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Pharmacology > The Vascular System > Flashcards

The Vascular System Flashcards

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1
Q
  • Renin
A
  • released by the kidneys in response to  perfusion
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2
Q
  • Angiotensinogen
    (2)
A
  • released by liver
  • converted to angiotensin I by renin
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3
Q
  • Angiotensin I
    (2)
A
  • no known activity
  • converted to angiotensin II by ACE
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4
Q
  • Angiotensin II
    (2)
A
  • causes vasoconstriction, salt retention, vascular growth
  • stimulates release of aldosterone
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5
Q

Direct renin inhibitor
(aliskiren)
MOA

A

Blocks renin activity on angiotensinogen

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6
Q

ACE inhibitors
(captopril, enalapril, etc..)
MOA

A

Prevents ACE from converting angiotensin I to
angiotensin II

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7
Q

Angiotensin receptor blockers
(candesartan, valsartan, etc..)
MOA

A

Blocks angiotensin II activity at the AT1 receptor

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8
Q

Aldosterone antagonists
(eplerenone and spironolactone)
MOA

A

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

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9
Q

Aliskerin
Direct Renin Inhibitor
* Brand name: Tekturna®
* MOA:
* Use:
* ADRs: (3)
* Drug-Drug interactions:
* Increased levels when combined with

A

Direct renin inhibitor- prevent conversion of
angiotensinogen to angiotensin I
Hypertension
Diarrhea(frequent), dyspepsia(occasional), Hypotension
CYP3A4 inhibitors like macrolide
antibiotics

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10
Q

Aliskerin
Direct Renin Inhibitor- Dental Implications
(2)

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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11
Q

ACE inhibitors
Example: Lisinopril
* Brand name: Prinivil® or Zestril®
* MOA:
* Use: (4)
* ADRs: (6)
* Drug-Drug interactions:
(3)

A

inhibits the angiotensin converting enzyme blocking the
conversion of angiotensin I to angiotensin II
Hypertension, heart failure, post-MI, kidney disease
Cough, angioedema, hypotension, acute renal
insufficiency, hyperkalemia, taste disturbances/dry mouth(rare)

  • NSAIDs- reduced anti-hypertensive effect
  • Alcohol- increased anti-hypertensive effect
  • General anesthesia- increased anti-hypertensive effect
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12
Q

ACE Inhibitors
Dental Implications
(4)

A
  • Orthostatic hypotension: After supine positioning, have patient sit upright for
    at least 2 minutes before standing to avoid orthostatic
    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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13
Q

Angiotensin Receptor Blockers
Example: Candesartan
* Brand name: Atacand®
* MOA:
* Use: (3)
* ADRs: (3)
* Drug-Drug interactions:
(3)

A

Blocks the AT1 receptor of angiotensin II
Hypertension, heart failure, kidney disease
Hypotension, dizziness, and hyperkalemia

  • Sedative medications- increased anti-hypotensive effects
  • NSAIDs- reduced anti-hypertensive effect
  • General anesthesia- increased anti-hypertensive effect
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14
Q

Angiotensin Receptor Blockers
Dental Implications
(3)

A
  • Orthostatic hypotension:
  • After supine positioning, have patient sit upright for
    at least 2 minutes before standing to avoid orthostatic
    hypotension
  • Monitor vital signs
  • If dental surgery is anticipated evaluate risk of hypotensive episode
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15
Q

Angiotensin Receptor Neprilsyn Inhibitor (ARNI)
Mechanism of action
(2)

A
  • Sacubitril inhibits neprilysin
    resulting in elevated levels of
    B-type natriuretic peptide
    (BNP)
  • Valsartan blocks the
    angiotensin II AT1 receptor
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16
Q

Sacubitril/Valsartan
Angiotensin Receptor Neprilsyn Inhibitor (ARNI)
* Brand name: Entresto®
* MOA:
* Use:
* ADRs:(3)
* Drug-Drug interactions:
* ACE inhibitors- increased risk of —
* Dental implications: (1)

A

Sacubitril inhibits neprilysin resulting in elevated levels of
B-type natriuretic peptide (BNP) and valsartan blocks the
angiotensin II AT1 receptor
Heart Failure reduced ejection fraction (HFrEF)
Hypotension (18%), hyperkalemia (12%), angioedema (1-2%)
angioedema
Watch to hypotension upon rising

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17
Q

Aldosterone antagonists
Mechanism of action

A

Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)

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18
Q

Aldosterone Antagonist
Example: Spironolactone
* Brand name: Aldactone®
* MOA:
* May also be referred to as a —
* Use: (5)
* ADRs: (4)
* Drug-Drug interactions:
(3)

A

Competitively inhibits the action of aldosterone
potassium-sparing diuretic
Hypertension, heart failure, liver failure, edema, primary
hyperaldosteronism
Hyperkalemia, renal insufficiency, gynecomastia(males), dry
mouth

  • NSAIDs
  • reduced anti-hypertensive effect
  • Increased risk of nephrotoxicity
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19
Q

Aldosterone Antagonists
Dental Implications
(2)

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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20
Q

Key Mediators
* Vasoconstriction
(2)
* Vasodilation
(2)

A
  • Angiotensin II
  • Endothelin-1
  • Nitric oxide
  • Prostaglandin
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21
Q

Increase [Ca++] activates myosin light-chain kinase
(3)

A

1) Phosphorylation of myosin
2) Sensitization of the myofilaments to calcium
3) Inhibition of myosin phosphatase

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22
Q
  • Endothelin-1
A
  • Produced in vascular tissue, smooth muscle, brain,
    kidney, intestines, and adrenal gland
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23
Q
  • Endothelin-2
A
  • Produced in kidney and intestines
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24
Q
  • Endothelin-3
A
  • Produced in brain, kidney, intestine, adrenal gland
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25
* Receptor types * ETA- (3) * ETB- (2)
vasoconstriction, bronchoconstriction, increase aldosterone secretion vasodilation, inhibition of platelet aggregation
26
Nitric Oxide
* Activates guanylyl cyclase resulting in  cGMP   [Ca++] leading to relaxation
27
Prostaglandins
* PGI2- prostacyclin * Binds to I prostanoid receptor (IP) * Activates adenylyl cyclase resulting in increase cAMP = decrease [Ca++] leading to relaxation * Also inhibit platelet aggregation * PGG2 and PGH2- prostaglandin endoperoxide intermediates * Have some constricting activity
28
Direct Acting Vasodilators (5)
* Calcium Channel Blockers- * Minoxidil- * Nitroprusside (and other nitrates) - * Hydralazine- * Ethanol-
29
* Calcium Channel Blockers-
lower intracellular Ca++ concentration
30
* Dihydrodpyridine type are more selective for
smooth muscle
31
* Minoxidil-
opens KATP channels- turns off voltage-dependent Ca++ channels
32
* Nitroprusside (and other nitrates) -
increases intracellular nitric oxide (NO) concentration
33
* Hydralazine-
blocks intracellular release of Ca++
34
* Ethanol- unclear-
probably thru alteration of centrally controlled vasodilation
35
Dihydropyridine CCB (2)
* More selective for calcium channels in peripheral vasculature * More effective for hypertension
36
Non-Dihydropyridine CCB (2)
* More selective for calcium channels in myocardium * More effective for arrhythmias
37
Calcium channel blockers- ex: Amlodipine Direct Acting Vasodilators * Brand name: Norvasc® * MOA: * Use: (2) * ADRs: (6) * Drug-Drug interactions: (2)
Blocks L-type calcium channel in the vascular smooth muscle (Dihydropyridine type) Hypertension, and angina * Edema (common), dizziness, lightheadedness, hypotension, flushing, gingival enlargement (rare- more common with DHP type) * Hypotension with sedatives, opioids, general and inhaled anesthetics * NSAIDS reduce blood pressure lowering effect
38
Calcium channel blockers Dental Implications
* 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
39
Minoxidil Mechanism of action: (5)
* 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
40
Minoxidil Direct Acting Vasodilator * Brand name: Loniten® * MOA: * Use: * ADRs: (3) * Drug-Drug interactions: (2)
causes smooth muscle relaxation by opening KATP channels Severe resistant hypertension Hair growth, edema, photosensitivity(rare) * Reduced anti-hypertensive effect with NSAIDs and sympathomimetic * Increased anti-hypertensive effect with sedatives and other drugs used for conscious sedation
41
Minoxidil Dental Implications (3)
* 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
* Sodium Nitroprusside (2)
* Only available for intravenous administration * Used for acute control of hypertension
43
* Oral/topical nitrate formulation (2)
* Used mainly for angina * Not effective as anti-hypertensive agent, but may have hypotensive side effects
44
Sodium Nitroprusside Direct Acting Vasodilators * Brand name: Nitropress® * MOA: * Use: (1) * ADRs: (4) * Drug-Drug interactions: (1) * Dental implications: (1)
causes smooth muscle relaxation by increasing intracellular nitric oxide concentrations Hypertensive crisis Methemoglobinemia, hypotension, dizziness, thiocyanate toxicity * PDE-5 inhibitors (i.e. sildenafil) * none
45
Hydralazine Mechanism of action(maybe) Proposed MOA:
interference with action of IP3 on calcium release from sarcoplasmic reticulum
46
Hydralazine Direct Acting Vasodilator * Brand name: Apresoline® * MOA: * Use: (2) * ADRs: (4) * Drug-Drug interactions: (1)
Direct acting vasodilator thru interference with action of IP3 on calcium release from sarcoplasmic reticulum Hypertension, and heart failure * Headache, palpitations, GI disturbances, flushed face(rare) * Reduced anti-hypertensive effect with NSAIDs and sympathomimetic
47
Hydralazine Direct Acting Vasodilator-Dental Implications (3)
* 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
48
Pulmonary Hypertension * A rare disorder * Estimated prevalence of --- cases per million persons * Defined by a mean pulmonary artery pressure ≥ --- at rest
15-50 25mmHg
49
Pulmonary Hypertension Sub-divided into five classifications depending in etiology * Group I- * Group II- * Group III- * Group IV- * Group V-
Pulmonary arterial HTN (PAH) – primary pulmonary HTN Pulmonary HTN due to left heart disease Pulmonary HTN due to lung disease Chronic thromboembolic pulmonary HTN (CTEPH) Pulmonary HTN with unclear mechanism
50
Endothelin receptor antagonist (ERA) Mechanism of Action
Mechanism of action: * Block the ETA receptor * Decreasing the formation of IP3 * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation Most ERAs block both ETA and ETB - but have a high affinity for ETA
51
Bosentan Endothelin receptor antagonists * Brand name: Tracleer® * MOA: * Use: * ADRs: (4) * Drug-Drug interactions: (1) * Pregnancy category- --
Endothelin 1 receptor antagonist Pulmonary hypertension WHO FC III and IV * Headache, flushed face, dyspepsia, liver dysfunction * Increased levels when used with ketoconazole X
52
Bosentan Endothelin receptor antagonists-Dental Implications (5)
* 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
53
Phosphodiesterase 5 (PDE5) inhibitors Mechanism of Action
Mechanism of action: * Inhibit action of PDE5 * Increase intracellular cGMP concentration * Lowering the intracellular Ca++ concentration * Resulting in vascular smooth muscle relaxation PDE5 inhibitors are also used (more commonly) to treat erectile dysfunction
54
Sildenafil Phosphodiesterase 5 (PDE5) inhibitor * Brand name: Revatio™(PAH) or Viagra®(ED) * MOA: * Use: (3) * ADRs: (4) * Drug-Drug interactions: (2)
Phosphodiesterase 5 inhibitor Pulmonary hypertension, erectile dysfunction, and BPH * Headache, flushed face, dyspepsia, rash * Sodium Nitroprusside- avoid combination- severe hypotension * Increased levels with CYP 3A4 inhibition (i.e. erythromycin, clarithromycin, etc.)
55
Sildenafil Phosphodiesterase 5 (PDE5) inhibitor-Dental Implications (5)
* 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
56
Prostacyclin analogues Mechanism of Action (5)
Mechanism of action: * 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
57
Treprostinil Prostacyclin analogue * Brand name: Orenitram®(PO), Tyvaso™(INH), Remodulin™(IV/SQ) * MOA: * Use: * ADRs: (6) * Drug-Drug interactions: (1)
Prostacyclin analogue Pulmonary hypertension * Headache, flushing, hypotension, infusion site pain * jaw pain, inhibition of platelet aggregation ( increase r/o bleeding) * Other drugs that increased r/o bleeding (i.e. NSAIDS)
58
Prostacyclin analogues Dental Implications (4)
* 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
59
Selexipag Mechanism of Action Mechanism of action: (5)
* 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
60
Selexipag Selective prostacyclin IP receptor agonist * Brand name: Uptravi® * MOA: * Use: * ADRs: (2) * Drug-Drug interactions: (1)
IP receptor agonist Pulmonary hypertension Group I * Flushing, Headache(65%), diarrhea (42%) * Jaw pain (26%) * None noted
61
Selexipag Selective prostacyclin IP receptor agonist (3)
* Monitor vital signs * High risk patient * Acute pulmonary hypertension could occur * Limit or avoid vasoconstrictors
62
Soluble guanylate cyclase stimulator Mechanism of Action Mechanism of action: (4)
* 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
63
Riociguat Soluble guanylate cyclase stimulator * Brand name: Adempas® * MOA: * Use: * ADRs: (4) * Drug-Drug interactions: (2) * Pregnancy category- ---
Soluble guanylate cyclase stimulator Pulmonary hypertension group 1 and 4 (CTEPH) * Hypotension, dyspepsia, headache, edema * Avoid combination with PDE5 inhibitors * Decrease effects with CYP 3A4/2C8 inducers X
64
Riociguat Soluble guanylate cyclase stimulator-Dental Implications (4)
* 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

Pharmacology (13 decks)

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