Cardiovascular - NICOLE Flashcards
heart failure is
the inability of the heart to meet the metabolic needs of the peripheral tissues
pathophysiology of heart failure
-pump failure
- forward obstruction to blood flow
- regurgitant blood flow
-congenital shunts
- rupture of heart of vessels
- conduction disorders
decreased cardiac output leads to activation of what
sympathetic activation (a,B)
short and long term responses to underlying cardiovascular disease
increase heart rate
increase peripheral resistance
increase blood volume
redistribute blood flow
cardiac dilation
myocardial hypertrophy
pharmacological modification of cardiac function is usually achieved by modifying one or more of the following
chronotropy (heart rate)
inotropy (contractility)
peripheral resistance (vascular tone)
blood volume (diuresis, fluids)
rate of conduction (rhythm)
neurohormonal input to the heart
name some things you want to change with drugs?
preload, afterload, rate/rhythm, contractility, sympathetic/neurohormonal input
Frank-Starling Law - Cardiac output increases with ________ and decreases with _______
exercise, disease
the cardiac output of the diseased heart is reduced at any ________
preload
changes in preload have less of an effect on the output of the __________than on the output of the healthy heart
diseased heart
neurohormonal activation and excessive sodium and water retention leads to
elevated intracardiac and venous pressure (backward failure). Intravenous pressures >25 mg Hg results in signs of congestion
Diuretics move performances leftward along the Frank-Starling by reducing
preload and moving performances to a position below the threshold for congestion. Diuretics have little effect on cardiac output
cardiac injury can also result in low cardiac output (forward failure). What helps with this?
positive inotropes improve cardiac contractility, which improves output at any preload
patients with severe heart failure can exhibit signs of poor cardiac output and congestion (forward and backward failure). These patients require
positive inotropes and diuretics to shift the curve/improve function
The Frank-Starling Law states that the stroke volume of cardiac contraction ______________ as preload increases
increases
Inotropes - what mechanism/drugs
adrenergic drugs, inodilators, cardiac glycosides
chronotropes - what mechanisms/drugs
adrenergic drugs
cholinergic drugs
antiarrthymics - what classes
class 1 - sodium channel blockers
class 2 - beta blockers
class 3 - potassium channel blockers
class 4 - calcium channel blockers
positive inotropes
increase contractility
negative inotropes
decrease contractility
positive inotropes are useful in clinical situations when
decreased cardiac output is due to decreased myocardial contractility - ex dilated cardiomyopathy
negative inotropes have limited usefulness as a
first-line therapy but can be useful to allow cardiac relaxation and filling in hypertrophic cardiomyopathy. They also decrease cardiac oxygen consumption
when skeletal muscle contracts the calcium released by the SR is sufficient to
interact with all of the troponin, causing ALL potential actin-myosin interactions to occur
in cardiac muscle, NOT ALL troponin interacts with
calcium; thus, more or fewer actin-myosin cross bridges may form depending on intracellular calcium availability
WHATEVER CONTROLS THE CALCIUM WILL CONTROL
Cardiac contractility
examples of positive inotropes
digoxin, pimobendan, dobutamine, dopamine, epinephrine
is digoxin a good positive inotrope?
NO! because of high incidence of adverse effects and current availability of better options, digoxin is used infrequently in vetmed
inotropic mechanism of digoxin action
inhibition of the NA/K pump in the cell membrane results in decreased K+ in the cells. This leads to lower resting membrane potential/hyper excitability. It also increases Na+ inside the cell, which slows the action of the Na/Ca exchanger, with the net effect of increasing calcium concentrations within the cell. This improves contractility
Pimobendan is a
positive inotrope and vasodilators
pimobendan is not recommended for animals with
hypertrophic cardiomyopathy, aortic stenosis - caution with arrhythmias
what is the positive inotrope of choice in small animals
pimobendan
pimobendan has been shown in clinical trials to enhance
survival in dogs with heart failure due to DCM or Mitral Valve Insufficiency (MVI)
pimobendan mechanism of action (long one sorry) 4 things
- sensitizes troponin C complex to calcium, leading to increased strength of contraction
- causes venous and arterial dilation via phosphodiesterase III & V inhibition (reduces preload & after load)
- increases cardiac contractility without increasing myocardial oxygen consumption
- Appears to modulate neurohormonal input to heart
cAMP is an important second messenger in the regulation of cardiac contraction. cAMP, through various interactions with other intracellular messengers, increases the
strength and rate of contraction as well as the conduction of action potentials. Phosphodiesterase (PDE) breaks cAMP down to AMP. PDE III is inhibited in cardiac myocytes
pimobendan should be administered
orally, 1 hour before feeding
is pimobendan protein bound
yes, approx 93%
pimobendan half life
short - 30 min in dogs - active metabolite has 2 hr half life
how is pimobendan excreted
fecal excretion
adverse effects - pimobendan
usually well-tolerated
GI effects
tachycardia
pu/pd
CNS toxicity
B1 agonists are what
positive inotropes
examples of B1 agonists
dopamine, dobutamine
B1 agonists like dopamine and dobutamine have low bioavailability so must be given
IV
B1 agonists are useful in
an in-hospital setting
B1 agonists act on
beta receptors in the heart and blood vessels
in the heart, activation of beta-1 receptors by norepinephrine (or a beta-1 agonist) increases
cAMP concentrations. This activates a protein kinase (PK-A) to phosphorylate calcium channels in the cardiac myocyte resulting in increased calcium entry into the cell which enhances calcium release from sarcoplasmic reticulum during action potentials and increases the force of contraction
in the blood vessels, activation of beta2 receptors results in
increased cAMP, which results in vasodilation. This is because increased cAMP in vascular smooth muscle inhibits myosin light chain kinase, which is involved in myocyte contraction.
dobutamine is a positive inotrope that
does NOT increase heart rate
half life dobutamine
2 minutes, given as CRI
adverse effects dobutamine
-correct hypovolemia before administration!!!!
-incompatible with bicarbonate
-at high doses, can cause tachycardia
- SEIZURES IN CATS
Dopamine interacts with which receptors
Dopamine 1 (DA1), B1, a1, a2
- becomes less DA1 selective with increasing dose
DA1 receptor activation causes
vasodilation in the kidneys, mesentery, heart, and brain
B1 causes increased _________ and a1 activation increases _________
cardiac contractility, peripheral vascular resistance
dopamine half life -
very short half life - administer by CRI, less than 2 minutes
adverse effects dopamine
high doses can cause renal vasoconstriction
extravascular administration causes tissue necrosis
arrhythmias
dobutamine vs dopamine - which has more positive inotropic effects
dobutamine
dobutamine vs dopamine - chronotropic effects
dobutamine - less chronotropic effects
dopamine - more chronotropic effects
dobutamine vs dopamine which one dilates renal vascular bed
dopamine
indications for dobutamine
cardiogenic shock, endotoxic/septic shock, short-term treatment of refractory CHF (with pimobendan)
indications for dopamine
cardiogenic shock
endotoxic/septic shock
oliguria
epinephrine - a non-selective adrenergic agonist - increases
-myocardial oxygen demand and energy consumption
-arrythmogenic
epinephrine is used in
life threatening emergencies, not for management of CHF
- cardiac arrest, anaphylactic shock
negative inotropes - drug classes
B antagonists (blockers)
calcium channel blockers
certain antiarrhythmics
(all are rarely used specifically for their negative inotropic effects)
positive chronotropes
increase heart rate
negative chronotropes
decrease heart rate
negative chronotropes - drug classes
B antagonists (blockers)
muscarinic antagonists/anticholinergics
examples of beta antagonists (negative chronotropes)
-propranolol
-atenolol
-carvedilol
examples of anticholinergics (positive chronotropes)
atropine, glycopyrrolate
B antagonists are competitive antagonists of B adrenergic receptors - can be
selective or non-selective
B antagonists _________ heart rate
REDUCE
propranolol - effects
negative chronotrope and inotrope (B1 antagonism)
vasoconstrictor and bronchoconstrictor (B2 antagonism)
antiarrythmic
propanolol (non-selective, competitive beta blocker) is used for
-primarily used as an anti-arrhythmic
-sometimes used as short-term treatment for hypertension associated with thyrotoxicosis or pheochromocytoma
-treatment of CHF with tachycardia
-to slow ventricular rate during atrial fibrillation
- to decrease sympathetic input to heart
propanolol can be given
IV or orally
propanolol has a small/large first pass effect
large - oral doses are approximately 10X greater than IV doses
propranolol adverse effects
can be predicted as are effects of B blockade
bradyarrythmias, hypotension
bronchospasm (especially of concern in patients with poor lung function
negative inotropy
atenolol is a
beta 1 selective antagonist
atenolol has same B1 effects as propanolol, without the
b2 effects
uses of atenolol
treatment of tachyarrythmias and ventricular hypertrophy
treatment of hypertrophic cardiomyopathy in cats
adjunctive treatment for hypertension associated with chronic kidney disease (amlodipine first choice)
atenolol is a better choice than propanolol IF
there are concerns about pulmonary function
atenolol administered
orally - with excellent bioavailability
muscarinic antagonists block the
effects of acetylcholine (Ach) on M2 receptors in the cardiovascular system
the effects of M2 activation in the cardiovascular system are:
- slow heart rate through effects on SA node
-decreased atrial contractility and AP duration
-decreased conduction velocity at AV node
-decreased ventricular contractility
-antagonists have OPPOSITE EFFECTS
anticholinergics _____________ heart rate
increase
M2 receptors are mainly located in
the cells making up the SA and AV nodes. There are also some M2 receptors in cardiac muscle, but fewer, so the effects on cardiac myocytes of M2 antagonists are less important than their effects on the SA and AV nodes
Atropine is a
competitive muscarinic antagonist
atropine prevents the interaction of Ach with
its receptor, which attenuates the physiologic response to parasympathetic nerve stimulation. Atropine affects all muscarinic receptors, not just cardiac M2 receptors.
atropine has a non-specific nature, so its difficult to induce one of its effects without
inducing others, which can lead to undesirable side effects
atropine clinical use - mainly used for
acute, short term response
atropine is a positive chronotrope - useful for treating
bradycardia
increases cardiac output (bc of increase in HR)
atropine old uses
was used pre-anasthesia to decrease salivation and airway secretions, now only used in select cases
- was occasionally used in treatment of asystole but clinical benefit not confirmed
useful in treatment of certain toxicities
atropine adverse effects
due to non selective nature of atropine
-GI effects can cause colic in horses
-contraindicated in animals with glaucoma
glycopyrrolate is a drug that is very similar to atropine but with less
CNS penetration
Glycopyrrolate: basically the same as atropine but
more polar molecule - so less CNS penetration than atropine, less adverse CNS effects, does not cross placenta, and also lowers incidence of tachyarrythmias
conduction velocity is influenced by
parasympathetic and sympathetic inputs
ERP
effective refractory period - phase 0 to early phase 4
a new AP cannot be initiated during this time
cardiac nodal action potentials - do not have
fast sodium channels (AP in the SA and AV nodes are determined mainly by slow Ca and K currents)
these cells do not have a true resting potential, they spontaneously depolarize
causes of arrhythmia
-disturbances in automaticity of the pacemaker cells
-disturbances in impulse conduction or action potential generation
ventricular arrthymias originate in
the ventricles
atrial (supraventricular) arrhythmias originate in
the atria or atrial conduction system (can include AV node)
anti arrhythmic drugs alter
automaticity
conduction velocity
change excitability of cardiac cells during ERP
ALL anti arrhythmic drugs alter membrane ion conductance to
affect the action potential
Class 1 (Na-Channel blockers) examples
lidocaine, quinidine, procainamide
Na channel blockers bind to and block
fast Na channels responsible for rapid depolarization of cardiac myocytes. This reduces the slope and amplitude of phase 0 of the action potential - decrease conduction velocity in non-nodal cardiac tissue `
Na channel blockers may increase, decrease, or not change the
action potential duration and ERP
Na channel blockers reduce automaticity of
ectopic pacemakers
class 1 subtypes are based on
effects of ERP - due to nature of Na channel block and presence or absence of K channel block
class 1a also has
anticholinergic effects - ex quinidine
class 1b - example
lidocaine
lidocaine is used to treat
acute ventricular tachyarrythmias, particularly during anesthesia
does lidocaine have any effect on artia?
no - effect primarily seen in ventricles
lidocaine onset time
rapid onset after IV administration and quick metabolism (short half life)
lidocaine has a large
first pass effect, therefore not given orally
lidocaine adverse effects
vomiting, seizures, muscle fasciculation, usually stop when administration stopped
quinidine - prolongs the
ERP of atrial and ventricular muscle - allows atrial fibriliation conversion
procainamide - similar mechanism to quinidine but more effective for
controlling ventricular arrhythmias than atrial arrhythmias
Quinidine - USED FOR
ATRIAL ARRHYTHMIAS
Procainamide - USED FOR
VENTRICUALR ARRHYTHMIAS
quinidine vs procainamide - how to give
quinidine - PO in horses, IM or IV
Procainamide - PO, IM, or IV
K channel blockers - examples
sotalol
K channel blockers - prolong the
action potential and slow repolarization by blocking K channels
what is the most relevant class 3 anti arrhythmic in vet med
sotalol
sotalol is not only a k channel blocker but also
a B blocker
sotalol is used for control of
ventricular and some supra ventricular arrhythmias
does sotalol has a first pass effect
no! high bioavailability
calcium channel blockers - bind to and block
L-type Ca channels in vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue
Calcium channel blockers effect on blood vessels, chronotropy, inotropy
vasodilator, negative inotrope, negative chronotrope, negative dronotrope (decreases conduction velocity within the heart esp at AV node)
class 4 calcium blocker of choice for arrhythmias
diltiazem
diltiazem primarily acts on
the AV node
clinical use of diltiazem
supra ventricular tachycardia / atrial fibrillation in dogs - heart rate control
hypertrophic cardiomyopathy in cats - control heart rate (slow down rate to allow cardiac filling)
-peripheral vasodilation (reduces after load)
- negative inotropic effect (may allow more effective filling of heart because increases relaxation of heart muscle
