CVS 2 - Ischaemic heart disease Flashcards
Chronic Arterial disease
Stable Angina
Acute coronary syndromes
• Unstable Angina
Non ST elevated myocardial infarction (NSTEMI)
• ST-elevated myocardial infarction (STEMI)
Ischaemic heart disease
Ischaemic heart disease – reduced blood flow to region of heart Angina = resulting symptoms
Stable angina (Angina pectoris)
• Partial vessel block
• Exertion → O2 demand exceeds O2 supply because of
reduced blood flow →chest pain, radiating to arm & jaw. Pain resolves on rest. Transient ischaemia – no heart cell death
Unstable angina
- plaque ruptures →platelet aggregation →thrombus →blood vessel blocked further →pain even at rest.
- If thrombus lysed – recover blood supply
- No cardiac tissue damage
myocardial infarction
• NSTEMI – coronary artery still not fully blocked so some
tissue perfusion remains, relatively small area of tissue death
• STEMI – complete occlusion leading to a large area of tissue death
What reflects heart damage
elevated ST levels
Ischaemic heart disease Therapeutic goals: Stable Angina, NSTEMI, STEMI
Stable Angina
• Improve coronary blood flow
• Reduce cardiac oxygen demand
Unstable Angina/NSTEMI
• Prevent further thrombus formation and progression to STEMI
• Symptomatic relief
STEMI
• Re-establish perfusion
• Symptomatic relief
Stable angina : organic Nitrates
• NO - 1987: “EDRF* is NO”
• Organic nitrates produce NO
– arterial dilation (↓ resistance, ↓ workload)
– Venous dilation (major therapeutic effect) →↓ venous
return, ↓preload) → ↑ blood supply to heart, which
mostly occurs during diastole
– treat symptoms not cause
how do nitrates work
nitrates work by primarily venus dilation and improving blood supply to heart
Stable angina organic Nitrates: indications, pk, adr, caution, contraindication, interaction
• Indications
– angina, left ventricular failure
• PK
– Glycerol trinitrate
» usually preferred treatment for acute angina – fast onset
» extensive first pass metabolism & t1/2 ~ 5 min. To avoid:
– Sublingual (often used for acute attacks)
– Buccal (slow absorption formulation)
– Transdermal (slow absorption formulation)
– i.v.
– Isosorbide mononitrate
» slower onset
» Low first pass metabolism » t1/2 ~ 5h
– Isosorbide dinitrate
» Extensive first pass metabolism to mononitrate (active)
• ADR
– related to vasodilation→hypotension » dizzines, headache, flushing
– Tolerance
» Avoid with “Nitrate low” period
» once daily admin (levels fall overnight) or remove patch
• Drug interactions
– Drugs causing hypotensive effect (numerous examples including diuretics, drugs
affecting cardiac output, other drugs causing vasodilation), see diagram
– PDE inhibitors see diagram
– nitrates can increase excretion of heparin. Not understood!
• Caution
– avoid during pregnancy (affects placental blood flow)
• Contraindications
– hypotension
– hypovolemia
– hypersensitivity to nitrates
Pharmacodynamic interactions of drugs affecting b.p.
– Hypotension B antagonists Nitrates Diuretics ACE inhibitors Ca2+ antagonists (CCB’s) α2 agonists α2 antagonists Ang II receptor blocker
Combined effects augment ↓ b.p. (often called “additive effects”)
Pharmacodynamic interaction between glycerol trinitrate and sildenafil
Both drugs produce vasodilation and hence potential significant ↓ b.p.
Stable Angina: b adrenergic antagonists - Mechanism , drugs and indication
• Mechanism
– ↓rate & force of heart contraction & b.p : “negative chronotropic & inotropic effects”.
– Reduces myocardial oxygen demand
– Some drugs also cause vasodilation-
» β2 partial agonists (some peripheral vasculature)
» α1 antagonist
Don’t get confused with β1 adrenoceptor in cardiac muscle which promotes contraction (also through cAMP)
• Drugs
– atenolol, bisoprolol, metoprolol:
» relatively β1 selective antagonists -“cardioselective” –useful in patients where important to avoid β2 antagonism see diagram
– propanolol
» β1 & β2 - “non-selective” – sotalol
» non β selective and also inhibits K+ channels (useful in arrhythmia) – acebutolol, pindolol see diagram
» partial agonists (eg) →mild ↑ heart rate at rest (useful - less bradycardia)
» Still allows antagonism of b1- inhibit tachycardia during exercise (high NA)
• Indications
– For prophylactic treatment of angina – reduces cardiac workload
– also for hypertension, myocardial infarction, arrhythmia, heart failure, anxiety
• Stable Angina: b adrenergic antagonists PK – substantial differences between different drugs
– variable Foral between different b antagonists.
– some drugs -significant first pass metabolism by Cyp P450,
» extent of first pass varies between individuals
– some drugs excreted unchanged in urine
– t1⁄2 varies 10 min-22 hr
b adrenergic antagonists: Hypoglycaemia
- Hypoglycaemia activates sympathetic nervous system to restore blood Glc via β2
- β1 antagonist masks tachycardia and inhibits homeostatic response induced by hypoglycaemia.
- Hence β1 antagonists used with caution in diabetes