Flashcards in CVS S9 - Drugs and the CVS Deck (35):
What are some of the cardiovascular disorders that drugs can be used to treat?
Risk of thrombus formation
What about the cardiovascular system can drugs alter?
Rate and rhythm
Force of myocardial contraction
Peripheral resistance and blood flow
List the ways arrhythmias can arise?
Ectopic pacemaker activity
Explain how ectopic pacemaker activity can lead to arrhythmia
Damaged area of the myocardium can become spontaneously active
Latent pacemaker region due to ischaemia
This dominates over the SA node, causing arrhythmia
What are after-depolarisations?
Explain how after-depolarisations can lead to arrhythmia
Abnormal depolarisations following the action potenial thought to be caused by high intracellular Ca2+
This lengthened action potential causes an elongated QT interval (arrhythmia)
What is a re-entry loop?
Re-entry loops occur when excitation through a section of damaged myocardium is blocked from travelling in the normal direction (uni-directional block)
The excitation can spread through the surrounding myocardium and travel through the damaged myocardium in the wrong direction
This sets up a small circuit of excitation (re-entry loop) that can lead to arrhythmia
Give a typical example of how a condition caused by a re-entry loop occurs
Several small re-entry loops are set up in the atrial myocardium as a result of damage (E.g. being stretched over time)
What are the classes of anti-arrhythmic drug?
Voltage gated Na+ channel blockers
K+ channel blockers
Ca2+ channel blockers
Explain the action of voltage gated Na+ channel blocking drugs and give an example of a drug in this class
Normal AP firing is not stopped, but it prevents another AP being fired to soon after the previous AP
Channels in open or inactive states are blocked
The drug dissociates from the channels rapidly in time for the next AP
Explain the action of B-adrenoceptor antagonist drugs and give an example of a drug in this class
Give an example(s) of drug(s) in this class
Block sympathetic action by blocking B1 adrenoceptors in the heart
This inhibits adenylyl cyclase/cAMP levels
This in turn decreases the slope of the SAN pacemaker potential, decreasing heart rate
E.g. Propanolol, atenolol (beta-blockers)
Give a common use of B-adrenoceptor antagonists
Used after an MI
Reduces sympathetic activity and slow the heart, decreasing O2 demand of the myocardium, reducing ischaemia
Explain the action of drugs that block K+ channels?
Blocking K+ channels slows repolarisation and lengthens the absolute refractory period preventing another AP from occuring to soon after the last AP
Hence heart rate is decreased
Why are K+ channel blockers not commonly used?
Give an exception and its use
Not generally used as they can be pro-arrhythmic
Used to treat tachycardia related to Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
Explain the action of Ca2+ channel blocking drugs and give an example of a drug in this class
They decrease the slope of the SAN pacemaker potential as well as decreasing AV nodal conduction and decreasing the force of contraction
They also cause some coronary and peripheral vasodilation
Give an example of an anti-arrhythmic drug that doesn't fall into the 4 categories and explain its action
Acts on A1 receptors (Not Alpha 1, A the letter) at the AV node
This is a GPCR, adenosine inhibits adenylyl cyclase/cAMP levels leading to increased K+ conductance
This hyperpolarises cells in the conduction tissues
This causes the heart to 'reset'
What is heart failure?
Give some of the main features
Chonic failure of the heart to provide sufficient output to meet the body's needs
Reduced force of contraction
Reduced cardiac output
Reduced tissue perfusion
What are ionotropic drugs?
Drugs that affect the force of contraction of the heart
Can reduce or increase force of contraction
What are the two types of positive ionotropic drugs?
Ionotropic drugs include:
- Cardiac glycosides
- B-adrenergic agonists
Explain the action of cardiac glycosides and give an example of one such drug
Blocks Na+/K+ ATPase causing a rise in intracellular Na+
This leads to decreased NCX activity and rise in intracellular Ca2+ (more is stored in SR) leading to stronger contractions
Also increase vagal activity via the CNS:
- Slows AV conduction
- Slows HR
Explain the action of B1-adrenergic agonists on the heart, give an example of one such drug
What are some of the uses of these drugs?
Acts on B1 receptors to increase SAN pacemaker potential slope and increase heart rate
Used to treat:
- Cardiogenic shock
- Acute but reversible heart failure (E.g. in a post-op scenario)
What are the advantages and disadvantages to using positive ionotropic drugs to treat heart failure?
Increase the cardiac output, which alleviates symptoms
However making the heart work harder is not good long term
When are negative ionotropic drugs used?
Give examples a class of drugs that is negatively ionotropic
To reduce the workload of the heart, often following MI to limit damage
B-adrenergic antagonists are negatively ionotropic
What types of drugs can be used to reduce the workload of the heart?
What are ACE inhibitors?
Drugs that inhibit Angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II
Explain the action of angiotensin II
Angiotensin II works by promoting aldosterone release from the zona glomerulosa of the adrenal cortex
This increases Na+ and water reabsorption
Also a vasoconstrictor
Why are ACE inhibitors useful in the treatment of heart failure?
Decrease vasomotor tone (decrease blood pressure):
- Reduces afterload on the heart
Decreases fluid retention (decreases blod volume)
- Reduces pre-load on the heart
This reduces the workload of the heart
What is angina?
Myocardial ischaemia (O2 supply to myocardium is insufficient)
Ischaemia of the myocardium leads to pain, usually on exertion
Can be due to narrowing of the coronary arteries (atheromatous disease)
How is angina treated?
Give the drug classes that may be used
Reduce workload of the heart:
- B-adrenoceptor antagonists
- Ca2+ channel antagonists
- Organic nitrates
Improve blood supply to the heart:
- Organic nitrates
- Ca2+ channel antagonists
Explain the action of organic nitrates on the vasculature
Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released
NO2- is reduced to NO (nitric oxide)
NO is a powerful vasodilator
NO activates guanylate cyclase increasing cGMP
Lowers intracellular Ca2+
Causes relaxation of the vascular smooth muscle
How does the action of organic nitrates alleviate symptoms of angina?
- Reduces preload via venodilation
- Heart fills less and force of contraction reduced (starling's law)
- Lowers O2 demand
- Action of coronary arteries improves O2 delivery to the ischaemic myocardium
- Acts on collateral arteries not arterioles
- Collateral arteries dilate causing blood to be diverted into ischaemic areas (perhaps bypassing the atheromatous plaque causing ischaemia)
Why are anti-thrombotic drugs used?
Give examples of some cases when they might be used
Certain heart conditions can increase the risk of thrombogenesis
- Atrial fibrillation
- Acute myocardial infarction
- Mechanical prosthetic heart valves
Give some examples of anti-thrombotic drugs
- Inhibits thrombin
- Used acutely for short term action
- Normally IV
- Subcutaneous Fractionated Heparin can be given
- Antagonises action of Vit K
- Can be used long term
- Given orally
What are the two major factors that can cause hypertension?
Express blood pressure as the product of a mathematical equation
Increased blood volume
BP = Cardiac output x TPR
Pressure = Flow x Resistance
What are the major drug targets for treating hypertension?
Lower blood volume (also lowers cardiac output)
Lower cardiac output directly
Lower peripheral resistance