Pharmacology 1 Flashcards
What are the goals in heart failure management?
Improve quality of life and slow the progression and deteriation to end stage heart failure
What are cardiac failure drugs designed to do?
- Enhance systolic function
- Enhance diastolic function
- Ensure optimal cardiac rate and rhythm
- Counterct deterimental effects of neurohormonal activities (compensatory activities)
- Optimise distrubution of fluid within the circulation i.e. afterload and preload
What are the target organs of these drugs?
Heart, Kidneys, Vasculature and Lungs
What cardiac functions can be manipulated pharmacologically?
Heart Rate, Heart Rhythm, Cardiac Muscle Contractility
What receptors on cardiac muscle can be targeted by these drugs? give examples
Beta1-adrenoreceptors (binding of noradrenaline) stimulatory
Muscarinic2-receptors (binding of acetylcholine) inhibitory
Both examples of G-Protein coupled receptors (both linked to adenyl cyclase
Ion channels such as L-type calcium channels (slow) or fast sodium channels or even potassium channels
Enzymes such as sodium/potassium ATPase (cell membrane) or phosphodiesterase which breaks down cAMP
What does a sustained increase in heart rate (Tachycardia) cause?
- Increased myocardial oxygen metabolism
- Reduces diastole time (ventricle cant fill appropriatley)
- Reduces coronary blood flow time (less blood going to the heart tissues)
What types of drugs slow heart rate down (negative chronotropes)?
- Muscarinic (M) receptor agonists (decreases cAMP like ACh)
- Drugs that increase vagal tone centrally (parasympathetic stimulation)
- Antagonists of Beta1-adrenoreceptors (prevention of Noradrenaline binding)
What type of drugs increase heart rate (positive chronotropes)?
- Muscarinic receptor antagonists (prevents ACh binding)
- Beta1-adrenoreceptor agonists (performs same role as Noradrenaline)
What causes irregular heart beats or irregular heart rhythm (arrhythmias)?
Excessive sympathetic tone
What is the role of the different classes of antidysrhythmic drug?
Reduce/stabilise heart rhythm problems
1. Class I: blockage of voltage-dependent sodium channels
2. Class II: Antagonise Beta-adrenoreceptors (onoy class not involved with ion channels)
3. Class III: Inhibit potassium channels
4. Class IV: Inhibit L-type calcium channels
What are the approaches to improving poor myocardial contractility?
Compensatory mechanisms of the body stimuate heart muscle to increase the force of contraction e.g. noradrenaline
However, excess stimulation can cause an overload of calcium in the cell, tachycardia and can uncouple Beta receptors which makes effects on contractile force dwindle
What drugs could we use to help the bodies compensatory mechanisms for poor myocardial contractility?
- Use drugs that increase force without increasing rate
- Use drugs that bypass the sympathetic receptor system
- Use drugs that increase force without increasing calcium
- Inhibit noradrenaline stimulating cardiac muscle
What positive inotropic drug types can we use for cardiac muscle contractility?
- Cardiac glycosides (negative chronotropes also)
- Phosphodisterase (PDE) inhibitors or methylxanthines
- Benzimidazole derivatives (calcium sensitisation and PDE III inhibition)
- Sympathomimetic drugs agonists (selective for B-adrenoreceptors) e.g. dopamine
What is the mechanism of action of Cardiac Glycosides?
- Bind to K+ binding site on Na+-K+-ATPase
- Na+ and K+ not exchanged
- Increase in intracellular sodium
- Decrease in Sodium/Calcium exchange
- More intracellular calcium
- More forceful contraction
What is the mechanism of action of PDE Inhibitors?
- Inhibition of PDE III = Increased [cAMP]i
- Increases force of contraction (activation of PKA = phosphorylation of Na and Ca ion channels, Ryanodine receptor and SERCA2a on sarcoplasmic reticulum
- Vasodilation
