acetic acid derivate - structural analogue of GABA

0.85 L/kg

acetic acid derivative which is a structural analogue of
GABA.

Peak plasma levels within 2-3hrs

Non-Opiate Analgesic

Level 2

1. post-herpetic neuralgia
2. painful diabetic neuropathy
3. partial seizures with or without secondary generalization, and
4. neuropathic pain

600/800 mg tablets and 100/300/400 mg capsules

structurally related to GABA but does
not interact with GABA receptors. The binding site for the drug is the
alpha-2-delta subunit of voltage-gated calcium channels. Gabapentin does
not interact with sodium channels in vitro (cf. phenytoin, carbamazepine).

It may also:
1. partially reduce the response to the glutamate agonist NMDA
2. reduce the release of monoamine neurotransmitters in vitro
3. stimulate glutamate decarboxylase (the enzyme which converts
glutamate to GABA), and
4. increase the synaptic release of GABA

CNS Gabapentin has analgesic and anticonvulsant properties and improves
sleep in patients with neuropathic pain.

Dizziness, ataxia, nystagmus, somnolence, tremor,
diplopia, nausea, and vomiting occur with a frequency >5%.
Leucopenia,
erectile dysfunction, and weight gain

PO BA 60%

CSF concentration ~20% of plasma
Present in breastmilk

Not protein bound

Not metabolized

Renal – unchanged

T1/2: 5-7 hrs
Clearance proportional to creatinine clearance

- enhances analgesic effect of morphine
- removed by haemodialysis

PO only
900-3600mg/day in 3 divided doses
Dose reduced in renal failure
Discontinuation at least over a week

Anticonvulsant

-

- post-herpetic neuralgia
- painful diabetic neuropathy
- partial seizures with or without secondary generalization
- neuropathic pain.

Tablets 600/800mg
Capsules 100/300/400mg

- does not interact with GABA receptors.
- Binds to alpha-2 delta subunit of VGCC (voltage-gated calcium channels)
- does not interact with sodium channels in vitro (cf. phenytoin, carbamazepine)

May also:
- partially ↓ NMDA response
- ↓ release of monoamine neurotransmitters in vitro
- stimulate glutamate decarboxylase (glutamate → GABA)
- ↑ synaptic GABA release

CNS
- analgesic
- anticonvulsant
- improves sleep in patients with neuropathic pain

- Dizziness, ataxia, nystagmus
- somnolence, tremor, diplopia
- N/V (>5%)
- Leucopenia, erectile dysfunction, weight gain

PO BA 60%
Peak plasma levels 2-3hrs

CSF concentration 20% of steady-state trough plasma

no PB

not metabolized.

unchanged in urine

T1/2 5-7hrs.
Clearance proportional to creat clearance

- enchances morphine effect
- removed by haemodialysis
- BA dec with increasing dose
- Antacids decrease BA

PO.
Titration.
300mg TDS usual
Long term epilepsy dose: 900-3600mg/day
Needs weaning on discontinuation ~1 week
Reduce dose in renal impairment