Week 9 - Drugs Flashcards
What may result in ectopic pacemaker activity?
- Damaged myocardium becoming depolarised, and firing APs
- Ischaemia activating a latent pacemaker region
What are “after-depolarisations”?
Abnormal depolarisations following an action potential
What usually causes delayed after-depolarisations, and what is their consequence?
Usually triggered by increased intracellular calcium levels, which results in an early action potential, and hence tachycardia.
What are the three main causes of an arrhythmia?
- Ectopic pacemaker activity
- After-depolarisations
- Re-entry loop
What usually causes early after-depolarisations, and what is their consequence?
Prolonged action potential
Long QT syndrome
What is a re-entry loop?
If there is incomplete conduction damage (unidirectional block), excitation will travel the wrong way through the damaged area, creating a short circuit.
What causes atrial fibrillation?
Several re-entry loops in the atria, resulting in uncoordinated contraction.
Could also be due to ectopic excitation, however.
What is the difference between supraventricular tachycardia and ventricular tachycardia?
Supraventricular = tachycardia resulting from problem in atria or AV node. Ventricular = problem originates in ventricles, Purkinjie fibres or bundle of Hiss.
What types of drug can be used to treat arrhythmias?
- Voltage-sensitive Na+ channel blockers (class I)
- B-blockers (class II)
- Potassium channel blockers (class III)
- Calcium channel blockers (class IV)
- Adenosine
Give an example of a class I anti-arrhythmic drug
Lidocaine
What is the mechanism of lidocaine, a class I anti-arrhythmic drug?
Use-dependent voltage-sensitive Na+ channel blocker.
Blocks damaged areas of myocardium which are depolarised, and hence likely to fire APs.
In what situations may lidocaine be used?
After an MI, to prevent VF.
Give an example of a class II anti-arrhythmic drug, and state what the general function of these drugs is.
Propanolol.
B-adrenoreceptor antagonists (B-blockers)
Explain the mechanism by which B-blockers decrease heart rate, in reference to the pacemaker potential.
Act on B1-adrenoreceptors in the heart, hence decreasing sympathetic activity.
This means the slope of the pacemaker potential is decreased, and hence it takes longer to reach an AP threshold –> HR down.
How do B-blockers reduce ischaemia?
Reduce HR, so reduce O2 demand.
Apart from slowing heart rate, what else do B-blockers do?
Slow conduction at AV node, thus preventing supraventricular tachycardia.
What class of anti-arrhythmic drugs are potassium channel blockers?
Class III
What is the mechanism of potassium channel blockers?
Prolong the action potential, hence lengthening absolute refractory period, which delays the next action potential - i.e. slow heart rate.
Why are potassium channel blockers now usually not the choice drugs for tachycardia?
They can be pro-arrhythmic.
Give an example of a potassium channel blocker which IS still used.
What is it used for?
Amiodarone
Used to treat Wolff-Parkinson-White syndrome, in which extra conduction pathway leads to re-entry loops.
What class of anti-arrhythmic drugs does Verapamil belong to? What is their general action?
Class IV
Calcium channel blockers
What is the mechanism of calcium channel blockers?
Similar to B-blockers -
- decrease slope of pacemaker potential
- decrease AV nodal conduction
But also have -ve inotropic effect
What is the mechanism of adenosine?
Acts on a1-adrenoreceptors at the AV node
Enhances K+ conductance, which results in hyperpolarisation.
This briefly stops the heart so it can “reset”.
What are the two major types of positive inotropes?
Cardiac glycosides
B-adrenoreceptor agonists
Do positive inotropes work long-term?
When are they used?
No - increase cardiac output, but this stresses heart, so no real effect on long-term survival.
Used in palliative care to improve quality of life.
Give an example of a cardiac glycoside
Digoxin
How do cardiac glycosides act to increase the force of contraction of the heart?
Block Na+/K+-ATPase, hence Na+ is no longer extruded.
This means that a Na+ concentration gradient is not established, and therefore Na+ no longer enters the cell via NCX.
In turn, this means that Ca2+ does not leave the cell via NCX, and builds up –> stronger contraction.
Apart from a +ve inotropic effect, what other effect do cardiac glycosides have?
Increase vagal (parasympathetic) activity, therefore slowing the heart. Thus only used in tachycardia.
Give an example of a B-adrenoreceptor agonist.
Dobutamine
When might B-adrenoreceptor agonists be used?
Cardiogenic shock
Acute, but reversible, cardiac failure.
Name 3 types of drug which are used to reduce the workload of the heart.
ACE-inhibitors
B-blockers
Diuretics
What is the mechanism of ACE-inhibitors?
Block “angiotensin converting enzyme”, preventing production of angiotensin II.
This reduces both preload and afterload of heart, as it prevents angiotensin II acting as a vasoconstrictor and stimulating water retention.
What are the two general mechanisms by which angina may be treated?
Reduce workload of the heart, hence reducing O2 demand.
Improving blood supply, hence increasing O2 supply.
What 3 types of drug may be used to treat angina?
- B-blockers
- Organic nitrates
- Calcium channel antagonists
Give an example of an organic nitrate
Glyceryl trinitrate
How do organic nitrates cause vasodilation?
React with thiols in the vascular smooth muscle, to release NO2-, which is reduced to NO (nitric oxide).
NO activates guanylate cyclase, which increases cGMP.
In turn, this reduces the concentration of Ca2+ in the cell, hence reducing the smooth muscle contraction.
What is the primary site of organic nitrate action?
The venous system –> venodilation
This reduces preload
Where else, apart from the venous system, may organic nitrates act?
Why is this beneficial?
The collateral coronary arteries.
Means vessels providing a route around blockage can accommodate more blood.
What conditions make it more likely for blood clots to develop?
Atrial fibrillation
After an MI
If you have prosthetic heart valves
Which two types of drug may be used to prevent blood clot formation?
Anticoagulants
Antiplatelet drugs
Compare and contrast heparin and warfarin.
Both anticoagulants.
Heparin - only used short-term. Inhibits thrombin.
Warfarin - can be used long-term. Antagonises action of vitamin K.
Name a common antiplatelet drug.
Aspirin
What may cause hypertension?
Increase blood volume
Increased TPR
What are the 3 main ways that hypertensive drugs act?
- Reduce blood volume
- Reduce TPR
- Reduce cardiac output
Which 5 types of drug may be used to treat hypertension?
- Diuretics
- ACE-inhibitors
- B-blockers
- Calcium channel blockers
- a1 - adrenoreceptor antagonists
