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Drug treatment of ACS : Angina

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... results make ACS fairly protocol driven www.NICE.org.uk www.clinicalevidence.con Cochrane data base Guidelines for the management of acute coronary syndromes ... – PowerPoint PPT presentation

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Title: Drug treatment of ACS : Angina


1
Drug treatment of ACS Angina Myocardial
infarction
  • Judith Coombes
  • Conjoint Senior Lecturer, University of
    Queensland
  • Senior Pharmacist, Education, Princess Alexandra
    Hospital

2
Objectives
  • STEMI and NSTEACS
  • Acute treatment of unstable angina
  • Mechanism and evidence
  • Acute treatment of Myocardial infarction
  • Mechanism and evidence

3
Evidence
  • ACS has a huge number of large multicentre trails
    providing evidence for treatment choices.
  • Trial results make ACS fairly protocol driven
  • www.NICE.org.uk
  • www.clinicalevidence.con
  • Cochrane data base
  • Guidelines for the management of acute coronary
    syndromes 2006 (National Heart Foundation)

4
Causes of Death 1996 of all ages
5
(No Transcript)
6
Unstable Angina myocardial
Infarction
Acute Coronary Syndromes
High Risk Minor Myoc damage
ST Elevation
Low-Risk
Non-ST Elevation
Troponin
Cardiac Markers
mortality
CK
ECG - Normal ST Depr/Transient
elevation ST elevation
7
Unstable Angina
  • Due to rupture of arthersclerotic plaque -
    increased platelet aggregation (platelet
    thrombi), vasospasm and formation of clot.
  • Not a total occlusion of blood vessel
  • May be associated with some muscle damage
  • Recent onset- pain at rest
  • Crescendo
  • Angina occurring post MI

8
Principal Goals of Therapy
  • Correct O2 demand vs supply imbalance
  • reduce pre-load on the heart (amount of blood
    returning to be pumped out)
  • improve coronary artery circulation
  • reduce ionotropic (force) and chronotropic (rate)
    activity of myocardium - O2 demand
  • Stop formation of fibrin clot and progression of
    thrombus
  • Prevent myocardial infarction

9
Acute Treatment
  • Mrs UA with chest pain at the office
  • On route to hospital
  • s/l GTN - coronary dilation off load heart
  • 1-3 tablet/ sprays every 5 mins then 000
  • 3 month expiry on tablets, keep in glass
  • Aspirin 300mg - inhibit platelet aggregation
  • At emergency
  • Morphine and antiemetic
  • Oxygen
  • IV GTN
  • Heparin
  • MONA

10
Heparin Use in UA
  • Enoxaparin superior to UH heparin in reducing
    death and MI-in trials
  • Role for Acute of IV heparin whilst assessing
    need for intervention (angioplasty stent)

11
Mechanisms of action of antiplatelet agents
Clopidogrel
Dipyridamole
ADP
Phosphodiesterase
Gp IIb IIIa Fibrinogen Receptor
ADP
Activation
COX
Abciximab, tirofiban
TXA2
Collagen Thrombin TXA2
Aspirin
Adaptaed from Schafer Al Am J Med 1996
12
Aspirin
  • Antiplatelet activity
  • Decrease 35 day Mortality by 23
  • Halved incidence re-infarction stroke
  • In addition to thrombolysis decrease mortality by
    50
  • Saves 30 lives/ 1000 patients
  • Benefits sustained at 10 years

13
Glycoprotein IIb/IIIa antagonists
  • Platelets central to coronary thrombosis
  • G2b3a antagonists block platelets binding
    together eg ABCIXIMAB (Reoppro)
  • Tirofiban (Aggrostat) in combination with Aspirin
    UH reduced combined end points Death, MI angina
  • Use in High risk patients prior to angiography

14
Clopidogrel (Iscover, Plavix)
  • Act as inhibitor of platelet aggregation
  • 75mg daily
  • Used 4 weeks only with aspirin post angioplasty
    and stent
  • Suitable alternative to aspirin
  • Additive benefit to aspirin
  • Increased bleeding time

15
(No Transcript)
16
Unstable Angina myocardial Infarction
Acute Coronary Syndromes
High Risk Minor Myoc damage
ST Elevation
Low-Risk
Non-ST Elevation
Troponin
Cardiac Markers
mortality
CK
ECG - Normal ST Depr/Transient
elevation ST elevation No Q Wave Q or
no Q
17
Myocardial Infarction
  • Plaque rupture -
  • Involving total occlusion of one or more coronary
    arteries
  • Significant myocardial muscle damage (necrosis)
  • Risks of death, further MIs, heart failure,
    arrhythmia, CVA

18
Mr MI dob 1957
  • Ambulance gave Aspirin and GTN pain relief
  • Somewhere he fell ? GTN ? Laceration over eyebrow
    dressed
  • Emergency of another hospital
  • Acute inferior MI, ST elevation (STEMI)
  • 3mm ST elevation on ECG
  • Enzymes

19
Enzymes
DATE 26/3 0450 26/3 0650 26/3 2010 27/3
LDH 199 242 1400 1110
CK (20-200) 155 4130 5140
Tropinin (lt0.4) nd 2.79 2.22
20
Continued in emergency
  • Morphine 2.5mg
  • IV heparin
  • IV GTN
  • TNK tPA (tenecteplase iv)-resolution of ST
    elevation, further ST elevation 3 hrs later-so
    transfer
  • IV Metoprolol 2.5-5mg every 10 mins until HRlt60
    or BP lt90-heart block on transfer-STOP BETABLOCKER

21
For Percutaneous, transluminal coronary,angioplast
y PTCA
  • Clopidogrel 300mg as pre med then 75mg daily for
    1 month- 6 months- 12 months or longer for drug
    eluting stents

22
Regular Medications
  • Aspirin 100mg mane
  • Clopidogrel 75mg mane
  • Atorvastatin 40mg nocte
  • Captopril 25mg tds
  • Start metoprolol (12.5mg bd) at low dose the next
    day

23
Myocardial Infarction-What has to be prevented ?
  • Prevent secondary problems
  • Significant risk of
  • Death
  • myocardial necrosis LVF
  • Arrhythmias
  • Unstable angina
  • Re-infarction
  • TIME IS MUSCLE (was door to needle time now more
    like pain to reperfusion time)

24
Acute Treatment
  • 50 MI deaths - pre-hospital
  • Mortality at 1 month approx 10 in hospital
  • Nitrates s/l or Iv
  • Aspirin
  • PCI/Thrombolysis or angioplasty-to reopen the
    vessel
  • streptokinase, alteplase, retaplase (rtPA),
    tenecteplase

25
Aspirin
  • Antiplatelet activity
  • Decrease 35 day Mortality by 23
  • Halved incidence re-infarction stroke
  • In addition to thrombolysis decrease mortality by
    50
  • Saves 30 lives/ 1000 patients
  • Benefits sustained at 10 years

26
Lysis
  • Streptokinase
  • Urokinase (not in AUS)
  • Alteplase (tPA)
  • Reteplase (r-PA)
  • Tenecteplase (TNK t-PA)

27
Tissue Plasminogen activator
  • Plasmin is a proteolytic enzyme which cleaves
    fibrin
  • plasmin is active form of plasminogen
  • activated by tissue plasminogen activator
  • when fibrin is formed plasminogen and tpa are
    specifically absorbed onto fibrin

28
Contraindications
  • Absolute
  • Risk of bleeding
  • Active internal, nuerosurgery in last 6 months,
    intracranial bleed
  • Risk of intracranial bleed
  • Haemorrhagic stroke-ever, stroke in past year,
    cerebral neoplasm
  • Suspected aortic dissection
  • Relative
  • INRgt2-3, traumatic CPR, trauma, major surgery in
    past month, internal bleeding past 2-3 weeks,
    peptic ulcer, previous stroke or TIA

29
Beta-Blockers
  • -ve ionotrope chronotrope, anti-arrhythmic
  • Metoprolol and atenolol - not a class effect
  • Must use a dose to properly beta-block
  • Long term saves 35-60 lives/ 1000 at 3years
  • Prevents 60 infarcts/ 1000 at 3 years.
  • Prevents angina, arrhythmias, sudden death

30
Cautions
  • Hypotension, bradycardia, asthma
  • Relative contra-indications
  • ? Asthmatic
  • Heart failure
  • Diabetics
  • PVD
  • Awareness, lethargy, hypotension, cold
    peripheries, impotence
  • Ineffective dosing !

31
ACE-Inhibitors
  • Captopril (Capoten,Acenorm), lisinopril
    (Zestril,Prinvil), Ramipril (Tritace),
    Perindopril (Coversyl) - Class effect
  • Treat prevent left ventricular failure
  • 3-30 lives saved/ 1000 patients
  • Some patients short term (6/52) only
  • Start early and aim for highest doses Captopril -
    50mg TDS, Lisinopril 20mg D, Ramipril 10mg D

32
Cautions
  • Need baseline blood pressure and creatinine
  • Impaired renal function not contra indication
  • Hypotension some concern on first dose-
  • worse if dehydrated and on other vasodilators
  • Renal artery stenosis
  • Rapidly worsening renal function
  • Cough - ? swap drug
  • No post MI evidence for AGII Receptor antag

33
Dyslipidaemia- more chronic than acute
  • 35-50 of MI patients have cholesterol gt 5.5
    mmol/l
  • Statins significantly decrease mortality and
    re-infarction
  • Pravastatin, simvastatin, atorvostatin

34
Remember
  • Secondary prevention
  • Aspirin
  • Betablocker
  • ACE inhibitor
  • Lipid Reduction
  • EDUCATION-Cardiac rehabilitation
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