Canis ISSN: 2398-2942

Therapeutics: cardiovascular

Contributor(s): Serena Brownlie, Sonja Fonfara, Clare Targett, Lauren Trepanier

Myocardial stimulants

  • * Indicates drug not licensed for this use in this species.

Pimobendan

  • Positive inotrope:
    • Phosphodiesterase III inhibition → increased cAMP → promotes calcium entry into myocyte and triggers further release of calcium from sarcoplasmic reticulum.
    • Calcium sensitizing properties affect interaction of calcium with troponin C complex that increases extent of contraction for a given cytosolic concentration of calcium without increasing myocardial oxygen consumption or energy requirement.
  • Vasodilator:
    • Phosphodiesterase III and V inhibition → increased cAMP in vascular smooth muscle → arterio-and venodilation.
  • Effects on cytokines and neurohormones:
    • No sign of any activation of neurohormones: some studies have shown a reduction in neurohormonal activation and reductions in the level of pro-inflammatory cytokines.
  • Anti-platelet effects:
    • May inhibit platelet aggregation thereby reducing the likelihood of thrombosis.
  • Indication: congestive heart failure Heart: congestive heart failure.
  • Pimobendan Pimobendan was shown to improve quality and quanity of life in dogs with CHF caused by degenerative valvular disease (DVD) and dilated cardiomyopathy (DCM Heart: dilated cardiomyopathy (DCM) ).

Dobutamine*

  • Beta-adrenergic stimulating agent (beta1>beta2>alpha), potent inotropic effect (acts on beta1-receptors in cardiac muscle); minimal effect on heart-rate or systemic vascular resistance (beta2-stimulatory effect might lead to hypotension)  Dobutamine.
  • Used in cardiogenic shock Shock: cardiogenic.
  • As continuous rate infusion 5 µg/kg/min.
  • After stabilization long-term improvement possible.

Cardiac glycosides

  • Block sodium pump (Na+, K+, ATPase), which results in increased intracellular Na, which promotes calcium influx into myocardial cells via Na-Ca exchange → increase force of myocardial contraction (positive inotrope), but arrhythmogenic risk.
  • Increase refractory period of cells and decrease conduction throughout the myocardium → reduced rate of contraction.
  • Parasympathomimetic effects → slowing of the sino-atrial node rate, delayed atrioventricular nodal conduction.
  • Major indications: supraventricular tachycardias, especially atrial fibrillation with rapid ventricular response rate in pre-existing congestive heart failure; combination with calcium channel blocker (diltiazem Diltiazem ) might be necessary to control ventricular response rate.
  • Narrow therapeutic margin, so do not use loading doses and titrate dose slowly for each patient.
  • Bioavailability varies with gastrointestinal flora and lipid solubility of each preparation.
  • Any change in dose form, eg from tablet to elixir takes 6-8 days to reach new steady state.
  • Recheck blood levels 7-10 days after starting/adjusting dose of digoxin Digoxin 6-8 hours after administration. Blood levels of 0.5-1 µg/ml are aimed for. Low levels have positive therapeutic effect with reduced risk of toxicity Digoxin toxicity.
  • Toxicity more likely in:
    • Hypothyroidism.
    • Renal insufficiency, depressed renal blood flow (CHF, beta blocker).
    • Old age.
    • Obesity.
    • Hypokalemia.
    • Dehydration.
    • Drugs: amiodarone, Ca channel blocker.
    • Certain breeds: Dobermann, giant breeds.
  • Signs of toxicity:
    • Anorexia.
    • Diarrhea, vomiting.
    • Dysrhythmias.
    • Depression.
    • Azotemia.
  • In case of toxicity:
    • Discontinue drug, check blood levels and restart at lower dose once recovers.
    • Lidocaine Lidocaine in case of ventricular ectopy.
    • Phenytoin Phenytoin : 1b antiarrhythmic drug, reverses high degree AV block (via central machnism?). Rarely used.
  • DigoxinDigoxin 0.003-0.005 mg/kg every 12 hours; lower end for medium to large breed dogs, 0.25 mg should not be exceeded as initial dose.
  • Excretion mainly unchanged via the kidney → decrease dose if azotemia.
  • Half-life: 20-55 hours.
  • DigitoxinDigitoxin.
  • Hepatic metabolism → metabolites excreted in feces and urine.
  • Half-life: 8-12 hours.

Diuretics

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Vasodilators

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Drugs for tachyarrhythmias

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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.
  • Bernay F, Bland J M, Häggström J et al (2010) Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. JVIM 24 (2), 331-341 PubMed.
  • Atkins C, Bonagura S, Ettinger S et al (2009) Guidelines for the diagnosis and treatment of canine chronic valvular heart disease, ACVIM consensus statement. JVIM 23 (6), 1142-1150 PubMed.
  • Gelzer A R, Kraus M S, Rishniw M et al (2009) Combination therapy with digoxin and diltiazem controls ventricular rate in chronic atrial fibrillation in dogs better than digoxin or diltiazem monotherapy: a randomized crossover study in 18 dogs. JVIM 23 (3), 499-508 PubMed.
  • Häggström J, Boswood A, O'Grady M et al (2008) Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. JVIM 22 (5), 1124-1135 PubMed.
  • O'Grady M R, Minors S L, O'Sullivan M L et al (2008) Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy. JVIM 22 (4), 897-904 PubMed.
  • Smith P J, French A T, Van Israël N et al (2005) Efficacy and safety of pimobendan in canine heart failure caused by myxomatous mitral valve disease. JSAP 46 (3), 121-130 PubMed.

Other sources of information

  • Opie L H, Gersh B J (2009) Drugs for the heart. 7th edn. Saunders, Elsevier.


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