Anti epileptics Flashcards
(59 cards)
1
Q
Types of seizures
A
- Generalised seizure:
• GTCS/ myoclonic seizures/ JME
• absence seizures - Partial seizures
2
Q
Cause of generalised tonic clonic seizure
A
- Thalamus
- Spontaneous firing of T-type Ca channel
- Action potential
- In cortex: retrograde propagation of action potential
- Cortical neuron depolarisation
- Na channel opens
- Depolarisation of spinal cord segments
- Spontaneous contraction and relaxation of all muscles
3
Q
Mechanism of absence seizures
A
- Thalamus
- Spontaneous firing of T type Ca channels
- Action potential within subcortex
Does not involve:
- Cortex
- Motor neuron
4
Q
Mechanism of partial seizure
A
- Cortex occupying lesion like Neurocysticercosis, tumour, gliosis
- Firing of neurons downstairs via Na channels
- Specific neuron: action potential
- Specific segment of spinal cord
- Specific muscle
5
Q
Anti-epileptic drugs
A
1. Ca2+ channel 🅱️: Valproate, ethosuximide 2. Na+ channel 🅱️: Phenytoin, carbamazepine, rufinamide, Lacosamide, Topiramate 3. Both of the above: Lamotrigine, zonisamide 4. K+ channel opener: Ezogabine, topiramate 5. Glutamate 🅱️: Felbamate, perampanel,… 6. GABA 🔼: BZD,… Pregabalin, Gabapentin,…
6
Q
Treatment of generalised seizure
A
Both Ca and Na channel blockers can be used
DoC: valproate
Myoclonic seizure is worsened by 2 Na channel blockers: carbamazepine and phenytoin
7
Q
Treatment of partial seizure and absence seizures
A
DoC for partial seizure: Carbamazepine- Na channel blocker
DoC for absence seizures: valproate
8
Q
Add on anti epileptics
A
- K+ channel opener
- Decreasing glutamate effect
- Increasing GABA effect
9
Q
Duration of treatment of anti epileptics
A
Upto minimum 2 years of seizure free period except:
1. JME
2. Post infarction seizure
where it is life long therapy
10
Q
Mechanism of anti epileptic action of valproate
A
- Calcium channel blocker
- Sodium channel blocker
- Increases GABA by stimulating synthesis and inhibiting metabolism
- Inhibits histone deacetylase
11
Q
Uses of valproate
A
DoC in: 1. GTCS 2. Myoclonic seizures 3. Absence seizures 4. Lennox Gastaut syndrome: Also DoC in: 5. Rapid cyclers 6. Rheumatic chorea Treatment of: 7. Acute mania 8. Prophylaxis of migraine
12
Q
Lennox Gastaut syndrome
A
Mixed seizure syndrome
Seen usually in children
Refractory seizure- difficult to treat
DoC: valproate
13
Q
Side effects of valproate
A
- Nausea, vomiting: M/C
- Alopecia
- Obesity
- Polycystic ovarian disease
- Hepatotoxicity
- Pancreatitis
- Hyperammonemia
- Tremor
- Enzyme inhibitor
14
Q
Why valproate is not used as 1st line management
A
S/E like:
- Alopecia
- Obesity
- Polycystic ovarian disease
15
Q
Hepatotoxicity of valproate
A
Valproate in hepatotoxic especially in presence of enzyme inducers like phenytoin, carbamazepine
So C/I in:
1. Children < 2 years
2. In pregnancy: neural tube defect, cardiovascular disease
16
Q
Treatment of epilepsy (JME) during pregnancy on valproate
A
- Continue valproate (do not stop or change anti epileptics)
- TDM of valproate
- Folic acid:
• normal pregnancy: 400 μg/day
• h/o neural tube defect in previous pregnancy: 4000 μg/day
17
Q
Treatment of epilepsy (JME) on females on valproate planning pregnancy
A
Drug free interval: 1. Seizures absent Proceed with planned pregnancy 2. Seizures present: DoC: Levetiracetam Lamotrigine Clonazepam
18
Q
Ethosuximide
A
Calcium channel blocker DoC: Absence seizures in children <2 years S/E: 1. Nausea, vomiting - M/C 2. Neurotoxicity 3. Bone marrow suppression 4. SLE
19
Q
Phenytoin or diphenyl hydantoin
Uses
A
- GTCS
- Partial seizures
- Treatment of neuropathic pain
- Antiarrhythmic drug
- Given as slow IV as fosphenytoin for treatment of status epilepticus
Fast IV causes asystole
20
Q
Pharmacokinetics of phenytoin
A
- The only anti epileptic to follow zero order kinetics ➡️ increased risk of toxicity in case of overdose
- Increased plasma protein binding capacity
21
Q
Side effects of phenytoin
A
H. Hyperplasia of gums Hirsutism with acne Y. lYmphadenopathy D. abnormal vit D metabolism ➡️ hypocalcemia Diplopia A. Ataxia Anaemia N. Nystagmus T. Teratogenic O. Osteomalacia I. Induces vit K metabolism N. Neutropenia
22
Q
Lymphadenopathy of phenytoin
A
It resembles Hodgkins disease
23
Q
TDM is advised for phenytoin and carbamazepine when
A
Diplopia and ataxia are seen as side effects
24
Q
Fetal hydantoin syndrome
A
Teratogenic effect of phenytoin
Facial clefts
25
Vitamin K and phenytoin
Phenytoin induces vitamin K metabolism decreasing vitamin K, effects:
1. Pregnancy
Hemorrhagic disease is newborn
To prevent vitamin K supplements (10 mg/day) in 3rd trimester
2. Decreased bone matrix synthesis
26
Carbamazepine
| Recent derivatives
1. Oxcarbazepine: prodrug of eslicarbazepine
2. Eslicarbazepine
Both are:
Less toxic so less hypersensitivity
Less enzyme inducers
Uses: GTCS, partial seizure
27
Uses of carbamazepine
1. GTCS
2. DoC in partial seizures
3. DoC in trigeminal neuralgia
4. Bipolar disorder
5. Acute mania
28
Side effects of carbamazepine
```
H. Hyponatremia SIADH
Hypersensitivity
E. Eosinophilia
A. Agranulocytosis, Aplastic anaemia, Ataxia
D. Diplopia and blurring of vision
S. Splenomegaly
Stevens Johnson syndrome
```
29
Hyponatremia as side effect of carbamazepine
More with oxcarbamazepine
Delayed side effects
More common in elderly
30
SJS Stevens Johnson syndrome
It is seen with both phenytoin and carbamazepine
Associated with:
1. HLA B-1502 gene - Abacavir induced SJS
2. HLA B 5701 gene - allopurinol induced SJS
3. HLA B 5801 gene
31
Lamotrigine
| Mechanism
Wide spectrum:
1. Na+ channel blocker
2. Ca2+ channel blocker (2nd line treatment in absence seizure)
3. Decreased glutamate
32
Uses of lamotrigine
1. 1st line in GTCS, JME and partial seizure, safer drug in pregnancy
2. 2nd line in Lennox Gastaut syndrome
3. Bipolar disorder during depressive phase
33
Side effects of lamotrigine
1. Nausea, vomiting
2. Ataxia/ diplopia
3. SJS
Prevented by gradually increasing the dose - sensitisation
So, lamotrigine cannot be given in emergency
34
Topiramate
| Mechanism
Wide spectrum:
1. Na channel blocker
2. K channel opener
3. CA inhibitor
4. GABA A agonist
5. Blocks glutamate receptor of AMP-A and Kainate subtype
35
Uses of topiramate
```
1. GTCS
2 JME
3. Partial seizures
4. LGS
5. Bipolar disorder
6. Prophylaxis of migraine not responding to propranolol
7. Codependence of alcohol, smoking
```
36
Side effects of topiramate
1. CA inhibition:
• Metabolic acidosis
• Nephrolithiasis
• Hypohidrosis
Used as 2nd line in treatment of pseudotumour cerebri
2. Weight loss:
Used along with phentermine in treatment of obesity
3. 2° closed angle glaucoma:
Ophthalmic examination before prescribing
37
Zonisamide
```
• Blocks:
Na channel
Ca channel
• Free radical scavenger
Uses - partial seizure
S/E: CA inhibitor
1. Metabolic acidosis
2. Nephrolithiasis
3. Hypohidrosis
```
38
Rufinamide
```
Blocks Na channel
Metabolised by non-microsomal enzymes ➡️ no drug interactions
Uses: LGS
S/E:
1. QT interval shortening
2. Leukopenia
```
39
Lacosamide
Blocks Na channel
Only anti epileptic to cause slow inactivation of Na channels
Sources: amino acid L serine
Uses: partial seizure
S/E:
1. Prolonged PR interval
2. Suicidal tendency (FDA- black box warning)
40
Potassium channel opener as anti epileptics
```
Ezogabine/Retigabine
2nd line drug for partial seizure
S/E:
1. Pigmentation of skin, lips, nails
2. Tremors
3. Retinal deposits- so ophthalmological examination every 6 months
```
41
Drugs that decrease the effects of glutamate used as antiepileptic
```
1. NMDA receptor blocker:
Felbamate
Use: GTCS, partial seizure
2. AMPA antagonists:
Perampanel
Talampanel
Use: Partial seizure
```
42
Felbamate
```
NMDA receptor blocker
Decrease the effect of glutamate
Uses (not preferred):
1. GTCS
2. Partial seizures
S/E:
1. Bone marrow suppression
2. Hepatotoxic
```
43
Perampanel, Talampanel
```
AMPA antagonists
Decrease effects of glutamate
Use - partial seizure
S/E:
1. Somnolence
2. Mood abnormality
```
44
GABA receptors
```
Post synaptic
1. GABA-A:
Brain
Cl- channel
Antiepileptic
2. GABA-B:
Spinal cord
Gi subtype ➡️ K+ channel opener
Muscle relaxation
```
45
Antiepileptic effect of GABA increasing drugs
```
1. Direct antiepileptic effect- GABA-A agonist:
• Benzodiazepines
• Barbiturates
• Ganaxolone
• Stiripentol
2. Indirect antiepileptic effect:
• stimulating pre synaptic GABA release
• inhibiting its reuptake
• inhibiting its metabolism
```
46
Baclofen
GABA-B agonist
Mechanism: muscle relaxation
Use: Amylotrophic lateral sclerosis
47
Indirect antiepileptic drugs by increasing GABA
1. Stimulating release:
Pregabalin, Gabapentin
2. Inhibits reuptake: Tiagabine
3. Inhibits metabolism: Vigabatrin (GABA TRansaminase INhibitor)
48
Gabapentin and Pregabalin
| Mechanism and pharmacokinetics
```
Mechanism:
1. Binds to presynaptic Ca channel
2. Blocks Ca endocytosis
3. Increases GABA release
Pharmacokinetics:
Not metabolised ➡️ no drug interactions
Excreted unchanged by kidneys
```
49
Common uses and side effects of Gabapentin and Pregabalin
```
Uses:
1. Partial seizure
2. Peripheral neuropathy
S/E:
1. Weight gain
2. Oedema
```
50
Specific uses of Gabapentin
1. Prophylaxis of migraine
2. Bipolar disorder
3. Generalised anxiety disorder
4. Phobia
5. Post herpetic neuralgia
51
Tiagabine
```
Inhibits GABA reuptake
Use: partial seizure
S/E:
1. Paradoxical seizure in non-epileptics
2. Psychosis
```
52
Vigabatrin
```
Inhibits GABA transaminase
Uses:
1. Resistant partial seizure
2. Infantile spasm:
• associated with tuberous sclerosis
DoC: Vigabatrin
• not associated with tuberous sclerosis
DoC: ACTH/ steroids
S/E: irreversible visual field defects
```
53
Ganaxolone
GABA-A receptor agonist
Uses:
1. Partial seizure
2. Infantile spasm
54
Stiripentol
```
Mechanism:
1. GABA-A agonist
2. Increases GABA in synapse
Uses:
Dravet syndrome (DoC valproate) as an add on drug to valproate or clobazam
S/E: anorexia ➡️ weight loss
```
55
Synaptic vesicular protein inhibitor
Hypothesis: contraction of SV2A ➡️ excitatory NT
So, SV2A inhibitor 🅱️s excitatory NT (glutamate)
Drugs:
1. Levetiracetam
2. Brivaracetam
56
Levetiracetam
```
Mechanism:
1. SV2A inhibitor
2. N type Ca channel blocker
M/C in 🤰 for epilepsy:
1. Monotherapy- Levetiracetam DoC
2. Polytherapy:
Levetiracetam
Lamotrigine
Clonazepam
```
57
Uses and side effects of Levetiracetam
```
Uses:
1. GTCS
2. JME
3. Partial seizure
4. Status epilepticus
5. Levodopa induced dyskinesia
Safer in pregnancy
S/E:
1. Bone marrow suppression
2. Mood abnormalities
```
58
Brivaracetam
Mechanism:
1. SV2A inhibitor
2. Na channel blocker
Uses: partial seizure
59
Cannabidiol
```
Derivative of cannabis
Use:
1. Dravet syndrome
2. Lennox Gastaut syndrome
S/E: hepatotoxic
Monitor AST/ALT
CI: children <2 years
```
