Clinical Pharmacology of Stable Coronary Artery Disease Flashcards
Acute Coronary Syndromes
MI (STEMI, NSTEMI)
Unstable Angina
Stable Coronary Artery Disease
Angina pectoris
Silent Ischaemia
Risk Factors (6)
- Hypertension
- Smoking
- Hyperlipidaemia
- Hyperglycaemia
- Male
- Post-menopausal females
• In the atherosclerosis what are most of the changes in the intimal layer a result of?
Accumulation of monocytes, lymphocytes, foam cells and connective tissue
What is the origin of foam cells
Smooth muscle
What do these accumulations in the arteries contain
Necrotic core
Fibrous cap
How cab drugs correct the imbalance of supply and demand (2)
Decrease myocardial oxygen demand
Increasing the supply of oxygen to ischaemic myocardium
How can drugs reduce the myocardial oxygen supply (3)
Reduce heart rate
Reduce contractility
Reduce afterload
The purpose of the drug treatment (5)
- Relieve symptoms
- Halt the disease process
- Regression of the disease process
- Prevent MI
- Prevent death
Demand Ischaemia is determined by (4)
HR
Systolic blood pressure
Myocardial wall stress
Myocardial contractility
Supply Ischaemia is determined by (4)
Coronary artery diameter and tone
Collateral blood flow
Perfusion pressure
Heart rate (duration of diastole)
What is the action of beta blockers
Rate limiting
What is the use of beta blockers
Decrease the determinants of myocardial oxygen demand: HR, Contractility, systolic wall tension
What is the mechanism of beta blockers
Reversible antagonists of the B1 and B2 receptors
Block the sympathetic system
What are the contraindication for beta blockers (5)
Asthma Peripheral vascular disease Raynauds Syndrome Heart Failure Bradycardia/Heart block
Beta Blocker adverse drug reactions (5)
Tiredness/fatigue Lethargy Impotence Bradycardia Bronchospasm
What is the rebound phenomena
Sudden cessation of beta blocker therapy may precipitate myocardial infarction
Who is at risk of experiencing rebound phenomena
• Those at risk include patients with angina and men over 50 years receiving beta blockers for other reasons
Beta blocker + Hypotensive drugs
Hypotension
Beta Blocker + Rate limiting drug (verapamil or Diltiazem)
Bradycardia
Beta blocker + inotropic drugs (Verapamil, Diltiazem and Disopyramide)
Cardiac failure
Beta blocker + NSAIDs
Antagonise antihypersensitive actions
Beta blocker + Insulin or Oral Hypoglycaemics
exaggerate or mask hypoglycaemic actions
Calcium channel action can be
Rate limiting
Vasodilation
Rate limiting Calcium channel blockers use
Diltiazem and Verapamil reduce HR and force of contraction
Rate limiting calcium channel blockers mechnaism
Prevent calcium influx into myocyte and smooth muscle lining by blocking L-type calcium channels
Contraindications of Rate limiting calcium channel blockers
Post MI
Unstable angina
How does rate limiting calcium channel blockers Dihydropyridine work
inhibition of the smooth muscle L-type calcium current, thus decreasing intracellular calcium concentration and inducing smooth muscular relaxation
Adverse reactions of rate limiting calcium channel blockers (4)
Ankle oedema
Headache
Flushing
Palpitation
Action of non-rate limiting calcium channel blockers
Nifedipine or amlodipine produce reflex tachycardia
Mechanism of non rate limiting calcium channel blockers
Vasodilation
reduce vascular tone and reduce afterload
Contraindication of non rate limiting calcium channel blockers (2)
Never use Nifedipine immediate release can cause MI or stroke
Don’t use post MI in patients with impaired LV function
Action of Ivabradine
Rate limiting
Action of Ivabradine
Reduces heart rate and myocardial oxygen demand
Mechanism of Ivabradine
Selective sinus node channel inhibitor
Slows the diastolic depolarisation slope of SA node
Contraindications of Ivabradine (3)
Low heart rate
Allergy
Severe Hepatic disease
Adverse reaction of Ivabradine (5)
Visual disturbances Headache, dizziness Bradycardia Atrial fibrillation Heart block
Nitrates action
Vasodilators
Examples of nitrates
GTN
Isosorbide Mononitrate
Isosorbide Dinitrate
Action of Nitrates
Reduce preload and afterload to reduce myocardial oxygen consumption
Mechanism of Nitrates
Relax almost all smooth muscle by releasing NO which then stimulates the release of cGMP which produces smooth muscle relaxation
Complications of Nitrates
Tolerance
Requires nitrate free period
Adverse reactions of Nitrates
Headache (increase dose slowly)
Hypotension (GTN syncope)
Use of Clopidogrel
Prevents atherosclerotic events in PVD
Mechanism of Clopidogrel
Inhibits ADP receptor activated platelet aggregation
Nicorandil (4)
- Activate ATP sensitive potassium channels
- Entry of potassium into cardia myocytes inhibits calcium influx and so has a negative inotropic action
- Ischaemic pre-conditioning (cardioprotective)
- Vasodilation of coronary epicardial arteries
Ranolazine
- Inhibits persistent or late inward sodium current in heart muscle in a variety of voltage gated sodium channels
- Inhibition of current leads to reductions in calcium levels
- Reduction in calcium levels leads to reduced tension in the heart all and a reduced oxygen requirement for muscles
When would you use antiplatelet agents
- Adults unable to tolerate or have a contraindication to the use of beta-blockers
- Used in combination with beta blockers in patients that cannot be controlled with an optimal bet-blocker dose
Examples of Cholesterol Lowering Agents
• Simvastatin, Pravastatin, Atorvastatin
Action of • Simvastatin, Pravastatin, Atorvastatin
• HMG CoA Reductase Inhibitors
NICE Guiidelines for tretament
- Beta blocker first line for stable angina
- Inadequate control- calcium channel blockers are used
- Combination of the 2 can be used if symptoms are not controlled
Patients with stable angina due to atherosclerotic disease should be on
Long term aspirin and statin
Why should they be on statin even if blood cholesterol is good
Stabilise plaques
All patients with angina should be considered for treatment with
ACEi
Drugs for secondary prevention
- Aspirin 75mg daily (low dose to take into account risk of bleeding and comorbidities)
- ACEI for people with stable angina and diabetes
- Statin treatment
- Treatment for high blood pressure
1st line treatment
fast acting nitrates
Beta blocker/CCB
2nd line (5)
Ivabradine Long acting nitrates Nocorandil Ranolazine Trimetazadine
