Pharmacology of Cardiovascular Drugs Flashcards
what is heart failure or congestive heart failure?
heart is unable to adequately circulate blood to meet the needs of the body
what direct effects on the heart do cardiovascular drugs have?
chronotropy: rate, rhythm
intropy: contractility
how do cardiovascular drugs change vascular tone?
vasodilation/constriction
ateriodilation/constriction: decrease/increase peripheral resistance
venodilation: increase venous capacity
how do cardiovascular drugs change vascular volume?
change volume of blood: increase or decrease
change venous capacity: venodilation
many drugs effects both the heart and the vascular system directly, and there are ____________________________ between the two “systems”
homeostatic control mechanisms
what is increased survival from cardiovascular drugs linked to?
decreased sympathetic input to the heart, which decreases likelihood of fatal cardiac arrhythmias and decreases overall stress on the heart
decreased hormonal input that reduces secondary inflammation and remodeling (helps to decrease disease progression)
what drugs are chronotropes?
adrenergic drugs
cholinergic drugs
what drugs are inotropes?
adrenergic drugs
inodilators
cardiac glycosides
what are the class I antiarrhythmics?
sodium channel blockers
what are the effects of beta1 agonists?
increase rate and force of contraction
no direct effects on arteries
what is dopamine?
positive chronotrope/inotrope
what receptors is dopamine an agonist for?
dopamine
beta1
alpha-receptors
depends on concentration
what is dopamine IV used for?
immediate inotropic support
what does dobutamine do?
inotrope with little chronotropic effect
beta1
what are the main cardiac chronotropic effects of beta blockers?
decrease heart rate
slow AV conduction
prolong refractory period in conducting tissues
decrease spontaneous depolarization
suppress catecholamine-induced arrhythmias
what are beta blockers used for?
supraventricular tachycardias
what are some supraventricular tachycardias?
elevated heart rate
atrial fibrillation
what receptors do beta blockers affect?
block beta1 and/or beta2 receptors
when is dobutamine used?
acute, in hospital situations, for immediate inotropic support
what is the mechanism of anticholinergic agents (positive chronotropes)?
muscarinic receptor antagonists
what is atenolol?
selective beta-1 blocker
what is atenolol used for in cats?
hypertrophic cardiomyopathy
what are the adverse effects of positive chronotropes (anticholinergics)?
increased peripheral resistance
ileus
decrease salivary and bronchiolar secretions
urinary retention
mydriasis and associated photophobia
inotropes that also decrease neurohormonal (sympathetic) input to the heart have ______________________ or ____________________, depending on magnitude of decreases in neurohormonal input
neutral effects on survivability (digoxin)
beneficial effects (pimobendan)
how does pimobendan increase contractility?
increases affinity of troponin C complex for calcium, leading to increased contractility without increasing calcium concentrations
what is the key property of pimobendan?
increases cardiac contractility without increasing myocardial oxygen consumption
how does pimobendan cause vasodilation?
phosphodiesterase III inhibition
what does pimobendan do with the heart?
modulates neurohormonal input to the heart
what drug is the only positive inotrope that has been evaluated in clinical trials in the dog?
pimobendan
what is pimobendan approved for in dogs?
management of signs of congestive heart failure due to dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD)
what has pimobendan shown in dogs with changes in function or cardiomegaly that do not have CHF?
significant delayed onset of congestive heart failure and/or death for both dilated cardiomyopathy and myxomatous mitral valve disease
what does digoxin (cardiac glycoside, positive inotrope) do?
inhibits Na/K ATPase pump on cardiac myocytes
increases vagal tone
how is digoxin cleared?
primarily by kidney
what is the therapeutic range of digoxin like?
narrow: therapeutic drug monitoring useful
what are some adverse effects of digoxin?
gastrointestinal distress
arrhythmias
what are the clinical indications of digoxin?
primarily to slow ventricular response rate in dogs with atrial fibrillation
horses: protect against increased ventricular response rate
what is supraventricular arrhythmia?
abnormal rate/rhythm that originates above the ventricle
what is ventricular arrhythmia?
abnormal rate/rhythm that originates in the ventricle
what do antiarrhythmic drugs do generally?
alter automaticity
alter conduction velocity
change excitability of cardiac cells during effective refractory period
alter membrane ion conductance to affect the action potential
what are class 1 antiarrhythmic drugs?
Na-channel blockers
what are class 2 antiarrhythmic drugs?
beta-blockers
what are class 3 antiarrhythmic drugs?
K-channel blockers
what are class 4 antiarrhythmic drugs?
Ca-channel blockers
what class of antiarrhythmic drugs includes atropine and digoxin?
miscellaneous
what does lidocaine do?
blocks inactive Na-channels
no increase in effective refractory period
where does lidocaine have its greatest effect?
abnormal ventricular cardiac tissue
what is lidocaine a drug of choice for?
acute ventricular arrhythmias
what does procainamide do?
blocks open Na channels, slower off rate
increases effective refractory period
what does quinidine do?
blocks open Na channels, slow off rate
increases effective refractory period
significant vagolytic effect and is an alpha1-blocker
what is the primary treatment for atrial fibrillation in horses?
quinidine
what do class 3 antiarrhythmics do?
prolong action potential and extend effective refractory period
likely through effect on K-channels
what is the most clinically relevant class 3 antiarrhythmic/potassium channel blocker?
sotalol
how do class 4 antiarrhythmics work?
block slow calcium channels in cardiac cells and vascular smooth muscle
what do calcium channel blockers do?
slow heart rate (SA node) and AV conductance
decrease myocardial contraction
cause peripheral vasodilation
what is diltiazem?
calcium channel blocker
what is diltiazem used for?
atrial fibrillation in dogs
what drugs do we use in the adrenergic system to modify vasodilation and vasoconstriction?
alpha1 adrenergic receptor antagonists
alpha1 agonists
alpha2 agonists
beta-blockers and beta-agonists
what is amlodipine preferred for?
calcium channel blocker for peripheral vasodilation
what does amlodipine target?
systemic arteriolar smooth muscle
what is amlodipine used for?
severe mitral valve regurgitation in dogs
systemic hypertension
what do nitric oxide producers do?
cause arterial and venodilation by conversion to nitric oxide
what are nitric oxide producers used for?
acute management of cardiac failure
angiotensin converting enzyme is located primarily in the endothelial cells of the __________________. __________ quantitively most important
lungs and kidneys
lungs
what do angiotensin converting enzyme inhibitors lead to?
significant vasodilation
decrease in aldosterone, leading to diuresis
decrease sympathetic input to heart
what are the primary ACE inhibitors used?
benzapril
enalaprilremain
what are the approved veterinary ACE inhibitors?
enalapril
benazepril
are ACE inhibitors for acute therapy or management?
management
how do diuretics reduce blood volume?
by increasing urine production
what are the diuretics of choice?
furosemide
torsemide
what is spironolactone?
diuretic
aldosterone antagonist
how are ACE inhibitors diuretics?
decrease aldosterone production
what is key to prolonged survivability?
decreasing sympathetic and neurohormonal input to the heart
who is more sensitive to the CNS adverse effects of dobutamine?
cats
what do beta blockers do with atrial fibrillation?
decrease ventricular response rate
where are beta-2 receptors found other than the heart?
lungs
bladder
some vasculature
when should you avoid using beta-blockers?
animal in overt heart failure
pulmonary pathology present
what is propanolol?
non-selective beta blocker
largely supplanted by atenolol: beta-1 selective blocker
why is it important that carvedilol also blocks alpha-1 adrenergic receptors and mat possess antioxidant properties?
protects against increased resistance from unopposed beta-2 block
antioxidant properties may protect heart
what is generally the drug of choice for beta-blockade?
atenolol: selectivity, data, cost
what are the effects of cholinergic drugs?
SA node: slow heart rate
AV node: slow heart rate
atrium: decrease contractility
ventricle: decrease contractility
what are some positive chronotropes?
atropine
glycopyrrolate
does atropine and/or glycopyrrolate cross the blood-brain barrier?
atropine does
how do positive chronotropes increase heart rate?
inhibit M2 actions
what are some negative inotropes?
adrenergic antagonists
calcium channel blockers
what has been shown with life expectancy and pure positive inotropes?
negative impact
what is the half life of pimobendan’s active metabolite?
2 hours
what are the adverse effects of pimobendan?
relatively safe
diarrhea
tachycardia or ventricular arrhythmia
hyperexcitability
worsening dynamic outflow obstruction
what positive inotrope has been evaluated in clinical trials for dogs?
pimobendan only
what is the half-life of digoxin?
24 hours
what do arrhythmias with digoxin result from?
high vagal tone and direct effects on heart
how do anti-arrhythmics affect the action potential?
alter membrane ion conductance
do sodium channel blockers affect the SA/AV nodes?
not really directly
what are the adverse effects of lidocaine?
skeletal muscle fasciculation, vomiting
seizures
can you use lidocaine containing epinephrine?
no
how do potassium channel blockade drugs/class III affect the heart?
prolong action potential and extend effective refractory period
what does diltiazem do?
decreases SA/AV node with limited effect on inotropy
mild peripheral vasodilatory effect
what is phenylephrine?
alpha1 agonist: selective for alpha1 receptors, IV only
what is ephedrine?
alpha1 agonist: non-selective alpha/beta agonist and may stimulate release of norepinephrine
what is norepinephrine?
alpha1 agonist: alpha 1, 2, and beta-1 receptor agonist
what is the primary alpha1 adrenergic receptor antagonist?
prazosin
