Cardiovascular Pharmacology, Pt. 2 Flashcards
What mineralocorticoid receptor blocker is used to treat cardiac disease? What is its mechanism of action? What are 3 results?
Spironolactone - antagonizes intracytoplasmis aldosterone receptors in the late DCT and CD, which causes a decrease n ENAC and Na/K ATPase metabolism
- increased water excretion
- increased urinary Na+
- decreased K+ excretion (potassium-sparing)
What are the main 2 cardiovascular clinical use of Spironolactone? How is it used in cats?
- dogs with myxomatous mitral valve disease
- adjunctive therapy in dogs with ACVIM B2-D2
extra-label use to decrease aldosterone concentrations in Maine Coons with asymptomatic HCM
What are 2 common vasodilators used to treat cardiovascular disease? What are their mechanisms of action?
- Prazosin: α-antagonist that blocks vascular smooth muscle contraction
- Hydralazine hydrochloride: relaxes arteriolar smooth muscle with litter effect on the venous system
What are the 2 main cardiovascular indications for Prazosin usage?
- renal hypertension
- vesicourethral reflex dyssynergia
What are the 2 primary usages as Hydralazine hydrochloride (Apresoline)? What adverse effects have been associated with its usage?
- afterload reducer for adjunctive treatment of CHF
- antihypertensive agent in dogs and cats
tachycardia and hypotension
What calcium channel blocker is used to treat cardiovascular disease? What is its mechanism of action? What are 4 results?
Amlodipine - suppresses calcium ion influx through PM channels in myocardial cells, vascular smooth muscle, and other excitable cells
- reduction in myocardial contractility
- vasodilation in peripheral arterial beds
- reduced myocardial oxygen demand
- slowed AV impulse conduction
What is Amlodipine the preferred treatment for What adverse effects are associated?
systemic hypertension in cats
negative inotropic effects and vasodilator actions benefit hemodynamics to decrease cardiac workload, which can exacerbate hypotensive crisis (can be managed by altering dosage or dropping other drugs)
What nitrovasodilator is commonly used to treat cardiovascular disease? What is their mechanism of action?
nitroglycerine (nitrogen esters)
act as exogenous sources of nitric oxide (endothelium-derived relaxing factor, endogenous vasodilator) and activate guanylate cyclase, leading to the formation of cyclic guanosine monophosphate (cGMP) from GTP
- inhibits the contraction of vascular smooth muscle by decreasing the availability of calcium and interferes with myosin-actin interaction
What are 2 additional mechanisms of action of nitroglycerin and nitrovasodilators? What is the main indication?
- stimulate the synthesis of vasodilators PGI2 and PGE
- decrease myocardial O2 requirements to decrease the workload of the heart
short-term management of acute heart failure
What is the recommended route of administration of nitrovasodilators?
sublingual, topical, IV —> short half-life, significant first pass effects
Where is it recommended to apply topical nitroglycerin? What oral nitrovasodilators are available?
areas that lack hair, like the groin, axillary area, or ear pinna, or shaved portion of the body —> owners should wear exam gloves and thoroughly wash hands
- Isosorbide dinitrate
- Isosorbide mononitrate: better absorption
What phosphodiesterase type 5 inhibitor is used to treat cardiovascular disease? What is its mechanism of action? What is its main indication?
Sildenafil - prevents the degradation of cGMP, allowing for smooth muscle relaxation in pulmonary vasculature and systemic vessels (enhances nitrovasodilators)
pulmonary hypertension that is often a sequalae of chronic obstructive pulmonary disease, MMVD, and heartworm disease
What other drugs is Sildenafil commonly combined with? What are the 2 results of this combination?
- Furosemide
- Enalapril
- Pimobendan
- Digoxin
- Spironolactone
- Thiazide diuretics
- decreases systolic pulmonary arterial pressure
- increases exercise capacity and quality of life
What β-adrenergic receptor antagonist is used to treat cardiovascular disease? What is its mechanism of action? What are some adverse effects?
Carvedilol (β1 = β2 > α1 > α2) - decreases SNS activity causing reduced myocardial workload and a decreased heart rate and peripheral vascular resistance
- tachycardia and arrhythmias
- vasoconstriction with increased afterload
- RAAS activation
- myocardial remodeling
- fibrosis
What is the main indication for Carvedilol usage? How does the dosage change its effect?
experimental mitral valve regurgitation
- LOWER DOSE = decreased heart rate
- HIGHER DOSE = decreased heart rate, renal function, and arterial blood pressure
- start with a low dose and increase until target dose is reached without adverse effects
What additional therapy is recommended for congestive heart failure? What are the main 2 supplement combinations?
potent loop diuretics - Furosemide, Torsemide, Butemide
- TRIPLE THERAPY = ACEIs and pimobendane
- QUADRUPLE THERAPY = ACEIs, pimobendane, spironolactone
Why should patients on diuretics always be monitored? What further exacerbates this effect?
pronounced diuresis can reduce blood volume and lower preload (ventricular filling pressure), causing tension, increased myocardial oxygen demand, and predisposition for edema + decreased venous return leads to decreased cardiac output, renal perfusion, and drug clearance, and azotemia
inappetence and vomiting —> electrolyte loss
What 4 parameters are monitored in patients on diuretics for congestive heart failure?
- serum electrolytes
- renal values - BUN, creatinine
- body weight
- state of hydration - skin turgor, PCV, TP, albumin, sodium
What is characteristic of heart failure, MMVD, and DCM?
SNS and RAAS activation, elevated preload and afterload, high heart rate
contractility is maintained until the terminal stages
diminished contractility (required inotropic support with dobutamine CRI, digoxin, or pimobendan)
What is an arrhythmia? What can they lead to?
abnormality in the rate, regularity, or site of origin of electric impulses
very slow, rapid, or irregular heart rates of clinical importance is present with cardiac disease
What are 4 possible causes of arrhythmias?
- imbalance of the PSNS and SNS
- changes in serum electrolyte concentrations (K, Ca)
- excessive stretch of cardiac tissue
- mechanical trauma
What are the 4 classes of antiarrhythmic drugs?
I - local anesthetics
II - β-adrenergic blockers
III - potassium channel blockers
IV - calcium channel blockers
What are the 2 goals of treating bradyarrhythmias?
- decrease vagal tone (vagolytics)
- increase sympathetic tones
What are the 3 types of tachyarrhythmias? What drugs are used to treat each?
- sinus tachycardia - Pimobendan, ACEIs
- supraventricular tachyarrhythmias - Digoxin, Diltiazem (IV), Atenolol, Esmolol, Sotalol (II)
- ventricular tachyarrhythmias - Lidocaine (I), Mexiletine (I), Sotalol (II)
What 2 vagolytics are used to treat bradyarrhythmia?
- Atropine
- Propanntheline bromide - antimuscarinic that is variably absorbed in the GIT and can lead to tachycardia, increased salivation, or vomiting
What β-adrenergic agonist is used to treat bradycardia?
Isoproterenol (ISO) - β1 > β2»_space;» α
- increases heart rate by stimulated adrenergic receptors (β1, β2) in the sinus and atrioventricular node
How is Isoproterenol administered? What are 2 common adverse effects?
IV for short-term treatment (CRI)
- hypotension
- arrhythmias
- blood pressure and electrocardiography monitoring
What are 5 causes of sinus tachycardia?
- low blood pressure
- pain
- sepsis
- fever
- low cardiac output
What cardiovascular disease commonly causes sinus tachycardia? What drugs are indicated for treatment?
CHF —> low cardiac output
Pimobendan and ACEIs
What is the most common cause of supraventricular tachyarrhythmias? What kind of treatment is indicated?
primary cardiac disease and secondary atrial enlargement
not likely to resolve with antiarrhythmic drugs - slow down the rapid conduction through AV node with digitalis, calcium channel blockers, or β-adrenergic blockers
What digitalis is used to treat supraventricular tachyarrhythmias? What is its mechanism of action? How should treatment be done with CHF or myocardial dysfunction?
Digoxin - slows conduction of the AV node and slows ventricular response rate (decreased HR is not significant, so it needs class II or IV drugs also)
give digoxin, then atenolol or diltiazem once stablized
What 2 calcium channel blockers are used to treat supraventricular tachyarrhythmias? What effect do they have? What are the adverse effects seen in dogs and cats?
Diltiazem and Verapamil
slows the ventricular response rate
RARE:
- DOGS = bradycardia, AV block
- CATS = GI signs (vomiting, diarrhea)
What are the 3 most common β-adrenergic blockers used to treat supraventricular tachyarrhythmias?
- Atenolol
- Esmolol
- Sotalol
How is Atenolol used to treat supraventricular tachyarrhythmias? What do high doses lead to? What is it commonly used with?
specific β1 blocker that acts as a negative inotrope
bradycardia, exacerbates heart failure or myocardial dysfunction
Digoxin - slows the heart rate of patients with atrial fibrillation or rapid SVTA —> requires 24 hr Holter monitoring
How is Esmolol used to treat supraventricular tachyarrhythmias? What adverse effect is associated?
ultrashort-acting blocker used for IV administration for acute termination of SVTA
sinus bradycardia, decreased myocardial function, abrupt sinus arrest
How is Sotalol used to treat supraventricular tachyarrhythmias? How does it compare to other β-antagonists? What is it commonly combined with?
non-selective β-blocker and potassium channel blocker (II and III)
prolongs cardiac AP and QT intervals by delaying the slow outward K+ current for SVTA and VTA treatment
VERY SAFE AND EFFECTIVE - Mexiletine for refractory arrhythmias
What is the goal of treating ventricular tachyarrhythmias? What drugs are used to do this?
decrease the number of abnormal ventricular complexes
local anesthetics (IB) - Lidocaine, Mexiletine
How is Lidocaine able to treat ventricular tachyarrhythmias? Why is it only administered IV? What side effects are most common?
inhibits the inward sodium current and reduces the rate of AP rise
very high first-pass metabolism in the liver (not effective if administered orally)
neurological - depression, seizures, vomiting
What is the most useful local anesthetic used to treat ventricular tachyarrhythmias? What are the most common adverse effects?
Mexiletine
- neurological: depression, seizures, vomiting
- GI: mild loss of appetite or vomiting*
How does Mexiletine compare to Lidocaine? What is it commonly combined with?
good oral absorption —> can be give as oral capsules
Sotalol
Calcium channel blockers classifiction
- Non-dihydropyridines: verapamil and diltiazem
- Dihydropyridines: amlodipine and nicardapine
