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)
