Drugs for treating cardiac disease Flashcards
Drugs for treating heart failure can broadly be one of 3:
Drugs that decrease preload
Drugs that decrease afterload
Drugs that enhance inotropic function
Preload
the volume of blood/hydrostatic pressure within the ventricles at the end of diastole
Afterload
the force that opposes ejection of blood into the peripheral arterial system
Indications for drugs that decrease preload:
excessive preload causes signs of congestion (pulmonary edema, pleural effusion, ascites)
Most effective for these problems are:
・ Diuretics
・ Venodilators (dilate the pulmonary blood vessels)
Most frequently used drugs for patients with heart failure are…?
diuretics
Increase in the excretion of sodium ➝ reduction in extracellular fluid volume ➝ lower circulating fluid volume ➝
reduction in preload.
3 main classes of diuretics:
loop,
thiazide,
potassium sparing
Act on different parts of the nephron.
Thiazide acts on what part of the nephron
distal convoluted tubule
Sequential nephron blockade
Sequential nephron blockade involves combining loop and thiazide diuretics.
Has been proposed as a strategy to overcome diuretic resistance and improve fluid overload management.
What type of diuretic is spironolactone?
class: potassium sparing
Mechanism: blockade of aldosterone receptors.
Side effects of diuretics:
polyuria, polydipsia
Complications:
・ Hypotension
・ Azotemia
・ Hypokalemia (loop), hyponatremia
First choice diuretic drug
furosemide
(then K+-sparing, then thiazides)
Furosemide is a
loop diuretic
First line therapy for patients with signs of congestion.
Patients can become refractory to the drug with chronic treatment.
➝ Higher doses
➝ Coadministration of diuretics that act at different sites in the nephron (combine thiazide or spirono.)
➝ Or substitute for torsemide (also a loop diuretic)
Use Thiazide diuretics if
Patients are refractory to furosemide and spironolactone (means that the drug isn’t or no longer is, producing the desired effect)
Spironolactone is a
K+-sparing diuretic, aldosterone receptor antagonist.
・ Insufficient natriuretic potency to be used as the sole diuretic - administered alongside other diuretics to potentiate their effect.
・ Benefits associated with its administration extend beyond diuretic effects - blocks detrimental effects of aldosterone on the vasculature and cardiac remodeling.
NB Cats may experience cutaneous adverse drug reactions.
Venodilators ease heart failure by
decreasing preload
(note: NOT the same as a VASOdilator! (venodilators dilate the veins so in this case pulmonary blood vessels (and vasodilators effect the arteries’ diameter))
Example of a common venodilator (note: NOT the same as a VASOdilator!)
Nitroglycerin
・ Adjunctive treatment of acute heart failure (with a loop diuretic)
・ Transdermal available
Adverse effects: rashes at the application sites, hypotension, headache.
Left ventricular afterload reduction via
systemic vasodilation
name some vasodilators for Left ventricular afterload reduction - systemic vasodilation (4)
・ Nitroprusside (vasodilator)
・ ACEI - angiotensin converting enzyme inhibitors
・ Pimobendan (inotrope)
・ Ca channel blockers
Complications: hypotension (syncope, weakness, hypoperfusion).
Right ventricular afterload reduction via
pulmonary vessel vasodilation
Right ventricular afterload reduction - pulmonary vasodilation
・ Indication:
pulmonary hypertension
Examples of Right ventricular afterload reduction drugs (2)
Sildenafil - phosphodiesterase V inhibitor
Pimobendan may also have pulmonary vasodilatory properties in addition to its systemic vasodilating effects.
Nitroprusside effects?
Balanced effect - preload reduction through venodilation and afterload reduction through arteriodilation.
nitroprusside indications?
(reduces both preload and afterload)
Indications:
・ Acute/severe hypertension
・ Acute heart failure
・ In combination with dobutamine for refractory CHF.
・ CRI
・ Used only in ICU setting
Describe ACE-inhibitors.
e.g. Enalapril, benazepril
・ Inhibition of angiotensin converting
enzyme produces vasodilation, inhibits fluid
retention.
・ Part of chronic therapy for heart
failure.
・ Particularly beneficial in patients that are
also receiving diuretics.
Describe Ca channel blockers
Ca channel blockers are used to dilate vessels.
・ Numerous and varied cardiac electrophysiological and vascular effects
e.g. most commonly Amlodipine
Most frequently used for systemic hypertension.
・ In dogs, also as an afterload reducer for refractory heart failure (to patients already
receiving pimobendan and ACE-inhibitor).
Drugs that enhance inotropic function which means
Increased cardiac contractility ➝
increased cardiac output,
indirectly decreased preload
Myocardial contractility is frequently impaired in patients with heart failure.
3 main inotropic drugs in vet med
・ Dobutamine - acute treatment of heart failure
・ Pimobendan - chronic treatment of heart failure
・ Digoxin - treatment for atrial fibrillation (antiarrhythmic)
Describe Dobutamine
Sympathomimetic - stimulation of beta 1 receptors
・ Inotropic + lusitropic effects (myocardial relaxation)
・ CRI, in ICU setting
・ Ineffective after 48-72 h
Indications:
・ Acute signs of heart failure + hypotension/primary failure of myocardial contractility
・ Rescue agent in the treatment of patients with an acute crisis that are already receiving
chronic treatment for congestive heart failure of any cause (refractory to oral medication)
・ In shock patients when fluid therapy alone has not restored acceptable arterial blood pressure/cardiac output/tissue perfusion
・ Hypotension during general anesthesia
Define lusitropic effects
Lusitropy or lucitropy is the rate of myocardial relaxation.
The increase in cytosolic calcium of cardiomyocytes via increased uptake leads to increased myocardial contractility (positive inotropic effect), but the myocardial relaxation, or lusitropy, decreases.
Describe dopamine
Adrenergic/dopaminergic inotropic agent
・ CRI due to very short half-life
・ Clinical effects vary with dosage
・ Low doses (dopaminergic receptors): dilate the renal, mesenteric, coronary, intracerebral
vasculature
・ Intermediate doses (+ alpha 1, beta 1): positive cardiac inotropic activity, increased
organ perfusion and urine production
・ Higher doses (dopaminergic effects are overridden by alpha effects): increase systemic peripheral resistance (vasoconstriction) to increase blood pressure - increased cardiac afterload
Indications: in ICU setting severe hypotension/shock due to poor cardiac contractility and/or vasodilation, hypotension during general anesthesia.
Dobutamine is preferred but dopamine can be used if former unavailable.
Describe pimobendan (cardisure)
・ Phosphodiesterase inhibition and calcium sensitization - inotropic and vasodilatory properties (inodilator)
・ Enables cardiac output to be improved without a substantial increase in myocardial work due to the simultaneous reduction in afterload.
Indications:
・ Most dogs, some cats with heart failure (usually administered in addition to ACE-inhibitor and diuretic).
・ Dogs with preclinical heart disease
classification of Antiarrhythmic therapies
Vaughan Williams system: 4 classes I-IV
But this isn’t ideal because Some antiarrhythmic drugs have multiple classes of action (sotalol).
Also, Some drugs with important antiarrhythmic actions are not included in the classification at all (digoxin, anticholinergic agents, sympathomimetic agents).
Class I Antiarrhythmic drugs
Class I - block Na channels, depress depolarization
Three subclasses.
・ Class Ia - also prolong repolarization (class III action), indications: refractory ventricular
arrhythmias, supraventricular arrhythmias
・ Class Ib - depresses depolarization in abnormal myocardium (little effect on normal tissue), also shortens repolarization, indications: ventricular arrhythmias
・ Class Ic - most potent of class I, minimal effect on repolarization, not used in veterinary medicine
Class II Antiarrhythmic drugs
Class II - antiadrenergic drugs (mainly beta adrenergic receptor blockers)
indications: atrial tachyarrhythmias (AF), supraventricular tachycardia involving the AV node, ventricular arrhythmias
Class III Antiarrhythmic drugs
Class III - prolong repolarization, indications: ventricular arrhythmias, supraventricular
arrhythmias
Class IV Antiarrhythmic drugs
Class IV - Ca channel blockers, indications: atrial tachyarrhythmias (AF), supraventricular
tachycardia involving the AV node
Adverse effects of antiarrhythmic therapy
Ironically, arrhythmias.
・ They affect the electrophysiological properties of normal tissue so they may fix the original arrhythmia but can cause one in another area.
Cardiac systolic and diastolic function
・ Beta adrenergic receptor blockers and Ca channel blockers have negative inotropic effect - relative contraindication with overt CHF/myocardial failure.
Many class I drugs have CNS and GI effects.
Describe Lidocaine as an antiarrhythmic.
Class Ib
・ First-choice agent for treatment of ventricular tachyarrhythmias.
・ Hypokalemia - poor response to lidocaine
・ IV boluses, rapid onset of action, antiarrhythmic effects 10–15 minutes, CRI after boluses
Adverse effects:
・ CNS effects (obtundation, anxiety, tremors, seizures), cats particularly prone to
neurotoxicity - much lower dose
・ GI effects (anorexia, nausea, vomiting, diarrhea)
・ Adverse cardiac effects are rarely observed
Describe Mexiletine as an antiarrhythmic.
Class Ib
・ Similar to lidocaine but less rapid hepatic metabolism and longer elimination half life.
Indication: chronic therapy of ventricular tachyarrhythmias in dogs
・ Class Ib agents can be very neurotoxic in cats
・ Can be used in combination with beta adrenergic blocker (atenolol)
Describe Beta adrenergic blockers as an antiarrhythmic.
Class II
・ Action: reduced heart rate and excitability
・ Indications: supraventricular and ventricular tachyarrhythmias
・ Adverse effects: lethargy, collapse, bradycardia, hypotension, precipitation of CHF signs, bronchoconstriction
Most frequently used:
・ Atenolol (beta 1)
・ Metoprolol (beta 1)
・ Carvedilol (beta 1 and 2, alpha 1)
・ Esmolol (beta 1)
Describe Sotalol as an antiarrhythmic.
Beta blockers typically in class II but Sotalol in class III (+ class II action).
Prolong repolarizations + is a beta 1 and 2 blocker.
・ Indication: ventricular and supraventricular tachyarrhythmias
・ Most often used in boxers with arrhythmogenic cardiomyopathy!
・ In dogs with ventricular tachycardia that are refractory to lidocaine and procainamide.
Adverse effects:
・ Negative inotropy (exacerbation/precipitation of CHF - avoid use in poorly controlled CHF/patients at risk of developing CHF)
・ Negative chronotropy (bradycardia, lethargy, collapse)
・ Bronchoconstriction
Drug of choice for treatment of arrhythmogenic cardiomyopathy
(Most often boxers)
atypical beta blocker, Sotalol
Describe Diltiazem as an antiarrhythmic.
・ Class IV - Ca channel blocker
・ Actions: slowing of the sinus rate and AV node conduction, arteriodilator
・ Indication: supraventricular tachyarrhythmias
・ Adverse effects: bradycardia (dogs), vomiting (cats)
Describe Digoxin as an antiarrhythmic.
Digitalis glycoside (cardiotonic)
・ Actions with heart failure: increased myocardial contractility and cardiac output, diuresis, reduction of edema, reduction in heart size, heart rate, blood volume, pulmonary and venous pressures, no change in myocardial oxygen demand.
Indications: dogs with atrial fibrillation + CHF
・ Adverse effects (toxic serum levels, cats more sensitive than dogs): arrhythmias, worsening of heart failure clinical signs, GI signs
・ Monitor serum levels due to narrow therapeutic index!
Antithrombotic drugs for Prevention of ATE.
What is ATE?
Give two group examples of antithrombotics.
arterial thromboembolism (thromboprophylaxis)
Antiplatelet drugs - inhibition of platelet aggregation
Anticoagulant drugs - inhibition of coagulation
Antithrombotic drugs include: (2)
・ Antiplatelet drugs
・ Anticoagulant drugs
Antiplatelet drugs - inhibition of platelet aggregation. 2 examples
・ Aspirin (NSAID)
・ Clopidogrel (thienopyridine derivative)
Anticoagulant drugs, give 2 examples.
・ Warfarin (coumarin derivative) - not recommended in cats
・ Heparin
Sedative/analgetic agents may be used in heart failure cases in order to
decreases stress which will worsen the cardiac condition.
e.g. dyspnea
Sedative/analgetic agents used in cardiac cases (2)
Butorphanol
・ Opioid agonist/antagonist
・ To decrease stress (acute CHF)
Mu agonist (fentanyl)
・ Severe pain (FATE) (feline aortic thromboembolism) aka saddle thrombus
saddle thrombus alt. name
feline aortic thromboembolism (FATE)
relatively common in cats with heart disease: about one-sixth of cats with heart disease are affected.
Heart disease is the most common underlying cause of arterial thromboembolism. It leads to the formation of blood clots in the heart, which leave it with the bloodstream and obstruct larger blood vessels, in cats mainly the aorta at the outlet of the two external iliac arteries.
Drugs groups used in CPR - cardiopulmonary resus. (3)
Reversals
Vasopressors - maintain perfusion to vital organs
Anticholinergics (atropine)
Name 3 types of Reversals
・ Opioids - naloxone
・ Benzodiazepines - flumazenil
・ Alpha 2 agonists - atipamezole/yohimbine
What reverses opioids?
naloxone
What reverses Benzodiazepines?
flumazenil
Vasopressors - maintain perfusion to vital organs.
Explain their use.
・ Pulseless electrical activity, asystole
・ Should be administered every other cycle (every 4 minutes)
・ May be administered via endotracheal tube in venous access impossible due to collapse.
E.g. Epinephrine, Vasopressin
Describe Vasopressor Epinephrine
・ Catecholamine
・ Causes peripheral vasoconstriction by stimulating alpha1 receptors
Describe Vasopressor vasopressin
・ Vasoconstrictive effects via activation of peripheral V1 receptors
・ May be used instead of or in addition to epinephrine
Describe Anticholinergics in CPR (atropine)
・ No evidence of a harmful effect at the recommended dosage but also show no consistent benefit either.
・ Non-shockable arrest rhythms
・ Administered every other CPR cycle (1 cycle = 2 min)
・ Patients with documented bradycardic arrest/diseases predisposing to high vagal tone (gastrointestinal, respiratory, ophthalmic disease)
・ May be administered via endotracheal tube in venous access not gained.
Orthopnea is shortness of breath when lying down that’s relieved by standing or sitting up.
Acute treatment:
O2 therapy
furosemide - loop diuretic
a touch of butorphanol to calm them during presenting dyspnea
nitro, venodilator adjunctive treatment of acute heart failure
Chronic treatment:
furosemide PO
start on pimobendan maintenance
enalapril ACE-inhibitor home
define orthopnea
Orthopnea is shortness of breath when lying down that’s relieved by standing or sitting up.
Euthanasia is often best choice due to very poor prognosis for full recovery and complications of related CHF.
Thrombus removal not possible -> massive risk of reperfusion injury
But in case treat:
fentanyl
(ace sedation if not hypothermic)
warming
antithrombotics: aspirin or clopidogrel
technically heparin for next thrombus prevention
monitor for hyperkalemia because necrotizing muscles can cause this.
vasodilators for easing?
venodilators for easing?
(which cardiac parameter)
vasodilators for afterload
venodilators for preload
lusitropic effects mean?
myocardial relaxation
