Antiplatelet and thrombolytic drugs

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Antiplatelet and thrombolytic drugs These
slides were kindly provided by AstraZeneca
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Antithrombotic drugs
Fibrinolytics
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Antithrombotic drugs
Fibrinolytics
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Antithrombotic drugs
Fibrinolytics
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Antithrombotic drugs
Fibrinolytics
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The role of platelets
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The role of platelets
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The role of platelets
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The role of platelets
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Antiplatelet drugs
Antiplatelet drugs
Acetylsalicylicacid (aspirin)
GPIIb/IIIaantagonists
P2Y12 antagonists
Dipyridamole
Used widely in patients at risk of
thromboembolic disease
Beneficial in the treatment and prevention of ACS
and the prevention of thromboembolic events
Secondary prevention in patients following
stroke, often in combination with aspirin
Administered intravenously, are effective during
percutaneous coronary intervention (PCI)
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Acetylsalicylic acid mechanism of action
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Acetylsalicylic acid mechanism of action
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Acetylsalicylic acid mechanism of action
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Acetylsalicylic acid mechanism of action
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Acetylsalicylic acid mechanism of action
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Acetylsalicylic acid pharmacokinetics

• Rapid absorption of aspirin occurs in the stomach
  and upper intestine, with the peak plasma
  concentration being achieved 15-20 minutes after
  administration
• The peak inhibitory effect on platelet
  aggregation is apparent approximately one hour
  post-administration
• Aspirin produces the irreversible inhibition of
  the enzyme cyclo-oxygenase and therefore causes
  irreversible inhibition of platelets for the rest
  of their lifespan (7 days)

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Acetylsalicylic acid major use

• Secondary prevention of transient ischaemic
  attack (TIA), ischaemic stroke and myocardial
  infarction
• Prevention of ischaemic events in patients with
  angina pectoris
• Prevention of coronary artery bypass graft (CABG)
  occlusion

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Acetylsalicylic acid major drawbacks

• Risk of gastrointestinal adverse events
  (ulceration and bleeding)
• Allergic reactions
• Is not a very effective antithrombotic drug but
  is widely used because of its ease of use
• Lack of response in some patients (aspirin
  resistance)
• The irreversible platelet inhibition

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ADP-receptor antagonists mechanism of action
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ADP-receptor antagonists mechanism of action
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ADP-receptor antagonists mechanism of action
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ADP-receptor antagonists mechanism of action
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ADP-receptor antagonists pharmacokinetics

• Both currently available ADP-receptor antagonists
  are thienopyridines that can be administered
  orally, and absorption is approximately 80-90
• Thienopyridines are prodrugs that must be
  activated in the liver

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ADP-receptor antagonists major use

• Secondary prevention of ischaemic complications
  after myocardial infarction, ischaemic stroke and
  established peripheral arterial disease
• Secondary prevention of ischaemic complications
  in patients with acute coronary syndrome (ACS)
  without ST-segment elevation

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ADP-receptor antagonists major drawbacks

• Clopidogrel is only slightly more effective than
  aspirin
• As with aspirin, clopidogrel binds irreversibly
  to platelets
• In some patients there is resistance to
  clopidogrel treatment

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Dipyridamole mechanism of action
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Dipyridamole mechanism of action
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Dipyridamole mechanism of action
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Dipyridamole pharmacokinetics

• Incompletely absorbed from the gastrointestinal
  tract with peak plasma concentration occuring
  about 75 minutes after oral administration
• More than 90 bound to plasma proteins
• A terminal half-life of 10 to 12 hours
• Metabolised in the liver
• Mainly excreted as glucuronides in the bile a
  small amount is excreted in the urine

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Dipyridamole major use

• Secondary prevention of ischaemic complications
  after transient ischaemic attack (TIA) or
  ischaemic stroke (in combination with aspirin)

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Dipyridamole major drawbacks

• Is not a very effective antithrombotic drug
• Dipyridamole also has a vasodilatory effect and
  should be used with caution in patients with
  severe coronary artery disease chest pain may be
  aggravated in patients with underlying coronary
  artery disease who are receiving dipyridamole

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GPIIb/IIIa-receptor antagonists mechanism of
action
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GPIIb/IIIa-receptor antagonists mechanism of
action
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GPIIb/IIIa-receptor antagonists mechanism of
action
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GPIIb/IIIa-receptor antagonists mechanism of
action
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GPIIb/IIIa-receptor antagonists mechanism of
action
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GPIIb/IIIa-receptor antagonists
pharmacokinetics

• Available only for intravenous administration
• Intravenous administration of a bolus dose
  followed by continuous infusion produces constant
  free plasma concentration throughout the
  infusion. At the temination of the infusion
  period, free plasma concentrations fall rapidly
  for approximately six hours then decline at a
  slower rate. Platelet function generally recovers
  over the course of 48 hours, although the GP
  IIb/IIIa antagonist remains in the circulation
  for 15 days or more in a platelet-bound state

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GPIIb/IIIa-receptor antagonists major use

• Prevention of ischaemic cardiac complications in
  patients with acute coronary syndrome (ACS)
  without ST-elevation and during percutaneous
  coronary interventions (PCI), in combination with
  aspirin and heparin

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GPIIb/IIIa-receptor antagonists major drawbacks

• Can only be administered by intravenous injection
  or infusion and are complicated to manufacture
• Oral drugs have been investigated but were not
  effective and have therefore not reached the
  market

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Thrombolytic drugs mechanism of action
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Thrombolytic drugs mechanism of action
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Thrombolytic drugs mechanism of action
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Thrombolytic drugs mechanism of action
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Thrombolytic drugs pharmacokinetics

• The plasma half-life of the third generation
  drugs is 14-45 minutes, allowing administration
  as a single or double intravenous bolus. This is
  in contrast to second generation t-PA, which with
  a half-life of 3-4 minutes, must be administered
  an initial bolus followed by infusion

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Thrombolytic drugs major use

• Thrombolysis in patients with acute myocardial
  infarction (MI)
• Thrombolysis in patients with ischaemic stroke
• Thrombolysis of (sub)acute peripheral arterial
  thrombosis
• Thrombolysis in patients with acute massive
  pulmonary embolism
• Thrombolysis of occluded haemodialysis shunts

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Thrombolytic drugs major drawbacks

• Treatment is limited to acute in-hospital
  treatment. There is a high risk of bleeding
  inherent in this treatment
• Patients using anticoagulants are contraindicated
  for treatment with thrombolytics