Cardiovascular: Vasodilators

Question 1

What causes the resistance of blood flow?

Answer 1

degree of smooth muscle contractions

Question 2

What does increase contraction of smooth muscle cause?

Answer 2

increased resistance & increased blood pressure

Question 3

What controls the vascular smooth muscle contraction/ relaxation of blood vessels?

Answer 3

sympathetic neurotransmitters & hormones

Question 4

What does endothelial cells of the blood vessels secrete to dilate blood vessels?

Answer 4

nitric oxide, prostacyclin 2

Question 5

What does endothelial cells of the blood vessel secret to constrict blood vessels?

Answer 5

endothelin

Question 6

What are some neurotransmitters that cause vasodilation indirectly by causing nitric oxide release?

Answer 6

Ach, histamine, bradykinin

Question 7

How does nitric oxide cause vasodilation?

Answer 7

increasing cGMP formation

Question 8

What are some mechanisms that vasodilators use to relax smooth muscle?

Answer 8

• inhibit Ca2+ entry into cells through voltage-gated Ca2+ channels
• increase intracellular cAMP or cGMP concentration

Question 9

How does cAMP caues vasodilation?

Answer 9

inactivation of myocin-light chain kinase (hence no contraction)

Question 10

How does cGMP cause vasodilation

Answer 10

promote dephosphorylation of myocin, resulting in relaxation

Question 11

What do venodilators do?

Answer 11

• dilates veins and reduces filling pressure of right & left ventricles
• decreases myocardial oxygen demand
• decreases preload

Question 12

What does arterial vasodilator do?

Answer 12

• decrease the afterload
• improves forward flow
• reduce regurgitative blood flow

Question 13

Contraindication of vasodilators

Answer 13

animals with:
- cerebrovascular insufficiency
- coronary artery disease
- septic shock

Question 14

What are the benefits of vasodilators

Answer 14

• decrease preload
• decrease afterload
• increase tissue perfusion for animals that have increased sympathetic tone

Question 15

What are the indications of vasodilators

Answer 15

• congestive heart failure
• mitral valvular regurgitation
• renal failure
• hypertension

Question 16

What type of vasodilator is ACE inhibitor

Answer 16

mixed vasodilator (arterial &venous system)

Question 17

Mechanism of action of ACE inhibitor

Answer 17

inactivate the enzyme that converts angiotensin I to angiotensin II in the RAS system

Question 18

Beneficial mechanisms of ACE inhibitor

Answer 18

• decrease angiotensin II; vasoconstrictor (most important)
• decrease aldosterone; less Na+ retention
• decrease breakdown of bradykinin; vasodilator

Question 19

What does ACE inhibitor cause beneficially?

Answer 19

• reduce vasoconstriction
• reduce arterial resistance (decrease afterload)
• reduce venous hypertension (decrease preload)
• decrease salt & water retention
• increase cardiac output
• inhibit cardiac & vascular remodeling

Question 20

How does ACE inhibitor reduce heart rate?

Answer 20

• decreased circulation of catecholamine
• dilation of capacitance vein
  decrease baroreceptor sensitivity
• increased prostaglandin synthesis
• decrease sympathetic tone

Question 21

What is Enalopril?

Answer 21

• ACE inhibitor
• prodrug
• requires P450 metabolism to be activated (enalaprilat)

Question 22

How are enalopril excreted?

Answer 22

renal excretion

Question 23

What may require dose adjustment for enalopril

Answer 23

decreased renal function

Question 24

When to assess response after giving enalopril?

Answer 24

7-14 days due to slow onset

Question 25

What is benazepril?

Answer 25

- ACE inhibitor - prodrug - metabolized to active benazeprilat

Question 26

Benefit of using Benazepril

Answer 26

not as dependent on renal clearance (still requires dosing adjustment in renal failure patients)

Question 27

What is captopril?

Answer 27

- older ACE inhibitor

Question 28

When are captopril used?

Answer 28

- preferred in animals with severe hepatic disease - not a prodrug

Question 29

Adverse effects of Captopril

Answer 29

greater chance of hypotension or GI irritation

Question 30

General adverse effects of ACE inhibitor

Answer 30

- dose-related hypotension - GI upset - hyperkalemia (when used with spironolactone)

Question 31

What drug would potentially interact with ACE inhibitors?

Answer 31

NSAIDs

Question 32

How can the use of furosemide & ACE inhibitor complement each other?

Answer 32

Furosemide acts quickly while ACE inhibitor takes a few weeks for the ACE inhibitor to reach steady state

Question 33

What are the adverse effects of Furosemide in combination with ACE inhibitor

Answer 33

volume depletion and hypotension can lead to renal insufficiency

Question 34

What protocol should we follow to avoid adverse effects of the furosemide & ACE inhibitor combination?

Answer 34

- start animal on furosemide - add on ACE inhibitor once patient is stable - decrease furosemide dose by 25~50% as the ACE inhibitor starts to work

Question 35

What are some angiotensin II receptor antagonists?

Answer 35

Telmisartan

Question 36

Mechanism of action for Angiotensin II receptor antagonist

Answer 36

- competitive inhibitor of angio tensin II at the ATII1 receptor - long-lasting binding - no affinity to other ATII receptors

Question 37

What does ATII1 receptor cause?

Answer 37

- vasoconstriction - Na & water retention - increased aldosterone synthesis - organ remodeling

Question 38

What does giving Angiotensin II receptor antagonist result in?

Answer 38

- decrease renal vasoconstriction - Na+ & water retention - decrease aldosterone synthesis

Question 39

Indications of Angiotensin II receptor antagonist

Answer 39

- reduction of proteinuria in cats with chronic renal disease - treatment of systemic hypertension

Question 40

Pharmacokinetics of Angiotensin II receptor antagonists

Answer 40

- highly lipophilic - metabolized in liver - excreted mainly in feces as unchanged drugs

Question 41

Adverse effects of angiotensin II receptor antagonists

Answer 41

- mild transient GI effects - transient hypertension

Question 42

What can an overdose of Angiotensin II receptor antagonist cause?

Answer 42

hypotension, anemia, increased urea

Question 43

contraindication of angiotensin II receptor antagonist

Answer 43

- animal with hypotension -

Question 44

Why does chronic renal disease cause hypertension?

Answer 44

- impaired Na+ handling - excessive RAAS activation - increased sympathetic stimulation - release of endothelial factor

Question 45

Wht use Angiotensin II receptor antagonist in combination with ACE inhibitor?

Answer 45

provide better decrease in proteinuria & chronic renal disease associated hypertension

Question 46

What is nitrate?

Answer 46

- venodilator - prodrug

Question 47

Nitrate mechanism of action

Answer 47

- converted into nitric oxide once in blood - act as endogenous nitric oxide and increase cGMP formation - dilate blood vessels due to increased intracellular cGMP concentration and inhibit smooth muscle contraction

Question 48

What does nitrate do at low doses

Answer 48

- dilate veins - reduce venous pressure (decrease preload)

Question 49

What does nitrate do at higher doses?

Answer 49

- dilates veins & arteries which decreases the pre- & afterload - increase in the coronary vasodilation and improves oxygenation of the blood to heart

Question 50

What is special about nitroglycerin?

Answer 50

- topical formulation only due to significant first pass effect - repetitive use can cause development of tolerance

Question 51

Effects of nitroglycerin

Answer 51

- dilate both arteries & veins - primarily used to decrease preload

Question 52

Indications for nitroglycerin

Answer 52

acute therapy in patients with pulomnary edema & congestive heart failure

Question 53

Adverse effects of nitroglycerin

Answer 53

hypotension