Cardiovascular 2 Flashcards
Arteriodilators
- types of drugs
- Calcium channel blockers (CCB)
- Amlodipine
- Hydralazine
Mixed Vasodilators
- types of drugs
- ACEi’s > Benazapril
- Angiotensin Receptor Blockers > Telmisartan, Nitroprusside, Sildenafil
Calcium channel blockers (CCB) - effects
- Have several effects; vascular smooth muscle (VSM) vs myocytes
> arteriodilator
> negative inotrope
> antiarrhythmic
Amlodipine
- what is it, what does it do?
- uses
- CCB preferentially in VSM…….primarily an arteriodilator
> Reduces afterload
> increase SV and decrease in MVO2
<><><><> - Used in to treat severe mitral regurgitation in dogs with chronic valvular disease (CVD)
<><><><> - Also used to treat hypertension
> Primarily renal secondary hypertension in cats; also hyperthyroidism and diabetes mellitus
Amlodipine toxicity
- Slight negative inotropic effects
- Compared to hydralazine:
> Less reflex tachycardia
> Less clinically significant hypotension
Hydralazine
- effects, uses
- Directly relaxes VSM……PGI2 mediated ???
pharmaforte.com.sg - Used in severe regurgitation; mitral or aortic insufficiency, VSD
> Reserved for heart failure refractory to other dilators eg. ACEi’s or when sodium nitroprusside is impractical
<><><><> - Potent arteriodilator
> Reflex tachycardia possible
> Hypotension a concern in heart failure patients
> Titrate dose to effect; reduces risk of tachycardia and hypotension
Benazapril
- type of drug
- uses
ACEi’s (angiotensin converting enzyme inhibitor’s)
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- Benazapril is a prodrug; converted to the active metabolite benazaprilat by the liver
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- Used in dogs and cats for heart failure
> Agents only licensed for use in dogs for heart failure (DCM or MR)
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- Benazapril also licensed for use in cats for kidney disease with proteinuria; heart failure use in cats is extra-label
ACEi’s (eg. Benazapril)
- general use?
- mechanism
- effects
- adverse effects
ACEi’s used as first line therapy in heart failure
- Block conversion of ATI to ATII by ACE
- Weak balanced vasodilation
> decrease afterload and preload
<><>
Neuromodulatory effects are most important
> blunts R-A-A-S and SNS activity and their detrimental effects
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ACEi’s can promote hypotension
> Renal hypoperfusion can promote azotemia
> Hypotension greatest when other agents
are used concurrently eg diuretics and other vasodilators
Telmisartan
- Approved in cats for proteinuria associated with chronic renal insufficiency in cats
- Blocks the AT-1 receptor that normally binds AT-II
> Blocks peripheral vasoconstriction
> Blocks release of adrenal catecholamines and aldosterone
> Blocks cellular hypertrophy and hyperplasia; remodelling
<><><><> - May be useful in CHF and hypertension in dogs and cats
> Limited veterinary data
Nitroprusside
- use
- mechanism
Use is limited for short term CRI in fulminant heart failure
> Half-life is very short; minutes
<><><><>
Vasodilation is the result of NO release from nitroprusside once
inside the VSM cell
> Tolerance to nitroprusside does not occur
Nitroprusside
- toxocity, considerations
- Hypotension is possible warranting titrating doses upwards to effect while monitoring blood pressure
> Concurrent use of positive inotropes is helpful - Cyanogen and thiocyanate build up and toxicity possible with prolonged treatment and/or renal compromise
Sildenafil
- mechanism
- uses
- Vasodilation (arteries and veins) is the result of inhibition of phosphodiesterase V enzymes that breakdown cGMP primarily in the pulmonary vasculature
> cGMP increases NO mediated vasodilation
<><><><> - Is used to treat pulmonary hypertension of varying causes in the dog and foals
<><><><> - Available in tablets, oral powder and injectable
Sildenafil toxocity
q Hypotension is possible
q GI upset reported in humans as well as
cutaneous flushing in the inguinal area
Negative Inotropes/Chronotropes
- what they do?
- use?
- These agents decrease inotropy, decrease chronotropy but increase lusitropy (improve myocyte rate of relaxation)
<><> - This group of drugs is used primarily to treat conditions with ventricular hypertrophy
> Hypertrophic cardiomyopathy
> Aortic, subaortic or pulmonic stenosis
<><> - Also used as antiarrhythmics
Negative Inotropes/Chronotropes
- drugs in this class
- Calcium channel blockers
> Diltiazem
<><> - β-adrenergic blockers
> Atenolol, Propranolol, carvedilol
Diltiazem
- use
- Preferential myocyte CCB
- Main use is feline HCM
> Directly improves myocardial relaxation
> Reduces contractility
> May reduce heart rate
Diltiazem overdose issues
Overdose: bradycardia, vasodilation > syncope and collapse
β-adrenergic blockers
- how they work?
- concerns?
- drugs and what they do
Beta blockers indirectly enhance relaxation of myocytes by reducing heart rate
- Limited experience with these agents in veterinary CHF
- Concern with decompensated HF due to worsening of signs
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- Atenolol; selective β-1 adrenergic blocker
- Propranolol; nonselective β-blocker is also used
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- Carvedilol; nonselective β-blocker with some ⍺1 antagonism
> Lower HR and reduce TPR that can reduce cardiac workload
> Same concerns as beta blockers
Spironolactone
- what is this and what does it do?
- Aldosterone receptor antagonist-potassium sparing diuretic
- Weak diuretic action
- Aldosterone blockade may slow progression of heart failure
> Myocardial fibrosis and remodeling
> Vascular fibrosis
> Limited studies in veterinary medicine
Drugs Used in Feline Thromboembolism
- Antithrombotics > aspirin, clopidogrel
- Anticoagulants > Heparin, Enoxaparin, Warfarin, Rivaroxaban
- heparin and enoxaprin > what are they, what do they do?
Anticoagulants for feline thromboembolism
- Acute injectable anticoagulants preventing new thrombus formation by enhancing antithrombin III activity
> Heparin inactivates both thrombin (factor II) and factor Xa
> Enoxaparin inactivates factor Xa, but not thrombin
Warfarin - what is it, what does it do?
Oral maintenance anticoagulant that antagonizes vitamin K actions on clotting factors II, VII, IX and X; used as chronic preventative therapy……….. Less use in veterinary medicine now
Rivaroxaban - what is it, what does it do?
Anticoagulant
q Inactivates factor Xa directly
q Being used more in veterinary medicine
q Given orally
q Use primarily in dogs thus far
