Drugs Affecting the Heart Flashcards
What are the criteria for classifying cardiac arrhythmias?
1 - Origin of the arrhythmia.
2 - Effect on heart rate.
What is the current classification system for antiarrhythmic drugs?
The Vaughan Williams classification (classes I-IV).
In non-pacemaker cells, which ion is responsible for the initial rising phase of action potentials?
Na+.
What is the target of class I antiarrhythmic drugs?
What is their effect on the target?
What is their effect on the profile of electrical activity of the heart?
- Voltage gated Na+ channels.
- They block the channels.
- They alter the slope of the rising phase of cardiac action potentials.
List two examples of class I antiarrhythmic drugs.
1 - Lidocaine.
2 - Flecainide.
What is the target of class II antiarrhythmic drugs?
What is their effect on the target?
What is their effect on the profile of electrical activity of the heart?
- Beta receptors.
- They block the receptors.
- They decrease sympathetic effect on cardiac action potentials and in turn decrease the slope of pacemaker potential.
Give an example of a class II antiarrhythmic drug.
Metoprolol.
What is the target of class III antiarrhythmic drugs?
What is their effect on the target?
What is their effect on the profile of electrical activity of the heart?
- K+ channels.
- They block the channels.
- They prolong the repolarisation phase of the action potential.
List two examples of class III antiarrhythmic drugs.
1 - Amiodarone.
2 - Sotalol.
What is the target of class IV antiarrhythmic drugs?
What is their effect on the target?
What is their effect on the profile of electrical activity of the heart?
- L-type Ca2+ channels.
- They block the channels.
- They prolong the action potential where Ca2+ influx is implicated (mostly on nodal cells but also on the plateau of contractile cells).
Give an example of a class IV antiarrhythmic drugs.
Verapamil.
For which area of the heart does verapamil exhibit relative cardioselectivity?
Why?
- The AV node.
- Because the AV node has a particularly high concentration of L-type Ca2+ channels.
List 2 drugs that are not classified under the Vaughan-Williams classification system.
1 - Adenosine.
2 - Cardiac glycosides such as digoxin.
Where in the heart are adenosine receptors found?
In the SA and AV nodes.
What occurs as a result of adenosine binding to adenosine receptors?
What is the consequence of this event on the profile of electrical activity of the heart?
- K+ channels open.
- This will cause hyperpolarisation, and therefore a longer refractory period.
What type of drug is caffeine?
An adenosine receptor antagonist.
List the effects of digoxin on heart activity.
1 - Increased vagal activity.
2 - Decreased AV conduction rate.
3 - Decreased ventricular conduction rate.
On which components of the body does digoxin act?
The CNS and on myocytes directly.
List 4 criteria that are relevant in determining drug choice for cardiac arrhythmias.
1 - Type of arrhythmia.
2 - Cause of arrhythmia.
3 - Comorbidities.
4 - Drug interactions.
List 2 conditions for which a drug that affects force of contraction might be needed.
1 - Heart failure.
2 - Anaphylaxis.
In a well-functioning heart, what is the determinant of force of contraction?
Intracellular Ca2+.
What are the 3 classes of inotropic drugs?
1 - Sympathomimetics (not covered in this lecture).
2 - Cardiac glycosides.
3 - Phosphodiesterase inhibitors.
What is the effect of inotropic drugs on the physiological conditions of the myocyte?
They increase intracellular Ca2+.
*Ino = fibre, tropic = change.
Describe the mechanism of action for cardiac glycosides such as digoxin.
- Cardiac glycosides partially inhibit the Na+/K+ ATPase.
- This diminishes the concentration gradient of Na+, which is normally abundant on the outside of the myocyte membrane.
- This decreases the functioning of the Ca2+ / 3Na+ antiporter, which relies on the concentration gradient of Na+ to export Ca2+.
- This results in an increased intracellular Ca2+.
Why are there many side effects of cardiac glycosides?
List 4 side effects of cardiac glycosides.
- Because Na+/K+ ATPases are ubiquitous throughout the body.
1 - Arrhythmia.
2 - Neurological disturbance.
3 - GIT problems.
4 - Gynaecomastia
Why is gynaecomastia a side effect of digoxin?
Because digoxin has a similar structure to oestrogen.
Explain the drug interaction between digoxin and diuretics.
- Some diuretics can cause hypokalaemia.
- Digoxin inhibits the Na+/K+ ATPase by binding to the same site of the ATPase as K+.
- A decrease in K+ therefore results in an increased effect of digoxin as more binding sites become available.
List 2 phosphodiesterase inhibitors.
1 - Milrinone.
2 - Enoximone.
What is the function of phosphodiesterase?
Catalyse the breakdown of intracellular messengers such as cAMP and cGMP.
What is the role of cAMP in cardiac myocytes?
They increase opening of the Ca2+ ion channels, causing calcium-induced calcium release (positive inotropic effect).
Describe the mechanism of action for phosphodiesterase inhibitors in cardiac myocytes.
- Inhibiting phosphodiesterase leads to an increase in intracellular cAMP.
- An increase in intracellular cAMP leads to an increase in Ca2+ channel opening.
- An increase in open Ca2+ channels leads to an increase in intracellular Ca2+, and therefore an increase in calcium-induced calcium release.
Which type of phosphodiesterase is most abundant in the heart?
Type 3 phosphodiesterases.
How does the half life of phosphodiesterase inhibitors compare to that of other inotropic drugs?
Phosphodiesterase inhibitors have a particularly short half life.
Which section of the cardiac action potential is affected by ivabradine?
The pacemaker potential.
List 3 types of drugs that affect the heart but do not act directly on the heart.
Why do these drugs have an impact on the heart?
1 - Diuretics (decrease blood volume).
2 - Vasodilators (increase blood volume).
3 - Angiotensin converting enzyme (ACE) inhibitors (decrease blood pressure).
