cardiovascular Flashcards
afterload
-resistance in the aorta/ pulmonary artery.
-increased afterload heart works harder to pump blood out.
preload
-pressure from venous system into R side heart by great veins.
-too much preload (excess blood in the heart ) decrease CO. heart cant stretch anymore leading to hypertrophy.
hypertrophic cardiomyopathy HCM
-most common form of heart failure in CATS
-excess afterload, increase ventricular pressure leads to venticular concentric hypertrophy
-increased systole
-smaller volume in chamber, muscle is thick
Dilated cardiomyopathy DCM
-most common form of heart failure in DOGs
-ecentric hypertrophy
-increased diastolic
-certain breeds predisposed (boxers, pinchers)
-cats develop if low taurine diet.
cardiac insufficiency/ failure
-due to reduced stroke volume/ cardiac output caused by: reduced preload, impaired contractility, increased afterload, inadequate valve function, abnormal rates.
heart failure symptoms
-cardiomegaly (enlargement)
-LV failure: not filling properly or not enough force to generate SV. blood accumulates in lungs, edema.
-RV failure: blood backs up into great veins, leads to brisket edema, ascites, hepatojugular refelx.
-FAILURE ON ONE SIDE LEADS TO FAILURE ON OTHER SIDE.
positive inotrophic agent
Pimobendan
-great for heart failure, extends life in dogs with DCM and mitral valve insifficiency.
-phosphodiesterase inhibitor which increases CAMP, Ca++
-positive inotrope (increase contractility) and arterial vasodilator (decreases afterload)
-increases well being and appetite.
positive inotrophic agent
digoxin
-digitalis glycosides isolated from foxglove
-inhibits Na/K atpase (sodium pump)
-increases contractility non selectively
-negative chronotrophic and dromotrophic effects decreases HR, increase CO.
-HIGHLY TOXIC
-increases peripheral tissue perfusion
digoxin mechanism of action
-acts on conductor cells to decrease chrono and domotrophy, HR, contractility.
-inhibits Na pump which resets ion gradient in cytoplasm.
-increases Na/Ca exchanegr and leads to ore Ca+ released Ca and contraction.
digoxin effects
-increased parasympathetic tone and decreased sympathetic tone (baroreceptor)
-ADE: death, anorexia, vomiting, diarrhea, AV block and arrythmias which can be made worse by hypokalemia.
-so using diaretics which decrease K can make even normal dose toxic.
-hyperkalemia blocks digoxin effects.
B blockers in heart failure
-end in LOL
-are useful in HCM and DCM due to inhibition of B1 stimulated renin release.
-B1 selective antagonists are prefered. ex metoprolol
vasodialators in Heart failure
-ends in pril
-ACE inhibitors
-enalapril, benzapril, imidipril
-prevent Ang II and Ang I formation by inhibiting angiotensin.
-ang I receptor antagonists (ARB’S) (valsartan or telmisaran)
effects of vasodialators ACE inhibitors and AT1 receptor blockers
-cause vasodilation-from no angII, reduce venous and arterial pressure and edema.
-prevent aldosterone release and decrease fluid retention and edema
-enalapril extends life 92% in HR
-Ace inhibitors prevent breakdown of bradykins which can lead to tickle cough
vasodialators best use of treatment/ misc
-acute treatment or in severe cases.
-ex. nitroglycerin, sodiul nitripusside break down into NO which can decrease pre and afterload.
-all vasodialators may cause hypotension, refelx tachycardia and activation of the RAAS system.
-best for short term decompensated animals
diuretics in heart failure therapy
-pulmonary edema is a huge problem as animal cant breath and is uncomfortable
-best treatment for pulmonary edema
-excessive use can lad to loss of venous return so you need to hydrate
-beware of hypokalemia making digoxin more toxic
digoxin
-use: heart failure, but mostly atrial fibrilation
-inhibits Na-L atpase and secondarily increases Ca+
-effects: positive ionotrope, negative chrono and domotrophe
dobuatamine
-used in acute treatmentof severe HF
-B1 agonist
-positive ionotrope
pimobendan
-best HF drug
-phosphodiasterase inhibitor (PDE3) in heart and BV
-positive inotrope, vasodilator
meteprolol
-used for hypertrophic cardiomyopathy
-slows HR and relaxes ventricales for better diastolic filling and increased CO
-B1 blocker.
Enalapril, Benazepril, Imidipril
-used for HR, hypertension
-inhibits angiotension converting enzyme
-reduced ang II –> vasodialtion and decreased aldosterone
valsatan, telmisatan
-AT1 receptor antagonists
-inhibiting actions of ang II
-causes vasodilation and reduces aldosterone release
nitroglycerine, nitroprusside
-used for HF
-exogenous sources of nitric oxide
-venodilation and reduced prelaod
prazosin and hydralazine
-used for HF and hypertension
-A1 ardenergic receptor agonsits
-arteriole dialaton and reduced afterload
sildenafil
-used for pulmonary hypertension
-phosphodiesterase inhibitor prevent cGMP breakdown.
-vasodilation in the lung and penile circulation and pulmonary pressure
supraventricular tachycardia
-any change which decreases the time required for depolarization from the maximal diastolic potential and threshold potential. which causes increased automaticity.
premature venticular contractions ventricular tachycardia
-afterdepolarzations from abnormal Ca+ influx into cardiac cells or after phase 3 of ventricular AP.
ventricular tachycardia retrograde condution
-unidirectional block and retrograde conduction
-ischemic tissue causes decremental conduction and a one way block
antiarrythmics class 1 drugs
-Quinidine
Procainamide
Lidocaine
-Na channel inhibitor
-decreses Na and prolongs QRS phase reducing HR and cardiomyocyte excitability
-used for ventricular arrythmias mostly tachycardias
anti arrythmic drug class II metaprolol, atenolol
-B1 ardenergic receptor antagonists
-Negative chronotrope,
dromotrope & inotrope
-used for supraventicular tachycardias where there is excess sympathetic stimulation
aminodarone, bretylium, sotalol
-class III antiarythmic
-K channel inhibitor
-decreases K current therby prolonging repolarization phase and reducing heart rate
-used for refractory venticular tachycardias
verapramin, dilitazem
-class IV anti-arrhythmic
-Ca channel inhibitors
-decreases CA current, negative chronotrophe, slows depolarization in pacemaker cells
-used for supraventricular tachycardias
actions of different class 1 anti-arrythmics
-class 1A: targets all cardiac cells, including ventricular myocytes
-class 1B targets damaged ventricular myocytes
-class 1C targets all cardiac cells with some preference for conduction cells.
Sympathetic nervous system
-thoracic and lumbar nerves with short preganglionic and long post ganglionic fibers.
-adrenal medulla secretes NE and EPI into blood.
-chain ganglion response is all or nothing
Parasympathetic nervous system
-crainial and sacral nerves (vagus is major player)
-long pre and short post ganglionic fibers
-targeted discrete activation
autonomic nervous system receptors
-Ach activates cholinergic receptors which are muscarinic and nicotinic receptors
-Ne and EPI activate ardenergic receptors which are a and B receptors
A1 receptor sympathetic stimulation effects
-pupillary dilation
-lacrimal secretion
-Blood vessels: constriction, large SNS stimulation leads to B1 activation in heart and causes dilation.
B2 broncocontriction
-Gi tract: decreased motility
-ejaculation, relax detrusor muscle
M2 muscarinic receptor parasympathetic stimulation effects
-heart: decrease rate acts on SA node only
decreases contractility, conduction.
-increase lacrimal and salivary secretions
-no PNS innervation in arterioles
-GI: increases motility
-erection
ANS signal transduction
-Beta receptors increase camp
-phophodiesterase breaks down camp to AMP active form which prolongs the secondary messenger
-Alpha 2 recepor and M2 receptors inhibit camp.
-nitric oxide action M3 on vascular endothelium leads to activation of IP3 and Ca release makes NO acts on smooth muscle and cGMP and causes vasorelaxation.
drugs which affect ANS neurotransmission by inhibiting release of neurotransmitter
-affecting cholinergic neurotransmission = botulinum toxin
-affecting adrenergic neurotransmission =beryllium
drugs which affect ANS neurotransmission by increasing release of a neurotransmitter
-affecting cholinergic neurotransmission = black widow spider venom
-affecting adrenergic neurotransmission =amphetamine
drugs which affect ANS neurotransmission by inhibiting reuptake of a neutotransmitter
-affecting adrenergic neurotransmission =cocaine
drugs which affect ANS neurotransmission by inhibiting metabolism of neurotransmitter
-affecting cholinergic neurotransmission = cholinesterase inhibitors (neostigmine)
-affecting adrenergic neurotransmission =monoamine oxidase inhibitors
acetylcholine and carbachol as cholinergic agonists
-direct acting agonists
-non selective cholinergic N=M
-effects everything nitotinic + muscarinic
-large PNS effect
nicotine as cholinergic agonist
-direct acting agonist
-used pharmacolically in insecticides
-nicotinic sensitive N>M
-receptors in skeletal muscle/ ganglion effects SNS, PNS can lead to muscle twitching
muscarine, bethanechol, pilocarpine as cholinergic agonists
-muscarinic selective
-M>N
-can stop heart with M
-direct agonist
indirect acting cholinergic agonists (AChE inhibitors)
-non selective cholinergic N=M
-more PNS can lead to toxicity (SLUD)
-irreversible inhibitors cause ACh accumulation: oraganophosphate, insecticides
-reversible: inhibit: edrophonium, neostigmide=will reverse paralysis in skeletal muscle
cholinergic antagonists
-atropine/ipratropium
-muscarinic selective M»N
-competative agonists for Ach binding at M.
-treat insecticide poisoning and reduces salivation and resp secretions
cholinergic antagonists
-hexamethonium/ trimethaphan
-Nn blocker (ganglion blocker)
-cuts out baroreceptor reflex
-dont use in consious animal, used for control of hypotension due to low BP
epinephrine and norepinephrine receptor selectivity as ardenergic agonists
-EPi: activate all receptors a1,a2,b1,b2
-Ne: all but not B2
isopreterenol
-ardenergic agoist with (B1=B2).»>a receptor affinity.
-used for heart function a cardiac support drug in emergency
dopamine
-ardernergic agonist D1>B1>B2>a affinity.
-D1 in renal vasculature so dialates kidneys so animal gets blood flow even in shock.
-loses selectivity at high doses.
-B1 can maintain cardiac function in crashing animals
dobutamine
-adenergic agonist B1>B2>a
-less peripheral vasodialation and pure B1 heart stumulation
phenylephrine
-adenergic agonist a1>a2>B
-decongestant, vasoconstriction, decrease secretions
clonidine/ xylazine
-ardenergic agonist a2>a1>B
-decrease SNS leads to sedation
beta 2 agonists
-terbutaline, clenbuterol, salbutamol
-used for bronchoconstriction, asthma, can lead to tachycardia
-B2>B1>a
alpha antagonists
-prazosin a1»»a2
-phenoxybenzamine (reversible)
-phentomaline
-tolazine, atipamezole
prazosin
-competititve alpha agonist
-very selective a1»»>a2
-a1 in arteries and arterioles cause constriction so this antagonizes it and causes vasodialation
-antihypertensive
mixed ardenergic antagonits
-labentalol, caredilol
-used in heart failure
-B1=B2>a1>a2
-anti arythmic
-a1 receptor will antagonize compensation from heart failure by decrease Hr and vasoconstriction
beta antagonists (B blockers)
-anti arrythmic
-metoprolol, acebutolol, atenolol B1»>B2
-good for asthma, cardiac or renal
-for non selective agonists if you block B2 you will inhibit SM relaxation which is a problem in asthma attacks.
epi vs Ne injection in the cardio system
-NE: a1=a2>B1 leads to a1 vascoconstriction and increased peripheral resistance.
-NE leads to reflex bradycardia.
-EPI: all receptors a1=a2, B1=B2.
-EPI: causes vasodilation and central constriction B2.
-in crashing animal EPI is better because NE can increase pulse rate and decrease heart rate too much. EPIs central vasoconstriction leads to decrease pulse rate.
atrial flutter
-multple P values on ECG,
-a round circut in the heart so it is always excited leads to AV block.
-can treat with digoxin which helps heart work harder and keeps AV node less excitable and decreases the ventricular rate
-monitor blood levels for signs of toxicity
hypertrophic cardiomyopathy treatment
-dont use positive ionotrophes (digoxin or pimobendan)
-use B blocker and diuretic instead
class 1 antiarrythmics mechansms of action and uses
-Na channel blockers
-used for ventricular arrythmias and tachycardias
class 2 antiarrythmics mechansms of action
b1 antagonists, negative chronotroph, domotroph and ionotroph
class 3 antiarrythmics mechansms of action and use
-K channel inhibitors, decreases K so prolongs repolarization and reducing HR, prolongs the plateau phase.
-refractory ventricular tachycardias
class 4 antiarrythmics mechansms of action
-Ca channel inhibitors
-decreases Ca so negative chronotrophy slowing spontaneous depolarization in pacemaker cells.
-used supraventricular arrythmias and hypertrophic cardiomyopathy
-acts similar to class II B blockers
-verapamil, ditiazem
-you do not want these acting anywhere other than the pacemakers if it acts in ventricals in cardiomyocytes it will decrease contractility as a negative side effect.
-do not use in DCM but good more HCM
RAAS system and what drugs block it
-B-ardenergic antagonists: block renin from kidneys
-ACE inhibitors block ang II formation
-Ang II leads to aldosterone release and vasoconstriction so blocking ang II leads to vasodilation and no aldosterone so not retaining water and less edema.
