Gabapentin and pregablin

3. Pharmacologic classification:1-amino-methyl
cyclohexoneaceticacid
Therapeutic classification: anticonvulsant
Pregnancy risk : category C

4. Tablet:600 mg,800 mg
Capsule:100mg,300mg,400mg
Oral solution 250 mg per 5 mL

5. -Gabapentin was initially synthesized
to mimic the chemical structure of
the neurotransmitter gamma-
aminobutyric acid (GABA), but is
not believed to act on the same
brain receptors.Its exact
mechanism of action is unknown,
but its therapeutic action on
neuropathic pain is thought to
involve voltage-gated
N-type calcium ion channels. It is
thought to bind to the α2δ subunit
of the
voltage-dependent calcium channel
in the CNS ,modulate calcium
influx in hyperexcited neuron
,reduce neurotransmitter release…

6. Adjunctive therapy in treatment of partial seizures with or
without secondary generalization in patients older than 12 yr
of age with epilepsy; adjunctive therapy for partial seizures in
children 3 to 12 yr of age; management of postherpetic
neuralgia in adults.
Unlabeled Uses
Agitation in dementia; alcohol withdrawal; bipolar disorder;
cocaine withdrawal; diabetic neuropathy; fibromyalgia;
headaches; hiccups (singultus); hot flashes (cancer- and/or
postmenopausal-related); hyperhidrosis; nausea (cancer-
related); neuralgia/neuropathy/chronic pain; prevention of
migraine; pruritus (brachioradial/cholestatic/uremic); rectal
administration; restless leg syndrome; tremors in multiple
sclerosis.

7. Children 2–12 yr: 15–35mg/kg/24hr in 3
   
divided doses (max: 50mg/kg/24hr).
   
Children >12 yr and adults: Start 300mg
 
daily, then daily increase by 300mg to 900–
 
3,600mg/24hr in 3 divided doses.
   

8. If Cr Cl is more than 60ml/minute give
400mg P.O t.i.d.daily
If Cr Cl is 15 to 30ml/minute give
300mgP.O.t.i.d daily
If Cr Cl is less than 15ml/minute give
300mg P.O other day.
Patients on haemodialysis should receive a
loading dose of 300mg-400mgP.O,then
200mg to 300mg P.O. after q4 h of
haemodialysis

9. Absorption: Gabapenten bioavailability is not dose
proportional. A400mg dose, for example is about 25% less
bioavailable than 100mg dose. Over the recommended
dose range of 300 to 600mg t.i.d, however differences in
bioavailability are not large and bioavailability is about
60%.Food has not effect on the rate or extent of
absorption..
Distribution: Gabapentin circulate largely unbound (less
than3%) to plasma protein.Cross BBB with approximately
20% of the corresponding plasma conc. Found in CSF.
.

10. Metabolism: is not appreciably metabolized in
human.
Excretion :is eliminated from the systemic
circulation by renal excretion as unchanged drug,
it elimination t1/2is5-7hr,gabapentin can removed
from plasma by haemodialysis
Contraindication: contraindicate in patients
hypersensitive to the drug

11. Interaction: Antacid decreases the absorption of
gabapentin .Administration of the two drugs
should be separate by at least 2 hr.
Laboratory Test Interactions
False-positive readings for Ames N-Multistix SG
dipstick test when gabapentin is added to other
antiepileptic drugs. Sulfosalicylic acid
precipitation procedure is recommended
to determine the presence of urine protein.

12. CNS: fatigue, somnolence ,dizziness ,ataxia ,nystagmus,
tremor ,nervousness ,dysarthria ,amnesia , depression ,
abnormal thinking ,twitching , incordoration
CV: peripheral odema , vasodilation.
EENT: diplopia, rhinitis, phyringitis, dry throat ,coughing
,amblyopia.
GU: impotence.
Haematologic: leukopenia ,decrease WBC count
Skin: pruritis ,abrasion
Other: dental abnormalities , increased appetite,
weight gain , back pain , myalgia, fracture

13. Acute over dose of gabapentin may cause double
vision, slurred speech , drowsiness ,lethargy
and diarrhea.
Supportive care is recommended. In addition
gabapentin can removed by haemodialysis and
may be indicated by the patient’s clinical state
or in plasma with significant renal impairment.

14. If gabapentin therapy is discontented or alternative
medication is substituted ,do so gradually over at
least 1 week to minimize the risk of precipitating
seizure. Do not suddenly withdraw other
anticonvulsant drugs in patients starting gabapentin
therapy
Breast feeding
It is not known if gabapentin excreted in human milk.
Because many drug are excreted in human milk.
Gabapentin should be used in breast feeding patient
only if the benefit clearly out-weight the risks.

15. *Warn patient to avoid driving or operating
heavy machinery until adverse CNS effects of
the drug are known.
*Instruct patient to take first dose at bed time
to minimize drowsiness , dizziness, fatigue ,
and ataxia.
*Inform patient that he can take gabapentin
without regard to meal

16. Pregablin
(lyrica)

18. Clinical study
Objective: To compare the dose-response (seizure frequency) relationship of
pregabalin and gabapentin add-on treatment in patients with refractory partial
epilepsy.
Background: Pregabalin (Lyrica®) and gabapentin (Neurontin®) are antiepileptic
drugs that appear to have a similar mechanism of action through binding to the α2-
δ subunit of voltage-gated calcium channels. Preclinical studies with pregabalin
and gabapentin indicate similar anticonvulsant pharmacological profiles; however,
pregabalin shows 3- to 6-fold greater potency. Pregabalin, unlike gabapentin,
exhibits linear absorption , increasing proportionally with dose. In contrast, the
extent of gabapentin absorption decreases with increasing dose.

Results: Pregabalin (50–600 mg/d) and gabapentin (600–1800 mg/d) showed an
asymptotic dose-related decrease in seizure frequency. Both pregabalin- and
gabapentin-treated patients demonstrated a dose-response relationship; however,
the maximal decrease in seizure frequency from baseline with pregabalin was
100%, while the maximal decrease with gabapentin therapy was 24.5%. Based on
this information, pregabalin was estimated to be 4 times more effective than
gabapentin in patients who responded to treatment. Pregabalin was also 2.5 times
more potent than gabapentin in responding patients, as measured by the dose that
reduced seizure frequency by 50%.
Conclusions: The observed improvement in potency and effectiveness combined with
the pharmacokinetic-pharmacodynamic properties of pregabalin relative to
gabapentin offer distinct advantages over standard gabapentin therapy for the
treatment of refractory partial seizures.