10. Arrythmias & drug actions

Question 1

What are some causes of tachycardia?

Answer 1

Afterdepolarisations
Atrial flutter/ fibrillation
Re-entry loop
Ectopic pacemaker activity

Question 2

What are some causes of bradycardia?

Answer 2

• Sinus bradycardia- drugs, sick sinus syndrome

- Conduction block

Question 3

When are delayed after-depolarisations most likely to occur?

Answer 3

When [Ca2+] is high - DIGOXIN overdose

Question 4

When are early after-depolarisations most likely to occur?

Answer 4

Prolonged action potential with lengthened QT inverval- hypokalaemia

Question 5

What is AV node re-entry?

Answer 5

Fast and slow pathways in the AV node create a re-entry loop for continuous depolarisation

Question 6

What is ventricular pre-excitation?

Answer 6

Accessory pathway between atria and ventricles creates a re-entry loop
- Wolf parkinson White syndrome

Question 7

What are the 4 classes of drugs that affect CV rate and rhythm?

Answer 7

1. Block V-gated Na+ channels
2. B-adrenoceptor antagonists
3. K+ channel blockers
4. Ca2+ channel blockers

Question 8

What is an example of a voltage-gated sodium channel blocker?

Answer 8

Lidocaine

Question 9

What effect does lidocaine have on normal cardiac tissue?

Answer 9

Little effect as blocks during depolarisation, which is followed by a refractory period anyway.
Dissociates quickly before following action potential is generated.

Question 10

When is lidocaine used?

Answer 10

Following MI if the patient has signs of ventricular tachycardia when damaged areas of myocardium may be depolarised and fire automatically.

Question 11

What effects do B1 antagonists have?

Answer 11

Slow conduction at AV node

Reduces O2 demand

Question 12

Why are B1-antagonists used following MI?

Answer 12

MI causes increased sympathetic activity with increases risk of arrythmia.Beta blockers prevent ventricular arrythmias.
Reduces oxygen demand, reducing myocardial ischaemia.

Question 13

Othen than following an MI, when else are beta-blockers used?

Answer 13

• Prevent supraventricular tachycardias

- Patients with AF - slow ventricular rate

Question 14

What effect to K+ channel blockers have?

Answer 14

Prolong the action potential by lengthening the absolute refractory period.

Question 15

Why are K+ blockers rarely used?

Answer 15

Pro-arrythmic, likely to lead to after depolarisations.

Question 16

Which is the only K+ blocker that is used, how does this differ to the others?

Answer 16

Amiodarone

Lacks specificity, also blocks B1 receptors and calcium channels.

Question 17

What is amiodarone used to treat?

Answer 17

Tachycardia associated with wolf-parkinson-white syndrome (re-entry)
Suppressing ventricular arrythmias following MI

Question 18

How do Ca2+ blockers affect the action potential?

Answer 18

Decrease the slope of the AP at the SA node.

Decreases AV node conduction and force of contraction

Question 19

What are dihydropyridines?

Answer 19

CCB that is not effective in preventing arrythmias but act on vascular smooth muscle to cause vasodilation.
E.g Amlodipine

Question 20

What is the MOA of adenosine?

Answer 20

Acts on A1 receptors at AV node to enhance K+ conductance, hyper polarising cells of conducting tissue.
Very short half life

Question 21

What is adenosine used to treat?

Answer 21

Anti-arrythmic - terminating re-entrant SVT

Question 22

What approach is taken when treating HF?

Answer 22

Aiming to reduce the workload of the heart rather than increase its contractility as better outcomes in the long run. Positive inotropes not routinely used.

Question 23

What drugs increase myocardial contractility?

Answer 23

Cardiac glycosides - improve symptoms but not long term outcome
B-adrenoceptor agonists

Question 24

What is an example of a cardiac glycoside?

Answer 24

Digoxin

Question 25

What is the MOA of digoxin?

Answer 25

Inhibits Na+/K+ ATPase which leads to a rise in intracellular [Na+] and decreases the activity of NCX. This increases intracellular [Ca2+] and increases inotropy.

Question 26

How can cardiac glycosides affect heart rate?

Answer 26

Increase vagal activity: - Slow AV conduction - Slows HR

Question 27

When are cardiac glycosides used?

Answer 27

In HF when there is an arrhythmia - e.g AF

Question 28

What is an example of a B1 adrenoceptor agonist?

Answer 28

Dobutamine

Question 29

When is dobutamine used?

Answer 29

Cardiogenic shock | Acute but reversible HF (following surgery)

Question 30

What drugs function to reduce the workload of the heart?

Answer 30

ACE Inhibitors B-adrenoceptor antagonists Diuretics

Question 31

How do ACE inhibitors reduce the cardiac workload?

Answer 31

Inhibiting AngII formation: Decrease fluid retention - reduce preload Decrease vasomotor tone - reduce after load

Question 32

What drug is often used if ACE inhibitors are not tolerated?

Answer 32

Angiotensin II receptor antagonists

Question 33

What are the aims of angina treatment?

Answer 33

1. Reduce workload of the heart (oxygen demand) | 2. Improve blood supply of the heart

Question 34

What drugs are used in angina to reduce the workload?

Answer 34

beta blockers CCBs Organic nitrates

Question 35

What drugs are used to treat angina by improving the blood supply to the heart?

Answer 35

Organic nitrates | CCBs (vasodilation)

Question 36

What is an example of an organic nitrate?

Answer 36

Glyceryl trinitrate (GTN)

Question 37

What is the MOA of organic nitrates?

Answer 37

Organic nitrates react with tools in VSMCs to cause NO2- to be released. NO2- is reduced to NO, a potent vasodilator.

Question 38

How does NO lead to vasodilation?

Answer 38

Stimulates guanylate cyclase, which converts GTP to cGMP, which activates PKG, PKG decreases intracellular calcium conc, causing relaxation of the VSMC.

Question 39

What is the primary action of organic nitrates?

Answer 39

Acts on venous system primarily - venodilation lowers preload Less filling therefore contractility reduced (Starling) which lowers oxygen demand.

Question 40

What is the secondary action of organic nitrates?

Answer 40

Acts on coronary collateral arteries to improve oxygen delivery to the ischaemic myocardium (minor contribution). Note: there are not many coronary collateral arteries, end arteries.

Question 41

What blood vessels do organic nitrates NOT affect?

Answer 41

Arterioles

Question 42

Why do organic nitrates preferentially act on veins?

Answer 42

Less endogenous NO present, so most marked effect, | Little effect on arteries but no effect on arterioles.

Question 43

When might anti-thrombotic drugs be given?

Answer 43

Atrial fibrillation Acute MI Mechanical prosthetic valves

Question 44

What is heparin, when is it used?

Answer 44

Anticoagulant that inhibits thrombin. | Used acutely for short term action - given IV

Question 45

How does warfarin act as anticoagulant, when is it used?

Answer 45

Antagonises the action of vitamin K | Given orally

Question 46

Give an example of an anti-platelet drug?

Answer 46

Aspirin

Question 47

When is aspirin given?

Answer 47

Following acute MI or high risk of MI