an overview of what's stroke and how to treat it.

1. Stroke treatment and prevention
Longjun ZHU
Longjun.zhu@gmail.com 2012/10/29

2. Outlines
Introduction Treatment & prevention perspective
2

3. 1
Introduction
3

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. Cerebrovascular disease
≈20 %
>80 %
5

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. Stroke will lead to permanent cerebral injury
8

8. transient ischemic attack
(TIA , mini stroke )
Sudden severe and
unusual headache
Sudden numbness
of arms and legs 9

9. 10

10. Clot forms in body and breaks
off, blocking the brain's blood vessels
11

11. Obstruction of a blood vessel by a
blood clot forming locally
12

12. Thrombus vs embolus difference 13

13. occurs when a blood vessel ruptures and bleeds into the brain
14

14. 15

15. Main arterial blood supply to the brain. 16

16. Other Factors:
Poor diet
Metabolic syndrome
Modifiable Risk Factors
Physical inactivity
Alcoholism
Drug use
……
17

17. 1 2
Treatment and Prevention
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. CT scans
Diagnosis
MRI scans
Arteriography
Doppler
ultrasound 20

20. Therapies
Antithrombotic
 antiplatelet agents
 Anticoagulant
Neuroprotective
 Free Radical Scavengers
 Minocycline
 Growth Factors
Surgery
 Carotid endarterectomy
 Carotid stenting
 craniotomy 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. Antithrombotic
Homeostatic balance between procoagulant and anticoagulant mechanisms
23
Jonathan Cohen Nature 420, 885-891(19 December 2002) doi:10.1038/nature01326

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. Antiplatelet agents
standard treatment :Aspirin + extended-release Dipyridamole
Clopidogrel:When aspirin allergy or concurrent symptomatic coronary
artery disease 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. Prasugrel Vorapaxar
Elinogrel
27

27. Anticoagulation drugs
Anticoagulants such as warfarin(over 50 years) one of
the most biologically effective
28

28. 29

29. Anticoagulant
Source: Brunton LL, Chabner BA, Knollmann BC: Goodman & Gilman's The Pharmacological Basis of Therapeutics,12th Edition30
www.accessmedicine.com

30. The Good News
Dabigatran Rivaroxaban Apixaban
an alternative to warfarin
31

31. The Bad News
Warfarin
Rivaroxaban
Apixaban
Dabigatran
The Coagulation Cascade 32

32. neuroprotective
• Free Radical Scavengers
Edaravone NXY-059
Antibiotics
Minocycline
Growth Factors
Epoetin Beta,Trafermin, Filgrastim
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. 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. 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. 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. Growth Factors
Epoetin Beta Basic fibroblast growth factor (bFGF) Filgrastim
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. 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. 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. 1 2
3
perspective
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. 44

44. 45