Arrhythmias And Drugs Flashcards

1
Q

What are some tachycardic causes of arrhythmias?

A
  • Ectopic pacemaker activity
    • Damaged area of myocardium becomes depolarised and spontaneously active
    • Latent pacemaker region activated due to ischaemia (dominate over SA node)
  • Afterdepolarisations
    • Abnormal depolarisations following the action potential (triggered activity)
  • Atrial flutter / atrial fibrillation
  • Re-entry loop
    • Conduction delay
    • Accessory pathway
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2
Q

What are some bradycardia causes of arrhythmia?

A
  • Sinus bradycardia
    • Sick sinus syndrome (intrinsic SA node dysfunction)
    • Extrinsic factors such as drugs (beta blockers, some Ca channel blockers)
  • Conduction block
    • Problems at AV node o bundle of His
    • Slow conduction at AV node due to extrinsic factors (beta blockers, some Ca2+ channel blockers)
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3
Q

When are delayed after-depolarisations most likely to occur?

A

Delayed after-depolarisations

Most likely to happen if intracellular Ca2+ high

Ca2+ causes depolarisations when shouldn’t and could cause tachycardia

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4
Q

When are early after-depolarisations most likely to occur?

A
  • Early after-depolarisations are more likely to happen if AP prolonged
  • Occur before repolarisation
  • Can lead to oscillations - Can lead to pronounced ventricular tachycardia
  • Longer AP and longer QT interval
  • Long QT syndrome or Drug induced (pro arrhythmic effects) as interfere with K channels in the heart.
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5
Q

Re-entrant mechanisms for generating arrhythmias

A

Problem occurs if there is incomplete conduction damage (unidirectional block)

Excitation can take a long route (as long, allow normal side to depolarise) to spread the wrong way through the damage area, setting up a circus of excitations.

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6
Q

When do multiple re-entrant circuits occur?

A

If they occur in the atria, it can lead to atrial fibrillation.

It is possible to get several small re-entry loops in the atria, leading to atrial fibrillation.

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7
Q

When can a re-entry loop be created?

A

AV-node Re-entry:

Fast and slow pathways in the AV node create a re-entry loop.

Ventricular pre-excitation:

An accessory pathways between atria and ventricles creates a re-entry loop such as in Wolff-Parkinson-White syndrome.

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8
Q

What are the 4 basic classes of anti-arrhythmic drugs?

A
  1. Drugs that block voltage-sensitve sodium channels
  2. Antagonists of B-adrenoreceptors
  3. Drugs that block potassium channels
  4. Drugs that block calcium channels.
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9
Q

How does Lidocaine work?

A

This is class Ib.

It is a drug that blocks the voltage gated Na+ channels.

Use-dependant block. Only blocks voltage gated Na+ channels in open or inactive state - therefore preferentally blocks damaged depolarised tissue.

Little effect in normal cardiac tissue because it dissociates rapidly.

Blocks during depolarisation but dissociates in time for next AP

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10
Q

Lidocaine

A

Sometimes used following MI

  • Only if patient shows signs of ventricular tachycardia
  • Given IV

Damaged areas of myocardium may be depolarised and fire automatically

More Na+ channels are open in depolarised tissue

  • Lidocaine blocks these Na+ channels (use dependant)
  • Prevents automatic firing of depolarised ventricular tissue

NOT used prophylactically following an MI

  • Even if the patient is in VT, generally use other drugs.
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11
Q

How to B-adrenoreceptor antagonists work?

A
  • Class II
  • E.g. Propanalol, Atenolol (betablockers)
  • Block sympathetic action
  • act at B1 adrenoreceptor in the heart
  • Decrease slope of pacemaker potential in SA node and slow conduction at AV node.
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12
Q

What are B blockers use for?

A
  • Can prevent supraventricular tachycardia
    • B-blockers slow conduction in AV node
    • Slow ventricular rate in patients with AF
  • Used following MI
    • MI often caused increased sympathetic activity
    • Arrhythmias may be partly due to increased sympathetic activity
    • B-blockers prevent ventricular arrhythmias.
  • Also reduce oxygen demand
    • Reduced myocardial ischaemia
    • Beneficial following MI
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13
Q

How do class III anti-arrhythmic drugs work?

A
  • Drugs that block K+ channels
  • Prolong the action potential - mainly by blocking the K+ channels
  • This lengthends the absolute refractory period
  • In theory, would prevent another AP occuring too soon - BUT in reality it can be pro-arrhythmic.
  • They are not generally used because of this property.
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14
Q

Amiodarone?

A
  • This is included as a type III anti-arrhythmic but has other actions in addition to blocking K+ channels.
  • It is used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
  • Effective for suppressing ventricular arrhythmias post MI.
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15
Q

What is verapamil?

A
  • A Drug that block Ca2+ channels
  • Decrease slope of AP at SA node.
  • Decreases AV nodal conduction
  • Decreases force of contraction (negative intropy)
    • Also some coronary and peripheral vasodilation.
  • (Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias but do act on vascular smooth muscle. - e.g Amlodipine, felopidine, nicardipine ect)
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16
Q

How does Adenosine work?

A
  • Produced endogenously at physiological levels
  • BUT, can also be administered IV
  • Acts on A1 receptors at AV node but has a very short half-life (seconds).
  • Enhances K+ conductance
    • Hyperpolarises cells of conducting tissue.
  • Anti-arrhythmic
    • Doesn’t below in any classes mentioned
    • Useful for terminating re-entrant SVT.
17
Q

What are ACE inhibitors?

A
  • EG perindopril
  • They inhibit the action of angiotensin converting enzyme.
  • Important in the treatment of hypertension AND heart failure.
  • Prevents conversion of angiotensin I to angiotensin II
    • Angiotensin II acts on the kidneys to increase Na+ and water reabsorption
    • Angiotensin II is also a vasoconstrictor
  • ACEi can cause a dry cough (excess bradykinin) Very valuable in treatment of heart failure
18
Q

What is the effect of ACE inhibitors?

A

They decrease the vasomotor tone (decrease BP)

Reduce afterload of the heart

ALSO decrease fluid retention - decrease blood volume

Reduce preload of the heart

BOTH effects reduce the work load of the heart

19
Q

What are ARBs?

A
  • Angiotensin II receptor blockers
  • Inpatients that can’t tolerate ACEi
  • There are used in treatment of heart failure and hypertension.
  • E.g. Losartan
20
Q

Diuretics

A
  • Used in treatment of heart failure and hypertension
  • Loop diuretics useful in congestive failure.
  • e.g. ferusemide
  • Reduces pulmonary and peripheral oedema
  • Other diuretics such as thiazide diuretics useful in more mild cases of congestion.
21
Q

Ca2+ channel blockers

A
  • Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias but act on vascular mouth muscle.
  • E.g. Amlodipine, Nicardipine
    • Decrease peripheral resistance
    • Decrease arterial BP
    • Reduce workload of the heart by reducing afterload.
  • Other types of Ca2+ blockers eg verapamil and dilitiazem act on heart
    • Reduce workload of heart by reducing force of contraction.
  • Ca2+ channel blockers useful in hypertension, angina, coronary artery spasm and SVTs.
22
Q

What are positive inotropes?

A
  • Positive inotropes increase contractility and thus cardiac output.
  • Cardiac glycosides - Dioxin
  • B-adrenergic agonists - Dobutamine.
23
Q

How do cardiac glycosides work?

A

Primary mode of action is to block Na+/K+ ATPase

  • Ca2+ is extruded via the Na+-Ca+ exchanger
  • Driven by Na+ moving down concentration gradient
  • Cardiac glycosides block Na+/K+ ATPase
  • Leads to a rise in the intracellular Na+
  • Ths results in a decrease in activity of Na+-Ca2+ exchanger
  • It causes an increase an increase in intracellular Ca2+so more Ca2+ is stored in the SR
  • Increased force of contraction.

Work but make heart work harder so no long term benefits - need to reduce workload of heart.

24
Q

What effect do cardiac glycosides have on heart rate?

A

Cardiac glycosides also caused increased vagal activity.

  • Action via central nervous system to increase vagal activty
  • Slows AV conduction
  • Slows heart rate

Cardiac glycosides may be used in heart failure where there is an arrhythmia such as AF

25
Q

B-receptor agonists?

A
  • Not used in normal Heart failure
  • BUT, if in cardiogenic shock or acute but reversible heart failure (eg following cardiac surgery. )
  • Selective B1 adrenoreceptor stimulate B1 receptors present at SA node, AV node and on ventricular myocytes.
26
Q

How do you treat heart failure?

A
  • Cardiac glycosides will relieve symptoms by making heart contract harder
  • But there is no long-term benefits
  • Making the heart work harder is not good in the good in the long run
  • Better to reduce workload
  • ACEinhibitors or ARBs and diuretics better for heart failure
  • Beta blockers can also reduce workload of the heart
27
Q

Angina?

A
  • Angina occurs when oxygen supply to the heart does not meet its need
    • But of limited duration and does not result in death of myocytes
  • Ischaemia of heart tissue - Chest pain
  • Usually pain with exertion
28
Q

Organic nitrates?

A
  • Reaction of organic nitrates with thiol (-SH) in vascular smooth muscle causes NO2- to be released
  • NO2- is reduced to NO
  • Nitric oxide is released endogenously from endothelial cells
  • e.g:
    • GTN spray (quick, short acting)
    • Isosorbide dinitrate (loNger acting)
  • NO is a powerful vasodilator PARTICULARLY EFFECTIVE ON VEINS
29
Q

Why do organic nitrates preferentially act on veins?

A

Maybe because there is less endogenous nitric oxide in veins.

At normal therapeutic doses it is MOST EFFECTIVE ON VEINS.

Very little effect on arterioles.

30
Q

How do Nitric Oxides work?

A
  • Nitric Oxide causes vasodilation
  • NO activates guanylate cyclase
  • Increases cGMP
  • Lowers intracellular Ca2+ concentration
  • Causes relaxation of vascular smooth muscle
31
Q

How do NO help alleviate symptoms?

A
  • Primary action:
  • Action on venous system venodilation lowers preload
    • Reduces work load of the heart
    • Heart fills less therefore force of contraction reduced (Starling’s Law)
    • This lowers O2 demand
  • Secondary action:
  • Action on coronary arteries collateral arteries improves O2 delivery to the ischaemic myocardium
    • Acts on collateral arteries NOT arterioles
32
Q

What is the main action of organic nitrates?

A
  • Venodilation
  • Venodilation reduces venous pressure and the retun of blood to the heart
  • Veins are capacitance vessels
  • This reduces the work of the heart (Starling’s Law of the Heart)
  • Reduces oxygen demand.
33
Q

Why don’t nitrates work by dialating arterioles?

A

That would be bad as arterioles are already fully dilated in the Ischaemic region.

34
Q

How else can you treat angina?

A

Reduce the work load of the heart

  • Organic nitrates (via venodilation)
  • B-adrenoreceptor blockers
  • Ca2+ channels antagonists

Improve the blood supply of the heart

  • Ca2+ channels antagonists
  • Minor effect of orgnic nitrates
35
Q

What conditions increase the risk of thrombus formation?

A

Certain heart conditions carry an increased risk of thrombus formation:

  • Atrial Fibrilation (increased risk of stroke)
  • Acute MI
  • Mechanical prosthetic heart valves.
36
Q

What drugs are antithrombotic?

A
  • Anticoagulants
  • Prevention of venous thromboembolism
    • Heparin
      • inhibits thrombin,
      • used acutely for short-term action.
    • Fractionated heparin (subcutaneous injection)
    • Warfarin (orally)
      • Antagonises actions of vitamin K
    • Direct acting oral thrombin inhibitors such as diabigatran.
  • Antiplatelet drugs
    • Aspirin
    • Clopidogrel
      • following acute MI or high risk of MI