Core pharmacology

Class Group

Non-Opiate Analgesic

Legacy Cicm Level

Level 2

Introduction

GABA analogue ((s)-3-(aminomethyl)-
5-methylhexanoic acid).

Indications Uses

1. peripheral and central neuropathic pain
2. partial seizures with or without secondary generalization and
3. generalized anxiety disorder

Presentation

Capsules (containing lactose monohydrate) of varying strengths from 25-300mg.

Mechanism of action

Pregabalin is 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.

Physiological effects

CNS Pregabalin has analgesic, anticonvulsant, and anxiolytic properties

Adverse Effects Toxicity

PD: Side Effects / Toxicity Very safe SE profile. Safe in ped,preg.
Toxicity – hepatic and renal toxicity. plasma levels should be plotted on a nomogram and consideration of NAC infusion commenced as appropriate. ALT is a marker of damage. Increased salivation - Upper airway reflexes intact  laryngospasm - Hypotension if given in shock states - Emergence delirium Worsen renal function by inhibiting PGE2 and causing vasoconstriction.
 risk of thromboembolic events.
Increased risk of GI bleeding and ulceration, GORD.
Impair platelet function
May reduce the beneficial eff¬ects of aspirin Dysphoria,Euphoria. Miosis (excitation of Edinger-Westphal nucleus)
N/V -CTZ stim. Serotonin syndrome with SSRI /SNRI/MAO/TCA
Less resp dep than morphine
analgesic effect in CYP2D6 deficiency Dizziness, ataxia, nystagmus, somnolence, tremor,
diplopia, nausea, and vomiting occur with a frequency >5%.
Leucopenia,
erectile dysfunction, and weight gain
Weight gain in diabetic patients
Dizziness, somnolence
Blurry vision, reduced visual acuity, diplopia

Absorption

PO BA >90%
Rapidly absorbed in fasted state

Distribution

Crosses placenta and seen in breastmilk

Protein binding

Not protein bound

Volume of distribution

0.56 L/kg

Metabolism

Minimal
0.9% N-methylated pregabalin

Excretion

Renal – 98% unchanged

Half-life

T1/2: 6.3hrs

Special Points

Avoid in galactose intolerance, lactase deficiency or glucose-galactose malabsorption
- Removed by haemodialysis (conc reduced by 50% after 4hrs)

Route And Dose

PO only
150-600mg/day in 2-3 divided doses
Dose reduced in renal failure
Discontinuation at least over a week