Equis ISSN 2398-2977

Therapeutics: cardiovascular system

Contributor(s): Graham Munroe, Nicola Menzies-Gow

Myocardial stimulants

  • Indicated for myocardial failure.
  • Systolic failure.
  • Atrioventricular valve failure - controversial use because they increase regurgitation flow as well as forward flow.

Myocardial stimulants, ie inotropes, do not have proven long-term benefit, but they are a standard drug used in cases of myocardial failure.

Cardiac glycosides

Action
  • Positive inotropes: increase intracellular calcium influx → increase force of myocardial contraction.
  • Negative chronotrope: increases refractory period of cell, decreases myocardial conductivity → reduced rate of contraction.
  • Parasympathomimetic effect → slows sino-atrial firing and delayed atrioventricular conduction → slows heart rate.

Do not use digitoxin in horses, it is not licensed and there is a greater risk of toxicity.

Digoxin

Use
Pharmacokinetics
  • Narrow therapeutic margin.
  • Digitalize slowly: measure blood concentration 8 h after administration.
  • Half-life: 12-48 h (horses).
  • Therapeutic concentration: 0.5-2.0 ng/ml serum conc.
  • Bioavailability varies with preparation, route of administration, gastrointestinal conditions and excretion rate → high degree of individual variation in time to therapeutic levels and half-life, therefore drug monitoring is essential: 1 h, 12 h and 3-6 days post-dosing is recommended.
  • Excreted unchanged via the kidney.
  • Enterohepatic recirculation of the drug may occur.

Reduce dose in cases of kidney disease or decreased renal perfusion.

Reduce dose by half for every 50% increase in plasma urea concentration Blood: biochemistry - urea; measure serum digoxin levels and titrate dose thereafter.

Toxicity
  • Risks increase with:
    • Hypothyroidism.
    • Renal insufficiency.
    • Old age.
    • Obesity.
    • Hypokalemia (due to diuretic therapy).
  • Side effects:
    • Dysrhythmias - treat with phenytoin Phenytoin.
    • Depression.
    • Gastrointestinal disturbances, eg anorexia, colic, diarrhea.

Withdraw drug immediately if side effects appear.

  • Overdosage:
    • Slow heart rate → reduced cardiac output → hypoperfusion → renal dysfunction.
Preparations
  • Digoxin Digoxin:
    • Route: IV or PO.
    • Dose: 2.2 ug/kg IV BID; 11 ug/kg PO BID.

Concurrent treatment with quinidine may predispose to digoxin toxicity.

Concurrent treatment with drugs that affect dignoxin's renal excretion may predispose to digoxin toxicity, eg verapamil, amiodarone, propafenone.

  • Pimobendan: currently being evaluated in dogs and proving useful.

Methyl xanthines

  • Bronchodilators.
  • Mild diureses, positive chronotropes and inotropes, eg aminophylline, etamiphylline Etamiphylline or theophylline.

Diuretics

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Vasodilators

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Antidysrhythmics

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Adrenoceptor stimulants

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Anticoagulants

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Mogg T D (1999) Equine cardiac disease. Clinical pharmacology and therapeutics. Vet Clin North Am Equine Pract 15( 3), 523-534, vii PubMed.

Other sources of information

  • Marr C M (2010) Cardiology of the Horse. 2nd edn. Eds: Marr C M & Bowen I M. Saunders, London. ISBN: 9780702028175.
  • Bertone J J & Horspool L J I (2004) Eds Equine Clinical Pharmacology. Saunders, London. ISBN: 0702024848.
  • Derived from The Veterinary Formula. (2004) 6th edn. Ed: Bishop Y. British Veterinary Association and Royal Pharmaceutical Society. ISBN: 0853695792.


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