Stable ischaemic heart disease and angina therapy Flashcards
Acute coronary syndromes are a type of Ischaemic heart disease
What are the different types of acute coronary syndromes?
Myocardial infarction:
- STEMI
- NSTEMI
Unstable angina pectoris
Stable coronary artery diseases are a type of Ischaemic heart disease
What are the different stable coronary artery diseases?
Stable angina pectoris
Silent ischaemia
What are the risk factors for ischaemic heart diseases?
Hypertension Smoking Male Hyperlipidaemia Hyperglycaemia (diabetic) Previous CAD Peripheral vascular disease Post-menopausal females
What causes Stable coronary artery disease (SCAD)?
Mismatch between myocardial demand for/supply of oxygen
Attacks of angina (chest pain) are due to any factor that increases cardiac work and thus it’s oxygen demand:
- ie - factor that increases HR, BP or SV
The mismatch between supply and demand of oxygen for the heart in myocardial ischaemia can be thought of as ‘supply ischaemia’ & ‘demand ischaemia’
What factors determine the supply of oxygen to the myocardium?
Coronary artery demand & tone
Collateral blood flow
Perfusion pressure
Heart rate (duration of diastole)
Heart rate is one of the determinants of myocardial oxygen supply
How does heart rate (duration of diastole) affect the amount of oxygen reaching the muscle?
Blood can only flow through the coronary arteries during diastole
The mismatch between supply and demand of oxygen for the heart in myocardial ischaemia can be thought of as ‘supply ischaemia’ & ‘demand ischaemia’
What are the determinants of demand of oxygen for the myocardium?
Heart rate
Systolic blood pressure
Myocardial wall stress
Myocardial wall contractility
What are the problems posed by hyperlipidaemia?
Atherosclerosis of muscular, narrow arteries
Accounts indirectly for half of annual mortality:
- In coronary arteries, it causes IHD which causes MI
- Leads to stroke
Drugs can help reduce the imbalance between supply of/demand for oxygen in the myocardium
How do they do this?
Drugs usually aim to reduce DEMAND for oxygen by either:
1) Reduce heart rate
2) Reduce myocardial contractility
3) Reduce afterload
Some aim to increase oxygen supply to myocardium
What is the purpose of treating heart disease (applies to lots of diseases) with drugs?
Relieve symptoms Halt the disease process Regression of the disease process Prevent myocardial infarction Prevent death
What drugs for IHD aim to reduce heart rate?
rate limiting
Beta-adrenoceptor antagonists (blockers):
- Atenolol or Bisoprolol
Ivabradine:
- Used as alternative to B blockers
Calcium channel blockers (rate limiting CCBs):
- Diltiazem or Verapamil
What drugs for IHD are vasodilators?
Calcium channel blockers (vasodilating CCBs):
- Amlodipine or Felodipine
Nitrates:
- Oral
- Sublingual (GTN)
Aside from drugs aimed to reduce heart rate, or cause vasodilation…
What other drugs are prescribed to people with IHD?
Potassium channel openers
Aspirin/Clopidogrel/Tigagrelor
Cholesterol lowering agents (Statins):
- HMG CoA reductase inhibitors
- Fibrates
Explain the action of Beta blockers
Eg Atenolol, Bisoprolol
Reversibly inhibit B1 & B2 receptors thus blocking effects of sympathetic stimulation
Newer agents are cardioselective and act primarily on the Beta 1 receptors
Reduced demand:
- Decreases HR
- Decreases Contractility
- Decreases systolic wall tension
Increases supply:
- Longer diastole period so longer time for blood to pass through coronary arteries
There is a medical risk associated with prescribed beta blockers
What is this risk?
Rebound phenomena
Sudden cessation of beta blocker therapy may precipitate myocardial infarction
Those at risk include patients with angina and men over 50 years receiving beta blockers for other reasons
Summarise the contraindications associated with Beta blockers such as Atenolol or Bisoprolol
Asthma
Peripheral vascular disease
Raynauds syndrome
Heart failure
Bradycardia / heart block
Why is there a contraindication with beta blockers and Raynauld’s syndrome?
Those with Raynaud’s suffer decreased blood flow to their fingers (digits)
Beta blockers can make this worse and increase the risk of digital infarcts
Explain the link/contraindication between beta blockers and heart failure?
Can cause heart failure in patients who rely on sympathetic drive (which BBs stop)
Beta blockers should only be prescribed to those who have stable angina, not unstable angina
What are the adverse drug reactions associated with beta blockers?
Tiredness / fatigue
Lethargy
Impotence
Bradycardia
Bronchospasm
Rebound phenomena:
- Sudden cessation of BB’s can precipitate to myocardial infarction
Summarise the Drug-drug interactions that Beta blockers can undergo
Hypotension:
- If used with other hypotensives
Bradycardia:
- If used with other rate limiting agents such a verapamil or diltiazem
Cardiac failure:
- If used with negatively inotropic agents such as Verapamil, diltiazem or Disopyramide
Exaggerate and mask hypoglycaemic actions of insulin or oral hypoglycaemics
What is the effect of drug-drug interactions that NSAIDs such as Aspirin, ibuprofen undergo?
NSAIDs antagonise anti-hypertensive actions
What is the general effect of Calcium channel blockers?
Prevent calcium influx into myocytes and smooth muscle lining arteries and atrerioles by blocking the L-Type calcium channel
What are the 2 types of calcium channel blockers, and examples of each?
Rate limiting:
- Verapamil
- Diltiazem
Vasodilators (dihydropyridines):
- Amlodipine
- Nifedipine
What is the effect, on the heart, of Rate limiting CCBs?
Reduce heart rate & force of contraction
Therefore, reduce the cardiac work & oxygen demand
What effect may be caused by vasodilating CCBs?
Reduce vascular tone
Produce vasodilation
Reduce afterload
Overall, reduce myocardial workload so oxygen demand decreases
If a patient is on a beta blocker for angina, but they require a Calcium channel blocker as well…
What type of calcium channel blocker do you prescribe first?
Vasodilating CCBs such as Amlodipine or Nifedipine
If the patient took Beta blockers & rate limiting CCBs, then there is a risk that their HR would drop too low
What is the danger associated with Nifedipine?
The CCB, Nifedipine, must only be given as a gradual release medication
There is evidence that the use of rapidly acting vasodilatatory-CCBs (nifedipine) may precipitate acute MI or stroke
What are the contraindications of Calcium channel blockers?
Nifedipine may precipitate acute MI or stroke
CCBs may increase morbidity & mortality in post MI patients, who have impaired LV function
Unstable angina:
- Evidence that dihydropyridines may increase infarction rate and death
What adverse drug reactions are associated with calcium channel blockers?
Ankle oedema
- Affects 15-20% of patients
- Does not respond to diuretics
Headache
Flushing
Palpitation
What are the 3 main Nitrovasodilators?
Glyceryl Trinitrate (GTN)
Isosorbide Mononitrate
Isosorbide Dinitrate
How can GTN be administered?
Sublingual, buccal, transdermal
Most commonly a spray under the tongue
How is isosorbide mononitrate administered?
Sustained release formulation, tablets
Metabolised to active form in liver
How is Isosorbide dinitrate administered?
Sustained release formulation, tablets
Metabolised to active form in liver
How do nitrovasodilators work?
Release NO which stimulates release of cGMP which produces smooth muscle relaxation…
Arteriolar dilation:
- Reduces cardiac afterload
Peripheral venodilation:
- Reduces venous return ∴ reduces preload
Relieve coronary vasospasm
Redistribute myocardial blood flow to ischaemic areas of the myocardium
Nitrovasodilators seem all spicy and good but are they medically useful?
Relieve symptoms
Don’t reduce mortality though
Summarise the uses of Nitrovasodilators
GTN:
- Rapid relief of angina pain or
- Pre-cardiac stress prophylaxis
Oral nitrovasodilators:
- One per day sustained release formulation
- Prophylaxis
When are intravenous nitrates used?
To treat unstable angina
Used in combination with heparin (anticoagulant)
What problem may develop over a long time of taking nitrates?
Patient may develop tolerance
To stop this:
- Asymmetric doses
- Sustained release tablets means there is a free period from nitrates before they are metabolised
When nitrates are first prescribed, the dosage is increased slowly
Why is this?
Avoid headaches
adverse drug reaction from nitrates
A patient has a GTN spray for her angina:
She has an episode of pain and decides to sit down, take her spray and rest.
When she stands up again, she faints.
Why is this?
GTN spray has an adverse drug reactions of causing hypotension
The hypotension can cause ‘GTN syncope’
“The effect of Short acting nitrates is ______”
Vasodilation
“Beta blockers decrease ______ & ______”
Decrease heart rate & decrease myocardial contractility
“Long acting nitrates cause ________”
Vasodilation
What is the effect of DHP Calcium channel blockers?
Vasodilation
What is the effect of Non-DHP calcium channel blockers?
Decrease heart rate & myocardial contractility
What are the newer types of treatments for myocardial ischaemia?
Metabolic modulation - (Trimetazidine)
- Primarily inhibition of FA oxidation in myocytes
Sinus node inhibition - (Ivabridine)
Late Na+ current inhibition - (Ranolazine)
Ischaemic preconditioning - (Nicorandil)
How does Nicorandil work?
Nicorandil works by:
1)
- Activating ATP sensitive potassium channels
- Entry of potassium into cardiac myocytes inhibits calcium influx and so has a negative inotropic action
- This also causes dilation of coronary resistance arterioles
2)
Nicorandil forms* nitrate moiety produces relaxation of vascular smooth muscle with dilation of systemic venous circulation and epicardial coronary arteries.
What is Ivabridine used for, and with who?
Selective sinus node If channel inhibitor:
- Slows the diastolic depolarisation slope of the SA-node
- Reduction in heart rate
It is only used in patients with HR 70 or above
(Not used on patients with Afib)
What is Ranolazine?
Late Na+ current inhibition by acting on a variety of Sodium channels in myocardium
Inhibiting current reduces intracellular calcium levels
This in turn leads to reduced tension in the heart wall, leading to reduced oxygen requirements for the muscle.
What is the main antiplatelet agent that we used for IHD?
Low dose Aspirin (75-150mg)
Aspirin is a potent inhibitor of platelet thromboxane production
Thromboxane stimulates platelet aggregation and vasoconstriction
In acute MI, what is Aspirin given with?
Streptokinase
What is the risk with Aspirin?
GI bleeding
Low dose aspirin is the most common cause of admission with GI bleed
- Risky with the elderly
Clopidogrel is alternative if patient does not tolerate it well, however it has the same risk of bleeding (but not GI bleeding)
How does Clopidogrel work?
Inhibits ADP receptor activated platelet aggregation
(anti-platelet basically)
Used to prevent atherosclerotic events in PVD & to treat acute coronary syndromes
