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
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
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
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.
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