antiepileptic drugs classification
revision notes based on lecture notes
high yield topic
glutaminergic transmission
ethosuximide
revision notes based on lecture notes
high yield topic
29. Barbiturates
• Phenobarbitone & primidone
• MOA
• GABAagonist increased chloride conductance
• Reduces Ca2+ dependant release of NT
• Uses
• GTCS & partial seizure
• GTCS in infants (DOC)
TONY SCARIA 2010 KMC
30. Phenytoin
• Nonsedative oral
• Antiarrythmic class Ib (digitalis induced arrhythmia)
• MOA preferential binding to and prolongation of the inactivated
state of the Na+ channel
TONY SCARIA 2010 KMC
32. PK
• 80 -90 % protein bound low Vd
• Enzyme inducer
• Metabolised by hydroxylation of CYP 2C19 & 2C9 & as well as by
glucuronide conjugation
• Excreted in urine as glucocoronide conjugate
• Saturation kinetics
• Zero order kinetics at higher dose
• Narrow TI 10 -20 ug/ml
TONY SCARIA 2010 KMC
34. S/E of phenytoin
• Hyperplasia of gums
• Hirsutism
• Hypersensitivity reaction
• Hyperglycemia
• Hypersensitivity
• Hydantoin syndrome
• d/t toxic epoxide metabolism
• Impaired DNA synthesis d/t FA deficeicny
• Cleft palate hypoplastic phalanges microcepahly
• Lymphadenopathy Pseudolymphoma
TONY SCARIA 2010 KMC
35. Gingival hyperplasia d/t phenytoin
• Mc manifestation in
children & adults
• d/t inhibition of
collagenase enzyme
responsible for
breakdown of
collagen
TONY SCARIA 2010 KMC
36. Other drugs causing gingival hyperplasia
• Phenytoin
• CCB
• Sirolimus
• Cyclosporine
• Lamotrigine
TONY SCARIA 2010 KMC
37. Drug interactions of phenytoin
• Induces enzymes
• OCP digitoxin doxycycline theophylline rifampicin levodopa
• carbamazepine & phenytoin
• Increase each others metabolism
• Displacement from PPB of valproate
• Sucralfate binds to phenytoin in GIT decrease its absorption
TONY SCARIA 2010 KMC
40. Uses of phenytoin
• In all types of seizures
• Except absence seizure & myoclonic seizure
• Trigeminal neuralgia
• 2nd choice
• Cardiac arrhythmia
• d/t digitalis toxicity
TONY SCARIA 2010 KMC
41. Fosphenytoin
• Water soluble
• IV/IM
• Given as slow infusion to Px arrhythmia / CV collapse & coma
• Used in emergency
• Increased risk of hyperphosphatemia
TONY SCARIA 2010 KMC
44. Carbamazepine PHARmacokinetics
• Oral form only
• Well absorbed
• 80 % protein bound
• Enzyme inducer
• Induces its own metabolism
TONY SCARIA 2010 KMC
46. S/e of carbamazepine
• Hypersensitivity reactions
• Rashes photosensitivity hepatitis
• Lupus like syndrome
• Agranulocytosis
• Aplastic anemia
• Water retention & hyponatremia (SIADH)can occur in elderly
TONY SCARIA 2010 KMC
47. Risk of carbamazepine induced in SJS is
increased in presence of
• HLA B 1502
• May also be allergic to phenytoin lamotrigine & oxcarbazepine
TONY SCARIA 2010 KMC
48. Uses of carbamazepine
• GTCS
• Simple & complex partial seizure
• Trigeminal neuralgia
• Glossopharygengeal neuralgia
• Post herpetic neuralgia
• In Diabetis insipidus
TONY SCARIA 2010 KMC
49. Oxcarbazepine
• Analog of carbamazepine
• Converted to licarbazepine
• No autoinduction
• Enzyme inducer (less than carbamazepine)
• Higher risk of hyponatremia & hepatotoxicity
TONY SCARIA 2010 KMC
50. Drug Moa ADR Use
Lamotrigine Block Na+ & Ca2+ channel Sedation / skin rases / SJS
/ataxia
Partial seizure
Safe drug in pregnancy
Gabapentin Increase release &
inhibits uptake of GABA
(inhibit presynaptiv N
type ca2+ channels)
Sedation ataxia Partial & grandmal
seizure
Neuropathic pain
Vigabatrin inhibits GABA – T Psychosis
Permanent & progressive
painless loss of vision
Partial seizure
LGS (add on)
Infantile spasm with
tuberous sclerosis
Tiagabine Inhibits glial & neuronal
uptake of GABA
Tremors ataxia mental
confusion
Refractory partial seizure
TONY SCARIA 2010 KMC
51. Drug MOA ADR Use
Levitiracetam SV2A protein inhibitor Associated with anger &
aggression
Refractory partial seizure
Felabamate NMDA blocker Hepatotoxicity
Aplastic anemia
Weight loss
Resistant epilepsies
LGS
Zonisamide (sulphonamide derivative)
Voltage gated Na+ & ca2+
channel inhibitor
Renal stone Refractory partial seizure
Topiramate (weak
carbonic anhydrase
activity)
Blocks Na + channel
Increase GABA activity
Decrease glutamate
action
AMPA blocker
Renal stone
Weight loss
Drowsiness dizziness
Partial seizure
Grandmal seizure
Migraine prophylaxis
Alcohol dependence
TONY SCARIA 2010 KMC
52. Drug MOA ADR Use
MgSO4 Toxicity is monitored by
patellar reflex
Eclampsia
Lacosamide Blocks Na channel &
CRMP2
Partial onset seizures
Ganaxolone Neurosteroid • Absence seizure
• Infantile spasm
• Catamenial epilepsy
Rufinamide Block Na+ channel • LGS
Retigabine Block K channel • Add on in partial
seizure
Perampanel
Telampanel
AMPA antagonist • Partial seizure
Pregabalin Inhibit N type Ca2+
channel in presynaptic
neuron
Sedation • Fibromyalgia
TONY SCARIA 2010 KMC
61. Valproate
• Blocks voltage gated Na+ channel
• Blocks T type Ca2+ channels
• facilitate glutamic acid decarboxylase (GAD) increase GABA
• inhibitory effect on the GABA transporter GAT-1
• inhibits GABA transaminase in the brain
• Decrease release of aspartate (excitatory NT) in brain
TONY SCARIA 2010 KMC
62. PK of valproate
• Available as capsule syrup IV capsule
• High oral bioavailability
• Enzyme inhibitor
• All others are inducers
TONY SCARIA 2010 KMC
63. S/E of valproate
• Increased appetite & weight gain
• PCOD
• Acute pancreatitis
• Hepatotoxicity in children <2 yrs
• Therefore in children < 2years DOC In absence seizure is ethosuximide
• Alopecia
• Teratogenic NT defect
TONY SCARIA 2010 KMC
64. Valproate can cause hyperammonemia
• d/t blockage of ura
cycle
• Carnitine deficiency
TONY SCARIA 2010 KMC
65. Uses of valproate
DOC in seizure disorder Also used in
• GTCS
• Myoclonic
• Atonic
• Clonic
• Atypical absence
• LGS
• Partial
• Infantile spasm
• Absence
Valproate is also used in
• Bipolar disorder with rapid cycling
• Migraine headache prophylaxis
• Neuropathic pain
TONY SCARIA 2010 KMC
72. S/E of AED
Antiepileptic causing weight loss TOFE Antiepileptic causing renal stone TOPAZ
• Topiramate
• Felbamate
• Topiramate
• Zonismaide
TONY SCARIA 2010 KMC
73. S/E of AED
Lymphadenopathy Phenytoin
Hairloss Valproate
Permanent visual field loss Vigabatrin
Anemia Carbamazeoine
Felbamate (bonemarrow suppression)
Hepatotoxicity Valproate
Carbamazepine
SJS Carbamazepine
Lamotrigine
Weight gain Valproate
TONY SCARIA 2010 KMC
74. First line Second line
Partial seizure with or
with out GTCS
Carbamazepine
valproate
Lamotrigine
Phenobarbital
Lamotrigine
Gabapentin
GTCS Valproate
Lamotrigine
Phenytoin
Topiramate
Absence seizures Valproate
Ethosuximide
Lamotrigine
Clonazepam
Zonisamide
Myoclonic jerks Valproate Lamotigine
Felbamate ]
TONY SCARIA 2010 KMC
75. Infantile spasm
• DOC is ACTH
• Incase of infantile spasm with tuberous sclerosis vigabatrin is used
TONY SCARIA 2010 KMC
76. Lennox gestaut syndrome
• First line
• Valproate (DOC)
• BZD (clonazepam clobazam)
• Rufinamide
• Second line
• Felbamate
• Topiramate
TONY SCARIA 2010 KMC
77. Treatment of seizures in pregnancy
• Preconception counselling
• To be stabilised under minimum effective dose with same drug
• If new drug has to be started LAMOTRIGINE DOC
• Folic acid (0.4mg/day) & vitamin K supplementation
• Periodic screening for teratogenicity
TONY SCARIA 2010 KMC
78. Teratogenic effects of AED
Valproate NT defects spina bifida
Phenytoin Fetal hydantoin syndrome (microcephaly short
phalanges cleft lip)
Carabamazepine Cleft lip & palate
Topiramate Limb agenesis in rodents
Hypospadiasis in males
Zonismaide Teratogenic
TONY SCARIA 2010 KMC
79. • Absence seizures (>2 years)
• GTCS
• Tonic seizure
• Clonic seizure
• Myoclonic seizure
• Atonic
Valproate
• Absence seizure (<2 years) Ethosuximide (d/t hepatotoxicity valproate is not used
)
• Febrile seizure Rectal diazepam
Partial seizure Carbamazepine
Infantile spasm ACTH
Infantile spasm with tuberous sclerosis Vigabatrin
Lennox gastaut syndrome Valproate
Febrile seizure Diazepam (per rectal)
Status epilepticus Lorazepam
Seizure in eclampsia MgSO4
Mesial temporal sclerosis Surgery
TONY SCARIA 2010 KMC
82. Drugs causing seizures
Drug of abuse Anesthetic & analgesic Psychotropics Sedative hypnotic drug
withdrawal
• Amphetamine
• Cocaine
• Phencyclidine
• Methylphenidate
• Meperidine
• Tramadol
• Local anesthetic
• Antidepressants
• Antipsychotics
• Lithium
• Alcohol
• Barbiturate
• BZD
TONY SCARIA 2010 KMC
83. Types of ca2+ channel Drugs acting on them
N type of ca2+ channel • pregabalin
• Gabapentin
T type of Ca2+ channel • Ethosuximide
• Valproate
L type Ca2+ • CCB
TONY SCARIA 2010 KMC