Antiepileptics for partial seizures and generalize TC's, the Narrow Spectrum agents

Question 1

What are the narrow spect agents?

Answer 1

Carbamazepine
Phenytoin
Fosphenytoin

Gabapentin
Pregabalin

Vigabatrin
Tiagabine

Question 2

Mechanism of Carbamazepine

Indications

Answer 2

Inhibits Voltage gated Na+ channels. Binds and stabilizes the inactive form.

• Trigeminal neuralgia
• Partial, focal seizures

Question 3

Mechanism of Phenytoin

Indications

Answer 3

Inhibits voltage gated Na channels, prolongs inactive state.

• for focal or tonic-clonic seizures
• Fosphenytoin for maintenance therapy in patients after status epilepticus (along with i.v. benzos to halt the acute episode)

Question 4

Gabapentin and Pregabalin

Mechanism and indications

Answer 4

DONT AFFECT GABA CHANNELS, but

• Increase presynaptic GABA release.
• Block voltage gated CALCIUM channels

Indications:
Neuropathic pain
Fibromyalgia
Post-herpetic neuralgia

Question 5

Vigabatrin mechanism and indications

Answer 5

Irreversibly inhibits GABA transaminase, decreased GABA metabolism,
increases CNS GABA levels

indication
Adjunct treatment for partial seizures only

Question 6

Tiagabine mechanism and indications

Answer 6

Inhibits GAT-1

presynaptic GABA reuptake protein

Increases ynaptic GABA

indication
Adjunct treatment for partial seizures only

Question 7

Vigabatrin SE.

Answer 7

30% of patients experience VIsual field loss with VIgabatrin

Question 8

Carbamazepine SEs (a lot)

Answer 8

Diplopia - usually the first SE

Ataxia

SIADH

Potentially fatal Marrow suppression.
-Agranulocytosis
-Aplastic anemia
Routine blood counts are required

CYP inducer (shiny car bumper)

DRESS syndrome

Teratogenic - Neural tube defects

SJS and TEN, especially in Asians with a known HLA allele, screen for prior to admin.

Liver damage

Liver function tests required.

Withdrawal seizures if stopped abruptly.

Question 9

Carbemazepine metabolism

Answer 9

Is both a CYP substrate AND a potent CYP inducer.
So, doses should be monitored.

Also is highly protein bound, competes with phenytoin, valporate, sulfonamides.

Question 10

Phenytoin SEs ( a lot )

Answer 10

Diplopia AND Nystagmus

Ataxia

Folate Deficiency
-Megaloblastic anemia

Gingival hyperplasia in FIFTY PERCENT of patients after 3 months.
From increased PDGF and increased alveolar BONE growth.

Hirsuitism

Drug induced SLE

DRESS syndrome

SJS and TEN, also especially in Asians with known HLA

Teratogenic
CYP inducer

Decreases Bone density,
-Calcium and vitamin D supplemjent, as well as bone monitoring are indicated

Phenytoin injections i.m. WILL cause tissue necrosis
to give parenterally, you must use the Fosphenytoin formulation that is converted to phenytoin in blood.

Withdrawal seizures if stopped abruptly

Question 11

Phenytoin kinetics

Answer 11

variable oral bioavailability from differences in first pass metabolism

RAPIDLY SATURABLE
Kinetics switch from first order to zero order at moderate/high doses.
Concentration increases rapidly once saturated.
Not easily predictable, and should be monitored.

Highly protein bound also, competes with phenytoin and carbamazepine.

Liver metabolized, CYP substrate AND inducer, like Carbamazepine.

Question 12

Gabapentin and pregabalin SEs

Kinetics

Answer 12

SEs
Ataxia, Dizziness, falls

Kinetics

• Excreted by kidney, must be lowered in kidney disease
• Non-linear, zero order saturable ABSORPTION, making its dose unpredictable.