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stroke treatment and perspective

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stroke treatment and perspective

  1. 1. Stroke treatment and prevention Longjun ZHU Longjun.zhu@gmail.com 2012/10/29
  2. 2. Outlines Introduction Treatment & prevention perspective 2
  3. 3. 1 Introduction 3
  4. 4. (2008) Ischaemic heart disease 12.8% Stroke & other cerebrovascular disease 10.8% Lower respiratory infections 6.1% Chronic obstructive pulmonary disease 5.8% Diarrhoeal diseases 4.3% HIV/AIDS 3.1% Tuberculosis 2.4% Trachea, bronchus, lung cancers 2.4% Diabetes mellitus 2.2% Road traffic accidents 2.1% 4 http://www.who.int/mediacentre/factsheets/fs310/en/index.html
  5. 5. Cerebrovascular disease ≈20 % >80 % 5
  6. 6. What’s stroke? A stroke is caused by the interruption of the blood supply to the brain, usually because a blood vessel bursts or is blocked by a clot. 6
  7. 7. Stroke will lead to permanent cerebral injury 8
  8. 8. transient ischemic attack (TIA , mini stroke ) Sudden severe and unusual headache Sudden numbness of arms and legs 9
  9. 9. 10
  10. 10. Clot forms in body and breaks off, blocking the brain's blood vessels 11
  11. 11. Obstruction of a blood vessel by a blood clot forming locally 12
  12. 12. Thrombus vs embolus difference 13
  13. 13. occurs when a blood vessel ruptures and bleeds into the brain 14
  14. 14. 15
  15. 15. Main arterial blood supply to the brain. 16
  16. 16. Other Factors: Poor diet Metabolic syndrome Modifiable Risk Factors Physical inactivity Alcoholism Drug use …… 17
  17. 17. 1 2 Treatment and Prevention 18
  18. 18. Signs of Stroke Stroke Heroes Act F.A.S.T 120 Heart Disease and Stroke Prevention and Control Program 19 Massachusetts Department of Public Health
  19. 19. CT scans Diagnosis MRI scans Arteriography Doppler ultrasound 20
  20. 20. Therapies Antithrombotic  antiplatelet agents  Anticoagulant Neuroprotective  Free Radical Scavengers  Minocycline  Growth Factors Surgery  Carotid endarterectomy  Carotid stenting  craniotomy 21
  21. 21. Antithrombotic Tenase complex Mechanism of blood coagulation cascade 22 Segers K, Dahlbäck B, Nicolaes GAThromb Haemost:2007 Sep;98(3):530-42
  22. 22. Antithrombotic Homeostatic balance between procoagulant and anticoagulant mechanisms 23 Jonathan Cohen Nature 420, 885-891(19 December 2002) doi:10.1038/nature01326
  23. 23. Antithrombotic Abciximab Tirofiban Eptifibatide Mechanism of action of main antiplatelet agents. ADP adenosine diphosphate, cAMP cyclic adenosine monophosphate, COX cyclooxygenase, TXA2 thromboxane A2 http://what-when-how.com/myeloproliferative-neoplasms/primary-and-secondary-antithrombotic-prophylaxis-specific- 24 issues-of-treatment-in-pv-and-et-myeloproliferative-neoplasms-part-1/
  24. 24. Antiplatelet agents standard treatment :Aspirin + extended-release Dipyridamole Clopidogrel:When aspirin allergy or concurrent symptomatic coronary artery disease 25
  25. 25. Ticagrelor The 1st reversible P2Y12 ADP receptor antagonist Better than Clopidogrel ADP Ticagrelor BRILINTA Brilique & Possia US (2011/06/20) in the EU (2010/12/03) N Engl J Med 2009; 361:1045-1057September 10, 2009DOI: 10.1056/NEJMoa0904327 26 Core Evid. 2011; 6: 31–42. Published online 2011 March 17. doi: 10.2147/CE.S9510
  26. 26. Prasugrel Vorapaxar Elinogrel 27
  27. 27. Anticoagulation drugs Anticoagulants such as warfarin(over 50 years) one of the most biologically effective 28
  28. 28. 29
  29. 29. Anticoagulant Source: Brunton LL, Chabner BA, Knollmann BC: Goodman & Gilman's The Pharmacological Basis of Therapeutics,12th Edition30 www.accessmedicine.com
  30. 30. The Good News Dabigatran Rivaroxaban Apixaban an alternative to warfarin 31
  31. 31. The Bad News Warfarin Rivaroxaban Apixaban Dabigatran The Coagulation Cascade 32
  32. 32. neuroprotective • Free Radical Scavengers Edaravone NXY-059 Antibiotics Minocycline Growth Factors Epoetin Beta,Trafermin, Filgrastim 33
  33. 33. Edaravone • Free Radical Scavengers •1st free radical scavenger for stroke •Exerts antioxidant effects •Inhibiting radical- dependent and -independent lipid peroxidation •Marketed solely in Japan For the treatment of acute brain ischemia and subsequent cerebral infarction. Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):85-93. BMC Neuroscience 2008, 9:75 doi:10.1186/1471-2202-9-75 BIOMEDICAL REPORTS 1: 7-12, 2013 DOI: 10.3892/br.2012.7 34 METABOLIC BRAIN DISEASE Volume 23, Number 3 (2008), 335-349, DOI: 10.1007/s11011-008-9096-3
  34. 34. NXY-059 (CeroviveR) • Free Radical Scavengers •Nitroxide spin trap • Stable free radicals that react with O2-. •Marginally positive clinical trial (SAINT I) http://www.nitrone.com/ http://www.centpharm.com/ Stroke. 2006 Dec;37(12):2970-8. Epub 2006 Oct 26. N Engl J Med 2006; 354:588-600February 9, 2006DOI: 10.1056/NEJMoa052980 35 N Engl J Med 2007; 357:562-571August 9, 2007DOI: 10.1056/NEJMoa070240
  35. 35. Why did NXY-059 fail??? • Physiochemical shortcomings polar, nonlipophilic nature, poor blood–brain barrier penetrability, nonphysiological oxidation potential, and low potency (Ginsburg, Stroke 2007) • Lack of biomarker assessing oxidative stress • Heterogeneity in individual responses to drug treatment • Stroke is a formidable disorder only one approved therapy to date Ann Pharmacother March 200640:461-471 36 The Journal of Experimental Biology 207, 3221-3231
  36. 36. Minocycline • Antibiotics acne vulgaris Exert inhibition of microglial activity, glutamate toxicity and caspase 1-dependent apoptosis produced by ischemic insults. Lampl Y, Boaz M, Gilad R et al. (2007): Neurology 69 (14): 1404–10 37
  37. 37. Growth Factors Epoetin Beta Basic fibroblast growth factor (bFGF) Filgrastim 38
  38. 38. Surgery A. carotid angioplasty B. Carotid stenting C. craniotomy remove stenosis large metal coil (stent) a type of surgery to (atherosclerotic is placed in the carotid remove blood clots or narrowing) of the artery much like a stent repair bleeding in the carotid artery. is placed in a coronary brain. 39 artery.
  39. 39. Prevention of Stroke Antihypertensive Drugs Valsartan, Losartan, Eprosartan and Telmisartan , Perindopril Lipid - Lowering Drugs Atorvastatin,Simvastatin,Pravastatin,Rosuvastatin, Eicosapentaenoic Acid Hypoglycemic Drugs Pioglitazone 40
  40. 40. Novel therapies  stem-cell therapy  repetitive transcranial  magnetic stimulation  transcranial direct-current stimulation  motor imagery  virtual reality  dopamine agonists  Antidepressants  novel robotic therapies 41
  41. 41. 1 2 3 perspective 42
  42. 42. Advancement of anti-platelet therapy may be achieved either by dose adjustment of the drug based on functional testing by changing drug combination or by the introduction of more potent and safer drugs. 43
  43. 43. 44
  44. 44. 45

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