Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

VASODILATORS
resistance (e.g. 2000 dyn.s.cm −5 .m 2 ), twice as much
blood will be ejected into the left atrium in systole as is
ejected into the aorta (i.e. 67% of the stroke volume
will be ejected into the left atrium and 33% will be
ejected into the aorta). In dogs with severe CVD more
than 75% of the total left ventricular stroke volume
may go backward into the left atrium.
Resistance to blood flow into the systemic circulation
depends primarily on the cross-sectional area of the
systemic arterioles. Resistance to blood flow through a
defect like a leaky mitral valve depends on the size of
the defect. Defect size is relatively fixed (unless a surgeon
intervenes) in the short term but does progress over time
as the disease progresses. Systemic vascular resistance,
however, is labile and can be manipulated with drugs.
If an arteriolar-dilating drug is administered to a patient
with CVD, the decrease in systemic vascular resistance
(e.g. to 1000 dyn.s.cm −5 .m 2 ) will result in an increase in
forward flow into the aorta and systemic circulation.
This will result in a decrease in backward flow into the
left atrium and so a decrease in left atrial and pulmonary
capillary pressures. In this example, the percentage
of the stroke volume ejected into the left atrium will
decrease from 67% to 50%, which would represent a
large change, but even modest reductions in regurgitation
fraction (5%) would be clinically significant.
Venodilators relax systemic venous smooth muscle,
theoretically redistributing some of the blood volume
into the systemic venous reservoir, decreasing cardiac
blood volume and reducing pulmonary and hepatic congestion.
The net result is reduced ventricular diastolic
pressures, decreased pulmonary and systemic capillary
pressures and diminished edema and ascites formation.
Consequently, venodilators are used in the same situations
as diuretics and sodium-restricted diets.
Vasodilators are also classified according to their
mechanism of action (Table 17.5). ACE inhibitors not
only produce vasodilation, they inhibit the RAAS and
are thus neuroendocrine modulators resulting in less
sodium and water retention.
Therapeutic endpoints
The therapeutic endpoint of vasodilator therapy is
reduction in edema (reduced pulmonary capillary pressure
and venous pressures) for venodilators and
improved forward perfusion (elevation of cardiac
output) for arteriolar dilators in patients with diseases
such as DCM. When regurgitation or left-to-right shunting
is present, arteriolar dilators reduce pulmonary
edema formation and improve forward flow.
While it may not be feasible to measure these parameters
directly, close monitoring of clinical signs and
radiographic appearance of the lungs is realistic. Therapeutic
response is seen as a decrease in cough, return of
normal respiratory rate and effort, improved capillary
refill time and color (sometimes hyperemic), improved
distal extremity perfusion and temperature, improved
attitude and possibly exercise tolerance, resolution of
ascites and radiographic resolution of the pulmonary
edema or pleural effusion. Mean or systolic systemic
arterial blood pressure is usually reduced by 10–
20 mmHg after the administration of a potent arteriolar
dilator. Mean systemic arterial blood pressure should
be maintained above 60 mmHg.
Adverse effects
While vasodilators enable one to achieve better therapeutic
results, with their use comes the potential for
adverse effects. These drugs are often used in critically
ill canine or feline patients or patients with multiple
problems that may be on several medications at the time
of evaluation or during the course of treatment. These
patients, in general, are at greater risk for experiencing
adverse effects from a drug.
Table 17.5 Vasodilator drugs commonly used in veterinary medicine
Vasodilator Type (mechanism) Route Dose
Dogs
Cats
Pimobendan* Balanced (inodilator) PO 0.25-0.3 mg/kg q.12 h
Amlodipine** Arterial (Ca channel blocker) PO 0.01-3 mg/kg PO q.12-24 h (usually 12) 0.625 mg/cat q.24 h
Hydralazine Arterial (↑ PGI 2 ) PO 0.5–3 mg/kg q.12 h 2.5–10 mg/cat q.12 h
Prazosin Balanced (α 1 -blocker) PO 0.5–2 mg/dog q.8–12 h 0.6 cm/cat q.6–8 h
Nitroglycerin Venous (cGMP formation) Cutaneous 0.6 cm per 5 kg q.6–8 h
Nitroprusside Balanced (cGMP formation) IV 1–15 µg/kg/min
Benazepril* Balanced (ACE inhibitor) PO 0.3–0.5 mg/kg q.24 h 0.2-0.7 mg/kg q.24 h
Enalapril* Balanced (ACE inhibitor) PO 0.5 mg/kg q.12–24 h (usually used q.12) 0.5 mg/kg q.12–24 h
* Authors’ preferred agents for HF.
** Authors’ preferred agent for systemic hypertension.
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