Veterinary Cardiovascular Drugs: VETC 2020

• Cardiovascular drugs are used in veterinary medicine
• This material recaps information for VETC 2020

Cardiovascular Drug Classes

• Positive Inotropic Drugs
  • Catecholamines
  • Cardiac glycoside
• Inodilators
  • positive Inotrope and vasodilator
• Vasodilator Drugs
  • Arterial Vasodilators
  • Venous Vasodilators
  • Mixed Vasodilators
• Other: Antithrombotic
• Sedatives & Tranquilizers

Positive Inotrope: Catecholamines

• These drugs stimulate Beta 1 Adrenergic Receptors
  • That increases HR and contractility
• It also improves cardiac contractility and Ca++ availability
• Sympathomimetic effects includes potent peripheral vasoconstriction, increased heart rate, increased cardiac contractility, and Bronchodilation
• Possible side effects include non-selective for all adrenergic receptors
• Short acting and administered via IV

Positive Inotrope: Cardiac Glycoside: Digoxin

• Improves cardiac contractility via increased Ca++ availability
• Decreases ATPase pump
• Effective for cats and dogs
• Long half life equates to better client compliance
• Narrow therapeutic index requires toxicity monitoring
• Eliminated via kidneys, plasma levels must be monitored, and caution with double dosing

Inodilator: Pimobendan

• Increases calcium binding and contractility, unlike catecholamines which increase Ca+ release
• This inotrope decreases blood pressure and cardiac pre-load and after-load
• Used in CHF and DCM
• It can be expensive
• Mostly none for side effects, but contraindicated when dangerous to increase force of contraction (e.g. hypertrophic cardiomyopathy)

Arterial Vasodilators

• Used to treat hypertension
• Vasodilation occurs via blocking Ca+ channels that contribute to cardiac muscle contraction
• Reduces afterload by dilating arteries
• Can cause fluid retention, typically prescribed with a diuretic or beta blocker
• Amlodipine trade names include Norvasc, ExpressVet
  • the MOA is as a Ca+ channel blocker
  • Used for dog hypertension and for cat hypertension from CKD, hyperthyroidism, DM
• Hydralazine trade name is Apresoline and is also a Ca+ channel blocker
  • Used in dogs mostly
  • Eases the work for CHF heart and MVD
• Common suffix = PINE, INE, OR AMIL

Venous Vasodilators

• Nitroglycerin trade name is Nitro-Bid
  • Mode of action is dilating venules and coronary arterioles
  • Improves blood flow to myocardium, lower blood pressure, better blood supply to heart, easy application for clients, improves cardiac output
  • Used for pulmonary edema in CHF
  • Applied as a cream or patch
  • Caution when using, must wear gloves, can't allow dog/cat to lick, risk of accidental exposure of veterinary personnel
  • Possible tolerance, and metabolized quickly

Mixed Vasodilators

• Nitroprusside creates nitric oxide that inhibits muscle contraction
  • Reduces preload and afterload
  • Is beneficial in cases of pulmonary edema secondary to heart failure
  • Side effects include potent and short active (IV CRI)
• Enalapril trade name is Enacard
• Captopril and Benazepril trade name is Fortekor
  • The MOA for all three is ACE Inhibitors that prevent formation of angiotensin II and aldosterone that cause vasoconstriction of both veins & arteries
  • Patients with CHF and left sided HF have marked improvement; no need to put patient on a sodium restricted diet
  • Caution with animals that are hyponatremic (No LOW Na) and watch out for hyperkalemia – potassium sparing diuretics
  • Imidapril trade name is Prilium (liquid)
    • Maybe inotropic properties
• Common suffix = PRIL

Renin-angiotensin-aldosterone system (RAAS)

• Vasodilators work by blocking RAAS
• Blocking RAAS reduces production of angiotensin II and aldosterone
• Angiotensin II causes vasoconstriction
• Aldosterone causes water retention in the kidney
• Renin-angiotensin cascade can be started by anything that decreases arterial blood pressure
  • Blood loss, dehydration, shock
• The decreased arterial blood pressure reduces blood flow to the kidney and decreases urine filtration
• The kidney senses this change and releases renin into the blood
• Renin converts angiotensinogen into angiotensin I
• Angiotensin I goes to the lungs where angiotensin-converting enzyme (ACE) turns it into angiotensin II
• Angiotensin II stimulates the adrenal gland to produces aldosterone
• Aldosterone, which causes increased reabsorption and retention of sodium and water in the blood, the blood volume
• The combination of vasoconstriction of precapillary arterioles and increased blood volume raises the arterial blood pressure back to normal

Diuretics

• Increase urine formation and promote water loss
• Refer to Clinical Pharmacology & Therapeutics for Veterinary Technicians (5th ed.), chapter 5, pages 137-140 for further information

Indications for Use

• Accumulation of tissue fluid from cardiovascular diseases
  • Pulmonary edema
  • High blood pressure
  • Congestive heart failure
    • These cases need decreased workload on heart

Sided Heart Failures

• Right sided failure: heart is unable to eject all blood, blood backs up and accumulates causing systemic edema and congestion = effusion of fluid in abdomen = ascites
• Left sided heart increases HR and BP in left
• Left-sided failure is the most common form of CHF
• When heart contracts, some blood leaks through the mitral valve back into the left atrium and into lungs
• Results in pulmonary edema
• Heart will enlarge and push against trachea
• Coughing, dyspnea, syncope, exercise intolerance, weight loss
• Right-sided failure causes poor venous blood return to heart
• Blood backs up into the right atrium instead of heading to lungs
• Causes blood to back up into the circulatory system and body becomes congested
• Ascites, abdominal distention, weight loss, peripheral edema

MOA of Most Diuretics

• Shared mechanism
  • Prevent reabsorption of Na+ or K+ from the renal tubules
  • Enhance secretion of Na+ or K+ into the tubules
  • Net increase in Na+ or K+ in the renal tubules creates an osmotic force that draws water into the renal tubules

General Physiology

• Fluid/blood regulation and blood pressure occurs in the kidneys relates to urine filtration
• Urine filtration occurs in the nephron of the kidney, with loop diuretics working on the loop of Henle

Diuretic Drug Classes

• Loop Diuretics
• Thiazide Diuretics
• Potassium-Sparing Diuretics
• Osmotic Diuretics
• Carbonic Anhydrase Inhibitors

Loop Diuretics

• Most used diuretic in vet med and trade names include Lasix and Salix
• First line of defense for edema associated with CHF
• Loop refers to the kidney's loop of Henle
  • This is where the drug produces diuresis
• Loop diuretics inhibit the reabsorption of sodium (Na+) from the urine without resulting in sodium loss from the body
• Forms: IV, PO
• Side effects can include polyuria and strain on the kidneys (increases creat & BUN)
• Prolonged use can result in potassium loss
• May cause hypokalemia if the animal's diet is not supplemented with additional potassium.
• Prolonged use can also damage convoluted tubules in kidneys reducing its effectiveness
• Furosemide works in the loop of Henle, 90% of sodium is reabsorbed here
• Is effective as a first line of defense for edema associated with heart failures or pulmonary edema

Decreasing Preload

• Drugs that negatively affect preload are diuretics, decreasing venous blood volume to the heart and reducing cardiac Preload
• For example, drug Furosemide that comes in injectable or oral forms

Affecting Preload

• Intravenous fluids and Blood products that add volume positively impact preload
• Administration results in increased venous blood volume to the heart
• in the ventricles at the end of diastole (preload)
• Drug Examples can stimulate sympathetic activity will increasing preload such as Vasopressin to induce vasoconstriction

Thiazide Diuretics

• Generic drugs can include chlorothiazide and hydrochlorothiazide
• Not often used by themselves in veterinary medicine
• Furosemide is more effective as it, or it can be combined with Furosemide if it has become ineffective alone
• Less potent than loop diuretics, and forms include oral tablets
• MOA is to decreases resorption of sodium and chloride in the initial segment of the distal convoluted tubule

Potassium-Sparing Diuretics

• Spironolactone is a generic drug and is a competitive antagonist of aldosterone
• The hormone that normally increase blood volume by sodium reabsorption from the distal renal tubules and collection ducts
• RAAS is stimulated in CHF from decreased BP
• Increases diuresis by preventing reabsorption

Osmotic Diuretics

• Mannitol is a carbohydrate (sugar)
• Retains water in the renal tubules by its physical presence within the lumen
• Increases urine production and diuresis
• Most often used for cerebral edema, rather than for diuresis for cardiac episodes
• Is an injectable form that can crystallize; pre-warm and / or use a filter

Carbonic Anhydrase Inhibitors

• Acetazolamide is the generic drug
• Aren't often used as systemic diuretics in veterinary medicine but may be used to decrease production of aqueous humor in the eye and reduce intraocular pressure in animals with glaucoma
• Because of its relatively weak diuretic effect and the ready availability of more effective diuretics, acetazolamide isn't used to treat cardiac problems in veterinary patients.

Diuretic Examples

• Furosemide is a loop diuretic
• Chlorothiazide or Hydrochlorothiazide are Thiazide Diuretics
• Spironolactone is a Potassium-Sparing Diuretic
• Mannitol is a Osmotic Diuretic
• Acetazolamide is a Carbonic Anhydrase Inhibitor

Diuretic Recap

• Get the water out!
• Squeeze the sponge!
• Given to animals who may be showing signs of fluid build up
• Always be careful with dosing
• Diuretics can be used for SCENARIOS
• Easy access
• Goal is to enhance secretion of NA+ and K+ via the kidneys