONS
AED Serum Concentration (mg/l)
Carbamazepine 4-12
Phenytoin 10-20
Valproic acid 50-100