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Pharmacology II > Cardiovascular: Vasodilators > Flashcards

Cardiovascular: Vasodilators Flashcards

1
Q

What causes the resistance of blood flow?

A

degree of smooth muscle contractions

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2
Q

What does increase contraction of smooth muscle cause?

A

increased resistance & increased blood pressure

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3
Q

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

A

sympathetic neurotransmitters & hormones

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4
Q

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

A

nitric oxide, prostacyclin 2

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5
Q

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

A

endothelin

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6
Q

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

A

Ach, histamine, bradykinin

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7
Q

How does nitric oxide cause vasodilation?

A

increasing cGMP formation

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8
Q

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

A
  • inhibit Ca2+ entry into cells through voltage-gated Ca2+ channels
  • increase intracellular cAMP or cGMP concentration
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9
Q

How does cAMP caues vasodilation?

A

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

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10
Q

How does cGMP cause vasodilation

A

promote dephosphorylation of myocin, resulting in relaxation

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11
Q

What do venodilators do?

A
  • dilates veins and reduces filling pressure of right & left ventricles
  • decreases myocardial oxygen demand
  • decreases preload
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12
Q

What does arterial vasodilator do?

A
  • decrease the afterload
  • improves forward flow
  • reduce regurgitative blood flow
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13
Q

Contraindication of vasodilators

A

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

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14
Q

What are the benefits of vasodilators

A
  • decrease preload
  • decrease afterload
  • increase tissue perfusion for animals that have increased sympathetic tone
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15
Q

What are the indications of vasodilators

A
  • congestive heart failure
  • mitral valvular regurgitation
  • renal failure
  • hypertension
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16
Q

What type of vasodilator is ACE inhibitor

A

mixed vasodilator (arterial &venous system)

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17
Q

Mechanism of action of ACE inhibitor

A

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

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18
Q

Beneficial mechanisms of ACE inhibitor

A
  • decrease angiotensin II; vasoconstrictor (most important)
  • decrease aldosterone; less Na+ retention
  • decrease breakdown of bradykinin; vasodilator
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19
Q

What does ACE inhibitor cause beneficially?

A
  • reduce vasoconstriction
  • reduce arterial resistance (decrease afterload)
  • reduce venous hypertension (decrease preload)
  • decrease salt & water retention
  • increase cardiac output
  • inhibit cardiac & vascular remodeling
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20
Q

How does ACE inhibitor reduce heart rate?

A
  • decreased circulation of catecholamine
  • dilation of capacitance vein
    decrease baroreceptor sensitivity
  • increased prostaglandin synthesis
  • decrease sympathetic tone
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21
Q

What is Enalopril?

A
  • ACE inhibitor
  • prodrug
  • requires P450 metabolism to be activated (enalaprilat)
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22
Q

How are enalopril excreted?

A

renal excretion

23
Q

What may require dose adjustment for enalopril

A

decreased renal function

24
Q

When to assess response after giving enalopril?

A

7-14 days due to slow onset

25
Q

What is benazepril?

A
  • ACE inhibitor
  • prodrug
  • metabolized to active benazeprilat
26
Q

Benefit of using Benazepril

A

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

27
Q

What is captopril?

A
  • older ACE inhibitor
28
Q

When are captopril used?

A
  • preferred in animals with severe hepatic disease
  • not a prodrug
29
Q

Adverse effects of Captopril

A

greater chance of hypotension or GI irritation

30
Q

General adverse effects of ACE inhibitor

A
  • dose-related hypotension
  • GI upset
  • hyperkalemia (when used with spironolactone)
31
Q

What drug would potentially interact with ACE inhibitors?

A

NSAIDs

32
Q

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

A

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

33
Q

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

A

volume depletion and hypotension can lead to renal insufficiency

34
Q

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

A
  • 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
35
Q

What are some angiotensin II receptor antagonists?

A

Telmisartan

36
Q

Mechanism of action for Angiotensin II receptor antagonist

A
  • competitive inhibitor of angio tensin II at the ATII1 receptor
  • long-lasting binding
  • no affinity to other ATII receptors
37
Q

What does ATII1 receptor cause?

A
  • vasoconstriction
  • Na & water retention
  • increased aldosterone synthesis
  • organ remodeling
38
Q

What does giving Angiotensin II receptor antagonist result in?

A
  • decrease renal vasoconstriction
  • Na+ & water retention
  • decrease aldosterone synthesis
39
Q

Indications of Angiotensin II receptor antagonist

A
  • reduction of proteinuria in cats with chronic renal disease
  • treatment of systemic hypertension
40
Q

Pharmacokinetics of Angiotensin II receptor antagonists

A
  • highly lipophilic
  • metabolized in liver
  • excreted mainly in feces as unchanged drugs
41
Q

Adverse effects of angiotensin II receptor antagonists

A
  • mild transient GI effects
  • transient hypertension
42
Q

What can an overdose of Angiotensin II receptor antagonist cause?

A

hypotension, anemia, increased urea

43
Q

contraindication of angiotensin II receptor antagonist

A
  • ## animal with hypotension
44
Q

Why does chronic renal disease cause hypertension?

A
  • impaired Na+ handling
  • excessive RAAS activation
  • increased sympathetic stimulation
  • release of endothelial factor
45
Q

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

A

provide better decrease in proteinuria & chronic renal disease associated hypertension

46
Q

What is nitrate?

A
  • venodilator
  • prodrug
47
Q

Nitrate mechanism of action

A
  • 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
48
Q

What does nitrate do at low doses

A
  • dilate veins
  • reduce venous pressure (decrease preload)
49
Q

What does nitrate do at higher doses?

A
  • dilates veins & arteries which decreases the pre- & afterload
  • increase in the coronary vasodilation and improves oxygenation of the blood to heart
50
Q

What is special about nitroglycerin?

A
  • topical formulation only due to significant first pass effect
  • repetitive use can cause development of tolerance
51
Q

Effects of nitroglycerin

A
  • dilate both arteries & veins
  • primarily used to decrease preload
52
Q

Indications for nitroglycerin

A

acute therapy in patients with pulomnary edema & congestive heart failure

53
Q

Adverse effects of nitroglycerin

A

hypotension

Pharmacology II (8 decks)

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