Vasodilators
| Specific Therapeutic Objective(s) |
Clinical State(s) |
Drug(s) (Class) |
| Increase venous capacity long-term |
Congestive heart failure |
Nitroglycerine (nitrate)
Enalapril (ACE-I) |
| Increase venous capacity short-term |
Acute decompensated heart failure |
Nitroprusside (Nitrate-like)
Nitroglycerine (Nitrate)
Furosemide (loop diuretic)
Enalaprilat (ACE-I)
Morphine (Opiate
Acepromazine(α-blocker)
Prazosin (α-blocker)
|
| Reduce arterial resistance long-term |
Congestive heart failure
Mitral insufficiency
Primary Hypertension |
Enalapril (ACE-I)
Hydralazine (Nitrate-like)
Amlodipine (Ca Channel) |
| Reduce arterial resistance short-term |
Acute decompensated heart failure |
Nitroprusside (Nitrate-like)
Enalaprilat (ACE-I)
|
| Reduce fluid retention |
Congestive heart failure |
Enalapril (ACE-I) |
General Concepts
Vascular Plumbing:
| "Normal" | "Heart Failure" |
 |
 |
- Afterload is only affected by changes between the left ventricle and the capillaries.
- Vascular tone (the only IMPORTANT change)
- Preload can be changed by altering things between the capillary bed and the left atrium.
Nitrates
Nitrates include amyl nitrate, isosorbide dinitrate, nitroglycerin, and pentaerythritol tetranitrate, in oral tablets, buccal tablets, sublingual tablets, inhalers, topical patches (sustained release) and topical ointment. Only nitroglycerin topical ointment and patches are are in widespread clinical use.
Nitroglycerin
Mechanism of Action
Direct relaxation of arterial and venous smooth muscle
- Venodilation predominates at therapeutic doses which reduces preload
- Arteriodilation at high doses (high therapeutic/toxic) which produces hypotension
compensated by sympathetics (heart/vascular)to produce tachycardia
Toxicity
- Hypotension
- Methemoglobinemia (cyanosis)
- Dermatitis (topical irritation)
Drug Interactions
- Interfere with action of:
- Sympathomimetics (α adrenergic agonists)
- Heparin (may need to increase heparin dose)
- Additive hypotension with:
- Other vasodilators
- Diuretics
- β-1 blockers
Clinical Uses
- Acute decompensation - pulmonary edema
- Particularly cats because other drugs are unsuitable - (no need for IV)
- Topical on relatively hairless area (inside ear, shaved area inside thigh)
- Caution - wear gloves while administering
- Chronically - to reduce preload
- Adjunct to diuretics to reduce dose or enhance effect
Other Vasodilators (non-nitrate)
Nitroprusside
Mechanism of Action
- Direct relaxation of arteriolar and venous smooth muscle
- Reduced preload and afterload (at therapeutic doses)
Toxicity
- Excessive vasodilation and hypotension
- Nausea
- Vomiting
- Loss of consciousness
- Reflex tachycardia
- Accumulation of thiocyanate with prolonged use (see cyanide poisoning, toxicology notes)
- Toxic psychosis
- Metabolic acidosis
- Pink color (mucous membranes)
Pharmacokinetics
Extremely short half-life
- Must be administered intravenously
- (Use only freshly prepared solution - product degrades rapidly)
- Rapid steady state
- Rapid change in clinical response with dose rate change
- Rapid abatement of hypotension when rate reduced.
Drug Interactions
Interfere with action of:
- Sympathomimetics (α adrenergic agonists)
Reduced hypotensive action
- Estrogens
- Sympathomimetics
Excessive hypotension
- Other vasodilators
- Diuretics
Clinical Uses
- Reduce afterload for acute decompensation (Blood pressure can be titrated)
- Combine with positive inotrope (especially dobutamine)
- Force of contraction may be insufficient to maintain pressure with (appropriate) afterload reduction.
- In order of use: oxygen, diuretic, dobutamine; nitroprusside
Hydralazine
Mechanism of Action
- Direct relaxation of arteriolar smooth muscle
- Increased heart rate (reflex tachycardia)
- Increased stroke volume (provided contractility sufficient)
Toxicity
- Hypotension - excessive tachycardia, syncope, etc.
- GI - constipation or diarrhea
- Lupus-like syndrome (Myalgia, arthralgia, fever, ANA)
Drug Interactions
- Reduced effect of hydralazine
- NSAIDs
- Estrogens
- Sympathomimetics
- Enhanced effect of hydralazine
- Other vasodilators
- Diazoxide and other drugs which are anti-hypertensive
Clinical Uses
Congestive heart failure especially...
- Severe mitral regurgitation
- Reduction of left atrial enlargement
(in combination with diuretic +\- β blocker to control reflex tachycardia)
Administration
Usually incremental doses to determine effective dose (Clinical studies show that titration is important to success)
Prazosin
Mechanism of Action
Selective α-1 adrenergic antagonism reduces mean arterial pressure
Toxicity
- First dose hypotension and loss of consciousness
- Unusual in animals (think about postural effects on blood pressure)
- Tachycardia
- Possible but not generally produced
- Block is competitive
- α-2 still active (central)
- Hypersensitivity
Clinical Uses
Afterload reduction
- Other agents are preferred
- Relative tolerance develops quickly
- Initial improvement, poor response long term
Angiotensin Converting Enzyme (ACE)
Inhibitors
Enalapril, Captopril
Mechanism of Action
Inhibits conversion Angiotensin I to Angiotensin II
- Reduces arterial resistance (afterload)
- May improve cardiac output
- May improve renal blood flow
- Reduces venous tension (preload)
- May improved cardiac output
- Reduces pulmonary edema, tissue edema, ascites
- Reduces in aldosterone secretion
- Decreases sodium retention
- Decreases fluid retention
- Reduces preload
Pharmacokinetics
- Food impairs absorption
- less with enalapril than captopril
- Eliminated by kidneys
- slowed with renal failure
- Dose rate (enalapril) should be reduced by at least 50% if renal disease is evident.
- Injectable (Enalaprilat - the active metabolite of enalapril)
Toxicity
- Gastrointestinal disturbances (Big problem with captopril, less with enalapril, lisonopril?)
- Hypotension (particularly first dose) and especially with aggressive diuretic therapy
- Hyperkalemia
- Hypersensitivity
- Neutropenia (rare)
- Proteinuria - especially in renal disease patients
- Renal failure (has been reported in dogs) may also be protective of renal function for some disease states
Drug Interactions
- Enhanced hypotensive effect
- Reduced hypotensive effect
- NSAIDs
- Estrogens
- Sympathomimetics
- Potassium imbalance
Clinical Uses
Congestive Heart Failure
- to reduce Preload
- Reduce Fluid Retention
- Reduce Venous tone
- to reduce Afterload
- Reduce Arterial tone (there is some clinical Evidence for improved exercise tolerance)
Additional ACE inhibitors
| Enalaprilat | (iv administration, renal elimination only) |
| Lisinopril | (renal elimination only) |
Calcium channel blockers
Calcium channel blockers vary in the level of activity against cardiac (antiarrhythmic) and smooth muscle (vasodilation) calcium channels. These two have particularly potent activity against smooth muscle calcium channels:
Nefedipine
- hypotensive action leads to sympathetic increase
- indicated for extreme hypertension
- role in veterinary patients?
Amlodipine
- Dominant activity in calcium channels of vascular smooth muscle.
- Has been evaluated for treatment of hypertension in cats.
Topic Summary (Vasodilators)
- Individual vasodilators produce decreases in preload, afterload, or both.
The choice of a vasodilator should be based on the needs of the individual
patient for modification of either of these parameters.
- Vasodilators and ACE inhibitors are most likely to produce improvement in
exercise tolerance (as opposed to positive inotropes).
- ACE inhibitors ultimately produce both vasodilatation and a reduction in
fluid retention secondary to Na retention. This balance of effects may improve
exercise tolerance and help reduce the total doses of diuretics required by
these patients.