Clinical Pharmacology of the Stable Coronary Artery Disease Flashcards
What are epicardial arteries?
on surface
What is microcirculation?
perforates through all muscle
What is stable angina?
A clinical syndrome of predictable chest pain precipitated by exercise or emotional stress, which increase myocardial oxygen demand.
Features of stable angina?
Predictable: The symptoms of stable angina usually occur with a predictable pattern, such as during exercise or exertion, and they tend toimprove or go away with rest.
Consistent: The symptoms of stable angina tend to be consistent over time, with similar frequency, intensity, and duration from episode toepisode.
Relieved by medication:Effective in both preventingand resolving acute attacks
Not an emergency: Although stable angina can be uncomfortable,it isnot usually a medical emergency anddoes notrequire immediatemedical attention.
What is Atypical angina?
Defined as stable angina but with symptoms not clearly identifiable as ischaemic chest pain.
Breathlessness
Burning/reflux/burping
Risk factors?
hypertension
smoking
diabetes
hyperlipidaemia
(modifiable)
family history
post menopausal females
other arterial disease
male
(non modifiable)
Why does angina arise?
Angina arises because of a mismatch between myocardial oxygen supply and the myocardial demand.
Cure for angina?
So, increase myocardial blood flow and reduce the demand
What increases myocardial demand?
Heart rate
Preload
Afterload
Myocardial contractility – systolic function
Myocardial relaxation – diastolic function
Myocardial wall stress
How do we treat?
Relieve symptoms
Reduce workload- beta blockers
Improve coronary blood flow
Slow/halt the disease process
Prevent myocardial infarction
Prevent premature death
Pharmacotherapy for symptoms ?
Rate Limiting
Beta-adrenoreceptor antagonist
Calcium channel blocker (L-type)
Ivabradine (f-channel)
Vasodilators
Nitrates – nitric oxide
Calcium channel blocker
Potassium channel activator
Sodium channel activators
Ranolazine
Pharmocotherapy for disease modifying?
Antiplatelets-
Aspirin
Clopidogrel
Ticagrelor
Prasugrel
Cholesterol lowering-
HMG-CoA reductase inhibitors
Fibrates
PCSK-9 inhibitors
Mechanism of action of Beta Blockers (Beta-adrenoreceptor antagonist)
?
Reversible inhibitor of the beta1 and beta2 receptors
Block the sympathetic system
Selective vs Non-selective
Cardio selective beta blockers?
Bisoprolol
Metoprolol – shorter acting
Atenolol (cardio selective-ish)
Non selective beta blockers?
Carvedilol
Propranolol
Side effects of beta blockers?
Asthma
Peripheral vascular disease
Raynaud’s syndrome
Acute heart failure
Bradycardia or heart block
Fatigue
Impotence
Benefits of beta blockers?
Decrease major determinants of myocardial oxygen demand
Heart rate – reduce myocardial workload
Contractility
Systolic wall tension – improve relaxation
Increases diastolic perfusion time
Reduces rate of ischaemic events and mortality
What are the rate limiting calcium channel blockers?
non dihydropyridine
Verapamil
Diltiazem
What are the reducing systemic vascular resistance calcium channel blockers?
dihydropyridine
Amlodipine
Felodipine
Nifedipine
Mechanism of calcium channel blockers?
Prevent calcium influx into myocytes and smooth muscle arteries/arterioles by blocking L-type Ca channel
Dihydropyridine mostly relax smooth muscle
Non-dihydropyridines mostly reduce heart rate
Benefits of calcium channel blockers?
Heart rate - Exclusively NDHP like Verapamil/Diltiazem
Reduce contractility (NDHP)
Reduce afterload (DHP)
Increases diastolic perfusion time (NDHP)
Side effects/ cautions of calcium channel blockers?
Peripheral oedema (DHP)
Bradycardia/heart block (NDHP)
Hypotension (Both)
Reduced LV function
Headache
Flushing
What do nitrates (vasodilators ) do?
nitrates release nitric oxide which potentiates smooth muscle relaxation
Mechanism of action of vasodilators?
Nitric Oxide mediated smooth muscle relaxation
Non-selective
Long-acting preparations most effective
Sublingual has utility for acute attacks
Side effects of vasodilators?
Severe aortic stenosis
Hypotension
Headache
Benefits of vasodilators?
Reduce preload and afterload – Therefore myocardial workload
Improve coronary flow via vasodilation (Epicardial arteries and improve blood supply)
Doesn’t reduce mortality
Mechanism of action of vasodilator (Nicorandil)- potassium channel activator?
Activates ATP sensitive potassium channels
causing potassium influx
Resultant inhibition of Calcium influx
Negative inotrope
Smooth muscle relaxation (coronary and peripher
Side effects of nicorandil?
Hypotension
GI ulceration
Mechanism of action of second line - rate limiting “Ivabradine”?
Inhibits the ‘funny’ channels located in SA node.
Only works when patient is in sinus rhythm
Side effects of ivabradine?
Bradycardia
SA node disease
Benefits of Ivabradine?
Heart rate – when in sinus rhythm
Reduces rates of infarction
Mechanism of action of Ranolazine?
Inhibits late sodium current in myocardial cells
Inhibits rapid phase of delayed potassium rectifier current. Therefore,Na+/K+ balance across membrane). This also reduces intracellular calcium.
Theorised metabolic action via alpha 1 and beta 1 mediation of fatty acid oxidation
Side effects/ cautions of Ranolazine?
Avoid use with CYP enzyme inhibitors
Prolongs QTc
Benefits of Ranolazine?
Reduced O2 demand due to reduced wall stress (easier to perfuse microcirculation)
? Beneficial antiarrhythmic effects via Na+/K+ channels (uncertain utility).
Slow disease progression- lipid lowering therapy?
HMG-CoA Reductase inhibitors
Reduces cholesterol production
Atorvastatin
Simvastatin
Rosuvastatin
Reduce cholesterol absorption
Ezetimibe – inhibits cholesterol uptake in the gut
Liver forced to increase uptake from blood stream therefore lowing LDL levels
Often used in conjunction with a statin
Fibrates
Bezafibrate
Fenofibrate
Benefit
Reduced rate of MI
Plaque stabilisation
Reduce LDL and increase HDL
LDL Targets
Low risk – 3.0
Moderate risk – 2.5
High risk (recent MI) – 1.8
Antiplatelets?
Thromboxane A2 inhibitor
Aspirin
Inhibits platelet activation via TXA2 pathway
P2Y12 inhibitors
Clopidogrel
Ticagrelor
Prasugrel
Inhibits platelet activation via ADP mediated pathway
