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)
- 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
- 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
Diuretics (covered in Week 15).
(already covered in antihypertensives Week 9 Pharmacology).
- GTN – patch, isosorbide mononitrate
- Ca Channel blockers eg nicorandil, amlodipine
- Perhexaline – inhibits a mitochondrial enzyme –> increased ATP –> increases myocardial efficiency
Less Common usage of in Emergency Department setting and never asked Amrinone / Milrinone.
- 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.