Ischaemic Heart Disease and its pharmacological treatment Flashcards
Regulation of Coronary Blood Flow
- endothelium
- derived relaxing factor: NO
The Nitrate Mechanism
How is cardiac workload (force of acontraction) regulated?
- regulate the preload, by the sympathetic system RAAS
- Heart Rate; sympatheitc system/ Ca2+
- Contractility: sympatheitc system/ Ca2+
- Total Peripheral resistance: sympatheitc system/ RAAS
What is the action of Nitrates in the Heart?
- Increased NO lead to vasodilation increaseing blood supply to the coronary arteries
- CGMP leads to decreased CA2+ causing vasodilation
- Vasodilation leads to reduced preload, therfore decreased cardiac workload
Side effects of Nitrates
- Postural hypotension
- headsche: vasodilation of the mengigies in the brain (increased pressure)
- Dizziness
- Glceryl trinitrate: give to those with infreqquently occuring Angina
Action of Beta Blockers and the RAAS mechanism
Action of Ca2+ Channel antagonists
- used in those who cannot take Betablockers
- cardiac selective calcium channels
Side effects of Ca2+ channels
- Brachycardia
- obstruction of signals to the ventricles
Action of Ivabradine
- Blocks the pacemaker of the funny current (Ih/f) in the nodal tissue in the heart
Side effects
- luminous phenomena in the retinsa
- blurred vision
- dizziness
explain the pathology that requires the action of Ranolazine
- works on the late compnent on the voltage gated Na+ channels
- Na+ channel open for a longer period of time in a pathological presentation
- NCX channel, causes Na+ to be removed from the cell and Ca++ is umped into the cell
- causes further contractions of the heart
- Ronolazine
what treatment is there to reduce hypercholesterolaemia 2y prevention?
Statins: drugs designed to inhibit the uptake of cholesterol from the GI tract or reduce the production of cholesterol by the liver
- Simvastatin
- Atorvastatin
How do statins work?
- decrease production in the liver by inhibiting HMG CoA enzyme
- liver cells express LDL receptors –> LDL cholesterol is taken up form the plasma
- reduces the plasma LDL
What are other 2y prevention methods to prevent IHD?
- Aspirin: antiplatelet agent (clopidogrel)
- ACE inhibitors and ARB: reduce blood pressure, hence reducing the workload of the heart
Give examples of antiplatelet agents and explain their site of action
- Aspirin: irreversibly inhibits COX
- COX helps platelet activation through the production of Thromboxane A2
- Clopidogrel and Prasugrel: ADP antagonists and block P2y12 receptors
- platelets are not stimulated to express receptors, therefore fibrinogen can not bind on them preventing cross-linkage between platelets
Explain the mechanism of action of the antiplatelets: clopidogrel, prasugrel and ticagrelor
- Prodrug: only activated when metabolised, this increases its the ability to get into the body, but also might be metabolised before it enters the blood stream
What is the immediate treatment for an MI?
Pain Relief
- Diamorphine (pi)-opioid receptors
- these decrease pain, anxiety, sympathetic drive and vasodilators
Oxygen
Aspirin/GTN
Clot-busting drugs
- tenecteplase
What is the follow-up treatment for an MI?
Beta-blockers: metoprolol (short-acting, hospital), bisoprolol (longer-acting community)- decrease cardiac workload
Ace inhibitors: Ramipril- decrease cardiac workload, prevents remodelling development of heart failure
Anticoagulant: warfarin/apixaban/rivaroxaban/dabigatran - prevents thrombus formation in case of long term bed rest
Describe the use and action of Digoxin
- is an old drug they previously used
- works to bring the heart back to its previous output: however, adds to the damage
- inhibits the action of NA/K ATPase
- increases the Na+ ions inside the cardiomyocytes
- increase inhibits Na/CA exchanger → build-up of Ca2+ inside the myocyte → stronger contraction
What is the treatment of dysrhythmias?
Amiodarone
- K+ channel blocker that increases the refractory period of ventricular, myocytes and can terminate arrhythmias
- prolongation of the refractory period allows time for sinus rhythm to return
- the re-entry mechanism (the triangle thing)
