Vascular Pharmacology

Question 1

List 4 drugs that act on the peripheral vascular system

Answer 1

inodilators like pimobendan

Ca channel blockers

adrenergic agonists and/or antagonists

nitric oxide producers

Question 2

What are the physiologic controls of vascular tone

Answer 2

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

Question 3

How does vascular tone impact the heart

Answer 3

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

Question 4

List 3 ways vasodilators can be beneficial for heart failure

Answer 4

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

Question 5

What is the outcome/effect of arterial vasodilation

Answer 5

It reduces the afterload
- reducing the resistance the heart must pump against

it enhances forward flow

Question 6

What is the outcome/effect of venous vasodilation

Answer 6

It reduces the pre load
- reduced filling of the heart
- reduced myocardial oxygen demand

Question 7

What are 3 stimuli that trigger smooth muscle contraction

Answer 7

passive stretch

AP/electrical

chemical stimulation through receptor binding

Question 8

What is the process of smooth muscle stimulation/contraction

Answer 8

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

Question 9

How does smooth muscle contraction differ from cardiac muscle contraction

Answer 9

There is no pacemaker/spontaneous depolarization

No troponin

Question 10

What is the mechanism of action of amplodipine

Answer 10

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

Question 11

What situations indicate the potential use of amlodipine

Answer 11

cats with hypertension and chronic renal failure

dogs with mitral valve regurgitation (it will reduce the afterload)

Question 12

Can you use amlodipine for arrhythmia tx

Answer 12

Not a good choice because it acts preferentially on vascular smooth muscle not cardiac

Other Ca channel blockers would be a better option

Question 13

What should you consider when presented with an animal to be treated for hypertension

Answer 13

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

Question 14

What is the effect of alpha 1 agonists on vascular tone

Answer 14

vasoconstrict

Question 15

What is the effect of alpha 2 agonists on vascular tone

Answer 15

vasoconstriction followed by ‘pre-synaptic’ vasodilation

They stimulate nitric oxide release which causes local vasodilation

Question 16

Provide 3 examples of alpha 2 agonists

Answer 16

xylazine
detomidine
dexmedetomidine

Question 17

What is the effect of alpha 1 receptor antagonists on the heart and vasculature

Answer 17

They vasodilate arteries and veins
- less impact on veins

It causes a reduction in afterload because it preferentially impacts arteries

Question 18

What other non-alpha 1 antagonist drugs have alpha 1 antagonist effects

Answer 18

acepromazine
quinidine
carvediol

Question 19

What are 2 consequences of alpha antagonism overdose

Answer 19

hypothermia
reduced perfusion

Question 20

What is the effect os nitroglycerin? What is it used for?

Answer 20

vasodilation
- it converts to nitric oxide

used for the acute management of heart failure

Question 21

What are 3 types of drugs with indirect effects on the cardiovascular system

Answer 21

diuretics

ACE inhibitors

angiotensin 2 receptor blockers

Question 22

What is the function of diuretic use for cardiovascular disease

Answer 22

reduce blood volume and mobilize edema

reduce preload

Question 23

What is the primary diuretic used in the treatment of cardiovascular disease

Answer 23

furosemide

Question 24

What are the 3 effects of ACE inhibitors on the body

Answer 24

vasodilation resulting in reduced TPR and afterload

diuretic due to reduced aldosterone and preload

reduced SNS input to the heart

Question 25

What are the adverse effects of ACE inhibitors

Answer 25

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

Question 26

What are 2 examples of common ACEI used

Answer 26

enalapril

benazepril

Question 27

What are the pharmacokinetics of ACEI and how does it influence its implementation

Answer 27

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

Question 28

What is the function of telmisartan and what is it used for?

Answer 28

reduce blood pressure - similar to an ACEI

used mainly for hypertension and proteinuria associated with CKD

Question 29

What are the adverse effects of telmisartan

Answer 29

GI
hypotension
anemia
fetotoxic!