Patofisiologi dan Manajemen Up date Diabetik Neuropati

Patofisiologi dan Manajemen
Diabetik Neuropati
Dr. Syamsudin, M.Biomed, Apt
Fakultas Farmasi Universitas Pancasila
The 2nd Indonesian Pharmacist Update
Dokter & Apoteker Partnership dalam Kualitas Pelayanan Kefarmasian
2-3 Mei 2013 di JCC.
Complex syndrome of
neurological
abnormalities caused
by the metabolic and
vascular
complications of
diabetes.
•
•
•
Hyperglycemia
Microvascular Disease
Oxidative Stress
–
–
•
•
•
Free radicals produced from an advanced
glycation lead to damaged neurons
Relieved by improving blood flow
Sorbitol Concentration
–
Excess sorbitol within the nerve causes it to
retain water and nerve edema/compression
Myoinositol Depletion
–
–
Myoinositol helps nerves conduct electricity
K+, Na+, and Ca+ are regulated by Myoinositol
Neurotrophic Factors
–
Diabetic nerves are folate, B6, and B12 deficient
Vinik A. The Amer. Journal of Med. August 1999.
Distal symmetrical sensorimotor polyneuropathy
is the most common form of DPN. Signs and symptoms
may progress from distal to proximal over time.
SIGNS
•Diminished vibratory perception
•Decreased knee and ankle reflexes
•Reduced protective sensation, such as
pressure, hot and cold, pain
•Diminished ability to sense position of
toes and feet
Boulton AJ, et al. Diabetes Care. 2005;28(4):956-962.
SYMPTOMS
• Numbness, loss of feeling, prickling,
tingling
• Aching pain
• Burning pain
• Lancinating pain
• Unusual sensitivity or tenderness
when feet are touched (allodynia)
Argoff et al. Mayo Clin. Proc. 2006:81 (S4)
Boulton AJM et al. Diab. Care 27, 2004
M. Clin. Diab. 23, 2005
DPN
Painful
Neuropathy
Impairment
Disability
Handicap
Sensory Loss
Mortality
Foot Ulcers
Quality of
Life
Infection
(skin, bone)
Surgery,
Amputation
Cost
Cause of diabetic
amputation
Neuropathy or vascular disease
Trauma
Ulcer
Failure to heal
Infection
Amputation
Treatment Based on
Pathophysiology Mechanisms

The Pathways
responsible for
Diabetic Neuropathy
1. Polyol pathway
2. PKC-pathway
3. AGE pathway
4. Hexosamine
pathway

Drug therapy for
symptomatic relief in
Diabetic Neuropathy
Aldose reductase inhibitor
acetic acid compounds: Epalrestat
Tolrestat
Alrestatin
Zopolrestat
 Antioxidants
-lipoic acid
 Advanced Glycation Inhibitor
Benfotiamin
 Protein Kinase Inhibitor
Ruboxisturine
 Glycaemic
 Agents increasing Nerve Blood Flow
Vasodilator: ACE Inhibitor

Drug Therapy for symptomatic relief in DPN
• INDICATIONS
–
–
–
–
DPNP
Fibromyalgia
Post herpetic neuralgia
Adjunctive seizure medication
• DOSAGE
– DPNP
• Start at 50mg tid and may increase to 100mg tid within one week
– Fibromyalgia
• 150mg tid
– Post-herpetic neuralgia
• 200mg tid
• SIDE EFFECTS
– Dizziness, drowsiness, dry mouth, edema
• DRUG INTERACTIONS
– Alcohol and drugs that cause sedation may increase the sedative effects
of those agents.
– No pharmacokinetic interactions have been demonstrated in vivo.
• Pregabalin selectively binds to α2-δ subunit of calcium channels
• Modulates calcium influx in hyperexcited neurons
• Reduces neurotransmitter release
•Pharmacologic effect requires binding at this site
•The clinical significance of these observations in humans is currently unknown
Taylor. CNS Drug Rev. 2004;10:183-188.
Rosenstock et al. Pain 2004; 110:628-638.
Rosenstock et al. Pain 2004; 110:628-638.
Lidocain
Recent Clinical Trials
 High
Concentration Capsaicin Patch
 Lacosamide
 Combination Therapies
-Pregabaline + Oxycodone
-Nortriptyline + Gabapentine
- Pregabaline + Topical 5% Lidocaine
Dworkin et al., Mayo Clin Proc, 2010:85(3)(Suppl):S3-14
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