Cardiovascular + diuretics Flashcards
What is the effect of vasopressors on a hypovolemic patient
- Venoconstricton -> decreased venous return due to increased resistance to venous flow (and no volume to “push forward”)
- Arterioconstriction -> increased afterload
=> decreased CO and tissue perfusion despite improved BP
Catecholamine table :)
See picture
What is the effect of vasopressors causing venoconstriction on cardiac output
Depends on the balance between venous capacitance and venous resistance -> will increase venous return by decreasing venous capacitance but will decrease venous return by increasing venous resistance. Will improve CO in volume-loaded patients vs hypovolemic patients.
What are the actions of dopamine? At what doses?
- Direct alpha- and beta-agonist
- Precursor of norepinephrine -> other way to stimulate alpha- and beta-adrenergic receptors
- Stimulation of D1 receptors (post-synaptic) -> vasodilation
- Stimulation of D2 receptors (pre-synaptic) -> inhibition of norepinephrine release
- Low dose (1-4 mcg/kg/min) -> mostly vasodilatory dopaminergic effects
- Medium dose (5-10 mcg/kg/min) -> beta effects predominating
- High dose (> 10 mcg/kg/min) ->alpha effects predominating
(But overall causes a modest vasoconstriction and increase in BP with little increase in CO)
What is a potential adverse effect of dobutamine in cats
Seizures -> use lower range of doses (5-10 mc/kg/min)
What is the mechanism of action of ephedrine
- Increases release of norepinephrine from sympathetic nerve endings
- Has some direct beta-agonist effects
What is the risk with repeated / prolonged use of ephedrine
Exhaustion of stores of endogenous norepinephrine -> decreased efficiency
What catecholamine has the longest duration of action and can be used as a “push-dose” (= bolus)
Phenylephrine
List and explain 3 metabolic / electrolytic effects of catecholamines
- Hyperglycemia
- Alpha effects -> decreased insulin production, increased glycogenolysis
- Beta effects -> increased glucagon and cortisol synthesis + stimulation of lipolysis - Hypokalemia
- Stimulation of Na/K ATPase -> K entry into cells - Hyperlactatemia
- Increased glycolysis
+/- Mitochondrial dysfunction
What is the effect of catecholamines on the immune system
Mostly immunosuppressive effect
What is the mechanism of action of vasopressin on vascular smooth muscle
- Stimulation of Gq receptors -> activation of phospholipase C -> IP3 pathway -> increased intracellular iCa -> contraction
- Inhibition of K-ATPase in vascular smooth muscle cells -> prevents hyperpolarization and allows depolarization
List all the receptors of vasopressin and their locations
- V1: vascular smooth muscle (-> contraction) + platelets (->activation via calcium entry)
- V2: basolateral membrane of distal tubule cells and in principal cells (-> AQP2 synthesis and expression + urea transporter expression) + vascular endothelium (-> release of vWF and fVIII) + bone marrow (-> release of platelets)
- V3: anterior pituitary (-> release of ACTH) + CNS (memory, BP, temperature, sleep)
- Oxytocin receptor (-> uterine contraction + mammary contraction + vasodilation of umbilical vein, aorta, pulmonary artery)
- P2 class of purinoreceptors (-> NO-mediated and prostacyclin-mediated vasodilation + positive inotropy)
Name 2 selective V1 receptor agonists and 1 selective V2 receptor agonist
V1: Terlipressin, selepressin
V2: Desmopressin
What are the different indications of vasopressin therapy and associated doses
See picture
Name 3 effects of ACE inhibitors contributing to their anti-hypertensive effect
- Vasodilation due to decreased angiotensin II (venodilation and arteriodilation)
- Decreased aldosterone -> less retention of Na and water
- Decreased metabolism of bradykinin -> further vasodilation
- Decrease proteinuria (ATII promotes glomerular protein loss through preferential efferent constriction)
Why is amlodipine not recommended as a sole agent for management of hypertension due to glomerular disease
Amlodipine causes vasodilation of afferent arteriole preferentially -> increased glomerular pressure and GFR -> risk of worsening glomerulopathy
Name 2 non-selective beta-blockers and 2 selective beta-blockers
Non-selective:
- Propranolol
- Timolol
(- Sotalol)
Selective (b1):
- Esmolol
- Atenolol
Mechanism of action of hydralazine
Alteration of smooth muscle intracellular calcium metabolism -> decreased vascular resistance
Mechanism of action of sodium nitroprusside
Releases NO -> NO activates guanylyl cyclase in endothelial cells -> increased cGMP -> decreases intracellular iCa -> relaxation
What vessels (arterioles vs veins) are dilated by nitroprusside / nitroglycerin / hydralazine
- Nitroprusside: both arteries and veins
- Nitroglycerin: both but mostly veins
- Hydralazine: almost exclusively arteries
True or false: Sodium nitroprusside and nitroglycerin can cause cyanide toxicity
False.
Nitroprusside only.
What potentially anti-hypertensive drug category should never be used as a sole agent in dogs with pheochromocytoma
Beta-blockers (will lead to worse hypertension due to un-opposed vasoconstriction from alpha effect)
Mechanism of action of fenoldopam
Selective agonist of dopamine-1 receptor -> peripheral and renal vasodilation (due to Gs receptor effect: increase in cAMP -> myosin light chain phosphatase ->vasodilation)
+ increased GFR
+ decreased Na reabsorption
Name one mixed alpha- and beta-antagonist
Labetalol
(-> decreases BP due to decreases vascular resistance and prevents reflex tachycardia)
Mechanism of action of pimobendan
- Calcium sensitizer:
Increases the affinity of the regulatory site on troponin C for calcium -> increased calcium binding -> increased interaction between actin and myosin -> increased cardiomyocyte contraction -> positive inotropy + lusitropy - Phosphodiesterase III inhibitor -> increased cAMP and cGMP
cAMP -> activation of protein kinase in cardiomyocytes leading to increased calcium influx during systole and increased calcium sequestration during diastole -> positive inotropy
cAMP and cGMP -> increased calcium uptake in vascular smooth muscle -> decreased intracellular calcium -> relaxation
(+ cAMP activates MLCP -> relaxation)
Suppresses production of NO –> increase cardiac contractility
What is the benefit of pimobendan vs. catecholamines to increase cardiac contractility
Pimobendan does not increase myocardial oxygen consumption and does not cause arrhythmias.
What are the overall effects of pimobendan
- Positive inotropy
- Positive lusitropy
- Arterial and venous vasodilation
+/- platelet inhibitor (nothing proven at clinical doses)
What is the metabolism / elimination of pimobendan
- Metabolized to an active metabolite in the liver
- Eliminated mostly in the feces (minimal renal excretion)
Indicate on which phases of the action potential the different classes of anti-arrhythmics work
- Class IA -> inhibit phase 0 + prolong phase 3
- Class IB -> inhibit phase 0 + shorten phase 3
- Class II -> inhibit phase 2 + inhibit phase 4 in nodes
- Class III -> inhibit phase 3
- Class IV -> mostly inhibit phase 0 in nodes
What is the effect on the duration of action potential of anti-arrhytmics of class IA, IB, II, III, IV
IA: prolongs
IB: shortens
II: no change
III: prolongs
IV: no change
What is a proposed anti-arrhythmic mechanism of MgSO4
Blocks Na, Ca, and K channels
Cofactor of Na/K ATPase
What are the 2 currents inhibited by beta-blockers responsible for their anti-arrhythmic properties
- Funny Na current (If)
- L-Ca current
What is the only diuretic that does not reach its site of action through the urinary space
Spironolactone
Why is the efficiency of most diuretics decreased in case of severe proteinuria
Most diuretics except mannitol are highly protein-bound -> hypoproteinemia leads to lower plasma concentration of diuretic + the small portion that does get secreted in the urine binds proteins in the urine and get neutralized
Name a few effects of mannitol that are theoretically beneficial for the kidneys
- Prostaglandin-mediated renal vasodilation
- Decreased renal vascular congestion
- Decreased hypoxic cellular edema
- Protection of mitochondria and decreased oxidative damage
Name the 6 classes of diuretics, their site of action, and their effect on electrolytes and minerals
See table
What is the mechanism of action of acetazolamide and its indiction
Carbonic anhydrase inhibitor (cytosolic and membrane) in the proximal tubule -> inhibits reabsorption of HCO3- and Na+ in proximal tubule
Limited effect because HCO3- quickly gets less filtered and Na gets reabsorbed more distally
Indicated in management of glaucoma because decreases production of aqueous humor
Name 2 mechanisms of resistance to furosemide
- Increased Na reabsorption in distal tubule and collecting duct
- Short half life of furosemide -> rebound Na reabsorption between doses
What are the mechanisms of diuresis induced by furosemide
- Inhibition of Na-K-2Cl transporter ->decreased reabsorption of Na and Cl ->decreased reabsorption of water
- Inhibition of Na-K-2Cl transporter -> decreased osmolarity of interstitium -> loss of cortico-medullary gradient
- Inhibition of Cl flux to macula densa -> decreased tubuloglomerular feedback
Mechanism of action and indications of thiazide diuretics
- Inhibition of Na-Cl transporter in distal tubule
- Indicated for prevention of urolithiasis (decrease calciuresis) + can have a paradoxical anti-diuretic effect in diabetes insipidus (by decreasing circulating volume)
Name 3 potassium-sparing diuretics
- Spironolactone
- Amiloride
- Triamterene
Name a new class of aquaretic diuretics
Vaptans = V2 receptor inhibitors
Name indications of diuretic therapy and their associated diuretics
See table
List 2 adverse effects of ACE inhibitors
- Worsening GFR and renal function through dilation of efferent arteriole in dehydrated patients (or if diuretics on board)
- Hyperkalemia (inhibition of aldosterone) - unlikely clinically relevant
What is the mechanism of action of spironolactone?
Selective aldosterone antagonist, blocks its effects in distal convoluted tubule and collecting duct
May block detrimental effects of aldosterone on the vasculature and cardiac remodeling
What is the mechanism of action of amlodipine?
Calcium channel blocker –> decreases calcium flux into vascular smooth muscle cells –> vasorelaxation and reduces SVR
Name 2 selective alpha-1 receptor antagonists
Prazosin
Phenoxybenzamine
What is the mechanism of action of atenolol?
Selective beta-1 antagonist –> decreases HR an contractility + decreases renin release and PVR
List 5 categories of oral antihypertensives
- ACE inhibitors
- Angiotensin receptor blockers
- Aldosterone antagonists
- CCB
- Alpha-1 blockers
- Beta-1 blockers
- Arteriol vasodilators
If injectable antihypertensives are not available, what medications can be considered to address a hypertensive crisis?
Oral hydralazine or amlodipine as they have rapid onset of action
What physiological conditions enhance lidocaine’s mechanism of action?
- Acidosis
- Hyperkalemia
List 3 contraindications of using beta-blockers
- Evidence of sinus node dysfunction
- AVN conduction disturbances
- CHF
- Pulmonary disease
What is the mechanism of action of stall and how does it vary with dose?
Beta-blocker + sinus and AVN depression at lower doses
Inhibition of depolarization (I kr)
Why is sotalol’s negative inotropic effect less than expected?
Prolongs action potential duration –> can result in enhanced Ca entry during action potential plateau
What are adverse effects of amiodarone?
- Vomiting
- Anorexia
- Hepatopathies
- Thrombocytopenia
- Effects of vasoactivee solvent of IV formulation –> hypotension, anaphylaxis, bradycardia, acute hepatic necrosis, death
Why is lidocaine not effective in SVT?
Atrial myocytes lack plateau phase –> fewer inactivated Na channels blocked by lidocaine (which works by inhibiting Na channels)
With which drug should digoxine be combined in order to adequately slow the ventricular rate?
Diltiazem
