Pharmacology of CVS Flashcards
What is angina pectoris
Feeling of cramping and severe constriction in the chest
May be associated with shortness of breath, sweating, nausea and increase heart rate
How is angina pain stimulated
1) Angina pain originates from heart muscle when there is a build up of lactic acid during anaerobic respiration
2) Activates myocardial pain receptors
3) Signal sent via sensory neurones (cardiac nerves and upper posterior nerve roots) to the brain
4) Pain perception
Traditional classification of angina
Typical angina
Atypical angina
Non-anginal
Typical angina
- Substernal chest discomfort of characteristic quality and duration
- Provoked by exertion or emotional stress
- Relieved by rest and/or nitrates within minutes
New classification
Stable angina
Unstable angina
Prinzmetal angina
Microvascular angina
Stable angina aetiology
1) Narrowed coronary artery lumen
2) Restricted blood flow to area to myocardium it supplies
3) The oxygen it receives is insufficient when the heart must work harder
4) Anaerobic respiration
5) Pain
Characteristics of stable angina
- Follows a set pattern/predictable
- Recurrent episodes tend to have similar onset pattern, duration, and intensity
- Short duration radiation to left arm, neck, jaw or back
- builds to a peak and lasts 2-5 minutes
- Precipitated by exertion/ increase cardiac O2 demand
- Not life threatening but can be warning sign for something serious e.g. Heart attack/stroke
- Relieved by rest or taking medications
- Symptoms attributed to myocardial ischemia
Unstable aetiology
1) Clot formation occludes artery
2) Critical reduction in blood flow so that oxygen supply is inadequate at even at rest
3) Pain
Characteristics of unstable angina
- Unpredictable
- Pain symptoms more severe, can persist and lasts longer
- Happens at rest with little exertion
- May not have a trigger
- Not usually relieved by rest and medications
- Progression from stable angina – impossible to predict who will progress
- Serious, regarded as emergency, patients are advised to go to hospital
- Is an emergency because it could be MI. part of heart dies, and it doesn’t regenerate
Prinzmetal angina aetiology
1) Coronary spasm (can be caused by drugs like cocaine)
2) Critical reduction in blood flow so that oxygen supply is inadequate (can happen at rest)
3) Pain
Characteristics of Prinzmetal angina
- Associated symptoms include heart burn, nausea, sweating, dizziness, palpitation, migraines and Raynaud’s phenomenon
- Usually due to a spasm in the coronary arteries and tends to come in cycles
- Usually occurs while resting and during the night or early morning hours
- Episodes tend to last around 5 to 15 minutes (longer in some cases)
- Rare (1 in 100 angina cases)
- Younger patients present with this kind of angina
- Attacks are usually severe – described as very painful
- Pain may spread from the chest to the head, shoulder, or arm
- Cocaine use is a leading cause of coronary vasospasms
- Can be relieved by taking medication
Microvascular aetiology
1) Impaired coronary circulation
2) Reduced coronary prefusion
3) Pain
The capillaries going through constriction
Impaired vasoconstriction - due to endothelium due to release of NO
Characteristics of microvascular angina
- Impaired coronary circulation due to coronary microvascular dysfunction from abnormal vasodilation or increased vasoconstriction
- Patients do not have obstructive coronary artery disease
- Occurs with exertion and at rest but may response less well to nitrates
- Treatment will vary depending on cause of the microvascular angina
What are the aims of treatment
- To enhance quality of life through reduction of symptoms
- To improve prognosis and prevent complications such as MI and premature death
- Well tolerated, and cause minimal side effects
Precipitating factors for angina
Increase sympathetic activity
Increase contractility
Vasoconstriction
Angina treatment strategy
Improve perfusion
Reduce metabolic demand
Prevention
How will improving perfusion treat angina
Increase oxygen delivery by improving coronary blood flow
What examples of treatment can improve perfusion
Coronary vasodilators
How will reducing metabolic demand treat angina
Reduce oxygen demand by decreasing cardiac work
What examples of treatment can reduce metabolic demand
Vasodilators - reduce after load and preload
Cardiac depressants - reduce heart rate and contractility
What examples of treatment can prevent angina
- Prophylactic to reduce the risk of subsequent episodes
- Lipid lowering drugs
- Anti-coagulants
- Fibrinolytic
- Anti-platelet
Examples of nitrate drugs - anti-anginal
GLYCERYL TRINITRATE
ISOSORBIDE MONONITRATE
The effects of nitrate durgs
- Peripheral venodilation which decrease intraventricular pressure decreases cardiac preload
- Arterial dilation then decrease total peripheral resistance (TPR) which reduces afterload
- Both actions lower oxygen demand by decreasing the work of the heart
Adverse effects of nitrate
- Throbbing headache, flushing and syncope (arterial dilation) - Vessels in brain dilate so increase pressure in brain
- Postural hypotension (venodilation)
- Reflex Tachycardia (sympathetic outflow)
Mechanism of action of nitrates
Organic nitrates mimic the effects of endogenous nitric oxide
Examples of β-blockers that are anti-anginal drugs
ATENOLOL
BISOPROLOL
Effects of β blockers
- Inhibits pacemaker current in the SAN (AV conduction) this decreases HR
- Reduce the force of cardiac contractions which improves exercise tolerance
- Slower heart rate, lengthens diastole and gives more time for coronary perfusion which effectively improves myocardial oxygen supply
Adverse effects of β blockers
Bronchospasms
Fatigue
Postural hypotension
Mechanism of action of β blockers
Reduce the sympathetic activity of noradrenaline and adrenaline on β1 adrenoreceptors in heart
Examples of Ca2+ channel blocker drugs
- DIHYDROPYRIDINES (Vascular) – AMPLODIPIDINE, NIFEDIPINE
- BENZOTHIAZEPINES (Cardiac) – VERAPAMIL
- DIPHENYLALKYAMINES (Both) – DILTIAZEM
Effects of Ca2+ channel blocker
- Reduce Ca2+ entry into cardiac myocytes/vascular smooth muscle cells thus reducing contractility
- Direct coronary vasodilation so more coronary blood flow
- Reduce TPR/BP/afterload so heart works less hard to eject blood
- Reduce force of contraction so less O2 consumption
Adverse effects of dihydropyridine
- Lower limb oedema (increase capillary pressure in lower limbs)
- Flushing and headache (excess vasodilation)
- Reflex tachycardia – vasodilation – increase sympathetic activity (baroreflex) – increase HR/contractility
- Constipation – because there is fewer muscle contractions in the gut
Mechanism of action of Ca2+ channel blocker
- Reduce Ca2+ influx through voltage gated L type Ca2+ channels in smooth and cardiac muscle
- Drugs which can block VGCC’s and prevent Ca2+ entry reduce force of contraction in ventricular myocytes and cause vasodilation in vascular smooth muscle
Other anti-anginal drugs
IVABRADINE
NICROANDIL
RANOLAZINE
Effects of nicroandil
- Potassium channel activator, hyperpolarisation which decrease VGCCs and Ca2+ entry, coronary vasodilation
- Has nitrate moiety, so part of its vasodilator (venodilation) action is via generation of NO
Effects of ivabradine
- Specific inhibitor of the If current in the SAN which slow sinus heart rate
- Decreases pacemaker potential frequency which decreases heart rate to reduce myocardial O2 demand
Effect of ranolazine
- Late sodium current inhibitor which reduces Ca2+ in ischaemic myocardial cells this reduces oxygen demand, reduce compression of small intramyocardial coronary vessels which improves myocardial perfusion
Prophaylactic drugs for angina
Aspirin
Clopidogrel
Statins
How does aspirin work
Inhibit COX, decrease thromboxane A2 and platelet aggregation
How does clopidogrel work
Inhibit ADP receptor on platelets
Reduce aggregation
How does statins work
HMG CoA reductase inhibitor
Decrease cholesterol levels
