Anti convulsants

1. ANTI-CONVULSANTS
By
DR. SAJJAD ALI
PHARM-D, R.Ph., M.Phil (Pharmacology)

2. Epilepsy
 It is a group of chronic
syndromes that involves
recurrence of seizures,
which may lead to loss of
consciousness, abnormal
movements of shorter
duration but recur if
untreated
 Seizures: Limited period of
abnormal discharge of
cerebral neurons

5. Classification of seizures
1. Partial seizures:
 Involve only one part of brain
 Consciousness is preserved
i. Simple Partial Seizures
 Consciousness are normal
ii. Complex Partial seizures
 Altered consciousness

6. Generalized Seizures
1. Tonic-clonic seizures:
It is characterized by loss of consciousness
followed by Tonic (continuous contraction) and
clonic (rapid contraction and relaxation phases.
2. Absence seizures:
 These are characterized by brief and abrupt
loss of consciousness
 These are begin in childhood and cease by the
age of 20 years

7. 3. Myoclonic Seizures:
 These are characterized by single and multiple
myoclonic muscle jerks.
4. Status epilepticus:
 Series of seizures without recovery of
consciousness between attacks.
 It is life threatening emergency

11. Anti-epileptic Drugs
Drugs for the treatment of Partial and Tonic-
Clonic Seizures:
 Carbamazepine
 Phenytoin
 Valproic Acid
 Lamotrigene

12. Drugs for the treatment of Absence Seizures:
 Ethosuximide
 Clonazepam
 Valproic Acid
Drugs for the treatment of Myoclonic Seizures:
 Lamotrigene
 Clonazepam
 Valproic Acid

13. Back and Adjunctive Drugs:
 Gabapentine
 Topiramate
 Felbamate
 Phenobarbital
 Vigabatrine
 Zonisamide

14. Treatment strategies
 The general effect of anti-epileptic drugs is to
suppress the generation of repetitive action
potential in the epileptic foci in the brain
 Different mechanisms are involved in the
achieving this effect
1. By blockage of voltage gated sodium
channels
2. By calcium channel blockage
3. By increasing GABA related effects

15. Carbamazepine
 It is related to tricyclic antidepressants
Mechanism of Action:
 The general purpose of anti-epileptic drugs is
to suppress the generation of repetitive action
potential in the epileptic foci of brain
 Carbamazepine does this by blocking voltage
gated sodium channels that are in inactive
state
 Thus they prolong or slow their recovery

17. Uses:
Carbamezepine is used for the treatment of
Partial seizures and tonic-clonic seizures
Adverse affects:
 Dizziness
 Drowsiness
 Headaches
 Allergic reactions

18. Phenytoin
Mechanism of action:
 The general purpose of anti-epileptic drugs is to
suppress the generation of repetitive action potential
in the epileptic foci of brain
 Phenytoin does this by following mechanisms;
a. By blocking voltage gated sodium channels which
are in their inactive state thus slow their recovery
b. At high conc. Phenytoin can block voltage
gated calcium channels

19. Pharmacokinetics:
Phenytoin is 90% bound to plasma albumin
Clinical uses:
 Partial seizures
 Generalized tonic clonic seizures
 Status epilepticus

20. Adverse effects:
 It may cause cardiotoxicity. Fosphenytoin may be
proved safer
 Nystagmus (Involuntary movement of eye balls)
 Gingival hyperplasia (causes gums to grow over
teeth)
 Hirsutism
 Long term use may causes osteoporosis

21. Nystagmus

22. Gingival hyperplasia

24. Ethosuximide
Mechanism of Action:
 Ethosuximide reduce the low threshold
calcium current particularly in thalamic
neurons, without modifying the voltage
dependent inactivation or recovery from
inactivation of sodium channels
 Thus they suppress the generation of
repetitive action potential in epileptic foci of
brain

25. Uses:
Used for the treatment of Absence seizures
Adverse effects:
 Head aches
 Dizziness
 Drowsiness
 Nausea
 Vomiting

26. Uses:
Used for the treatment of Absence seizures
Adverse effects:
 Head aches
 Dizziness
 Drowsiness
 Nausea
 Vomiting

27. Valproic Acid
Mechanism of Action:
 Valproic acid block the repetitive generation of
action potential in epileptic foci of brain by
following mechanisms;
i. Blockage of voltage gated sodium channels,
thus prolong the inactivation state of sodium
channels
ii. It reduces calcium current in thalamic neurons
iii. At high conc. It inhibits enzyme GABA amino-
transaminase

28. Clinical use
 Partial seizures
 Tonic-clonic seizures
 Absence seizures
 Myoclonic seizures

29. Adverse effects:
 Nausea
 Vomiting
 Dizziness
 Drowsiness
 Skin rashes

30. GABA Related targets
 Gabapentine
 Vigabatrine
 Barbiturates
Mechanism:
 Benzodiazepine and barbiturates facilitate the
inhibitory action of GABA
 Benzodiazepines bind with receptor on the GABA
receptor-chloride ion channel macromolecular
complex and increase the frequency of chloride
ion channel opening

31.  Barbiturates bind/interact with different receptor
on chloride ion channels and increase duration of
chloride opening
 Action of GABA is terminated by GABA amino-
transaminase (enzyme) this is irreversibly
inactivated by vigabatrin at therapeutic
concentration
 Valproic acid also inhibits this enzyme at higher
concentration
 Other drugs includes, felbamate, topiramate etc.

32.  Gabapentin is structural analog of GABA, but
does not activate GABA receptors directly and
its mechanism of anti-epileptic action is
unclear

33. Status Epilepticus
 For short term control
-I/V diazepam/ Lorazepam
 For Long term term control
- I/V Phenytoin is given because it is less
sedating than benzodiazepine, however it may
cause cardiotoxicity
- Fosphenytoin (water soluble) my prove to be
safer

34. - In severe status epilepticus that may not
respond to these drugs general anesthesia may
be used