[Bài giảng] Cơ chế tác dụng của thuốc điều trị đau thần kinh

 

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CƠ CHẾ TÁC DỤNG CỦA THUỐC ĐIỀU TRỊ

ĐAU THẦN KINH

Nguyễn Lê Trung Hiếu
8.12.2019

Nội dung

1. Đau thần kinh
2. Cơ chế tác dụng của thuốc
3. Thông điệp

1. Đau thần kinh
(Neuropathic pain)

Hội chống đau Tp.HCM
Hội đau Việt Nam

Khái niệm

Neuropathic pain
(Đau thần kinh)

Pain caused by a lesion or disease of the

somatosensory nervous system

https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698

Dẫn truyền đau

Ralf Baron, Andreas Binder, Gunnar Wasner, Neuropathic pain: diagnosis, pathophysiological mechanisms, and
treatment,the lancet neurology Vol 9 August 2010

Kathleen Meacham, Andrew J Shepherd, Durga P Mohapatra, Simon
Haroutounian, Neuropathic Pain: Central vs. Peripheral Mechanisms,
Current Pain and Headache Reports 2017

Đau thần
kinh

Trung
ương

Não

Tủy sống

Ngoại
biên

Thần kinh
ngoại biên
Hạch gại

Cơ chế

Ralf Baron, Andreas Binder, Gunnar Wasner, Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment,
Lancet Neurol 2010; 9: 807–19

Nociceptive neuron*
A central or peripheral neuron of the
somatosensory nervous system that
is capable of encoding noxious
stimuli.
Nociceptor*
A high-threshold sensory receptor of
the peripheral somatosensory
nervous system that is capable of
transducing and encoding noxious
stimuli.
Noxious stimulus*
A stimulus that is damaging or
threatens damage to normal tissues.

https://www.iasp-
pain.org/Education/Content.aspx?ItemNumber=1698

Cơ chế

http://www.benhvien103.vn/vietnamese/bai-giang-chuyen-nganh/dot-quy/tong-quan-chan-doan-va-dieu-tri-dau/1481

Nguyên nhân

MEDICINEWISE NEWS March 2018

Phân loại

NICE Guidelines 2018

Các kiểu đau thần kinh

Thuật ngữ Mô tả
Allodynia (Loạn cảm đau) Pain due to non-noxious stimuli (mechanical, dynamic

and thermal)

Anesthesia (Mất cảm giác) Loss of normal sensation to the affected region
Dysesthesia (Loạn cảm giác) Spontaneous or evoked unpleasant abnormal

sensations

Hyperalgesia (Tăng đáp ứng đau) Exaggerated response to a mildly noxious stimulus
Hyperpathia (Tăng cảm đau) Delayed and explosive response especially to a

repetitive stimuli

Hypoesthesia (Giảm cảm giác đau) Reduction of normal sensations to the affected region
Paresthesia (Dị cảm) Non painful spontaneous abnormal sensations to a

stimulus that is not unpleasant
Phantom pain (Đau ma) Pain arising from an amputated part
Anil Kumar et al, Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches, Arch Neurosci.
2017 January; 4(1):e28998.

2. Cơ chế tác dụng của thuốc

Điều trị đau thần kinh

NICE Guidelines 2018

Kiểm soát đau thần kinh

Khalid S, Tubbs R (October 06, 2017) Neuroanatomy
and Neuropsychology of Pain. Cureus 9(10): e1754.
DOI 10.7759/cureus.1754

Local anesthetics
Anti-inflamatory drugs
Local anesthetics
TCAs, SNRI
Opioids
Alpha-2 agonists

TCAs, SNRI
Opioids
Alpha-2 agonists

SNRI: serotonin-norepinephrine
reuptake Inhibitor

Thuốc điều trị đau thần kinh

Bridin P Murnion, Neuropathic pain: current definitionand review of drug treatment, Aust Prescr
2018;41:60–3

Cơ chế tác dụng (1)
Drugs (first line) Main mechanisms of action
Tricyclic antidepressants
Nortriptyline
Desipramine
Amitriptyline
Clomipramine
Imipramine

Inhibition of reuptake of monoamines, blockade of sodium
channels, anticholinergic effects

Serotonin–norepinephrine reuptake inhibitors
Duoxetine
Venlafaxine

Inhibition of serotonin and norepinephrine reuptake

Calcium channel alpha-2- delta ligands
Gabapentin
Pregabaline

Acts on alpha-2- delta subunit of voltage-gated calcium
channels, which decreases central sensitization

N. Attal, D. Bouhassira, Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain 156 (2015) S104–S114

Cơ chế tác dụng

Zeng L, Alongkronrusmee D, van Rijn RM,
Journal of Pain research, 2016

Drugs (first
line)

Main mechanisms of action

Tricyclic antidepressants
Nortriptyline
Desipramine
Amitriptyline
Clomipramine
Imipramine

Inhibition of reuptake of
monoamines, blockade of
sodium channels,
anticholinergic effects

Serotonin–norepinephrine reuptake inhibitors
Duoxetine
Venlafaxine

Inhibition of serotonin and
norepinephrine reuptake
Calcium channel alpha-2- delta ligands
Gabapentin
Pregabaline

Acts on alpha-2- delta subunit of
voltage-gated calcium
channels, which decreases
central sensitization

Cơ chế tác dụng (2)

Drugs (second line) Main mechanisms of action
Topical lidocaine
Lidocaine 5% plasters Block of sodium channels
Capsaicin
Capsaicin high
concentration patches
(8%)

TRPV1 (transient receptor
potential V1) agonist

Opioids
Tramadol
Tapentadol

Mu receptor agonist and inhibition of monoamine
reuptake

N. Attal, D. Bouhassira, Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain 156 (2015) S104–S114

Cơ chế tác dụng (3)

Drugs (third line) Main mechanisms of action
Opioids
Morphine, oxycodone Mu receptor agonists; oxycodone may also act as

k-receptor agonist

Botulinum toxin
Botulinum toxin type A Acetylcholine release inhibitor and neuromuscular

blocking agent.
Potential effects on neurogenic inflammation

N. Attal, D. Bouhassira, Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain 156 (2015) S104–S114

Các thuốc và phương pháp khác

 Ketamine, memantine, and N-methyl-d-aspartate receptor (NMDAR)
antagonists have been employed in several preclinical and clinical
studies, but they are not approved by the FDA.
 Several clinical studies suggest the efficacy of Cannabis sativa
derivatives in the modulation of neuropathic pain.
 Repetitive transcranial magnetic stimulation (rTMS)
Eugenio Cavalli, Santa Mammana, Ferdinando Nicoletti, Placido Bramanti and Emanuela Mazzon, The neuropathic pain: An overview of
the current treatment and future therapeutic approaches International Journal of Immunopathology and Pharmacology, Volume 33: 1–10,
2019
 Carbamazepine, Oxcarbazepine (voltage-gated Na+ channels and
GABA receptors)
 Lamotrigine…voltage-gated Na+ channels and GABA receptors)
Sascha R. A. Alles1 and Peter A. Smith, Etiology and Pharmacology of Neuropathic Pain, Pharmacol Rev 70:315–347, April 2018

Sascha R. A. Alles1 and Peter A. Smith, Etiology and Pharmacology of Neuropathic Pain, Pharmacol Rev 70:315–347, April 2018
Các thuốc và cơ chế (đang nghiên cứu)

Sascha R. A. Alles1 and Peter A. Smith, Etiology and Pharmacology of Neuropathic Pain, Pharmacol Rev 70:315–347, April 2018
Các thuốc và cơ chế (đang nghiên cứu)

2018

Tương lai

2019

Tương lai

https://www.medscape.org/viewarticle/413110_7
Cơ chế tác dụng

3. Thông điệp

Đau thần kinh

Neuropathic pain
(Đau thần kinh)

https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698

Thuốc điều trị đau thần kinh

Bridin P Murnion, Neuropathic pain: current definitionand review of drug treatment, Aust Prescr
2018;41:60–3

Ralf Baron, Andreas Binder, Gunnar Wasner, Neuropathic pain: diagnosis,
pathophysiological mechanisms, and treatment,the lancet neurology Vol 9
August 2010

Các bước điều trị đau thần kinh

Nhóm 1: TCAs, SNRI, Gabapentanoids, Topicals
4 – 6 tuần
Tramadol, Kết hợp các thuốc lựa chọn 1
4 – 6 tuần

Hội chẩn chuyên gia: SSRIs, Anticonvulsants, NMDA
antagonists,

Neuromodulation (stimulation)

Low dose opioids
4 – 6 tuần
Điều trị trúng đích