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Pharmacology MBBS > Anti epileptics > Flashcards

Anti epileptics Flashcards

1
Q

Types of seizures

A
  1. Generalised seizure:
    • GTCS/ myoclonic seizures/ JME
    • absence seizures
  2. Partial seizures
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2
Q

Cause of generalised tonic clonic seizure

A
  1. Thalamus
  2. Spontaneous firing of T-type Ca channel
  3. Action potential
  4. In cortex: retrograde propagation of action potential
  5. Cortical neuron depolarisation
  6. Na channel opens
  7. Depolarisation of spinal cord segments
  8. Spontaneous contraction and relaxation of all muscles
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3
Q

Mechanism of absence seizures

A
  1. Thalamus
  2. Spontaneous firing of T type Ca channels
  3. Action potential within subcortex

Does not involve:

  1. Cortex
  2. Motor neuron
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4
Q

Mechanism of partial seizure

A
  1. Cortex occupying lesion like Neurocysticercosis, tumour, gliosis
  2. Firing of neurons downstairs via Na channels
  3. Specific neuron: action potential
  4. Specific segment of spinal cord
  5. Specific muscle
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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,…
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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

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7
Q

Treatment of partial seizure and absence seizures

A

DoC for partial seizure: Carbamazepine- Na channel blocker

DoC for absence seizures: valproate

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8
Q

Add on anti epileptics

A
  1. K+ channel opener
  2. Decreasing glutamate effect
  3. Increasing GABA effect
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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

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10
Q

Mechanism of anti epileptic action of valproate

A
  1. Calcium channel blocker
  2. Sodium channel blocker
  3. Increases GABA by stimulating synthesis and inhibiting metabolism
  4. Inhibits histone deacetylase
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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
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12
Q

Lennox Gastaut syndrome

A

Mixed seizure syndrome
Seen usually in children
Refractory seizure- difficult to treat
DoC: valproate

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13
Q

Side effects of valproate

A
  1. Nausea, vomiting: M/C
  2. Alopecia
  3. Obesity
  4. Polycystic ovarian disease
  5. Hepatotoxicity
  6. Pancreatitis
  7. Hyperammonemia
  8. Tremor
  9. Enzyme inhibitor
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14
Q

Why valproate is not used as 1st line management

A

S/E like:

  1. Alopecia
  2. Obesity
  3. Polycystic ovarian disease
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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

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16
Q

Treatment of epilepsy (JME) during pregnancy on valproate

A
  1. Continue valproate (do not stop or change anti epileptics)
  2. TDM of valproate
  3. Folic acid:
    • normal pregnancy: 400 μg/day
    • h/o neural tube defect in previous pregnancy: 4000 μg/day
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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
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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
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19
Q

Phenytoin or diphenyl hydantoin

Uses

A
  1. GTCS
  2. Partial seizures
  3. Treatment of neuropathic pain
  4. Antiarrhythmic drug
  5. Given as slow IV as fosphenytoin for treatment of status epilepticus
    Fast IV causes asystole
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20
Q

Pharmacokinetics of phenytoin

A
  1. The only anti epileptic to follow zero order kinetics ➡️ increased risk of toxicity in case of overdose
  2. Increased plasma protein binding capacity
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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
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22
Q

Lymphadenopathy of phenytoin

A

It resembles Hodgkins disease

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23
Q

TDM is advised for phenytoin and carbamazepine when

A

Diplopia and ataxia are seen as side effects

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24
Q

Fetal hydantoin syndrome

A

Teratogenic effect of phenytoin

Facial clefts

25
Q

Vitamin K and phenytoin

A

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
Q

Carbamazepine

Recent derivatives

A
  1. Oxcarbazepine: prodrug of eslicarbazepine
  2. Eslicarbazepine
    Both are:
    Less toxic so less hypersensitivity
    Less enzyme inducers
    Uses: GTCS, partial seizure
27
Q

Uses of carbamazepine

A
  1. GTCS
  2. DoC in partial seizures
  3. DoC in trigeminal neuralgia
  4. Bipolar disorder
  5. Acute mania
28
Q

Side effects of carbamazepine

A 
H. Hyponatremia SIADH
 Hypersensitivity
E. Eosinophilia 
A. Agranulocytosis, Aplastic anaemia, Ataxia
D. Diplopia and blurring of vision
S. Splenomegaly 
 Stevens Johnson syndrome
29
Q

Hyponatremia as side effect of carbamazepine

A

More with oxcarbamazepine
Delayed side effects
More common in elderly

30
Q

SJS Stevens Johnson syndrome

A

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
Q

Lamotrigine

Mechanism

A

Wide spectrum:

  1. Na+ channel blocker
  2. Ca2+ channel blocker (2nd line treatment in absence seizure)
  3. Decreased glutamate
32
Q

Uses of lamotrigine

A
  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
Q

Side effects of lamotrigine

A
  1. Nausea, vomiting
  2. Ataxia/ diplopia
  3. SJS
    Prevented by gradually increasing the dose - sensitisation
    So, lamotrigine cannot be given in emergency
34
Q

Topiramate

Mechanism

A

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
Q

Uses of topiramate

A 
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
Q

Side effects of topiramate

A
  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
Q

Zonisamide

A 
• Blocks:
 Na channel
 Ca channel
• Free radical scavenger
Uses - partial seizure
S/E: CA inhibitor
1. Metabolic acidosis
2. Nephrolithiasis
3. Hypohidrosis
38
Q

Rufinamide

A 
Blocks Na channel
Metabolised by non-microsomal enzymes ➡️ no drug interactions
Uses: LGS
S/E:
1. QT interval shortening
2. Leukopenia
39
Q

Lacosamide

A

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
Q

Potassium channel opener as anti epileptics

A 
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
Q

Drugs that decrease the effects of glutamate used as antiepileptic

A 
1. NMDA receptor blocker:
 Felbamate
 Use: GTCS, partial seizure
2. AMPA antagonists:
 Perampanel
 Talampanel
 Use: Partial seizure
42
Q

Felbamate

A 
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
Q

Perampanel, Talampanel

A 
AMPA antagonists
Decrease effects of glutamate
Use - partial seizure
S/E: 
1. Somnolence 
2. Mood abnormality
44
Q

GABA receptors

A 
Post synaptic
1. GABA-A:
 Brain
 Cl- channel
 Antiepileptic 
2. GABA-B:
 Spinal cord
 Gi subtype ➡️ K+ channel opener
 Muscle relaxation
45
Q

Antiepileptic effect of GABA increasing drugs

A 
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
Q

Baclofen

A

GABA-B agonist
Mechanism: muscle relaxation
Use: Amylotrophic lateral sclerosis

47
Q

Indirect antiepileptic drugs by increasing GABA

A
  1. Stimulating release:
    Pregabalin, Gabapentin
  2. Inhibits reuptake: Tiagabine
  3. Inhibits metabolism: Vigabatrin (GABA TRansaminase INhibitor)
48
Q

Gabapentin and Pregabalin

Mechanism and pharmacokinetics

A 
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
Q

Common uses and side effects of Gabapentin and Pregabalin

A 
Uses:
1. Partial seizure
2. Peripheral neuropathy
S/E:
1. Weight gain
2. Oedema
50
Q

Specific uses of Gabapentin

A
  1. Prophylaxis of migraine
  2. Bipolar disorder
  3. Generalised anxiety disorder
  4. Phobia
  5. Post herpetic neuralgia
51
Q

Tiagabine

A 
Inhibits GABA reuptake
Use: partial seizure
S/E:
1. Paradoxical seizure in non-epileptics 
2. Psychosis
52
Q

Vigabatrin

A 
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
Q

Ganaxolone

A

GABA-A receptor agonist
Uses:
1. Partial seizure
2. Infantile spasm

54
Q

Stiripentol

A 
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
Q

Synaptic vesicular protein inhibitor

A

Hypothesis: contraction of SV2A ➡️ excitatory NT
So, SV2A inhibitor 🅱️s excitatory NT (glutamate)
Drugs:
1. Levetiracetam
2. Brivaracetam

56
Q

Levetiracetam

A 
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
Q

Uses and side effects of Levetiracetam

A 
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
Q

Brivaracetam

A

Mechanism:
1. SV2A inhibitor
2. Na channel blocker
Uses: partial seizure

59
Q

Cannabidiol

A 
Derivative of cannabis
Use:
1. Dravet syndrome
2. Lennox Gastaut syndrome 
S/E: hepatotoxic
 Monitor AST/ALT
CI: children <2 years

Pharmacology MBBS (19 decks)

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