Membrane stabilizer& Muscle relaxant 마취통증의학과 R2 민 진 기

1. Membrane stabilizer&Muscle relaxant마취통증의학과R2 민 진 기

2. MEMBRANE STABILIZER Central sensitization- alterations in the way that nerve fibers respond to and send subsequent input to CNS Tissue injuries affect the A-delta and C fibers, decreasing their threshold to activation  allodynia Neuronal membrane excitability increase with an increase in various ion channels being present at the site of pathology Sodium channel blocking agents Antiepileptics, local anesthetics and antiarrhythmics Calcium channel blocking agents Gabapentin, w-conopeptides and calcium channel blockers

3. SODIUM CHANNEL BOLCKERS Anticonvulsants, local anesthetics and antiarrhythmics The primary agents utilized for neuropathic pain are anticonvulsants Primary therapy or adjunctive treatment for trigeminal neuralgia, CRPS, diabetic neuropathy and post herpetic neralgia 일반적으로, 용량은 safety standards내에서 patient comfort에 적정되어야 한다

4. ANTICONVULSANTS Phenytoin (Dilantin) For diabetic neuropathy would not be considered first-line therapy for neuropathic pain unique to phenytoin, facial alteration including gum hyperplasia and a coarsening of feature activates the P450 enzyme system careful assessment of cotherapy is warranted

5. Carbamazepine (Tegretol) 화학적 구조가 TCA와 유사하다 Selectively blocks active fibers Primary therapy for trigeminal neuralgia ( tic doloreux), thalamic mediated poststroke pain, postherpetic neuralgia, and diabetic neuropathiy Nausea, vomiting and sedation common side effect Compression of the trigeminal nerve by the superior cerebellar artery Should have blood tests every 2 to 4 months( d/t agranulocytosis and aplastic anemia)

6. Oxcarbazepine The keto-analogue of carbamazepine: CNS 또는 혈액학적 부작용이 덜하다 Significant hyponatremia( <125mmol/L) may develop during first 3 months Better side effect profile of oxcabazepine to carbamazepine Valproic acid Acts at the GABA A receptor Efficacy in migrane therapy Side effect- gastrointestinal upset..

7. Lamotrigine (Lamictal) Unique to lamotrigine, in addition to acting as a sodium channel blocker, prevents release of glutamate Major use is in trigeminal neuralgia, indication for cold-induced pain Trigeminal neuralgia에 대해서 carbamazepine에 co-drug 또는 substitute로서 사용 use of lamotrigine may be indicated in carbamazepine-resistant trigeminal neuralgia lamitrigine may have a role in prevention of trigeminal neuralgia in susceptible pts. Patient suffering from diabetic neuropathy may receive benefit from lamotrigine Tx For HIV-associated polyneuropathy Rash- 가장 흔한 부작용

8. Topiramate (Topamax) In addition to affecting sodium and calcium channel, enhance GABA and inhibit AMPA type glutamate receptor As an adjunct Kidney stones and ocular glaucoma Levetiracetam (Kepppra) Relatrvely new antiepileptic

9. LOCAL ANESTHETICS Block the aberrant firing of the abnormal nerves; not block normally conducting nerves Lidicaine As an antiarrhythmic, bradycardia and cardiac depression is a potential risk- EKG 5% lidocaine is available in transdermal application EMLA-소아에서 venipuncture시 adjunct로 사용 Mexilitene Antiarrhythmic, oral analogue of lidocaine For diabetic neuropathy, thalamic stroke pain, spasticity and myotonia Risk for blood dyscrasia

10. CALCIUM CHANNEL BLOCKERS Six different calcium channel current types found in nervous tissue: L, N, P, Q, R, T Gabapentin Binds at the alpha-2-delta subunit of the L-type calcium channel GABA와 구조적으로 유사하나 GABA 수용체에 결합하지도 작용하지도 않는다 GABA의 uptake와 metabolism에도 영향을 끼치지 않는다 Patients with allodynic, burning, and lancinating pain are more likely to get positive benefit as opposed to patients with hyperalgesic dull and achy pain For postherpetic neuralgia, diabetic neuropathiy, CRPS, radiculopathy, postlaminectomy syndrome, poststroke syndrome, phantom limb pain, multiple sclerosis and etc. Favorable side-effect profile

11. Zonisamide (Zonegran) Blocking T-type calcium channels, and sodium channels w-conopeptides derived from the venom of a marine snail action on N-type calcium channels intrathecal administration opioid-resistant pain에서 HIV나 cancer population에서 연구되어옴 Nifedipine, Verapamil, Diltiazem, Nimodipine Decreasing central sensitization Do not have a role as monotherapy

12. Magnesium Antagonists of the NMDA receptor, including membrane stabilizing effect NUMBERS NEEDED TO TREAT (NNT) The number of patients treated with certain drug in order to obtain one patient with a defined degree of relief NNT50%

13. MUSCLE RELAXANT 1.Neuromuscular blocking agents 2. antispastic drug 3. drug that are useful in short-term relief of pain and muscle spasm ANTISPASTIC DRUGS Spasticity- involunraty increase in muscle tone that occurs during muscle stretch Mediated peripherally by muscle spindle primary Ia fibers( monosynaptic refles arc) Centrally through reticulospinal and vestibulospinal pathways Primarily caused by long-term reduction in inhibition rather than in increase in excitation of alpha motor neurons

14. two type of GABA receptor: GABA-A and GABA-B glycine- another neurotransmitter released by inhibitory interneurons CENTRALLY ACTING MUSCLE RELAXANTS Enhance inhibitory neurotransmission- BDZ, anticonvulsant, baclfen and tizanidine Benzodiazepine Only diazepam( Valium) and to a much lesser extent, clonazepam ( Klonopin) are used Facilitates the release of GABA and its binding to GABA-A receptor The majority of GABA neurons are interneuron Net result- decreased transmitter release from Ia afferents to motor neurons

15. Diazepam (Valium) Most effective in patients with spinal cord disease and injury Painful, persistent and disabling muscle spasm > periodic flexor spasm Side effect makes nonambulatory patients better candidates 간에서 대사되고 urine이나 feces로 배설된다 태반을 통과하고 breast milk에서 발견된다 Long term use carries risk of dependence and abrupt termination may lead to serious withdrawl symptoms Clonazepam (Klonopin) Anticonvulsant Gabapentin (Neurontin) and Tiagabine (Gabitril) may have antispastic properties

16. Baclofen (Lioresal) 구조적으로 GABA와 유사, GABA-B receptor agonist Particularly useful in the treatment of spasticity of the spinal cord origin Baclofen과 diazepam의 antispastic effect는 비슷하나 less sedation으로 baclofen이 선호되는 경향이 있다 약 30%는 serum protein과 결합하고 간에서 deamination 된다. 나머지는 변화되지 않은채 urine이나 feces로 배설된다 Small fraction만이 BBB를 통과 Intrathecal baclofen can be used Safe drug and is tolerated well even in large doses

17. Tizanidine (Zanaflex) Centrally acting alpha2 adrenergic agonist Structurally similarity to alpha2-agonist clonidine Most beneficial in reducing the frequency of muscle spasm and clonus but is less consistent in reducing muscle tone Better tolerated than diazepam and baclofen 항고혈압제와는 매우 주의깊게 투여해야함, and do not administer with alpha2 agonist

18. PERIPHERALLY ACTING ANTISPASTIC DRUGS Dantrolene (Dantrium) Directing acting muscle relaxant Blocks the release of calcium and dissociates excitation-contraction coupling Induced muscle weakness interferes with the patient’s ability to ambulate Not indicated in skeletal muscle spasm and pain from rheumatologic disorders Useful adjunct to dopamine agonists in the treatment of NMS Necessary to monitor LFT

19. Botulinum toxin Introduced in the late 1970s Produced by a Gram negative anaerobic bacterium Toxin type: A, B, C, D, E, F only A, B, E, F strains cause human disease A purified and attenuated form in available BTX-A( Botox), Dysport( in Europe) and BTX-B( myobloc) Kept in refrigerator until it’s use Acts on neuromuscular junction Does not cross the blood-brain barrier and therefore has no effect on central cholinergic pathways Current use Focal dystonia Nondystonic excessive muscle contraction Headache (migraine, tension headache

20. Myofascial pain Hyperhydrosis Genitourinary disorder (detruser-sphincter dyssnergia) Gastrointestinal disorder (achalasia, constipation, esophageal sphincter spasm) The average duration of benefit is approximately three months Not recommended during pregnancy and in lactating women Most commonly used to treat focal dystonias predominantly spasmodic torticollis and blepharospasm. Also in hemifacial spasm, limb dystonia

21. DRUG USED IN SHORT-TERM RELIEF OF PAIN AND MUSCLE SPASM Cyclobenzaprine Hydrochloride (Flexeril) Ineffective in spasticity due to CNS disease Primary action on brain stem For short term therapy Chlorzoxazone (Paraflex) Centrally acting agent Spasticity due to CNS disease is not relieved by this agent Carisoprodol (Soma) Inhibiting interneuronal activity in the descending reticular activating system and the spinal cord May experience tachycardia and postural hypotension Methocarbamol (Robaxin, Robaxisal) No proven muscle relaxant effect Primary CNS depressant로서 작용한다고 믿어진다