Heart Disease and Blood Pressure Flashcards
What does ACEi stand for? What does it do?
Angiotensin-converting enzyme inhibitors that disrupt the renin-angiotensin-aldosterone system (RAAS).
Which organs does angiotensin II act on and what is the outcome of its mechanism of action?
Converted from Angiotensin I by angiotensin-converting enzyme (ACE)
Angiotensin II is a hormone that binds to receptors in various tissues to exert various effects.
Acts on the adrenal cortex, causing it to release aldosterone.
stimulates vasoconstriction in systemic arterioles
Promotes sodium reabsorption in proximal convoluted tubules of the kidneys.
In the CNS:
It acts on the hypothalamus to stimulate thirst and encourage water intake
It induces the posterior pituitary to release antidiuretic hormone
It reduces the sensitivity of the baroreceptors’ response to increase blood pressure
What is the role of angiotensin-converting enzyme?
It converts Angiotensin I to angiotensin II.
What are some effects of angiotensin-converting enzyme inhibition (ACEi)?
decrease proteinuria
promote vasodilation and ventilation
reduce plasma volume
All of the above sums to decrease systolic blood pressure
ACEi can also decrease the metabolism of vasodilatory agent bradykinin resulting in decrease in vascular tone.
What is first line of treatment for systemic hypertension in dogs?
ACE inhibitors
What are two of the most common ACEi?
Enalapril and Benazepril
Is ACEi a recommended first line treatment for SHT in cats? Why?
ACEi is not a recommended fist line treatment for cats as it does not sufficiently nor consistently lower blood pressure.
Benazepril may be beneficial in conjunction with calcium channel blocker.
What is the concern with ACEi in patients who are dehydrated or azotemic?
There is potential to worsen glomerular filtration rate and renal function through preferential dilation of the efferent arteriole that would thereby decrease glomerular filtration pressure.
Overall risk is low unless the patient also being treated with diuretic therapy or the patient has severe azotemia.
Which electrolyte imbalance might ACEi administration contribute?
hyperkalemia secondary to inhibition of aldosterone. However, this is unlikely to be clinically relevant event when given in conjunction with aldosterone antagonist such as spironolactone.
What effects do angiotensin receptor blockers (ARBs) exert?
Blocks the ability of angiotensin II to activate its receptors.
It does not affect the metabolism of bradykinin.
What is a contraindication for angiotensin receptor blockers (ARBs)?
Do not use in severely dehydrated or azotemic patients
What class of drug is Spironolactone?
aldosterone antagonist
How do aldosterone antagonist exert their effects?
Block the effects of aldosterone on the distal convoluted tubule and collecting duct.
Aldosterone
It is a steroid hormone produced by the adrenal cortex when stimulated by Angiotensin II.
It helps control the balance of water and salts in the kidney by keeping sodium and releasing potassium from the body.
What are the effects of chronic exposure to aldosterone?
Induces vascular remodeling in the glomerulus to retain sodium and water resulting in systemic hypertension.
Aldosterone also exerts proinflammatory effects promoting fibrosis.
What is a primary indication for use of spironolactone?
Hyperaldosteronism
When is it reasonable to suspect hyperaldosteronism in cats?
hypertension
hypernatremia
hypokalemia
mostly in chronic kidney disease
What is a potential adverse effect of spironolactone?
development of hyperkalemia. However, this is unlikely unless used with ACEi, ARBs or Beta blocker
Dihydropyridines
Dihydropyridines are a type of calcium channel blocker (CCB) that block calcium channels located in the muscle cells of the heart and arterial blood vessels, thereby reducing the entry of calcium ions into the cells. By blocking these channels, CCBs promote:
vasodilation
increase strength in contractility
minimal effect on cardiac conduction though the decrease in blood pressure may trigger a reflex tachycardia.
E.g. Amlodipine and Nicardipine
What is first line treatment for antihypertensives in cats?
Amlodipine because it has shown to be more effective than ACEi.
If the cat is refractory to amlodipine, then it may require an addition of ACEi or ARB
Side effects of CCBs
Reflex tachycardia
weakness, lethargy and decrease in appetite
intrarenal hemodynamics –> CCB promotes preferential afferent arteriolar dilation over the efferent arteriole, which may result in increased intraglomerular pressure, resulting in damage to the glomerulus and worsening proteinuria.
Adrenergic Antagonist
It can help manage SHT, especially if the underlying mechanism is sympathetically driven.
Prazosin
Selective alpha 1 antagonist to promote smooth muscle vascular relaxation.
Acepromazine
Dopamine antagonist with the potential to cause hypotension and GI upset
Atenolol
Beta 1 selective antagonist
Decreases heart rate and contractility
Reduces renin release and peripheral vascular resistance
Used more in cats with SHT and hypethyroidism
Used in dogs as adjunct for refractory SHT with reflex tachycardia
Propanolol
Non-selective beta antagonist
Decreases heart rate and contractility
Reduces renin release and peripheral vascular resistance
What is an adverse side effect of atenolol
Excessive bradycardia
Labetalol
Injectable mix of alpha and beta antagonists.
Used to manage severe acute hypertension
promotes vasodilation and prevents associated tachycardia
The use has been explored in dogs undergoing craniotomy or adrenalectomy
Hydralazine
Promotes vasodilation by altering smooth muscle intracellular metabolism.
works primarily on arteries
Causes vasodilation, afterload reduction and lowering of blood pressure
The mechanism is not entirely understood but the end result is smooth muscle relaxation and decrease in peripheral vascular resistance.
It is not used as a first-line drug but used as an adjunct in chronic management.
Injectable form used in urgent/emergent treatment due to its potent vasodilatory effects, and rapid onset.
What are adverse side effects to hydralazine?
Arteriolar vasodilator
excessive or irreversible hypotension
reflex tachycardia
sodium and water retention
GI upset
Sodium nitroprusside (SNP)
Arteriolar vasodilator
promotes potent vasodilation through release of nitric oxide.
Nitric oxide diffuses to vascular smooth muscle
decrease influx of calcium, activation of actin/myosin chains and overall contractile forces
Effects: smooth muscle relaxation and decreased vascular tone and peripheral vascular resistance
The injectable form has a short half-life and is easy to titrate, so it is ideally used for hypertensive crises. Administer as CRI.
Used to treat acute hypertensive crises or fulminant CHF
Contraindicated in hypotensive patients
IV nitroglycerine
promotes potent vasodilation through release of nitric oxide.
Nitric oxide diffuses to vascular smooth muscle
decrease influx of calcium, activation of actin/myosin chains and overall contractile forces
Effects: smooth muscle relaxation and decreased vascular tone and peripheral vascular resistance
The injectable form has a short half-life and is easy to titrate, so it is ideally used for hypertensive crises.
No risk of cyanide poisoning
What are the adverse side effects associated with sodium nitroprusside?
generation of cyanide and thiocyanate at high doses and prolonged use.
Patients with kidney and liver disease have decreased metabolism, therefore greater risk of cyanide toxicity.
Clinical signs of toxicosis: metabolic acidosis, depression, stupor, seizures
Fenoldopam
Selective agonist of dopamine 1 receptor. Promotes peripheral and renal vasodilation and natriuresis
Increases glomerular filtration rate
Injectable has a short half life.
Good potential for application in hypertensive crisis, but needs further investigation in vet med.
Class 1 Antiarrhythmics
Sodium channel blockers
Interferes intracellularly with sodium conduction through sodium channels
Subclassification determined by potency of effects on sodium channel, activated/inactivated blockade and effects on other channel receptors.
Class 1A antiarrhythmic agents
Quinidine and procainamide
Effective against ventricular and supraventricular arrhythmias.
fast sodium channel blocking effects and moderate blockade of rapid component of the delayed rectifier potassium current resulting in action potential elongation.
Procainamide
Class 1 A antiarrhythmic
Sodium channel blocker
Depresses conduction velocity and prolongs refractory period in a variety of tissues, including atrial and ventricular myocardium
Administer slowly IV over 5-10 minutes to prevent hypotension
Adverse effects more commonly associated with cats and humans; include anorexia, nausea, and vomiting
Class IB Antiarrhythmic
Inhibits fast sodium channels, primarily in the open and inactivated state, with rapid onset.
Sodium current is also inhibited, resulting in the shortening of action potential in normal myocardial tissue
Lidocaine and mexiletine
Lidocaine
Class IB antiarrhythmic
Sodium channel blocker.
The ability of lidocaine to block sodium currents is better during acidosis.
Benefit: minimal hemodynamic, SA, AVN affect at standard doses
Hepatic clearance determines serum concentration
Heart failure, hypotension, and severe hepatic disease can decrease lidocaine metabolism and predispose patients to lidocaine toxicity.
Adverse effects: higher incidence in cats
Nausea, vomiting, lethargy, tremors, seizure activity (usually symptoms stop when lidocaine is discontinued)
Dosing: Bolus 2mg/kg over 20-30 seconds; bolus can be repeated up to 8mg/kg within 10 minute period barring adverse effects
CRI: 25-75mcg/kg/min
Mexiletine
Class 1B antiarrhythmic
most common oral class in dogs
Highly protein-bound and excreted by the kidneys
Use and adverse effects similar to Lidocaine (rarely used in cats because of adverse effects)
Tocainide
Class 1B antiarrhythmic
Similar to lidocaine, rarely used in small animals because of high incidence of serious adverse effects including renal failure and corneal dystrophy
Class 1C Antiarrhythmic
Potent blockade of the open state fast sodium channel with greater effects as the depolarization rate increases
These agents prolong the refractory period in atrial and ventricular tissues
Propafenone and Flecainide
Propafenone
Class 1C antiarrhythmic
used to treat narrow complex tachyarrhythmias
usually combined with diltiazem
also has mild beta blocking properties
Flecainide
Class 1C antiarrhythmic
potent negative inotropic properties
Side effects include GI, but not commonly seen
Rarely used in veterinary medicine
Monitor heart rate, blood pressure and ECG when administering
Class II antiarrhythmic
Beta-adrenergic antagonists or beta-blockers are the most used cardiovascular drugs.
Must be cognizant of animals’ underlying disease when prescribing.
Beta-blockers contraindicated in patients with evidence of sinus nodal dysfunction, AVN conduction disturbances, pulmonary disease or CHF (must be evaluated for fluid retention and condition must be stabilized before implementing beta-blockade).
Reduces heart rate and myocardial oxygen demand and increases atrioventricular conduction time.
Inhibits pacemaker current I(f) that promotes proarrhythmic depolarization in damaged cardiomyocytes
Inhibits calcium current by decreasing tissue cyclic adenosine monophosphate levels ; the magnitude of effects depends on the sympathetic state. Greater effect with higher adrenergic states
Beta-adrenergic antagonists slow AVN conduction in SVT by slowing sinus discharge rate in inappropriate sinus tachycardia and suppresses ventricular tachycardia that may be exacerbated by increased sympathetic tone.
Used to treat supraventricular and ventricular arrhythmias.
Also used in HCM to control heart rate and decrease myocardial oxygen demand
Can cause hypotension due to decreased heart output.
Extremely low dosages must be used with patients with systolic myocardial dysfunction. Because of that, beta blockers are not generally first choice for acute anti-arrhythmic therapy because the amount required is not well tolerated.
Propranolol
Non-selective beta receptor antagonist (targets both beta-1 and 2 receptors).
Function: decrease heart rate and contractility. Decrease renin release and peripheral vascular resistance
Esmolol
Class II Antiarrhythmic
Short-acting Beta-1 blocker that can help control sympathetically driving ventricular tachycardia . Administered as a CRI on telemetry.
Side effects: Negative inotropic effects may be too pronounced in some patients and cause cardiovascular collapse. Requires blood pressure monitoring.
Atenolol
Class II antiarrhythmic.
The most common oral beta blocker in small animals.
Relative beta 1 selectivity and long half-life compared to propranolol.
Water soluble and eliminated by the kidney.
Metoprolol
Class II antiarrhythmic.
Common oral beta blocker in small animals.
Long half-life compared to propranolol.
Metabolized and eliminated through the liver.
Class III Antiarrhythmic agents
Block the repolarization of I(k) resulting in prolongation of action potential durations and effective refractory period.
Blocks rapid component of I(k) instead of the slow component – therefore effects are accentuated at slower heart rates rather than at the problematic tachyarrhythmic rates.
Puts patients at risk of early afterdepolarization (accounts of proarrhythmic effects of class III AA drugs) - risk is increased in patients with hypokalemia, bradycardia, intact females, increasing age, macrolide antibiotic therapy/other drug therapies
Amiodarone
Class III Antiarrhythmic
Alpha and Beta blocking properties.
Effects on sodium, potassium, and calcium channels.
Broadest spectrum exhibiting properties of all 4 AA classes.
Makes action potential durations more uniform throughout the myocardium and has the least reported proarrhythmic activity of any of the class III agents.
Used for refractory tachyarrhythmias, both atrial and ventricular
Significant side effects in dogs, including hepatopathy and anaphylaxis.
Monitor heart rate, blood pressure and ECG with administer.
Available as oral or injectable.
Major drawback: associated with a host of multi-systemic adverse side effects that do not occur with sotalol.
Adverse side effects (more common with higher maintenance doses): vomiting, anorexia, hepatopathies, thrombocytopenia
Two brands:
Cardarone IV, Nextarone
