23A11: Exam Report

Outline the Vaughan Williams classification of anti-arhythmic drugs with examples (30% of Marks). Describe the relevant pharmacology of adenosine (70% of Marks)

67% of candidates passed this question.

The high pass rate of this question was largely due to the ability of most candidates to reproduce the VW classification, with correct information regarding each class with examples.

The pharmacology of adenosine was less consistently covered and whilst most kept to the usual pharmacology structure correct detail was often lacking to achieve high marks for this section.

G7iii / 23A11: Outline the Vaughan Williams classification of anti-arhythmic drugs with examples (30% of Marks). Describe the relevant pharmacology of adenosine (70% of Marks)

V – W classify antiarrhythmic in groups based on electrophysiological characteristics → based on micro-electrode studies

Class

I

SODIUM CHANNEL BLOCKERS

Example

IA – PROCAINAMIDE

IB – LIGNOCAINE

IC – FLECAINIDE

Mechanism of Action

Moderate Na+ channel block, ↑refractory period

Weak Na+ channel block, shortens AP

Strong Na+ channel block, no effect refractory period

Class

II

β-BLOCKERS

Non-selective

Selective

Intrinsic sympathomimetic activity

Example

PROPANOLOL

METOPROLOL

LABETALOL

Mechanism of Action

Antagonises effects of catecholamines at β receptors

In heart: – CHRONO, – DROMO, -INOTROPY

↓slope Ph 4 = more time to reach threshold = ↓discharge rate

Class

III

POTASSIUM CHANNEL BLOCKERS

Example

AMIODARONE

SOTALOL

Mechanism of Action

Blocks K+ channels

Prolongs refractory period of all cardiac time

Broad spectrum: blocks Na+ channel, K+ channel, Ca2+ channel & α + β adrenoreceptors

Class

IV

CALCIUM CHANNEL BLOCKERS

Example

DIHYDROPYRIDINES

BENZOTHIAPINES

PHENYLALKYLAMINES

Mechanism of Action

→ NIMODIPINE → Block Ca2+ channel of arteries

→ DILTIAZEM → AV node → inhibits inward Ca2+ current (↓rate conduction AV node)

→ VERAPAMIL → AV node → inhibits inward Ca2+ current (↓rate conduction AV node)

Class

OTHER

Example

Mechanism of Action

DIGOXIN

  1. Activates vagal nuclei = ↑ activity
  2. Inhibits Na/K/ATPase = RMP becomes less negative 2° ↑intrac. K (depol easier); AP shortens 2° ↑K conduction

ADENOSINE

A1 receptor on SA node → stimulates adenosine sensitive K+ channel → ↑K conductance = hyperpolarises – VE DROMOTROPY

MAGNESIUM

  1. Co-factor Na/K/ATPase
  2. L-type Ca2+ channel antagonist ECG prolongs R:R, ↑PR interval
  3. ↑AV conduction time

Sodium Channel Blockers

  • Inhibit Fast Na+ channel of fast AP cells
  • ↓slope of Ph 0
  • ↓amplitude AP
  • ↓conduction velocity (negative dromotrope) so that there is slower transmission of AP

→ Subdivided based on duration of AP (effect on refractory period)

IA – Procainamide

  • Moderate Na channel block
  • ↑refractory period → lengthens AP

IB – Lignocaine

  • Weak Na+ channel block
  • Shortens AP

IC – Flecainide

  • Strong Na+ channel block
  • No effect refractory period

Na+ channel block: IC > IA > IB

Lengthen AP: IA > IC > IB (decreases)

Flecainide

Beta Blockers

  • Competitive antagonists of β1/β2 adrenoreceptors
  • Antagonise effects of catecholamines
  • ↓slope of Ph 4 = more time to reach threshold = ↓discharge rate
  • – VE CHRONO, DROMO, INOTROPY

↓myocardial O2 consumption 

Potassium Channel Blockers

  • Block K+ channels responsible for repolarisation
  • Prolong AP
  • This ↑effective refractory period
  • On ECG → prolongs QT interval
Potassium Channel

Calcium Channel Blockers

  • Class 4 antiarrhythmics
  • Diverse & structurally unrelated
  • All block Ca2+ channels
  • Classified on basis of CHEMICAL STRUCTURE

Dihydropyridines → Nimodipine

  • Block Ca2+ channel of peripheral arteries
  • Via extracellular modulation of Ca2+ channel
  • Prevents Ca2+ entry into smooth m. cell

Benzothiapines → Diltiazem

  • Intermediate between the other 2
  • Predominate effect = AV NODE
  • Inhibits inward Ca2+ current
  • ↓rate conduction of AV Node → ↑PR interval

Phenylalkylamines → Verapamil

  • Predominant AV Node, SA Node
  • Physically occludes Ca2+ channel
  • ↓rate conduction → ↑PR interval

Adenosine

Adenosine

Chemical

An endogenous nucleotide present in all metabolising cells

Made of a purine base (adenine) & a sugar (ribose)

Use

  1. SVTs
  2. Differentiate flutter & SVT

Presentation

Clear, colourless solution 3mg/mL

Dose

(IV) 6mg → 12mg at q2mins

Give as centrally as possible with rapid flush

Route

IV

Onset

Rapid, needs to be flushed

OFFSET:

  • Rapid t ½ 10 secs

Deaminated to INOSINE + AMP in plasma or taken up by RBC

MoA (mechanism)

Agonist of adenosine receptors

Receptor

A1

SA Node

Atrium

 

Messenger

  1. Gi

↓

Inhibits AC

↓

cAMP

↓

↓Ca2+

  1. Stimulates adenosine sensitive K+ channels

↓

↑K+ conductance

↓

Hyperpolarises supraventricular myocytes

Effect

↓Ca2+ influx = negative INOTROPY

Inhibition of AV conduction = negative DROMOTROPY

Receptor

A2

Smooth muscle of arteries & coronary arteries!

Messenger

  1. G5

↓

Activates AC

↓

↑cAMP

↓

Inhibits M1CK

↓

Relaxes smooth m.

Effect

Vasodilation

↑coronary BF

ECG effects: ↓HR

PD

CVS

  • AV block à slows ventricular response

→ Terminates SVT

→ Reveals atrial arrythmia

RESP

  • ↑MV
  • A2 receptors of carotid body stimulated

CNS – ↑CBF

Metabolic – stimulates glycolysis

PK

A

Inactivated orally

D

Quick 10s t½

Needs to be followed by rapid IV bolus

M

Deaminated to INOSINE + AMP in plasma or taken up by RBC

E

Taken up by RBC

t ½ 10 secs

Adverse Effects

  • Transient flushing
  • Dyspnoea, bronchospasm
  • Chest discomfort
  • Profound bradycardia requiring pacing