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305 Cards in this Set
- Front
- Back
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What are the structural elements of myofibrils?
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actin- thin filaments
myosin- thick filaments structural proteins (titin) Regulatory proteins (troponins and tropomysin) |
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What is the functional unit of contraction?
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the sarcomere (z-line to z-line)
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Where is the critical store of calcium for muscle contraction?
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within the sarcoplasmic reticulum
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What is cross bridge cycling and what is its significance?
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it is when myosin heads interact with actin and the filaments ratchet and slide to shorten the sarcomere, requires the hydrolosis of ATP and it's how muscles contract
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What are the components of the Actin- troponin complex?
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TnC binds to calcium
TnI inhibits actin unless bound to TnC TnT distributes the TnI effects and Tropomyosin supports the actin |
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What cellular structures are critical to calcium movements?
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L-type calcium ion channels
Calcium release channel: Ryanodine receptor Sarcoplasmic reticulum calcium ATPase (SERCA) Phospholamban (regulates SERCA) PMCA- plasma membrane calcium ATPase Na/Ca pump (two-way exchanger) |
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What is the general process of muscle contraction?
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1. Cell depolarizes
2. Calcium enters the myocite (phase 2) 3. Triggers calcium release from the sarcoplasmic reticulum 4. Increased cystolic calcium leads to TnC binding and release of TnI inhibition 5. Actin and myosin myofilmaents slide 6. Myocyte contracts 7. Calcium both leaves and is re-sequestered in SR 8. The myocyte relaxes |
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What is the efferent transmission of the autonomic control of muscles?
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sympathetic: neural and adrenal
Parasympathetic- neural |
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Rank the cardiac SNS receptors in their effect on the heart:
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B1 >>>B2>>a1
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What type of receptors are on the cardiac parasympathetic nervous system?
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muscarinic receptors
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What are signals for myocardial contraction and relaxation?
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norepinephrine
epinephrine synthetic catecholamines acetylcholine |
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What are second messengers for myocardial contraction and relaxation?
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cyclic AMP
Inositol triphosphate (IP3) Cyclic GMP |
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What are the agonists for the beta 1 receptors within the cardiac muscles?
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norepinephrine and epinephrine
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What is the cascade of signals following stimulation of the beta 1 receptors in the myocardium?
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Receptor is a G-protein coupled receptor that releases adenylate cyclase and cyclic AMP, this opens the calcium channel and stimulates contraction
Also depresses phospholamban activity means less SERCA inhibition by phospholamban so there is increased calcium uptake by SERCA |
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What is the cascade of signals when the alpha receptors are stimulated in the myocardium?
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Norepinephrine agonist
stimulates phospholipase C which releases IP3 which increases the release of calcium from the sarcoplasmic reticulum |
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What is the function of the muscarinic receptors in the myocardium?
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agonist: acetylcholine
G protein- inhibits adenylate cyclase |
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What are the effects of sympathetic stimulation on heart function?
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It all goes up!
increased calcium influx increased strength of contraction increased development of peak ventricular pressure increased rate of pressure development increased rate of ventricular relaxation increased stroke volume increased ejection fraction increased aortic ejection acceleration and peak velocity increased heart rate increased speed of electrical conduction increased cardiac output increased arterial blood pressure |
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What are the effects of parasympathetic (vagal) stimulation on heart function?
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decreased calcium influx into myocytes and specialized cells
decreased strength of contraction decreased rate and magnitude of pressure development decreased ejection fraction, stroke volume, and cardiac output decreased heart rate decreased speed of electrical conduction, delayed conduction across the AV node decreased arterial blood pressure |
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What are physiologic agonists of the alpha, beta, and adrenergic receptors?
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norepinephrine, epinephrine
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What are the physiological agonists for muscarinic and cholinergic receptors?
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acetylcholine
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What are pharmacologic agonists for beta, alpha and adrenergic receptors?
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ephedrine, dopanine, dobutamine
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Isoproterenol is a pharmacologic agonist for which receptors in the myocardium?
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beta 1 and beta 2
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Phenylephrine is a pharmacologic agonist for what receptors in the myocardium?
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alpha 1
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What is the extrinsic autonomic control of the vascualr system?
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baroreceptor reflex is an important control on vascular tone
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What are the extrinsic hormonal control mechanisms of vascular tone?
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epinephrine (alpha and beta effects)
angiotensin II vasopressin (ADH) Natriuretic peptides (ANP, BNP) |
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What are the elements of local control of vascular tone?
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nitric oxide- potent vasodilator system
Endothelin- vasoconstrictor Prostaglandins- vasodilation and vasoconstriction Kinins and Histamine- mostly vasodilators |
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What effects does arteriolar constriction have on surrounding vasculature?
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increased vascular resistance and raises ABP
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What effects does arteriolar dilation have on surrounding vasculature?
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decreases vascular resistance and lowers ABP
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What effects does arterial vasodilation and vasoconstriction have on blood flow?
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vasoconstriction- decreases regional blood flow
vasodilation- increased regional blood flow and supports blood flow dependent organ function (kidneys, lungs, gut, genital tract) |
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what effect does venoconstriction have on blood parameters?
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increases capillary hydrostatic pressure, promotes edema and pools blood volume away from the heart.
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What is the equation to determine resistance in the vasculature?
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= 1/radius to the 4th power
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What effect do parallel vascular circuits have on resistance?
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they reduce total resistance
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What effect do serial vessels have on resistance?
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serial resistance is additive
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What percent of the cardiac output goes to muscles?
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15%
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What percent of cardiac output goes to the GI tract?
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20%
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What percentage of the cardiac output goes toward renal blood flow?
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20%
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What percentage of cardiac output actually stays with the heart?
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3-4%
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In what regions is the cardiac output largely "autoregulated"?
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coronary and cerebral
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What is the importance of regional cardiac output in skeletal muscle and how is it regulated?
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it is important in exercise and distribution
local and extrinsic regulation of blood flow |
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What is the importance of regional cardiac output regulation in the splanchic region and how is it controlled?
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it is important in the effects of exercise and digestion on blood flow
both extrinsic and local control of blood flow |
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What is the main factor creating resistance in arterioles?
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vascular smooth muscle
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What is the main cause of systemic vascular resistance?
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the arterioles maintain vascular tone constantly
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How is reflex vasoconstriction achieved?
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increase in smooth muscle tone and reflex vasodilation by a decrease in smooth muscle tone
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What is the site of the greatest pressure drop in circulation?
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across the arterioles
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What effects do the alpha and beta receptors have on vascular control?
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alpha 1- vasoconstriction (synaptic)
beta 2- vasodilation (extrasynaptic) alpha 2- vasoconstriction (synaptic) |
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What drugs block calcium influx through the calcium ion channel?
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amlodipine and diltiazem
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What modulates calcium ion influx?
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alpha- adrenergic receptors, endothelin (ET), angiotensin II (AT) receptors
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What drugs can be given to reduce vasoconstriction?
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alpha-1 adrenergic blocker, prazosin,
ET receptor blockers (bosentan) Drugs that reduce angiotensin II (enalapril) blod angiotensin II receptors (losartan) |
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What is the role of the ryanodine receptor in vasoconstriction?
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calcium ion influx stimulates the ryanodine receptor to release more calcium from the sarcoplasmic reticulum
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What is the role of MLCK in vasoconstriction?
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it binds the calcium that is carried by calmodulin
when it is activated in phosphorylates myosin light chains so they can interact with actin filaments |
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How is vasodilation mainly accomplished?
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by reducing the smooth muscle tone- either decreasing systolic calcium, or increased calcium re-uptake into the sarcoplasmic reticulum
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What is the role of SERCA in vasodilation?
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Sarco/Endoplasmic Reticulum Calcium ATPase returns some of the cystolic calcium to the sarcoplasmic reticulum
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What is phopholamban?
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it is a membrane protein that inhibits SERCA, but when it is phosphorylated by PKA or c'AMP it removes its inhibition on SERCA (increased calcium reuptake)
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What are the roles of cyclic nucleotides in vasodilation?
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c'AMP and c'GMP are intracellular messengers for the beta 2 receptors and for the muscarinic receptors stimulated by the vagus or ACh. They inhibit myosin light-chain kinase, leading to vasodilation and are degraded by intracellular phsophodiesterases (PDEs)
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what is the role of prostacyclin, natriuretic peptides and nitric oxide in vasodilation?
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ANP is released when the atria are dilated, BNP is released from the ventricle under conditions of icnreased wall stress (stretch)
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What catecholamines have vascular effects?
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norepinephrine- released into the synapse by post-ganglionic sympathetic nerves
alpha-receptor agonist- vasoconstriciton beta-receptor agonist- vasodilation epinephrine- adrenal medulla to blood, mixed agonist dopamine- precursor to NE (alpha and beta receptor agonist) **effects depend on density of available autonomic receptors** |
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What is the ultimate effect of the renin-angiotensin-aldosterone system?
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when activated, it increases arterial blood pressure
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What systems are involved in the renin- angiotensin aldosterone system?
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kidney, adrenal gland and vascular receptors and local tissue systems
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What is renin?
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it is a proteolytic enzyme that acts on the substrate angiotensiongen producing ATI
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What triggers renin release?
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decreased renal blood flow, increased SNS stimulation from the beta receptor, decreased sodium delivery
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How is renin converted to angiotensin II?
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renin-> angiotensinogen -> angiotensin I (ACE) -> Angiotensin II
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What is the action of angiotensin II?
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it is a vosconstrictor that acts on the AT receptor
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What hormone is releasede by activation of Angiotensin II?
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aldosterone
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How does the renin-angiotensin- aldosterone system increase blood pressure?
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by vasoconstriction and sodium and water retention (including plasma volume)
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What is ACE?
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angiotensin converting enzyme (kininase that breaks down arterial and venodilator (vasodilator) bradykinin
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How do ACE inhibitors work?
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they maintain higher levelse of kinins (vasodilators) as well as blocking the formation of angiotensin II
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What are the two mechanisms of release of vasopressin?
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dehydration increases the release of ADH which acts on renal V2 receptors to increase sodium-free water retention lowering serum sodium
OR Low BP, sensed by atrial stretch receptors causes the release AVP which acts as a vasoconstrictor via the V1 receptors found in the blood vessels |
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How does nitric oxide contribute to local vascular control?
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it is an endothelial-generated vasodilator that is highly diffusible.
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How is nitric oxide produced in the vasculature?
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by the action of nitric oxide synthase in vascular endothelium acting on the amino acid L-arginine
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What stimulates production of nitric oxide in the vasculature?
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acetylcholine with increase in cGMP
exercise- shear Drugs (nitroglycerine, Na+ nitroprusside) |
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How does giving L-arginine enhance NO synthesis?
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nitric oxide is made when nitric oxide synthase reacts with L-arginine
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What are the two ways that drugs can act on nitric oxide in the bloodstream?
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by increasing NO (nitroglycerine, Na+ nitroprusside) or preventing the breakdown of its second messenger, cGMP (sildenafil)
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What is endothelin?
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it is a peptide derived from vascular endothelium?
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What two receptors can endothelin bind to?
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ETA and ETB
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What action does endothelin have when it binds to blood vessels?
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vasoconstriction and sodium retention in the kidneys
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What action does endothelin have when it binds to endothelial cells?
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vasodilation
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What effects will excessive endothelin production have?
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in heart failure it can lead to arterial vasoconstriction;
in lung disease it can lead to pulmonary vasoconstriction and pulmonary hypertension |
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How is endothelin similar to angiotensin II?
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both can stimulate an inflammatory response and fibroblast proliferation
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What is thromboxane and what action does it have?
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it is an eicosanoid lipid that is synthesized in platelets from arachidonic acid via COX enzyme
produces vasoconstriction aggregates platelets |
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Why does aspirin help prevent clotting?
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aspirin effects the COX enzyme which decreases the production of thromboxane
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What is prostacyclin and what is its effect on blood?
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it is synthesized in vascular endothelial cells from PGH2 from arachidonic acid via the COX enzyme system and produces vasodilation
it inhibits platelet aggregation |
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What effects does bradykinin have on vasculature?
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it is a vasodilator of vascular smooth muscle (A and V)
constricts non-vascular smooth muscle increases vascular permeability |
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Where is bradykinin produced?
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by veins from the vascular endothelium
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What effects does histamine have on the vasculature?
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it has different effects related to receptors
vascular effects are similar to BK: arterial dilation (via H1 receptor) venoconstriction in some vascular beds (disease) increases vascular permeability |
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Where is histamine made?
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released from mast cellsa nd from basophils
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What is rheology?
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it is the science of flow and deformation of matter- relates to physical properties of blood
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How does a change in the PCV influence viscosity?
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increase in PCV leads to an increase in viscosity
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How does polycytehmia change blood flow?
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it increases blood viscosity and can impair blood flow and oxygen delivery to tissues: thrombosis may also occur
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What can cause excessive arteriolar vasoconstriction?
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alpha-adrenergic activity, angiotensin II, vasopressin, endothelin, impaired vasodilation
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What heart issues can cause vasoconstriction?
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mismatching: decreased LV stroke volume
higher ABP due to increased mitral regurg fraction impaired exercise capacity in HF ( Muscle) systemic vasoconstriction creates elevated venous pressure |
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What drugs are vasodilators?
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nitroglycerine topical- systemic venodilator
Na Nitroprusside (IV)- systemic arterial-venodilator Hydralazine- systemic arterial dilation ACE inhibitors- systemic arterial and venodilators Amlodipine- calcium channel antagonist |
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What is the action of nitroglycerine topical?
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it is a systemic venodilator
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What are the effects of Na nitroprusside?
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systemic arterial-venodilator
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What is the effect of hydralazine?
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systemic arterial dilation
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What is the effect of ACE inhibitors?
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systemic arterial and venodilator
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What is the effect of amlodipine?
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calcium channel antagonist
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What is the mechanism of action of nitrates and nitorprusside?
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nitric oxide mediated vasodilation using the cyclic GMP messenger
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What vasodilators are calcium channel blockers?
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amlodipine (Norvasc) and
Diltiazem (Cardizem) |
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What vasodilators are phosphodiesterase inhibitors
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milrinone and pimobendan, sildenaphil
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What is the mechanism of action of ACE inhibitors and alpha blockers?
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they inhibit endogenous vasoconstrictors
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What is the action of prazosin?
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it is an alpha one blocker and vasodilates
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What is the action of carvedilol?
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it is a beta and alpha one blocker
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What is the action of Losartan?
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it is a AT- 2 receptor blocker
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What effects do ACE inhibitors have on the endocrine system?
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increases blood At
decreases plasma At decreases plasma aldosterone increases renin total and active |
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How do venodilators change hemodynamics?
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they decrease preload
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How do arterial vasodilators change hemodynamics?
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they decrease afterload
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What are the arteriolar hemodynamic effects of vasodilators?
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lower ABP
decrease afterload on the LV increase cardiac output reduce mitral regurg- aortic valve opens sooner, less time for pure MR NEGATIVE: may activate VC systems or cause reflex tachycardia |
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What hemodynamic effects do vasodilators have on the venous system?
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decrease venous and atrial pressures
redistributes pulmonary volume decreased ventricular EDV decreased myocardial oxygen demand decreased tendency toward edema formation Nitrates: also coronary artery vasodilators and may improve relaxation |
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How can you identify an angiotensin converting enzyme inhibitor simply by its name?
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ends in _pril
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How does using an ACE inhibitor benefit chronic CHF patients?
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it inhibits RAAS, reduces myocardial fibrosis and CV tissue remodeling
increased AT2 enhances sympathetic activity which is a risk factor for mortality in CHF |
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Why is there no benefit to using ACE inhibitors in patients with mitral regurgitation?
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RAAS is inactive?
fundamental difference between VHD and DCM in small breed dogs? |
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What combination of drugs would you use for lung edema?
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ACEI and furosemide because it will reduce the pulmonary edema and symptom scores and eventually improve exercise capacity according to one study
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What drugs protect the cardiac system from neurohormonal injury?
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angiotensin converting enzyme inhibitors
beta blockers spironolactone omega 3 fatty acids |
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What is the benefit of ace inhibitors for pulmonary edema?
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nitroglycerine or sodium nitroprusside- venodilation reduces preload and decreases venous pressures- given along with diuretics
hydralazine and NP- arterial dilators: when needed to reduce MR fraction |
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Why is ACEI preferred for chronic CHF?
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it's the only vasodilators that prolong life in CHF
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What drugs are used to control systemic hypertension?
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amlodipine, or ACEI or sodium NP
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What are the target organs in hypertension?
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brain, eyes, left ventricle (hypertrophy increases work), kidneys, small arteries
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What are the adverse effects of vasodilators?
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systemic hypotension
reflex sinus tachycardia RAAS activation hyperkalemia acute renal failure |
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What is the mechanism by which vasodilators cause systemic hypotension?
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arterial vasodilation or decreased preload and decreased cardiac output
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What is the mechanism by which vasodilators create reflex sinus tachycardia?
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usually hydralazine
hypotension--> baroreceptors increase SNS |
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What is the mechanism by which vasodilators cause RAAS activation?
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NOT with ACEIs
it is a response to systemic hypotension |
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What is the mechanism by which vasodilators create hyperkalemia?
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with ACEI
they decrease aldosterone production |
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By what mechanism do vasodilator drugs cause acute renal failure?
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usually ACI and diuretics
Hypotension and dilation of the efferent arteriole decreased GFR |
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What should you monitor for a patient on vasodilator therapy?
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clinical signs
ABP monitoring Renal function Electrolytes (ACEI) |
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What are the two main factors that influence blood pressure?
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cardiac output (volume of blood into the aorta in one minute's time)
vascular resistance (arteriolar tone) |
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What factors affect vascular resistance?
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SNS efferent tone to arterioles; autonomic tone controlled by baroreceptor reflex
-angiotensin II (+) -arginine vasopressin (+) -endothelin (+) -nitric oxide (-) -natruiuretic peptides (-) -prostaglandins (+/-) |
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What are the components of arterial blood pressure?
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systolic pressure
diastolic pressure mean pressure pulse pressure |
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What are the short-term determinants of BP?
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Systolic blood pressure:
- ventricular stroke volume - aortic compliance Diastolic blood pressure: - systemic vascular resistance - aortic recoil Heart Rate Baroreceptor reflex |
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What factors affect blood pressure?
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Baroreceptors
Circulating catecholamines RAAS system Vasopressin (AVP) Local vascular factors Stress relaxation of arterioles Renal regulation of Na+ and plasma volume Central (CNS) factors |
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How does renal regulation of sodium and plasma volume affect blood pressure?
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sodium in vessels affects vascular resistance
increased sodium increases preload and cardiac output |
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How does stress affect blood pressure physiologically?
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it causes relaxation of arterioles, releases CNS factors, and releases epinephrine in the blood
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What is the normal baroreceptor reflex?
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negative feedback loop:
increased ABP stimulates the reflex to vasodilate |
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Where are the receptors for the baroreceptor reflex?
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high-pressure arterial stretch receptors:
-Aortic sinus, carotid sinus, ventricular c-fibers - Low pressure receptors: atrial and pulmonary V |
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What is the classic baroreceptor reflex arc?
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increased blood pressure ->
increased afferent impulses to CNS --> central NS integration of reflex--> increased vagal efferent traffic to CVS (increased Ach) --> decreased SNS efferent traffic to CVS (decreased NE) |
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What are the consequences of stimulation of the baroreceptor?
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slower HR, reduced contractility, and reduced systemic vascular resistance via vasodilation
Blood pressure is REDUCED |
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What are the cardiac consequences of the baroreceptor reflex?
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sinus node is depressed
heart rate slows contractility and stroke volume decrease cardiac output decreases |
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What are the vascular consequences of the baroreceptor reflex?
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arterioles dilate
vascular resistance decreases venous tone and decreased vascular resistance |
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What causes contractility failure in the heart?
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decrease in myocardial intropy
also called systolic dysfunction or LV dysfunction |
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What causes diastolic dysfunction?
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impaired LV or RV filling
Ventricular filling requires > normal EDP |
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What causes ventricular overload?
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increased ventricular workload
- pressure overload - volume overload |
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What causes cardiac arrhythmia?
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electrical disturbances:
Abnormality of heart rate, rhythm or conduction |
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What is the shortening fraction?
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the diastolic dimension minus the systolic dimension over the diastolic dimension
estimates ejection fraction normal ejection fraction >50% |
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What are the effects of a positive inotropic stimulus?
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larger VTI
faster acceleration smaller PEP/ET |
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How does dilated cardiomyopathy change the frank-starling relationship?
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systolic myocardial failure: FS relationship depressed down and to the right
LV failure: for any given preload the stroke volume is depressed |
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How will the m-mode echo change with dilated cardiomyopathy?
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LV hypokinesis
ventricular dyssyncrhonization |
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What effect does LV systolic failure have on aortic ejection velocity profile?
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ejection time shortens
pre-ejection period prolongs peak acceleration decreases area under curve (VTI) decreases |
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What is the prototype for diastolic heart failure?
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concentric LV hypertrophy due to hypertrophic cardiomyopathy
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What factors affect ventricular filling?
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venous pressure: plasma volume, venomotor tone
Active myocyte relaxation myocardial stiffness heart rate atrial contraction ventricular chamber compliance end diastolic pressure diastolic ventricular pressures |
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How does heart rate affect ventricular filling?
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it can abbreviate diastole if it is increased
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How does lusitropy change with age?
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it decreases- less active myocyte relaxation
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What does the diastolic pressure to volume relationship tell you about heart function?
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it tells you about overall diastolic function of the ventricle- filling of the ventricle leads to wall tension that is similar to the passive tension of stretching muscle strips
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What is the difference between compliance and distensibility?
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they are reciprocals- change in volume over change in pressure= compliance
change in pressure over change in volume = distensibility |
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What is the significance of teh slope of the tangent on the volume/pressure curve?
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indicates the overal compliance or distensibility of the ventricle: steep is a stiffer ventricle
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Why will a positive inotrope not help with concentric hypertrophy?
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the contraction of the heart is fine, need to give a beta-blocker to slow the heart rate
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What are the consequences of mild dystolic dysfunction?
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impaired relaxation
reduced rapid filling prominent atrial filling |
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What are the consequences of severe diastolic dysfunction?
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decreased compliance
steep P/V relationship |
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What will left ventricular dysfunction change on the pulse-wave doppler?
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E/A reversal- delayed early filling with accentuated atrial contribution to filling (shifted to later in diastole)
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What will restrictive ventricular filling change on pulse wave doppler?
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very high and brief early pattern
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What are normal left ventricular pressures?
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120 to <12
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What are normal aortic pressures?
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120 to 80
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What are normal left atrial pressures?
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12 to 0
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What are normal right ventricular pressures?
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25 to 5
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What are normal pulmonary artery pressures?
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25 to 12
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What are normal right atrial pressures?
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5 to 0
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What happens to blood flow if a hole develops between the aorta and pulmonary artery?
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it shunts blood from the left to the right, you will hear a murmur throughout
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What happens if a hole develops between the left and right ventricle?
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not enough pressure can be developed to drive the velocity of blood out of the heart
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What happens if the mitral valve leaks during systole?
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it will reduce pressure
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What happens if the systemic blood pressure is high?
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the left ventricular pressure will be high
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What happens if a narrowed pulmonic valve obstructs flow?
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increased pressure in ventricle to get RBCs across the pressure gradient
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What is ventricular pressure overload and what causes it?
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the ventricle must eject blood at a higher than normal systolic pressure
- high aterial blood pressure - stenosis (narrowing) of the outflow tract |
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What is ventricular volume overload and what causes it?
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the ventricle must eject a >normal total stroke volume with each contraction
- related to a shunt - caused by a regurgitant cardiac valve |
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What is the essential pathophysiology of elevated arterial pressure due to ventricular pressure overload?
|
increase ventricular systolic pressure must be generated to overcome hypertension
-elevated arterial pressure -systemic hypertension -pulmonary hypertension |
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What is the essential pathophysiology of outflow tract stenosis due to ventricular pressure overload?
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systolic pressure gradient across the obstruction changes
- high velocity of ejection across the obstruction - post obstruction disturbed flow |
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What is the essential pathophysiology of ventricular volume overload due to shunting?
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increased flow to the lower resistance (pressure) side of the heart/ circulation leads to L->R shunting of blood and increased pulmonary blood flow
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What is the essential pathophysiology of ventricular volume overload due to valvular regurgitation?
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regurgitation across and incompetent valve sends blood in the wrong direction into the lower pressure (receiving chamber), increased blood volume is found in the ventricle during diastole overloading that chamber
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What are the characteristics of heart failure?
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- cardiac lesions
- limited exercise capacity - neurohormonal activation - release of proinflammatory cytokines - release of proinflammatory cytokines - renal sodium (and water) tension - abnormal hemodynamics - fluid accumulation- congestive HF - related clinical signs in the patient |
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What is the progression of development of heart failure?
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cardiac lesion initiates HF, limited cardiac output initially only with exercise
neurohormonal activation in response to baroreceptors peripheral vasoconstriction altered regional circulations renal retention of Na with fluid retention increased venous pressure leads to edema and effusions |
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What are the clinical signs of heart failure?
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low cardiac output and reduced tissue perfusion
pulmonary venous congestion (edema) systemic venous congestion |
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What are patient problems with chronic heart failure?
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exercise intolerance
fluid retention pulmonary dysfunction: - tachypnea/dyspnea - coughing metabolic disturbances- Azotemia Cardiac cachexia Syncope Decreased quality and duration of life |
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What are the compensatory mechanisms in heart failure?
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1. sympathetic nervous system activation
2. arteriolar vasoconstriction 3. renal retention of sodium and water 4. cardiac remodeling with dilation, myocardial hypertrophy, changes in the intercellular matrix |
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What is the shift of homeostatic mechanisms in heart failure?
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vasoconstricting
sodium retaining systems growth promoting control systems |
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What is the affect of increased neuronal activity in CHF?
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increased contractility, HR, VC and MVO2
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What is the affect of increased renin release during CHF?
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increased activation of the RAAS
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What is the affect of myocardial cell injury due to sympathetic activation in heart failure?
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(increased NE kills cardiomyocytes)
hypertrophy and fibrosis |
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How does sympathetic activation in heart failure cause altered electrical activity and what are the supportive effects?
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increased serum calcium levels and oscillations
causes arrhythmias |
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What is the affect of increased AV node conduction during CHF?
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it increases the ventricular rate during atrial fibrillation
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What is the effect of the downregulation of cardiac B-receptors during heart failure?
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impaired responsiveness to SNS activity (inotropic)
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What is the effect of increased plasma norepinephrine concentration during heart failure?
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it correlates to prognosis- the higher it is, the faster they die
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Why do beta blockers increase survival in heart failure patients?
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they can prevent some of the effects of increased norepinephrine concentration
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Why is systemic blood pressure often normal in patients with heart failure?
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the vasoconstiction maintains blood pressure in the setting of low cardiac output by increasing vascular resistance
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What are the mechanisms for vasoconstriction in heart failure?
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sympathetic activity (NE)
angiotensin II activity arginine vasopressin increased endothelin activity release of vasopressin in CHF release of vasopressin in CHF impaired or overwhelmed endothelial vasodilator activity |
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How is GFR maintained when renal blood flow is reduced in heart failure?
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angiotensin II mediates vasoconstriction of the EFFERENT renal arteriole to maintain filtration pressure
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What chemical messengers released during heart failure are cardiotoxic and what are their effects?
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norepinephrine, angiotensin II and aldosterone
increase myocardial fibrosis, apoptosis, cell death and intercellular remodeling |
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How can you prolong survival and reduce clinical signs of chronic vasoconstriction in heart failure?
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use RAAS inhibitors to vasodilate
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Why are venous pressures elevated in relation to the renal retention of sodium and water during heart failure (esp r-sided)?
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atrial pressures are elevated due to a diseased pump or valvular disease
plasma volume expands due to sodium retention in the kidney |
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How does renal retention of sodium and water affect the hemic system in chronic heart failure?
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it causes changes in renal blood flow and renal function including increased filtration fraction
Aldosterone is released and Anti-diuretic hormone (AVP) causes free water retention |
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What is cardiac remodeling and when does it occur?
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the morphologic changes that develop in the heart as a consequence of a cardiac lesion and the neurohormonal responses to heart failure
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What are the effects of ventricular remodeling during heart failure?
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dilation of the ventricle or atrium
hypertrophy but less blood supply loss of cardiomyocytes- necrosis and apoptosis intercellular changes in the matrix, including intercellular or replacement fibrosis |
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What can cause myocardial hypertrophy?
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it can be a primary lesion (hypertrophic CM), or a response to increased cardiac work
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What type of myocardial hypertrophy will occur with increased pressure work?
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(systemic hypertension or pulmonic valve stenosis)
marked concentric hypertrophy- thickened ventricular walls with normal to small chamber size |
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What type of myocardial hypertrophy will occur with increased volume work?
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mitral valvular regurg or a PDA
eccentric hypertrophy (dilatation with increased ventricular mass) |
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What signalling chemicals in the blood can potentiate hypertrophy of myocardial cells?
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norepinephrine, RAAS and some cytokines
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What are the benefits of cardiac remodeling?
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hypertrophy reduces wall stress and maintains stroke volume
dilation activates the Frank-Starling effect In chronic MR or AR, forward SV often can be maintained by dilation and hypertrophy until the "cardiomyopathy of overload" develops |
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What is the Frank-Starling effect?
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the greater the volume of blood entering the heart during diastole, the greater the stroke volume during systole and vice versa
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What are the problems with cardiac remodeling in heart failure?
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-impairs ventricular relaxation
-can reduce distensibility/compliance - overdilation can result in loss of compliance - dilation increases wall tension - LV dilation predisposes to mitral regurg (interrupts valve support0 - remodeled myocardium can lead to arrhythmias- cause of sudden death in HF |
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How does heart compliance change with dilation of the ventricles?
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over dilation results in a loss of compliance- as the ventricle gets stretched it gets stiffer (think balloon)
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How does a failing ventricle's response to preload and afterload change?
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it becomes less sensitive to preload and more sensitive to afterload
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In contractility failure, how does the stroke volume relate to end diastolic volume?
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you reach a point where regardless of the end diastolic volume, the stroke volume will not go any higher- the ventricle can only push out so much
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What are the determinants of cardiac output?
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stroke volume x heart rate
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What are the determinants of stroke volume in a normal heart?
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intropy (contractility)
preload (filling) afterload (impedance to ejection) |
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How does cardiac output change in heart failure?
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can be normal to decreased
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How does arterial blood pressure change in heart failure?
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it can be normal to decreased unless hypertension exists as a co-disease
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How does vascular resistance change during heart failure?
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it is increased
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How does central venous pressure change during heart failure?
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it is the venous volume and is increased (water retention)
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How does pulmonary wedge pressure change during heart failure?
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it is an estimate of the left atrial pressure and is increased
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How do pulmonary arterial pressures change during heart failure?
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increased in L sided HF (backup of pressure behind)
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How does left sided congestive heart failure affect the right side of the heart?
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it causes pulmonary hypertension
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How does right sided congestive heart failure affect the left side of the heart?
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it reduces left sided filling and cardiac output
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What is the general mechansim by which pulmonary edema occurs during heart failure?
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Atrial pressure is elevated, so venous pressure is also elevated. This elevates capillary hydrostatic pressure and there is increased filtration across the capillary and increased lymphatic drainage. When the lymph system becomes overwhelmed, there is edema
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Left sided heart failure will cause edema where?
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in the lung
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Right sided heart failure will cause edema where?
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in the body cavities or subcutaneous tissues
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How do acute and chronic increases in atrial pressure have different effects on pulmonary edema?
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higher pressures can be tolerated in chronic HF because the lymphatics are more activated
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Why will ascitic fluid be high in protein when it's from right-sided CHF?
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hepatic sinusoids (capillaries) are very leaky and post-sinusoidal pressure elevations will cause them to leak and cause ascities
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What types of heart failure can cause pleural effusion?
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right ventricular, left ventricular or biventricular heart failure
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What is the basis for capillary pressure at the parietal pleura/
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from intercostal vessels (linked to right atrium)
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What circulation supplies the capillary pressure in the visceral pleura?
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bronchial circulation (bronchial veins linked to pulmonary veins, drain into the left atrium)
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Pleural effusion in the pericardial space could be due to congestive heart failure in which side of the heart?
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systemic veins-
Right atrium |
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Pleural effusion from the hepatic sinusoids is caused by failure in which side of the heart?
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hepatic veins
Right atrium |
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Lymph leakage can be caused by congestive failure of which side of the heart?
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Drains into vena cava
Right atrium |
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Increased right atrial pressure changes capillary filtration in what areas?
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pleural, pericardial, cutaenous capillaries, hepatic sinusoids and lymph drainage into systemic venous circulation is impeded
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What causes chylothorax?
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severe obstruction to lymphatic drainage causes lymph and chyle from the abdomen to leak into the pleural space
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What effects does increased left atrial pressure have on capillary filtration?
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it increases filtration at the visceral pleural surface and impairs right sided heart function and lymphatic drainage --> pulmonary hypertension
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What is the most common cardiac cause of pleural effusion in CHF?
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biventricular failure
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What are the "low output" signs of congestive heart failure?
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-exercise intolerance and weakness
-pale mucuous membranes and prolonged CRT -syncope -oliguria and azotemia - inadequate perfusion of organs - hypotension |
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What is "low output" causes in congestive heart failure?
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reduced blood pressure with peripheral vasoconstriciton and reduced tissue perfusion
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What causes the "congestive" signs of CHF?
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increased venous and capillary hydrostatic pressures
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What are congestive signs of CHF?
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pulmonary edema (L)
tachypnea, dyspnea, orthopnea, pulmonary crackles cough pleural effusion elevated jugular venous pressure- peripheral venous distension hepatomegaly and ascites subcutaneous edema (lg) altered intestinal absorption |
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What is the basis of positive inotropic drugs?
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control calcium influx into the myocardial cell
- increase cellular contractile response |
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What are the fundamental mechanisms of inotropic drugs?
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-increase myocyte cystolic calcium by affecting membrane pumps
- stimulate beta-adrenoreceptors and alpha adrenoreceptors to increase calcium entry - preventing the degradation of cAMP - sensitizing the contractile apparatus to calcium ions to increase cellular contractile response |
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How do positive inotropes affect left ventricular function in heart failure?
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the increase the stroke volume compared to the preload but will not make it completely normal
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What are the basic categories of positive inotropic drugs?
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Digitalis glycosides
Catecholamines Phosphodiesterase inhibitors calcium sensitizers |
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How does digoxin act as a positive inotrope?
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slows Na/K pump to increase the sodium level in the cell, the calcium pump then exchanges more calcium and increases the calcium level in the cell so there is a greater stimulus for contraction
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What are the systemic effects of digitalis glycosides (digoxin)?
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baroreceptors think ABP is low
increased vagal efferent tone reduces the resting HR decreased sympathetic efferent tone |
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What are the toxic effects of digitalis glycosides?
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they may induce ectopic activity (PVCs/ nodal rhythms)
may inhibit RAAS system |
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How often does digoxin need to be administered?
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BID in dogs with normal BUN
QD in horses QOD in cats steady state requires 5-7 days in dogs |
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What blood levels should be monitored with digoxin use?
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hypokalemia can occur
may interact with quinidine and other drugs |
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What are the indications for use of digoxin?
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CHF due to:
- DCM - chronic valvular disease A-fib: when HR control needed Atrial arrhythmias in CHF CHF in horses |
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What are the contraindications of digoxin?
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-mod to severe renal failure
-complex ventricular ectopic complexes -hypokalemia -diastolic heart failure from pericardial disease or HCM -hyperthyroidism -Acute hypoxia |
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What clinical signs should be monitored during digoxin therapy?
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-appetite and attitude
-GI signs -Arrhythmias |
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What should the trough concentration of Digoxin be during therapy?
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0.8-1.2ng/mL
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What are the signs of severe cardiac dysfunction from reduced myocardial contractility?
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-cardiogenic shock
-electrical-mechanical dissociation -severe CV depression as with prolonged general anesthesia ---> Low CO and hypotension |
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What are the autonomic receptors within the vessels and what are their effects?
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alpha (vasoconstriction)
beta 2 (vasodilation) dopaminergic (vasodilation) |
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What are the beta adrenergic effects of catecholamines?
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increased heart rate (B1 and B2)
increased contractility increased conduction velocity thru tissues increased relaxation of normal myocardium increased excitement of normal and subsidiary pacemaker cells in the heart |
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What are the alpha adrenergic effects of catecholamines?
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increased myocardial intropy
increased arterial and venous constriction |
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What are the catecholamines that are positive inotropes?
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Dobutamine (alpha, beta)
Dopamine (alpha, beta) Epinephrine (alpha, beta) Ephedrine (alpha, beta) Phenylephrine (alpha 1) Isoproterenol (beta 1,2) |
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What are the cardiovascular effects of dobutamine and dopamine?
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-increased contractility and SV
-increased HR (CO increase) -vasodilation= B2 -vasoconstriction at high doses (alpha 1) -Dopamine has more chronotropic effects, more alpha mediated vasoconstriction |
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What positive inotropic drugs are used most often?
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catecholamines (dobutamine and dopamine)
short-term inotropic support |
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What is the mechanism of positive inotropic action of phosphodiesterase inhibitors?
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milrinone
prevent break-down of cAMP |
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How does pimobendan act as a calcium sensitizer/ positive inotrope?
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sensitizes the contractile apparatus to calcium and is the current inotropic drug of choice in dogs
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What are the benefits of diuretics in CHF?
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prevent tubular resorption of Na, Cl and water
increase urine volume contrac the plasma volume decrease venous pressures |
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What type of diuretic is furosemide and how does it work?
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loop diuretic
inhibits the co-transporter of chloride so Cl, Na, K and water are lost can have venodilator effect if given IV |
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Which diuretics act on the distal nephron?
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thiazides and spironolactone
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What is the mechanism of action of thiazides?
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inhibit sodium reabsorption in the distal tubules and water
less potent but longer duration of action than furosemide |
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What is the mechanism of action of spironolactone?
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it antagonizes the effects of aldosterone distally
weak diuretic but spares potassium may also prevent myocardial fibrosis caused by excessive activity of tissue renin-AT-aldosterone |
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What is the main benefit of spironolactone?
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it spares potassium
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When should diuretics be used?
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Congestive heart failure:
-pulmonary edema -ascites or pleural effusion -subcutaneous edema Hypertension -with drugs that lower ABP Oliguric Renal Failure Other Causes of Edema |
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What causes resistance to diuretic drugs?
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reduced renal blood flow
poor delivery of the diuretic distal nephron cells hypertrophy or increase activity so sodium is retained --> activation of Na retaining hormonal systems |
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What are the issues with regards to diuretic therapy?
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monotherapy: activation of RAAS (ace-i)
potassium and magnesium loss need for combination in cases of refractory edema |
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What negative effects can volume depletion and reduced venous pressure from diuretics have on the CV system?
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it decreases cardiac filling and preload, decreases cardiac output and decreases blood pressure
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What adverse effects can diuretics have on the kidneys?
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reduced renal perfusion (w/ ACE-I) can lead to pre-renal azotemia/ renal failure
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What adverse effects can electrolyte losses due to diuretic therapy have on the kidneys?
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hypokalemia, hypomagnesemia
-muscle weakness -cardiac arrhythmias -digitalis intoxication |
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What is the typical drug combination to treat CHF?
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pimobendan
furosemide spironolactone |
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What dietary modifications and nutriceuticals can be used to help treat CHF?
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sodium restriction
omega-3 fatty acids vitamin E taurine L-carnitine L-arginine Co-enzyme Q10 |
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What is the general hospital treatment plan for congestive heart failure?
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FON(S)
Furosemide-oxygen-nitroglycerine- (sedation) |
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What should you add to the general hospital treatment plan for CHF in a patient with severe mitral regurgitation?
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nitroprusside or hydralazine for afterload reduction to decreased regurgitation
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What should you add to the general hospital treatment plan for CHF in a patient with hypotension and DCM?
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dobutamine to itnropy and cardiac output
need to volume deplete while increasing the strength of the pump |
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What is the general home treatment plan for medical therapy of CHF?
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Dietary modifications
Furosemide Spironolactone Inotropic drugs (pimobendan, digoxin) ACE-inhibitor ---- Sildenafil (severe PHT) Diltiazem (HR in A-fib) Carvedilol: beta blocker once dry to protect myocardium |
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What are beta agonist effects?
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increased ionized calcium
increased SA discharge increased AV nodal conduction velocity increased contractility increased myocardial oxygen demand |
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What types of drugs should you beware of mixing with beta-adrenoreceptor blockers?
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CCB
Anti-arrhythmics Anesthetics |
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How is atenolol different from other beta blockers?
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it is hydrophilic with renal elimination while the others are usually lipophilic with hepatic elimination
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What is a possible adverse effect of using beta blockers?
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bronchospasm (B2 blockade)
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What is an ultrasort IV beta blocker that is hydrolyzed by plasma esterases?
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Esmolol (Brevibloc)
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What are the effects of overdose of beta blockers?
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decreased HR, decreased stroke volume leading to decreased blood pressure
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What are the clinical uses of beta blockers?
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control heart rate in A-fib
reduce dynamic outflow obstruction in feline hypertrophic cardiomyopathy cardioprotection in DCM antihypertensive therapy |
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What is the mechanism by which beta blockers control heart rate in A-fib?
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they slow AV conduction
recommended co-therapy or monotherapy for premature complexes in many disorders |
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What is the mechanism by which beta blockers reduce dynamic outflow obstruction in feline HCM?
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decreased intropy and myocardial shortening
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What is the mechanism by which beta blockers can be used in antihypertensive therapy?
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decrease cardiac output and decrease renin release
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What are the physiologic effects of calcium influx on the heart?
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depolarization of SA nodal and AV nodal cells
Myocardial cell contraction Constriction in vascular smooth muscle |
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How do you explain the theraputic and toxic effects of calcium-channel antagonists?
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they decrease the magnitude of calcium influx by L channels and depress the physiologic effects of calcium--> decreased contractility
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What are the two types of calcium-channel antagonists and what is the difference in their pharmacology?
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Dihypdropyridines and non-DHP
-DHP have vascular selectivity, non-DHP have cardiac selectivity |
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What is the prototype for dihydropyridines?
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nifedipine
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What is the major effect of dihydropyridines like nifedipine and amlodipine?
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they are vasodilators and can be used to decrease ABP in systemic hypertension
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What is the major effect of non-DHP calcium channel antagonists like verapamil and Diltiazem?
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they decrease heart rate, decrease AV conduction and have a negative inotropic effect
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How are most calcium antagonists metabolized?
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they have hepatic metabolism
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What is the negative effect of diltiazem in horses?
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it dilates blood vessels and decreases BP, which causes a reflex tachycardia
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What are the clinical uses for calcium-channel antagonists?
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control HR in A-fib
increase lusitropy in HCM Antihypertensive effects Afterload reduction in CHF |
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What drugs interact with calcium-channel antagonists?
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digoxin and non-DHPs
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What are the effects of calcium-channel antagonist toxicity?
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depression of cardiac tissues:
decreased HR, stops AV nodal conduction, decreases myocardial inotropy b/c it impairs calcium entry OVERALL DECREASES BP |
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How are beta blockers classified in the antiarrhythmic drug classification?
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class II
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How are calcium channel blockers classified in the VW antiarrhythmic drug classification?
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class IV
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What are the class I antiarrhythmic drugs?
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Na channel blockers
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What are class II antiarrhythmic drugs?
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beta-adrenergic blockers
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What are class III antiarrhythmic drugs?
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prolong APD
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What are class IV antiarrhythmic drugs?
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calcium channel blockers
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What are typical uses of antiarrhythmic drugs?
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suppress ventricular ectopic complexes
prevent recurrent or sustained atrial arrhythmias control AV node conduction and ventricular HR in management of AF and supraventricular tachycardias |
