Week 13 - Antidysrhythmics

Question 1

the control of heart rhythm

Answer 1

1. Pacemaker generates wave of signals to contract
2. signals are delayed at AV node
3. Signals pass to heart apex
4. Signals spread throughout ventricles

Question 2

membrane potential

Answer 2

depends on the ion distribution and the “channels” that are open

Intracellular
Na2+ = 12 mmol/l. (+60 mV)
K+ = 150 mmol/l (-90mV)
Ca2+ = 0.1 µmol/l (+120 mV)
Cl- = 5 mmol/l (-90 mV)

Extracellular
145 mmol/l
2.4 mmol/l
2 mmol/l
125 mmol/l

Question 3

pacemaker cells

Answer 3

pacemaker cells in different parts of the heart fire spontaneous action potentials at different rates

(depolarise within x action potential/)

SA node: 70-80 ap/min
AV node: 40-60 ap/min
Purkinje fibres: 20-40 ap/min

non-SA node autorhythmic cells are latent pacemakers

Question 4

Effect of beta and muscarinic receptors on the heart

Answer 4

beta = when stimulated by adrenaline or noradrenaline=activate cAMP formation and then that leads to increase calcium influx= increase heart rate

muscarinic (parasympathetic) = activated by acetylcholine = block camp formation = decrease heart rate

Question 5

Ectopic focus leading to tachycardia

Answer 5

• physiological pacemaker is in the SA node; other cells can also exert pacemaker activity
• encouraged by sympathetic activity and partial depolarisation
• activation of beta1-adrenoceptors increases rate of depolarisation during phase 4 (pacemaker potential)

Question 6

formation of re-entrant circuits

Answer 6

re-entrant circuits are a major cause of clinical arrythmias, and occurs when depolarisation begins to travel in a continuous loop.

In order for a re-entrant circuit to develop there must be:
- an area of unidirectional loop
- an alternate pathway for conduction around the block
- the time taken for conduction via the alternate pathways must be greater than the refractory period of tissue adjacent to the block

Question 7

Afterdepolariations

Answer 7

(abnormally high [Ca++]i promotes afterdepolarisations)

potentially lead to cardiac arrhythmias(irregularities)

Question 8

Heart block

Answer 8

can occur when there is damage to the conducting system

different types of conduction block exist: from slowed partial conductions (long PR interval) to complete heart block

artificial pacemakers can be used in some cirsumstances

Question 9

Bradyaarhythmia

Answer 9

include various kinds of heart block and asystolic arrest

Defined by HR < 60 BPM,
Infants : 100 BPM

Fatigue, weakness, dizziness,
Potentially fainting due to
cerebral hypoperfusion

Question 10

Anti-dysrhythmic drugs
Vaughn Williams system

Answer 10

• Class I: Drug that block voltage-sensitive sodium channels (used-dependent block)
• Class II: β-adrenoreceptor antagonists
• Class III: Drugs that prolong the
  cardiac action potential
• Class IV: Calcium channel antagonists

Question 11

Na+ channels

Answer 11

exist in three distinct functional states:
resting, activated and refractory

channels rapidly switch from resting to activated with depolarisation

maintained depolairsation causes channels to move from activated to refractory

the membrane must be repolarised to restore channels to the resting state

Question 12

Class I – use dependent Na+ channel
blockers

Answer 12

Drugs with high use (frequency) dependence bind more avidly to the ion channels during faster heart rates and therefore exert more sodium channel blockade during tachycardia

Lidocaine blocks the open channel and reduces sodium influx and membrane depolarisation

Blockage of Na channels that open frequently

Tissue that gets frequently activated, gets preferably blocked by drug

Class I drugs (e.g. lidocaine=lignocaine) slow conduction velocity of pacemaker potentials throughout the heart – used for ventricular and atrial
tachyarrhythmias.

Side effects: bradycardia and
potential worsening of
arrhythmias, heart failure.

Question 13

Class II – β adrenoceptor antagonists

Answer 13

• β adrenoceptor antagonists = anti-sympathetic affects
• Reduced Calcium influx -> Slowed pacemaker maker potentials at SA and AV node
• β-blockers will reduce opening probability of funny Na channels (influenced via cAMP)
• AEs include bradychardia, bronchospasm, hypotension

Question 14

Ivabradine (Coralan)

Answer 14

New Drug

Cardiotonic agent used to manage angina pectoris (coronary heart disease) and chronic heart failure (reduces risk of death or MI by 0-36% depending on the clinical trial)

why cardiotonic ?
“No” effect on
contractile cells,
affects only
pacemaker cells

Question 15

Class III drugs – prolonging the action potential

Answer 15

Prolongation of the action potential increases the refractory period of sodium channels, preventing reentrant tachycardia and suppresses ectopic activity

Adverse effects: can worsen
dysrhythmias

Block of outward K channels that are
involved in repolarization -> prolonged plateau phase

Question 16

Class IV – calcium channel antagonists

Answer 16

• block voltage-sensitive L-type calcium channels
• slow conduction of AV and Sa nodes, reduced Ca2+ entry alos reduces the after-depolarisation .
• Ca2+ antagonists also reduce contractile force

e.g. verapamil & diltiazem (also acts on vasculature)

Reduced calcium influx -> slowed pacemaker maker potentials at SA and AV node
Side effect: shorter plateau phase,
reduced contractile force

Question 17

Adenosine

Answer 17

• produced endogenously from ATP/ADP =important chemical mediator
• acts as a cardiac A1 adenosine receptors that are coupled to Gi
  =works on AV node, then blocking calcium channels
• given IV to treat certain tachycardias
• short lived due to uptake and metabolism

Question 18

Drugs for bradyarrhythmia

Answer 18

1. Atropine
   - competitive antagonist of muscarinic receptors. used in IV to treat bradychardia and remove “brake” on heart rate
2. Isoprenaline
   - beta-agonist
   - heart will produce pos inotropic results
   - used to treat heart block or bradycardia
   AEs: flushing, headache etc

Question 19

stuff to treat tachycardia (classes and drugs again)

Answer 19

1. blockers of voltage sensitive sodium channels
2. beta blockers/ beta antagonists
3. drugs that prolong cardiac action potential
4. L-type calcium channel blockers
5. adenosine

Question 20

stuff to treat bradychardia (drugs)

Answer 20

1. atropine
2. isoprenaline