Cardiac pharmacology Flashcards
(32 cards)
What are acute coronary syndromes?
Cardiovascular conditions characterised by sudden occlusion of coronary arteries by thrombus blocking blood supply to cardiac muscle.
[STEMI, NSTEMI, unstable angina]
What are the principles of treating acute coronary syndromes?
- Increase oxygen supply to myocardium (by improving coronary blood flow and administering oxygen)
- Reduce oxygen demand of myocardium (by reducing heart rate/ force of contraction, reducing cardiac preload and cardiac afterload)
What is heart failure?
Inability of the heart to deliver oxygen at a sufficient rate to metabolising tissues throughout the body - caused by abnormality of cardiac structure or cardiac function
What is the treatment strategy for chronic heart failure?
- Improve contractibility using positive ionotropes - Sympathomimetics (e.g. Dobutamine) and sometimes a Beta Blocker
- Reduce oedema - loop diuretics commonly used (e.g. Furosemide)
- Reduce preload and afterload - ACE inhibitors (e.g. Ramipril) and Angiotensin II receptor blocker (e.g. Losartan)
Describe how a contraction is initiated in a vascular smooth muscle cell
- Calcium enters cell via L-type calcium channels and is also released from the sarcoplasmic reticulum (triggered by binding of Inositol Triphosphate to calcium channels on SR membrane) - IP3 release is triggered by binding of angiotensin II to angiotensin II-receptors on the cell membrane
- Calcium binds to Calmodulin (a calcium-binding protein)
- Calcium activates the enzyme Myosin Light Chain Kinase which phosporylates MLC initiating a contraction
What is the mechanism of action for calcium channel blockers?
Prevent opening of voltage-gated calcium channels (L-type) which reduces the influx of Ca2+ into muscle cells.
Has a vasodilator effect on resistance in vessels and reduced afterload
Generally act on arteries to improve blood flow (not veins)
What are the common calcium channel blockers?
Nifedipine
Amlodipine
What is the MoA of nitrate vasodilators?
- Metabolised to release Nitric Oxide
- NO stimulates Guanylate Cyclase
- Increased cGMP in vascular smooth muscle cells (via dephosphorylation of GTP)
- Drives dephosphorylation of myosin light chains via activation of MLC Phosphatase
- Increased intracellular cGMP inhibits influx of calcium ions into smooth muscle cells
= Vascular smooth muscle relaxation
What are the common nitrate vasodilators?
Glyceryl Trinitrate (GTN) Isosorbide Mononitrate (ISMN)
What are the key side effects of calcium channel blockers?
Ankle swelling
Palpitations
What is the key side effect of nitrate vasodilators?
Headache
How do nitrate vasodilators effect the heart?
Dilate arteries and veins
Reduce cardiac preload (by promoting venodilation)
Increased blood and oxygen supply to the myocardium (by promoting coronary artery vasodilation)
Reduce cardiac afterload (by promoting moderate arteriolar dilation)
What is the MoA of Beta Blockers?
Competitive inhibitors of adrenaline and noradrenaline at Beta-adrenoreceptor sites (thus inhibiting sympathetic stimulation of heart muscle) Negative inotropes (decrease HR) and negative chronotropes (decrease contractility), reducing workload of heart which relieves oxygen demand
What is a key example of a Beta1-antagonist selective for the heart?
Atenolol
Bisoprolol
What are the key side effects of Beta Blockers?
Dizziness
Constipation
What is the MoA of Neprilysin inhibitors?
Neprilysin is an enzyme involved in the breakdown and inactivation of natriuretic peptides - by inhibiting breakdown this prolongs the activity of these peptides to promote water and sodium excretion (ANPs act on principal cells in the late DCT and cortical collecting tubule to reduce NaCl reabsorption)
[Nb. new treatment for heart failure - used in combination with an ARB - Valsartan]
How does adrenaline work as a treatment for cardiac arrest?
Administered IV
Binds and stimulates cardiomyocyte Beta1-adrenergic receptors - activates cAMP cascade to increase intracellular calcium and initiate cardiomyocyte contraction
[Drug class = Sympathomimetic]
How is atropine used as a treatment for acute heart failure?
Administered IV to raise heart rate in patients with sinus bradycardia
Works by blocking muscarinic-type M2 acetylcholine receptors on cardiomyocytes thus inhibiting the effect of parasympathetic, cholinergic vagus nerve transmission (ACh)
Accelerates the repolarisation rate in cardiac muscles.
Give an example for the 2 types of antiplatelet drugs used in cardiac disease prevention
COX inhibitor = Aspirin
ADP receptor inhibitor = Clopidogrel
[Nb. do not affect BP]
How do ADP receptor inhibitors work in CVD prevention?
Blocks the function of ADP receptors on platelet surfaces thus inhibiting platelet activation and subsequent thrombus formation
How do COX inhibitors work in CVD prevention?
Inhibits the action of platelet COX enzymes thus inhibiting synthesis of Thromboxane A2 - this inhibits platelet activation and subsequent thrombus formation
How do HMG-CoA Reductase Inhibitors (statins) work in CVD prevention?
Reduce levels of circulating cholesterol by inhibiting the enzyme HMCCR which is essential in the cholesterol synthetic pathway (in liver).
Can also promote uptake of excess cholesterol from the bloodstream into the liver
Protection against development of atherosclerosis
[Nb. does not affect BP]
Give 2 examples of HMGCR inhibitors
Simvastatin
Atorvastatin
What pathologies does untreated hypertension put you at risk of?
Atherosclerosis
Left ventricular hypertrophy
