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Date post:03-Jun-2015
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  • 1. Ischaemic Heart Disease
    • Clinical Pharmacology

2.

  • Angina
    • Stable
    • Unstable
    • Prinzmetals
  • Myocardial Infarction
    • NSTEMI
    • STEMI

Ischaemic Heart Disease 3. Angina

  • Clinical syndrome exertional central chest tightness radiating to arms & neck
  • Oxygen demand exceeds supply
  • Factors contributing:
  • HR, preload(venous return), afterload, aortic impedance all determine myocardial O2 requirements

4. Management of stable angina

  • Relieved/prevented by:
  • Slowing HR
  • Reducing preload (impacts on LV wall stress thru LVEDP)
  • Reducing afterload - BP
  • Dilating coronary arteries
  • Reducing myocardial contractility
  • Also-
  • Correct anaemia, tachyarrhythmias
  • Modify CV risk factors: Hypertension, DM, smoking cessation, Wt loss, graded exercise
  • Prophylaxis before exercise

5. Nitrates

  • Reduce preload by venodilation, dilates coronaries, reduces afterload by systemic vasodilatation
  • Different modes of delivery: Spray, buccal, long acting, short acting, IV, patch
  • Tachyphylaxis
  • Lethal interaction with PDE5 inhibitors: profound hypotension
  • Adverse effects :
  • Headache
  • Drug free period to prevent tolerance LA preps - 12 hours free
  • Indications :
  • Angina, treatment of LVF

6. blockers

  • Reduce HR and contractility
  • Less cardiac demand for O2
  • Myocardium has 1 & 2 receptors, coronary and peripheral arteries 2 (sm. muscle dilation). Theoretic benefit for cardioselective agents but no significant differences. Nebivolol may have additional NO effects.
  • Adv Effects :
  • Worsen/ precipitate heart blocks
  • Lethargy
  • Worsening acute cardiac failure but used in chronic stable heart failure
  • Worsening COPD/asthma
  • Worsening peripheral vascular disease
  • Reduced mood / dreams CNS penetrating drugs
  • Indications : Primary prophylaxis of angina, secondary prevention (post MI ISIS 1 trial where reduction in deaths due to EMD). Not those with ISA, arrhythmias, HOCM, thyrotoxicosis,hypertension, stable mod to severe heart failure, phaeochromocytoma, migraine prophylaxis

7. Calcium channel blockers

  • 2 main types:
  • Dihydropyridines Nifedipine, Amlodipine, Lercanidipine
  • Reduce afterload by arteriolar dilation, dilate coronaries
  • Non-dihydropyridines Diltiazem, Verapamil
  • As above & negative chronotropy by acting on SA & AV nodes.
  • Most are negative inotropes (non DH >> DH) except Amlodipine which is
  • definitely safe in LV impairment
  • Adverse effects :
  • Flushing, dizziness esp instant release preparations of Nifedipine
  • Tachycardia (esp short acting preps - reflex tachycardia)
  • Ankle oedema not heart failure. No indication for diuretics
  • Non-DH: SOB, heart block (esp with concomitant -blockers)
  • Indications : Angina, hypertension, post SAH, Raynauds
  • Useful in vasospastic angina

8. Potassium channel activators

  • Vasodilatory properties (arterial and venous)
  • Similar to other agents may have additional benefits as an adjunct (ie 3 rdor 4 thline)
  • Nicorandil has a nitrate component
  • Adv effects : Headache esp on initiation
  • Indications : Angina
  • IONA study : When added to standard medications, nicorandil reduced death, NFMI by 17%

9. I fchannel inhibitor

  • New anti-anginal - Ivabradine
  • Blocks I f(ionic funny channel) an mixed Na-K inward current activated by hyperpolarization and autonomic nervous system -lowers pacemaker activity in the SA-node
  • Slows heart rate different mechanism from beta-blockers
  • Adverse effects : Luminous phenomena (retinal I hchannels similar to I fchannels) self-limiting
  • Indications : Angina
  • Restricted use

10. Management Strategy for Stable Angina

  • 1.ASA
  • 2.Lipid lowering agent
  • 3. S/L GTN
  • 4. -blocker or CCB which controls rate eg non-DH
  • 5. Add CCB to -blocker or nitrate to CCB
  • 6. CCB + -blocker(DH) + nitrate
  • 7.Nicorandil
  • 8. Coronary intervention PCI or CABG

11. 12. Acute Coronary Syndromes Stable Angina Unstable Angina STEMI NSTEMI Character of pain Exertional pain Rest pain Rest pain Rest pain Relievers Responds to GTN No GTN effect No GTN effect No GTN effect Enzymes Normal Normal Elevated Elevated ECG Often normal Often ST depression ST segment elevation No ST segment elevation 13. Acute Inferior MI 14. Acute coronary syndromes - management

  • Bed rest
  • Oxygen
  • Low molecular weight heparin
  • Aspirin
  • Clopidogrel
  • IV nitrate
  • Optimise oral therapy
  • Stratify risk -ETT, stress imaging angiography
  • Consider
    • Tirofiban
    • Intervention if pain fails to settle

15. Myocardial Infarction - management

  • Bed rest
  • Oxygen
  • ASA 300mg od stat
  • Analgesia: Diamorphine 2.5 5 mg IV (if no asthma/COPD) + antiemetic Metoclopramide 10mg IV
  • Thrombolysis SK, tPA
  • If typical pain within 12 hours of presentation at any age
  • New ST elevation or LBBB
  • Adv effects: haemorrhage, hypotension, bradycardia, reperfusion arrythmias, anaphylaxis

16. Myocardial Infarction

  • SK first choice, tPA for patients < 60 within first 6 hours and anterior changes, cardiogenic shock, prev anaphylaxis with SK
  • IV heparin to follow tPA
  • Contraindications to thrombolysis:
  • Within 28 days of bleed, trauma,traumatic resuscitation
  • Uncontrolled hypertension SBP > 200, DBP > 120 mmHg- Rx IV GTN
  • Aortic dissection
  • Coma
  • Known / suspected active peptic ulcer disease
  • Recent CVA
  • Defective haemostasis (warfarin per se is OK, unless INR very high - consult seniors)
  • Severe renal/liver disease
  • Acute pancreatitis
  • Pregnancy / lactation
  • Within 3 months of vascular surgery

17. Antithrombogens

  • Aspirin inhibits cyclo-oxygenase, prevents syntheses of TxA2 (pro-thrombotic)
  • Thienopyridines (clopidogrel, ticlopidine) irreversibly inhibit binding of ADP during platelet activation. Used with Aspirin with drug eluting stents & in NSTEMI. Expensive!!
  • Glycoprotein 2b3a antagonists potent inhibitors of platelet aggregation eg. abciximab, eptifibatide, tirofiban

18. IV -blockade - indications

  • Indication as for thrombolysis
  • Atenolol 5-10mg IV slow
  • Contraindications: Pulse < 50, SBP
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