Week 11 Pharmacology

Please review of cardiac contractility and excitation-contraction coupling.

Review of factors affecting cardiac output

  • CO = HR x SV
  • Pre load, afterload, contractility(starlings curve)
    Neural and hormonal factors

Digoxin (Important drug):

  • PK –
    • 70-80% oral bioavail
    • 20-30% protein binding
    • T1/2 – 26-46hrs
    • Renal excretion – glomerular filtration mostly and some tubular secretion (nearly all of it is excreted unchanged)
      Large VD (400L)
  • Pd
    • Cardiac glycoside
    • Inhibit Na/K ATPase –> increased intracellular Na and therefore higher intracellular Ca(due to Na/Ca ion channel)–> more Ca2+ release from sarcoplasmic reticulum–> more calcium to bind troponin C –> more cardiac contractility
    • Increased Parasympathetic tone
      • Decreased SA node firing and decrease conduction velocity
      • Increases AV block
      • Negative chronotrope, positive inotrope
  • Digoxin toxicity
    • Acute – nausea, vomiting, diarrhoea
    • Chronic – fatigue, visual disturbance, confusion
    • Arrhythmias, VT, VF, SA node block, AV block
    • Diarrhoea, abdo pain, headache, dizziness, confusion, delerium
  • Interactions
    • Increased effective dose in renal impairment
    • Excretion can be inhibited by amiodarone, verapamil, spironolactone
    • Increased risk of dig toxicity in hypoMg and hypoK
    • Quinidine inhibits renal clearance of digoxin
  • Digoxin-specific antibodies (Digibind).
    • Sheep antibodies used to treat digoxin toxicity


Other drugs used in CHF:



  • Give haemodynamic support in short term
  • Noradrenaline
  • Adrenaline

Diuretics (covered in Week 15).

ACE inhibitors
(already covered in antihypertensives Week 9 Pharmacology).


  • GTN – patch, isosorbide mononitrate
  • Ca Channel blockers eg nicorandil, amlodipine

B Blockers

  • Perhexaline – inhibits a mitochondrial enzyme –> increased ATP –> increases myocardial efficiency
Less Common usage of in Emergency Department setting and never asked Amrinone / Milrinone.


Viva questions:

  • Tell me about Digoxin
  • Tell me about Digoxin’s interactions
  • Tell me about Digoxin toxicity (Digibind)
  • What drugs are used in the treatment of CHF ?
    • Symptomatic Mx
    • Mortality benefit
    • Systolic vs diastolic dysfunction
  • Try to show a systematic approach to this sort of question; i.e. quickly list the different classes; they will probably then ask you to talk about a particular agent.