Anti epileptic drugs, lecture 1- dr.khadija.ppt

Certainly! Let's delve into antiepileptic drugs (AEDs). These medications play a crucial role in managing epilepsy and preventing seizures. Here's a concise overview:

1. **Mechanisms of Action**:
- AEDs act through various mechanisms to stabilize neuronal membranes, modulate ion channels, and inhibit excitatory neurotransmitters. Examples include:
- **Sodium Channel Blockers**: Drugs like phenytoin and carbamazepine inhibit voltage-gated sodium channels, reducing neuronal excitability.
- **GABA Enhancers**: Valproic acid and benzodiazepines enhance inhibitory GABAergic transmission.
- **Calcium Channel Blockers**: Ethosuximide targets T-type calcium channels, primarily used for absence seizures.
- **Glutamate Antagonists**: Topiramate and felbamate reduce glutamate-mediated excitotoxicity.

2. **Common AEDs**:
- **Phenytoin**: A classic sodium channel blocker. Adverse effects include gingival hyperplasia and hirsutism.
- **Carbamazepine**: Also a sodium channel blocker. Monitor for agranulocytosis and Stevens-Johnson syndrome.
- **Valproic Acid**: Broad-spectrum AED. Watch for hepatotoxicity and teratogenicity.
- **Lamotrigine**: Blocks sodium channels and inhibits glutamate release. Risk of Stevens-Johnson syndrome.
- **Levetiracetam**: Mechanism not fully understood. Well-tolerated with minimal drug interactions.

3. **Drug Interactions**:
- AEDs can interact with other medications. For instance:
- Phenytoin induces CYP450 enzymes, affecting warfarin and oral contraceptives.
- Valproic acid inhibits CYP450, increasing levels of lamotrigine and phenobarbital.

4. **Special Populations**:
- **Pregnancy**: Valproic acid and phenytoin pose teratogenic risks. Lamotrigine is safer.
- **Elderly**: Start with lower doses due to altered pharmacokinetics.
- **Liver Dysfunction**: Adjust dosages for hepatic impairment.

5. **Monitoring and Adverse Effects**:
- Regular monitoring of serum drug levels ensures therapeutic efficacy.
- Common adverse effects include dizziness, sedation, and cognitive impairment.
- Rare but serious effects include aplastic anemia (carbamazepine) and pancreatitis (valproic acid).

Remember, individual responses to AEDs vary. Always consult a healthcare professional for personalized advice.

1. Drugs For Epilepsy
Dr. Khadija Mastoor

2. Epilepsy

3. Learning Outcomes
Define epilepsy & its types
Classify antiepileptic drugs
Describe the uses and adverse effects of antiepileptic
drugs.

4. What is epilepsy?
•Chronic disease in which seizures result
from abnormal discharge of cerebral
neurons.
•It is recurrent, transient,
paroxysmal CNS disturbance
due to uncontrolled high
frequency repetitive
electrical discharge

5. WHAT IS A SEIZURE?
•Episode of abnormal electrical activity in brain that causes Transient
alteration of
•
• Behaviour
• Movements
• Thoughts
•Due to disordered, synchronous and rhythmic firing of some or
population of neurons in brain.

9. GENERALIZED SEIZURES
1; Tonic-clonic( grand mal)...loss of
consciousness
2; Tonic seizures.....increased muscle tone
3; Clonic seizures....spasms of muscle
contraction& relaxation.

10. Generalized seizures
4; Absence seizures.....brief loss of
consciousness…..>10 seconds
5; Atonicseizures..sudden loss of muscle tone
6; Myoclonicseizures....rhythmic, jerking
spasms
Status epilepticus

11. Causes of Epilepsy
•60-70% cases…..cause is unknown
•Other causes include
•Brain tumor
•Asphyxia
•Infection
•Head injury
•Metabolic causes…hypocalcemia
•Drugs…Phenothiazines, TCAs, antihistamines

12. CAUSES OF SEIZURES
Seizures are due to
•excessive activation of NMDA receptors by
glutamate
•suppressionof inhibitory neurotransmission of
GABA.
•increasein calcium influx via T-type calcium
channels in Thalamic neurons.

13. Classification of antiepileptics
1. Drugs for partial & generalized
tonic-clonic seizures
•Phenytoin and its congeners
•Carbamazepine
•Valproate( valproic acid)
•Phenobarbital

14. Classification of antiepileptics
2. Drugs for generalized
absence, myoclonic or atonic
seizures
•Ethosuximide
•Clonazepam
•Valproic acid
Lamotrigine &topiramate may
be useful.

15. Classification of antiepileptic drugs
•Adjunct drugs for partial &
generalized tonic-clonic
seizures
•Lamotrigine
•Levetiracetam
•Gabapentin
•Topiramate
•Pregablin
•Eslicarbazepine

16. Other drugs for epilepsy
Benzodiazepines
Diazepam
Lorazepam
Clonazepam ....sedation & tolerance limit use

17. General mechanism of action of antiepileptic drugs
•Inhibition of neuronal sodium channels
•Enhancement of GABA actions
•Inhibition of calcium channels

18. Phenytoin
•Phenytoin
•Mephenytoin
•Phenacemide
•Fosphenytoin

19. Pharmacokinetics of phenytoin
•Given orally
•ONLY fosphenytoin….i/v…..more water soluble
•Highly bound drug....90%....can potentially displace other
drugs from plasma proteins.
Half life....12-36hrs

20. Pharmacokinetics of phenytoin
•Metabolised by P450
•Exhibit dose-dependent kinetics
•1
st
-order kinetics
•zero -order kinetics
•Induces CYP 450 metabolic enzymes

21. Mechanism of action
•Blocksvoltage-gated sodium
channels by prolonging the
inactivation state of these
channels, thereby inhibiting the
repititive firing of neurons in a
seizure focus, stabilization of
membrane. ( use dependent)
•Decreases the synaptic release of
glutamate and enhances the
release of GABA..

26. Therapeutic uses
1; Generalized tonic-clonic seizures
2; Simple partial& complex partial seizures
3;Status Epilepticusafter giving diazepam
4; For treating arrhythmias

27. Toxicity
•Nystagmus…occurs early..no
dose adjustment
•
•Diplopia&Ataxia..most
common , dose related
•Gingival hyperplasia&
hirsutism. Occur in most
patients

29. Toxicity
Behavioural changes
•Confusion
•Hallucinations
Endocrinal disturbances
•Hirsutism
•Acne&Coarsening of fascialfeatures in children

30. Toxicity of phenytoin
.Megaloblastic anemia……(low folate),
•Osteomalacia,due to altered vit D metabolism
Idiosyncratic reactions…skin rash, fever

31. Toxicity of phenytoin
•Teratogenecity;
•Neural tube defects
•Spina bifida
•Oro-fascial deformities

32. Toxicity of phenytoin
•Rarely phentoin may cause
•Granulocytopenia
•Hepatotoxicity

33. Fetal hydantoin syndrome
Phenytoin taken during pregnancy
may cause
•Cleft lip
•Cleft palate
•Congenital heart disease
•Slow growth and mental
deficiency.

34. Carbamazepine

35. MECHANISM OF ACTION
1; BLOCKADE OF voltage-gated sodium channels
2; acts presynaptically and decreases synaptic
transmission
3; also interact with adenosine receptors.

36. Clinical uses
1; Partial seizures
2; Tonic-clonic seizures
3; Trigeminal neuralgia
4; Bipolar-affective
disorders(stabilize the mood)
5; Restless leg syndrome.

37. Toxicity of carbamazepine
1; Ataxia ,Diplopia (most common)
2; Drowsiness
3 ; Depression
4; Nausea and other GIT symptoms
.

38. Toxicity of carbamazepine
•Idiosyncratic reaction
•Aplastic anemia (rare), agranulucytosis,leukopenia
•Erythematous skin rash.
•Hepatotoxicity
•Steven johnson syndrome

40. STEVEN-JOHNSON SYNDROME

41. Carbamazepine
•Exclusively related to enzyme induction
•Reductionin its OWN steady state
concentration( auto-induction)

42. OXCARBAZEPINE
•Analogue of carbamazepine
•Less toxic
•Less potent.
•Used for partial &generalized seizures.

43. Your Turn
Which of the following drug is used to treat
trigeminal neuralgia?
A; ethosuximide
B; carbamazepine
C; phenytoin
D; levetiracetam.

44. Your turn again
•What is auto-induction?

45. Phenobarbital
•Oldest anti convulsant.
•Enhances GABA-mediated inhibition
•At higher dose blocks ca++ channels
•Used for treating:
Partial & generalized tonic-clonic seizures.

46. Mechanism of action of barbiturates

47. Primidone
•Is converted into phenobarbital in body
•Effective against partial & generalized seizures.
•Toxicity is similar to that of phenobarbital,but causes
drowsiness early in treatment.