Neuropati METIKOBAL
-
Upload
sovy-sultanah -
Category
Documents
-
view
310 -
download
9
Transcript of Neuropati METIKOBAL
Role of in Diabetic Neuropathy
DefinisiNeuropathy is a medical term describing disorders of the nerves of the peripheral nervous system (specifically excluding encephalopathy and myelopathy, which refer to the central nervous system.)
Dorland’s Medical Dictionary
DefinisiPeripheral neuropathy is defined as deranged function and structure of peripheral motor, sensory, and autonomic neurons, involving either the entire neuron or selected levels
Dyck PJ (1982). "Current concepts in neurology. The causes, classification, and treatment of peripheral neuropathy". N. Engl. J. Med. 307
Trauma atau tekanan pada saraf. Diabetes.Vitamin deficiencies. Alcoholism. Autoimmune diseases. Other diseases ( penyakit ginjal, penyakit
hati,hypothiroid)Penyakit keturunan. Terpapar racun. (obat-obat untuk
kanker)
Etiology
Gejala- Gejala 1.Sensasi menusuk.
2.Sensasi geli.
3.Sensasi terbakar.
4.Sensasi gatal.
5.Nyeri tusuk.
Neuropathic pain
neuropathic pain is "initiated or caused by a primary lesion or
dysfunction in the nervous system”.
Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms (2nd edition ed.)
JENIS – JENIS NYERI / PAINJENIS – JENIS NYERI / PAIN
Neuropathic Pain Nociceptive Pain
Nyeri disebabkan karena kerusakan pada sistem saraf (susunan saraf perifer ataupun pusat)
Nyeri disebabkan karena adanya luka pada jaringan tubuh
(otot, tulang, kulit, viseral)
Mixed PainNyeri dengan
komponen Neuropathic
dan Nociceptive
Contoh :
Contoh : Contoh :Perifer :- Diabetic Neuropathy- Post Herpetic Neuralgia- Trigeminal Neuralgia- Post Surgical Neuropathy- Post Traumatic NeuropathyCentral :- Post Stroke Pain
- Low back pain with radiculopathy - Cervical radiculopathy- Cancer pain - Carpal Tunnel Syndrome
- Nyeri karena inflamasi- Nyeri karena patah tulang- Nyeri sendi krn Osteoarthritis- Post Operative Visceral Pain
Neuropathic Pain Nociceptive Pain
Nyeri kronik (bulan/tahunan) Nyeri akut (bbrp jam/hari)
Disebabkan krn kerusakan atau penyakit pada saraf
Disebabkan karena kerusakan atau inflamasi yang mengenai
otot atau persendian
Nyeri ringan sampai menyiksa dan berlangsung terus-menerus
Nyeri sedang sampai berat yang akan hilang jika luka sembuh
Menyebabkan ‘extreme sensitivity’ pada sentuhan – memakai baju menyebabkan
nyeri
Menyebabkan gatal, pada sekitar luka
Penderita menjadi depresi karena merasa nyeri tidak dapat hilang
dan dapat menyebabkan gangguan tidur
Penderita mearasa cemas dan stress, tetapi optimis bahwa akan
bebas dari rasa nyeri
Wall PD. Textbook of Pain. 4th ed; 1999; Jude EB. Clin in Pod Med and Surg.1999;16:81-97; Price SA. Pathophysiology: Clinical Concepts of Disease Processes. 5th ed; 1997: Goldman L. Cecil Textbook of Medicine. 21st ed; 2000
Perbandingan Perbandingan Neuropathic Pain dan Neuropathic Pain dan
Nociceptive PainNociceptive Pain
Woolf CJ, Mannion RJ. Neuropathic Pain: Etiology, symptoms, mechanisms, and management. Lancet, 1999;353:1959-64.
Syndrome
Symptoms
Patophysiology
Etiology
Neuropathic pain
Stimulus-independent pain
Stimulusdependent pain
Mechanisms
Nerve damage
Traumatic
Toxic
Infectious
Metabolic
Hereditary Compression
Ischaemic
Th/ Pain killer, eg : gabapentin,
pregabalin
Th/ Based on etiology
Ex : Oral Anti Diabetic, Steroid, Anti biotics, etc.
Immune - mediated
Th/ nerve repaired
Methycobal – active cobalamin
Proses Patologi Pada NeuropathySegmental demyelinationExamples:Diabetic neuropathyAlcoholic neuropathyUremic neuropathyGuillain-Barre syndrome
Wallerian degenerationExamples:Spondylosis deformansHernia of intervartebral discCarpal tunnel syndromeFacial palsyGlaucomatous optic atrophy
Axonal degenerationExamples:Drug-induced neuropathies[Vincristine, isonicotinicacid hydrazide (INH), etc.]Herpes zoster
Direction of degeneration
Direction of degeneration
Nerve cell
Myelin sheathAxon
Muscle
Klasifikasi Neuropathy
Apakah kedua sisi tubuh terkena ? satu sisi asimetris
dua sisi simetris
Tipe dari saraf yang terkena; apakah saraf motorik, sensorik, atau autonom.
Berapa banyak saraf yang terkena?
bila satu saraf mononeuropathy,
bila lebih dari satu polyneuropathy
Klasifikasi Neuropathy
Bagian tubuh mana yang terkena? mendekati batang tubuh/menjahui batang tubuh.
Neuropathy pada tangan dan kaki disebut distal neuropathy, otot paha disebut proximal neuropathy
Diagnosa1. Ditemukan gejala, seperti kelemahan
otot; nyeri.
2. Pemeriksaan neurology.
3. EMG.
4. Standarized test ; seperti mengukur kekuatan otot, kemampuan saraf otonom.
5. X-ray.
Diabetic Neuropathy
Impact of Diabetic Impact of Diabetic NeuropathyNeuropathy
15% of Diabetics will develop an ulcer
85,000 amputations per year
27% direct medical cost of Diabetes
Diabetes Care 26:1790-1795, 2003
Diabetic Peripheral Neuropathy Symptoms
Asymptomatic
Painful
Sensory Loss
39%
11%
50%
Boulton AJM. Clin. Diab. 23, 2005Argoff C, Cole BE, Fishbain DE, Irving G. Mayo Clin. Proc. 2006:81 (S4)Boulton AJM et al. Diab. Care 27, 2004
Diabetic Neuropathy: SymptomsDiabetic Neuropathy: Symptoms
Hyperglycemia
Microvascular Insufficiency
Nerve Degeneration
Neuronal Dysfunction
Endothelial Dysfunction
Proposed Mechanisms in the Pathogenesis of Diabetic Neuropathy
Etiology of Diabetic NeuropathyEtiology of Diabetic Neuropathy
Vinik Aaron. Diabetic Neuropathy: Pathogenesis and Therapy. The Amer. Journal of Med. August 1999;107 (2B):17S-26S.
Painful Diabetic Neuropathy (PDN)
Neuropathy atau kerusakan saraf yang disebabkan oleh diabetes dan dapat timbul sebagai “insensate neuropathy” (hilangnya fungsi sensoris) atau painful neuropathy .
Painful Diabetic Neuropathy (PDN)
1.Pengontrolan gula darah yang kurang baik pada penderita DM.
2.Bisa berlangsung selama 12 bulan
Gejala-gejala PDN
Pencegahan & Terapi Neuropathy
1. Mengontrol berat badan, gula darah.
2. Medikamentosa.
3. Terpenting menghilangkan nyeri
Methycobal
An active form of cobalamin
Participates in transmethylation
Improves synthesis of proteins, nucleic acids and phospholipids which are needed in the repair of damaged nerves.
Difference between Methycobal and other types of Cobalamins
Structures of other types of CobalaminsStructure of Methycobal
CyanocobalaminHydroxocobalamin DBCC
Bagaimana beda preparat MBL dari preparat OH – B 12 dan
CN- B 12?
Preparat hidrokso dan ciano B 12 merupakan bentuk tidak aktif dan diindikasikan hanya untuk anemia dan neuropati akibat defisensi vit.B12. MBL mengandung CH3-B12, adalah bentuk aktif vitamin B 12 dan diindikasikan untuk pengobatan neuropati perifer.
Objective: Evaluate Methycobal transport to human C.S.F.Method : CH3-B12 - 1,000ug
:CN -B12 - 1,000ugOne I.M. inj.
Methycobal R
Nabuo Tanaka, et al.: Hakone Symp.”Nervous Sys. & Vit. B12”, p5, 1981
MethycobalSerum and C.S.F. with high levels of CH3-B12
Haruto Uchino et al,.:Kyoto Symp. Periph. Neuropathy and Methyobal,” p(1):1978
91.2%
73.2%
25.9%
0.9%
8.1%
0.7%
Human Health Care Company
Nucleic Acid and Protein Synthesis
Methycobal activates the synthesisof DNA in nerve cells and promotes
protein synthesis
①
Phospholipid synthesisMethycobal synthesizes lecithin,a major component of myelin sheath
②
Deoxyuridinemonophosphate
(d-UMP)
Thiamidinemonophosp
hate(d-TMP)
5 methyltetrahydrofolic acid(5-methyl THF)
5,10 methylenetetrahydrofolicacid
di-hydrofolic acid
tetra-hydrofolic acid
S-adenosylhomocysteine
Homocystine
Methyionine synthetase
Methionine
(SAM)S-adenosylmethionine
EthanolamineTransmethylationCholine
AcetylcholineLecithin
DNA
Kerja biokimia dari
John M. Scott et al : Lancet,337 ( 1981 ) Tashiro.S : Hakone Symposium“The nervous system and Methyl B12”,30 ( 1981 )
meningkatkan sintesa asam nukleat dan protein di dalam sel-sel saraf
CH3-
TransmethylationTransmethylation
5 methyltetrahydrofolic acid5 methyltetrahydrofolic acid Tetrahydrofolic acidTetrahydrofolic acid
MethionineMethionine
Methionine synthaseMethionine synthase
HomocysteineHomocysteine
S-adenosylhomocysteineS-adenosylhomocysteine S-adenosylmethionineS-adenosylmethionine
Methycobal
DNA
CH3
Methycobal 500µg®
Scot JM, et al.: Lancet 1981, 337
Thymine
meningkatkan sintesa lesitin, komp utama selubung myelin
Homocysteine Methionine
S-adenosylhomocysteine S-adenosylmethionine
Lechitin Cephalin
Tashiro S, et al.: Hakkone Symposium,”The Nervous System and Methyl B12,” 1981, p-30
Methycobal 500µg®
MethycobalCH3
Homocysteine Metabolism
Homocysteine and Diabetes
• Hyperhomocysteinemia ( 15 umol/l) significantly increases risk of DN (p=0.01)
• Logistic regression model shows homocysteine was the only significant variable associated with prevalence of DN, OR: 2.6 (95% CI 1.07-6.33)
0
2
4
6
8
10
12
14
16
18
Hom
ocys
tein
e (u
mol
/l)
Normal WCDM* PCDM*
WCDM – well-controlled DMPCDM – poorly controlled DM
Drzewoski et.al. Diabetes Nutr Metab 2000 Dec; 13(6): 319-24Ambrosch et.al. Diabet Med 2001 Mar;18(3):185-92
p <0.001
Improves subjective symptoms in diabeticneuropathy patients
0
0.5
1.0
1.5
2.0
2.3
42cases
Pacebo group:
Methycobal group:CH3 B12 1500μg/day 12 w eeks
12 w eeks
Numbness Pain Weakness Cramps Impotence NS NS P<0.005 NS P<0.02 NS P<0.002 NS P<0.03 NS
NS: Non significant Methycobal Placebo
Devathasan G. et al.: Clinical Trials Journal.23 (2), p.130, 1986
Mea
n S
co
re
Methycobal injection for acute cases in-patients:
1To study the effect of Methycobal inj. in diabetic neuropathy (treatment period: 12 weeks)
Method
Aim
Shiga Medical College Yasuda et al : , 25 ( 11 ) ,109( 1988 )
Patients with diabetic neuropathy8 casesSeverity: Moderate to Severe
12 weeks500μg×3A/weeks, intravenous
Methycobal injection for acute cases in-
patients: 2●Overall Improvement
●Improvement in subjective symptoms (%) (After 12 weeks)Lower limbs spontaneous painLower limbs spontaneous pain
Numbness
Loss of perception
Moderate improvement37.5
Slight improvement50.0
No change12.5
500 100(%)
4weeks
Remarkable Improvement
25.0 37.5 25.0 12.5
37.5 37.525.0
85.7
80.0
75.0
71.4
Result
8weeks
Shiga Medical College Yasuda et al : , 25 ( 11 ) ,109 ( 1988 )
12weeks
Drug InformationCompositionEach tablet contains 500 μg of mecobalamin.Each 1 ml ampule contains 500 μg of mecobalamin.
IndicationPeripheral neuropathiesMegaloblastic anemia dus to vitamin B12 deficiency(inj. only)
Usually for adults, orally administer 1 tablet 3 times a day (1,500 μg of mecobalamin).The dosage should be adjusted according to the age of patient and the severity ofsymptoms.
InjecitonPeripheral NeuropathiesThe usual abult dosage is 1 amplule, equivalent to 500μg of mecobalamin,administered intramuscularly or intravenously three times a week.The dosage should be adjusted according to the age of patient and the severity ofsymptoms.
Megaloblastic AnemiaThe usual abult dosage is 1 ampule,equivalent to 500μg of mecobalamin, administeredintramuscularly or intravenously three times a week.After about 2 months of administration one ampule should be administered every one tothree months as maintenance therapy.
AvailabilityTablet: Box of 30's & 100's Injection: Box of 10's
Dosage and AdministrationTablet
Efek Samping
Dilaporkan terjadi pada 146 penderita dari total 15.180 penderita (0.96%). Efek samping utama adalah anoreksia pada 52 penderita (0.34%), kelainan GI pada 38 penderita (0.25%), nausea/vomiting pada 18 penderita (0.12%, diare pada 17 penderita (0.11%) dan erupsi kulit pada 14 penderita (0.09%).