Vascular Pharmacology Flashcards
List 4 drugs that act on the peripheral vascular system
inodilators like pimobendan
Ca channel blockers
adrenergic agonists and/or antagonists
nitric oxide producers
What are the physiologic controls of vascular tone
Controlling endothelial cells and smooth muscle
systemic receptors like adrenergic receptors and angiotensin 2 receptors
local receptors for bradykinin, prostaglandin, and nitric oxide
Ca controls smooth muscle contraction
hormones also have a role
How does vascular tone impact the heart
It determines the peripheral resistance which impacts cardiac output (heart rate) and blood pressure
Vascular volume has an effect on blood pressure, afterload, and preload
List 3 ways vasodilators can be beneficial for heart failure
if there is excess venous congestion - reduce the preload with drugs
if there is reduced outflow due to regurgitant flow - use after load reducing drug
if there is reduced tissue perfusion due to excessive sympathetic tone - use after load reducing drug
What is the outcome/effect of arterial vasodilation
It reduces the afterload
- reducing the resistance the heart must pump against
it enhances forward flow
What is the outcome/effect of venous vasodilation
It reduces the pre load
- reduced filling of the heart
- reduced myocardial oxygen demand
What are 3 stimuli that trigger smooth muscle contraction
passive stretch
AP/electrical
chemical stimulation through receptor binding
What is the process of smooth muscle stimulation/contraction
stimuli causes Ca release
Ca and calmodulin interact and activate myosin light chain kinase
Myosin light chain kinase phosphorylates myosin light chains which initiates cross bridge formation and contraction
Relaxation occurs when there is reduced Ca thus reduced myosin light chain phosphorylation
myosin light chain kinase is inhibited due to the increase in cAMP
There is increased amounts of myosin light chain phosphatase
How does smooth muscle contraction differ from cardiac muscle contraction
There is no pacemaker/spontaneous depolarization
No troponin
What is the mechanism of action of amplodipine
it blocks Ca influx into vascular smooth muscle
- low intracellular Ca
- reduced ability for contraction
It act preferentially on the vasculature not the heart
It is the most potent vasodilator of the Ca channel blocker class
What situations indicate the potential use of amlodipine
cats with hypertension and chronic renal failure
dogs with mitral valve regurgitation (it will reduce the afterload)
Can you use amlodipine for arrhythmia tx
Not a good choice because it acts preferentially on vascular smooth muscle not cardiac
Other Ca channel blockers would be a better option
What should you consider when presented with an animal to be treated for hypertension
hypertension is always secondary - should find underlying cause
Use amlodipine or another drug that acts on RAAS
Avoid hypotension (<120 mmHg) - aim for < 160mmHg
- dont decrease too fast
What is the effect of alpha 1 agonists on vascular tone
vasoconstrict
What is the effect of alpha 2 agonists on vascular tone
vasoconstriction followed by ‘pre-synaptic’ vasodilation
They stimulate nitric oxide release which causes local vasodilation
Provide 3 examples of alpha 2 agonists
xylazine
detomidine
dexmedetomidine
What is the effect of alpha 1 receptor antagonists on the heart and vasculature
They vasodilate arteries and veins
- less impact on veins
It causes a reduction in afterload because it preferentially impacts arteries
What other non-alpha 1 antagonist drugs have alpha 1 antagonist effects
acepromazine
quinidine
carvediol
What are 2 consequences of alpha antagonism overdose
hypothermia
reduced perfusion
What is the effect os nitroglycerin? What is it used for?
vasodilation
- it converts to nitric oxide
used for the acute management of heart failure
What are 3 types of drugs with indirect effects on the cardiovascular system
diuretics
ACE inhibitors
angiotensin 2 receptor blockers
What is the function of diuretic use for cardiovascular disease
reduce blood volume and mobilize edema
reduce preload
What is the primary diuretic used in the treatment of cardiovascular disease
furosemide
What are the 3 effects of ACE inhibitors on the body
vasodilation resulting in reduced TPR and afterload
diuretic due to reduced aldosterone and preload
reduced SNS input to the heart
What are the adverse effects of ACE inhibitors
hypotension (without compensatory heart rate increase due to reduced SNS input)
reduced aldosterone
potentially hyperkalemia if given with spironolactone
if given with furosemide it can cause volume depletion/hypotension/and renal insufficiency
- should reduce the furosemide dose by 25-50% if giving ACE inhibitor as well
What are 2 examples of common ACEI used
enalapril
benazepril
What are the pharmacokinetics of ACEI and how does it influence its implementation
slow onset because it is a prodrug
- there is 1 -2 weeks to see a response or steady state
They are not for acute treatment - for management/increase lifespan
What is the function of telmisartan and what is it used for?
reduce blood pressure - similar to an ACEI
used mainly for hypertension and proteinuria associated with CKD
What are the adverse effects of telmisartan
GI
hypotension
anemia
fetotoxic!
