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Vascular System Flashcards

1
Q

Renin-angiotensin-aldosterone system image?

A
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2
Q

What are the parts of the renin-angiotensin-aldosterone system?

A
  • Renin
    — released by the kidneys in response to ↓ perfusion
  • Angiotensinogen
    — released by liver
    — converted to angiotensin I by renin
  • Angiotensin I
    — no known activity
    — converted to angiotensin II by ACE
  • Angiotensin II
    — causes vasoconstriction, salt retention, vascular growth
    — stimulates release of aldosterone
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3
Q

What is the job of renin?

A
  • released by the kidneys in response to ↓ perfusion
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4
Q

What is the job of angiotensinogen?

A
  • released by liver
  • converted to angiotensin I by renin
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5
Q

What is the job of angiotensin I?

A
  • no known activity
  • converted to angiotensin II by ACE
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6
Q

What is the job of angiotensin II?

A
  • causes vasoconstriction, salt retention, vascular growth
  • stimulates release of aldosterone
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7
Q

What is the mechanism of action of Direct renin inhibitor (aliskiren)?

A

Blocks renin activity on angiotensinogen

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8
Q

What is the mechanism of action of ACE inhibitors (captopril, enalapril, etc..)?

A

Prevents ACE from converting angiotensin I to angiotensin II

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9
Q

What is the mechanism of action of Angiotensin receptor blockers (candesartan, valsartan, etc..)?

A

Blocks angiotensin II activity at the AT1 receptor

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10
Q

What is the mechanism of action of Aldosterone antagonists (eplerenone and spironolactone)?

A

Blocks the activity of aldosterone in the kidneys and other tissues (i.e. heart, smooth muscle)

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11
Q

What are the common adverse drug reactions for direct renin inhibitor (aliskiren)?

A
  • diarrhea (frequent)
  • dyspepsia(occasional)
  • Hypotension
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12
Q

What are the common adverse drug reactions for ACE inhibitors (captopril, enalapril, etc..)?

A
  • Cough (up to 10%)
  • Angioedema (<1%) / Agranulocytosis (rare)
  • Potassium excess (hyperkalemia 1-10%)/Proteinuria (rare)
  • Taste change (2-4%)
  • Orthostatic hypotension (~5%)
  • Pregnancy (contraindication)
  • Renal artery stenosis- bilateral
  • Increased serum creatinine (1-10%- transient)
  • Leukopenia (rare) / Liver Toxicity (rare)
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13
Q

What are the common adverse drug reactions for angiotensin receptor blockers (candesartan, valsartan, etc..)?

A

Halt Dangerous Hypertension
- Headache / Hypotension
- Dizziness
- Hyperkalemia

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14
Q

What are the common adverse drug reactions for aldosterone antagonists (eplerenone and spironolactone)?

A
  • Hyperkalemia (16%)
  • Renal insufficiency
  • Gynecomastia (9% of males- spironolactone)
  • Dry mouth (rare)
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15
Q

What are the common drug-drug reactions for direct renin inhibitor (aliskiren)?

A

Increased levels when combined with CYP3A4 inhibitors like macrolide antibiotics

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16
Q

What are the common drug-drug reactions for ACE inhibitors (captopril, enalapril, etc..)?

A
  • NSAIDs- reduced anti-hypertensive effect
  • Alcohol- increased anti-hypertensive effect
  • General anesthesia- increased anti-hypertensive effect
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17
Q

What are the common drug-drug reactions for angiotensin receptor blockers (candesartan, valsartan, etc..)?

A
  • Sedative medications- increased anti-hypotensive effects
  • NSAIDs- reduced anti-hypertensive effect
  • General anesthesia- increased anti-hypertensive effect
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18
Q

What are the common drug-drug reactions for aldosterone antagonists (eplerenone and spironolactone)?

A
  • NSAIDs
    — reduced anti-hypertensive effect
    — increased risk of nephrotoxicity
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19
Q

What are the dental implications for direct renin inhibitor (aliskiren)?

A
  • Monitor vital signs
  • After supine positioning, have patient sit upright for at least 2 minutes before standing to avoid orthostatic hypotension
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20
Q

What are the dental implications for ACE inhibitors (captopril, enalapril, etc..)?

A
  • Orthostatic hypotension:
    — After supine positioning, have patient sit upright at least 2 minutes before standing to avoid hypotension
  • Monitor vital signs
  • ACE Inhibitor induced cough may make longer dental procedures difficult
  • If dental surgery is anticipated evaluate risk of hypotensive episode
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21
Q

What are the dental implications for angiotensin receptor blockers (candesartan, valsartan, etc..)?

A
  • Orthostatic hypotension:
    — After supine positioning, have patient sit upright at least 2 minutes before standing to avoid hypotension
  • Monitor vital signs
  • If dental surgery is anticipated evaluate risk of hypotensive episode
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22
Q

What are the dental implications for aldosterone antagonists (eplerenone and spironolactone)?

A
  • Monitor vital signs
  • Assess salivary flow as a factor in caries, periodontal disease, and candidiasis secondary to dry mouth from diuretic effect
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23
Q

What is the mechanism that results in smooth muscle contraction and relaxation?

A
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24
Q

What is the role of endothelin in vascular tone?

A
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25
What does endothelin do in vascular tone?
* Endothelin-1 --- Produced in vascular tissue, smooth muscle, brain, kidney, intestines, and adrenal gland * Endothelin-2 --- Produced in kidney and intestines * Endothelin-3 --- Produced in brain, kidney, intestine, adrenal gland * Receptor types --- ETA- vasoconstriction, bronchoconstriction, ↑ aldosterone secretion --- ETB- vasodilation, inhibition of platelet aggregation
26
What are the mechanism related to the arterial blood pressure control (image)?
27
What are the mechanism related to the arterial blood pressure control?
Nitric Oxide * Activates guanylyl cyclase resulting in ↑ cGMP → ↓ [Ca++] leading to relaxation Prostaglandins * PGI2- prostacyclin --- Binds to I prostanoid receptor (IP) --- Activates adenylyl cyclase resulting in ↑ cAMP → ↓ [Ca++] leading to relaxation --- Also inhibit platelet aggregation * PGG2 and PGH2- prostaglandin endoperoxide intermediates --- Have some constricting activity
28
What is the mechanism of action of calcium channel blockers?
Dihydropyridine CCB * More selective for calcium channels in peripheral vasculature * More effective for hypertension Non-Dihydropyridine CCB * More selective for calcium channels in myocardium * More effective for arrhythmias
29
What is the mechanism of action of minoxidil?
* Opening KATP channels * Resulting in hyperpolarization of cells * Turns off voltage dependent Ca++ channels * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
30
What is the mechanism of action of nitroprusside?
* Sodium Nitroprusside --- Only available for intravenous administration --- Used for acute control of hypertension * Oral/topical nitrate formulation --- Used mainly for angina --- Not effective as anti-hypertensive agent, but may have hypotensive side effects
31
What is the mechanism of action of hydralazine?
interference with action of IP3 on calcium release from sarcoplasmic reticulum
32
What is the common adverse drug rections for calcium channel blockers?
- Edema (common) - dizziness - lightheadedness - hypotension - flushing - gingival enlargement (rare- more common with DHP type)
33
What is the common adverse drug rections for minoxidil?
Hair growth edema photosensitivity(rare)
34
What is the common adverse drug rections for nitroprusside?
- Methemoglobinemia - hypotension - dizziness - thiocyanate toxicity
35
What is the common adverse drug rections for hydralazine?
- Headache - palpitations - GI disturbances - flushed face(rare)
36
What is the common drug-drug interactions for calcium channel blockers?
* Hypotension with sedatives, opioids, general and inhaled anesthetics * NSAIDS reduce blood pressure lowering effect
37
What is the common drug-drug interactions for minoxidil?
* Reduced anti-hypertensive effect with NSAIDs and sympathomimetic * Increased anti-hypertensive effect with sedatives and other drugs used for conscious sedation
38
What is the common drug-drug interactions for nitroprusside?
* PDE-5 inhibitors (i.e. sildenafil)
39
What is the common drug-drug interactions for hyralazine?
* Reduced anti-hypertensive effect with NSAIDs and sympathomimetic
40
What are the dental implications for calcium channel blockers?
* Gingival hyperplasia (up to 10%) --- Place on frequent recall to monitor for gingival hyperplasia * Monitor vital signs * Orthostatic hypotension: --- After supine positioning, have patient sit upright for at least 2 minutes before standing to avoid orthostatic hypotension * Use vasoconstrictors and inhaled anesthetics with caution
41
What are the dental implications for minoxidil?
* Monitor vital signs * Orthostatic hypotension: --- After supine positioning, have patient sit upright for at least 2 minutes before standing to avoid orthostatic hypotension * Avoid or limit dose of vasoconstrictor
42
What are the dental implications for nitroprusside?
none
43
What are the dental implications for hydralazine?
* Monitor vital signs * Orthostatic hypotension: --- After supine positioning, have patient sit upright for at least 2 minutes before standing to avoid orthostatic hypotension * Avoid or limit dose of vasoconstrictor
44
What are the different types of pulmonary hypertension?
* Group I- Pulmonary arterial HTN (PAH) – primary pulmonary HTN * Group II- Pulmonary HTN due to left heart disease * Group III- Pulmonary HTN due to lung disease * Group IV- Chronic thromboembolic pulmonary HTN (CTEPH) * Group V- Pulmonary HTN with unclear mechanism
45
What is the mechanism of action for Endothelin receptor antagonists (bosentan)?
* Block the ETA receptor * Decreasing the formation of IP3 * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
46
What is the mechanism of action for phosphodiesterase 5 (PDE5) inhibitors (sildenafil)?
* Inhibit action of PDE5 * Increase intracellular cGMP concentration * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
47
What is the mechanism of action for prostacyclin analogues (treprostinil)?
* Bind to prostacyclin receptor (IP) * Stimulate activity of adenylate cyclase (AC) * Increase intracellular cyclic AMP levels * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
48
What is the mechanism of action for selective prostacyclin IP receptor agonists (selexipag)?
* Selective prostacyclin IP receptor agonist * Stimulate activity of adenylate cyclase (AC) * Increase intracellular cyclic AMP levels * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
49
What is the mechanism of action for soluble guanylate cyclase stimulator (riociguat)?
* Sensitizes guanylyl cyclase to nitric oxide but also directly activates guanylyl cyclase * Increase intracellular cGMP concentration * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation
50
What is the common adverse drug reactions for Endothelin receptor antagonists (bosentan)?
- headache - flushed face - dyspepsia - liver dysfunction
51
What is the common adverse drug reactions for phosphodiesterase 5 (PDE5) inhibitors (sildenafil)?
Headache flushed face dyspepsia rash
52
What is the common adverse drug reactions for prostacyclin analogues (treprostinil)?
* Headache, flushing, hypotension, infusion site pain * jaw pain, inhibition of platelet aggregation (↑ r/o bleeding)
53
What is the common adverse drug reactions for selective prostacyclin IP receptor agonists (selexipag)?
* Flushing, Headache(65%), diarrhea (42%) * Jaw pain (26%)
54
What is the common adverse drug reactions for soluble guanylate cyclase stimulator (riociguat)?
- Hypotension - dyspepsia - headache - edema
55
What is the common drug-drug interactions for Endothelin receptor antagonists (bosentan)?
* Increased levels when used with ketoconazole
56
What is the common drug-drug interaction for phosphodiesterase 5 (PDE5) inhibitors (sildenafil)?
* Sodium Nitroprusside- avoid combination- severe hypotension * Increased levels with CYP 3A4 inhibition (i.e. erythromycin, clarithromycin, etc.)
57
What is the common drug-drug interactions for prostacyclin analogues (treprostinil)?
* Other drugs that increased r/o bleeding (i.e. NSAIDS)
58
What is the common drug-drug interactions for selective prostacyclin IP receptor agonists (selexipag)?
* None noted
59
What is the common drug-drug interactions for soluble guanylate cyclase stimulator (riociguat)?
* Avoid combination with PDE5 inhibitors * Decrease effects with CYP 3A4/2C8 inducers
60
What is the common drug-drug interactions for Endothelin receptor antagonists (bosentan)?
* Monitor vital signs * High risk patient --- Acute pulmonary hypertension could occur * Bleeding gums has been reported with endothelin receptor antagonists (no specific reports with bosentan) * Limit or avoid vasoconstrictors * Low risk of orthostatic hypotension
61
What is the common drug-drug interaction for phosphodiesterase 5 (PDE5) inhibitors (sildenafil)?
* Monitor vital signs * High risk patient- if using for PAH --- Acute pulmonary hypertension could occur * Limit or avoid vasoconstrictors * Avoid use of nitroglycerin of nitroprusside * Low risk of orthostatic hypotension
62
What is the common drug-drug interactions for prostacyclin analogues (treprostinil)?
* Monitor vital signs * High risk patient --- Acute pulmonary hypertension could occur --- Continuous infusion can not be interrupted * Increased risk of bleeding --- Inhibits platelet aggregation * Limit or avoid vasoconstrictors
63
What is the common drug-drug interactions for selective prostacyclin IP receptor agonists (selexipag)?
* Monitor vital signs * High risk patient --- Acute pulmonary hypertension could occur * Limit or avoid vasoconstrictors
64
What is the common drug-drug interactions for soluble guanylate cyclase stimulator (riociguat)?
* Monitor vital signs * High risk patient --- Acute pulmonary hypertension could occur * Limit or avoid vasoconstrictors * Increased risk of bleeding --- Risk of unanticipated bleeding during procedure

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