it's about diabetic periphearl neurpathy and treatment options.

2. NEUROPATHIC PAIN

3. IASP Definition of Pain
“Pain is an unpleasant
sensory and emotional
experience
associated with actual or
potential tissue damage or
described in terms of such
damage.”

4.  Nociceptive Pain
Pain from physical damage or potential damage to the body.
It develops when the nociceptive nerve fibers are triggered
by inflammation, chemicals, or physical events.
 Neuropathic Pain
Neuro means nerves, and pathy means abnormality
Neuropathic pain is a chronic condition which is caused by damage
or dysfunction in the nervous system
Definitions

5. Examples of Nociceptive and
Neuropathic Pain
• Arthritis
• Mechanical low
back pain
• Sports/exercise injuries
• Postoperative pain
Neuropathic
Nociceptive Mixed
• Painful DPN
• PHN
• Neuropathic low back pain
• Trigeminal neuralgia
• Central poststroke pain
• Complex regional pain syndrome
• Distal HIV polyneuropathy
Caused by
lesion or dysfunction
in the nervous system
Caused by
tissue damage
Caused by
combination
of primary
injury and
secondary
effects
• Low back pain
• Fibromyalgia
• Neck pain
• Cancer pain

6. What is Neuropathy?
• Neuropathy--also called peripheral
neuropathy--refers to any condition
that affects the normal activity of the
nerves of the peripheral nervous
system.

7. Neuropathy
• Neuropathy results when nerve cells, or
neurons, are damaged or destroyed.
• This distorts the way the neurons communicate
with each other and with the brain.
• Neuropathy can affect one nerve or nerve type,
or a combination of nerves.
• Neuropathy can be Hereditary or Acquired

8. Diabetic Peripheral
Neuropathy

9. Diabetic Neuropathy
• Damage to nerve fibres and capillaries
• Symptoms depend on nerves involved
– Motor fibres Muscular weakness
– Sensory fibres Loss of sensation
• also prickling, tingling, aching and pain
– Autonomic fibres loss of function
• functions not under conscious control such as
digestion, bladder, genitals, cardiovascular.

10. Pharmacological Treatment for
Neuropathic pain

11. EFNS NICE CPS NeuPSIG
Diabetic
neuropathy
Post-herpetic
neuralgia
Trigeminal
neuralgia
Central
neuropathic
pain
All
neuropathic
pain
Trigeminal
neuralgia
All
neuropathic
pain
Trigeminal
neuralgia
All
neuropathic
pain
First-line
therapy
Duloxetine
Gabapentin
Pregabalin
TCA
Venlafaxine
d
Gabapentin
Pregabalin
TCA
Lidocaine
plasters
a
Carbamazepine
Oxcarbazepine
Gabapentin
Pregabalin
TCA
Amitriptyline
Duloxetine
Gabapentin
Pregabalin
Capsaicin
Carbamazepin
e
Gabapentin
Pregabalin
Duloxetine
Venlafaxine
d
TCA
Carbamazepin
e
Gapabentin
Gabapentin
ER/enacarbil
Pregabalin
Duloxetine
Venlafaxine
d
TCAs
Second-line
therapy
Tramadol Strong opioids
Capsaicin
cream
Tramadol
Strong
opioids
One of the
remaining 3
oral drugs of
the First-line
therapy
Tramadol
Strong opioids
Lidocaine
cream
c
Lidocaine
patches
c
Capsaicin
patches
b
Lidocaine
patches
b
Tramadol
Third-line
therapy
Strong opioids Strong
opioids
One of the
remaining 3
oral drugs of
the First-line
therapy
Cannabinoids Botulinum
toxin type A
Strong opioids
Fourth-line
therapy
Lamotrigine
(in central
post-stroke
pain)
Cannabinoid
s (in multiple
sclerosis)
Other opioids
Lacosamide
Lamotrigine
Botulinum
toxin
Lidocaine
cream
Lidocaine
patches
International Guidelines Comparison

12. Drawbacks with common
treatment options
• Slow onset of analgesia : TCA ,cpsaicin
• Potentially limiting adverse effects with Opioids ,
carbamazepine ,TCAs
• Dependency to long term use with Oipoids
• Limited efficacy with SSRI –Venlafexine etc
• And dosage titration with Gabapentin

13. FIBROMYALGIA

14. What is Fibromyalgia?
• A clinical syndrome of widespread muscle pain
• Chronic,
• Non-inflammatory, with
• Fatigue &
• Tender points

15. Fibromyalgia
• Most common rheumatic cause of chronic
diffuse pain. 2nd or 5th most prevalent rheumatic
disorder
• Generalized pain & pain amplification syndrome
• Extremely common pain phenomenon
occurring in a defined pattern

16. What causes FM?
• Lower levels of
– Serotonin: Related to sleep, pain perception, mood
disorders
– Nor epinephrine :control alertness, emotions, sleeping,
dreaming and learning, as a neurotransmitter it reduces
feeling of pain.
– Dopamine: Related to pleasure, motivation, & motor
control; lower levels in FM patients secondary to pain
stimulus
– Growth hormone secondary to
sleep disruption: related to tissue repair

17. What causes FM?
• Abnormally high levels of Substance P in spinal
fluid in some patients
• Substance P important in transmission and
amplification of pain signals to and from brain
• Areas of brain activated with mild tactile
pressure: 2 in controls vs. 12 in FM
• “Volume control” is turned up too high in brain’s
pain centers

18. What causes FM?
• Familial tendency to develop FMS suggests
genetic role
• Can be triggered by physical, emotional or
environmental stressors such as car accidents,
repetitive injuries and certain diseases :
– Rheumatoid arthritis and SLE pts. are more likely to
develop FMS

19. Only 3 Meds are FDA Approved
for FM
• Duloxetine
• Pregabalin
• Milnacipran

20. Gabica Product Profile

21. What does Gabica do?
• Pregabalin reduces
neuronal calcium
currents by binding to
the alpha-2-delta
subunit of calcium
channels

22. What is A2D subunit
• The A2D subunit
is not a part of the
calcium channel
pore, but is an
associated protein
that modulates
calcium channel
activity in CNS .

23. Normal process of impulse
transmission
1. Calcium ions enters into pre
synaptic neurons through
voltage gated calcium
channels.
2. These voltage dependent
calcium channels are present
in areas of nervous system
dense in synaptic connections.
3. These channels allow the
selective permeability of
calcium ions across presynaptic
plasma membranes in
response to a presynaptic
action potential.

24. Normal process of impulse
transmission
5. Calcium activates the synaptic
vesicles in which
neurotransmitters are stored. It
results in release of excitatory
or inhibitory neurotransmitters.
6. The released neurotransmitters
cross the cleft, binding to
receptor molecules on the next
cell (Postsynaptic neuron),
prompting transmission of the
message along that cell's
membrane.
7. In normal conditions, these
neurotransmitters are destroyed
by specific enzymes in the
synaptic cleft, diffuse out of the
cleft, or are reabsorbed by the
cell.

25. What happens in Neuropathic pain?
1. In neuropathic conditions, the
neurons becomes hyperexcited
resulting in increased calcium
entry through voltage gated
calcium channels into
presynaptic neurons.
2. As a result, excessive amount
of excitatory neurotransmitters
are released .
3. As a result, more electric
signals are transmitted across
the neurons that result in
painful conditions like
neuropathic pain.

26. How Gabica works???
Gabica binds to
α2-δ subunit
Calcium entry in
Presynaptic nerve
terminal decreased
Reduction of release
of excitatory
neurotransmitters
( Glutamate ,
substance P etc)
Decreased Excitatory
neurotransmitters leads
to Analgesic action

27. GABICA
• No direct action on GABA, NMDA, or glutamate
receptors
• Inactive at GABAA and GABAB receptors, is not
converted metabolically into GABA or a GABA
antagonist, and does not alter GABA uptake or
degradation
• Does not block sodium or calcium channels or bind to
either cholinergic or opioid receptors.
• No impact on the arachidonic acid pathways (the
mechanism of action for NSAIDs and COX-2 inhibitors).

28. Therapeutic indications
• For the management of neuropathic pain associated with
diabetic peripheral neuropathy.
• Post herpetic neuralgia.
• As adjunctive therapy in adults with partial seizures with
or without secondary generalization.
• For the treatment of fibromyalgia syndrome (FMS)
• For the treatment of Generalized Anxiety Disorder (GAD)
in adults.

29. DOSAGE AND ADMINISTRATION
• GABICA (Pregabalin) is given orally with or
without food.
• When discontinuing GABICA (Pregabalin), taper
gradually over a minimum of 1 week.

30. DOSAGE AND ADMINISTRATION
Indications
Initial dose
in 2-3 divided
doses
Maintenance dose
Based on efficacy and
tolerability after interval
of 3-7 days
Maximum dose if
needed after 1
week
Diabetic Peripheral
Neuropathy
150 mg / day 300 mg / day 600 mg /day
Post herpetic
neuralgia
150 mg / day 300 mg/day 600 mg /day
Epilepsy 150 mg / day 300 mg/day 600 mg /day
Fibromyalgia 150 mg / day 300 mg/day 450 mg /day
Generalized Anxiety
disorder (GAD)
150 mg / day 300 mg/day 450 mg /day

31. Superiority of Gabica

32. Superior Mechanism of action
than Gabapentin
• Gabica (Pregabalin )
Selectively binds to α2-δ
subunit of Ca channels in
CNS tissues
• Gabica has 6-10 times
strong binding to α2-δ
subunit than Gabapentin.
• This results in superior
efficacy due to its superior
mechanism of action.

33. Superior Pharmacokinetics-
Absorption
• Feature:
– Pregabalin is absorbed orally and within 1.3 hours ,
Gabica achieves maximum concentration in blood
• Advantage:
– Rapidly reaches the blood
• Benefit :
– Swift onset of action

34. Superior Pharmacokinetics -
Bioavailability
• Feature:
– Gabica ( Pregabalin ) has bioavailability more than
90% on all doses ,
– whereas bioavailability of common used drug
Gabapentin varies with the dose – decreases as dose
is increased , 60-33% on doses 900mg-3600mg / day
• Advantage:
– More amounts reaches the blood to show its
therapeutic action
• Benefit:
– Superior and significant analgesic action

35. Superior Pharmacokinetics –
Plasma Half Life:
• Feature:
– Gabica ( Pregabalin ) plasma half life is 6.3 hours
• Advantage:
– 2-3 times dose daily
• Benefit:
– Simple dosage schedule leads to patient compliance

36. Superior Pharmacokinetics-
Protein Binding :
• Feature:
– Gabica ( Pregabalin ) does not bind to plasma protein
• Advantage :
– No pharmacokinetic interaction with others drugs
• Benefit :
– Safe to the patient when given with other drugs.

37. Superior Pharmacokinetics -
Metabolism :
• Feature :
– Gabica ( pregabalin ) undergoes negligible hepatic
metabolism , therefore it does not interact with other
drugs
• Advantage :
– No pharmacokinetic interaction with others drugs
• Benefit :
– Safe to the patient when given with other drugs.

38. Superior Pharmacokinetics
Renal Excretion :
• Feature:
– Gabica ( Pregabalin ) major route of excretion is
through kidneys , and 98% drug is excreted as
unchanges form
• Advantage:
– Can be given in hepatic patients
• Benefit:
– Gabica can be given in wide range of patients.

39. Swift and Sustained pain relief :
• Gabica provides swift onset of action and
sustained pain relief due to its swift onset of
action T-max 1.3 hours and steady state levels
–within 1-2 days. And sustained due to its strong
binding to alpha-2 delta receptors.
• Pain relief and improved sleep with Gabica
began during week 1 and in some studies
provides significant pain relief throughout one
year.

40. Safe and well tolerated :
• Gabica has no pharmacokinetic interactions
and can be given safely with other drugs.
• Gabica is generally well tolerated . Adverse
effects are mild to moderate and dose
dependent.
• Commonly reported adverse effects include
dizziness, somnolence, peripheral edema
and dry mouth.

41. Pregabalin in GAD

42. Pregabalin Vs. Lorazepam
Ref :
Pande, Crockatt, Feltner, Et al- Am J Psychiatry 160:533
540, March 2003

43. • In GAD, Pregablin has a more rapid onset of
effect than reported for SSRIs and Venlafaxine
and a low risk of abuse or dependence,
unacceptable adverse events & withdrawal
symptoms.
» Ref: Frampton JE, Foster RH. Cns Drugs 20, 685-
693 (2006).
• Pregabalin in clinical trials almost as effective as
benzodiazepines without withdrawal symptoms,
making it a potentially good alternative.
Pregabalin Vs. Venlafaxine