The Vascular System Flashcards
- Renin
- released by the kidneys in response to perfusion
- Angiotensinogen
(2)
- released by liver
- converted to angiotensin I by renin
- Angiotensin I
(2)
- no known activity
- converted to angiotensin II by ACE
- Angiotensin II
(2)
- causes vasoconstriction, salt retention, vascular growth
- stimulates release of aldosterone
Direct renin inhibitor
(aliskiren)
MOA
Blocks renin activity on angiotensinogen
ACE inhibitors
(captopril, enalapril, etc..)
MOA
Prevents ACE from converting angiotensin I to
angiotensin II
Angiotensin receptor blockers
(candesartan, valsartan, etc..)
MOA
Blocks angiotensin II activity at the AT1 receptor
Aldosterone antagonists
(eplerenone and spironolactone)
MOA
Blocks the activity of aldosterone in the kidneys
and other tissues (i.e. heart, smooth muscle)
Aliskerin
Direct Renin Inhibitor
* Brand name: Tekturna®
* MOA:
* Use:
* ADRs: (3)
* Drug-Drug interactions:
* Increased levels when combined with
Direct renin inhibitor- prevent conversion of
angiotensinogen to angiotensin I
Hypertension
Diarrhea(frequent), dyspepsia(occasional), Hypotension
CYP3A4 inhibitors like macrolide
antibiotics
Aliskerin
Direct Renin Inhibitor- Dental Implications
(2)
- Monitor vital signs
- After supine positioning, have patient sit upright
for at least 2 minutes before standing to avoid
orthostatic hypotension
ACE inhibitors
Example: Lisinopril
* Brand name: Prinivil® or Zestril®
* MOA:
* Use: (4)
* ADRs: (6)
* Drug-Drug interactions:
(3)
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
ACE Inhibitors
Dental Implications
(4)
- 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
Angiotensin Receptor Blockers
Example: Candesartan
* Brand name: Atacand®
* MOA:
* Use: (3)
* ADRs: (3)
* Drug-Drug interactions:
(3)
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
Angiotensin Receptor Blockers
Dental Implications
(3)
- 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
Angiotensin Receptor Neprilsyn Inhibitor (ARNI)
Mechanism of action
(2)
- Sacubitril inhibits neprilysin
resulting in elevated levels of
B-type natriuretic peptide
(BNP) - Valsartan blocks the
angiotensin II AT1 receptor
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)
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
Aldosterone antagonists
Mechanism of action
Competitive antagonist of the
aldosterone receptor
(myocardium, arterial walls, kidney)
Aldosterone Antagonist
Example: Spironolactone
* Brand name: Aldactone®
* MOA:
* May also be referred to as a —
* Use: (5)
* ADRs: (4)
* Drug-Drug interactions:
(3)
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
Aldosterone Antagonists
Dental Implications
(2)
- Monitor vital signs
- Assess salivary flow as a factor in caries,
periodontal disease, and candidiasis secondary to
dry mouth from diuretic effect
Key Mediators
* Vasoconstriction
(2)
* Vasodilation
(2)
- Angiotensin II
- Endothelin-1
- Nitric oxide
- Prostaglandin
Increase [Ca++] activates myosin light-chain kinase
(3)
1) Phosphorylation of myosin
2) Sensitization of the myofilaments to calcium
3) Inhibition of myosin phosphatase
- 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- (3)
- ETB- (2)
vasoconstriction, bronchoconstriction, increase
aldosterone secretion
vasodilation, inhibition of platelet aggregation
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 increase cAMP = decrease [Ca++]
leading to relaxation - Also inhibit platelet aggregation
- PGG2 and PGH2- prostaglandin
endoperoxide intermediates - Have some constricting activity
Direct Acting Vasodilators
(5)
- Calcium Channel Blockers-
- Minoxidil-
- Nitroprusside (and other nitrates) -
- Hydralazine-
- Ethanol-
- Calcium Channel Blockers-
lower intracellular Ca++ concentration
- Dihydrodpyridine type are more selective for
smooth muscle
- Minoxidil-
opens KATP channels- turns off voltage-dependent Ca++ channels
- Nitroprusside (and other nitrates) -
increases intracellular nitric oxide (NO)
concentration
- Hydralazine-
blocks intracellular release of Ca++
- Ethanol- unclear-
probably thru alteration of centrally controlled vasodilation
Dihydropyridine CCB
(2)
- More selective for calcium
channels in peripheral
vasculature - More effective for
hypertension
Non-Dihydropyridine CCB
(2)
- More selective for calcium
channels in myocardium - More effective for
arrhythmias
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
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
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
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
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
- Sodium Nitroprusside
(2)
- Only available for intravenous
administration - Used for acute control of
hypertension
- Oral/topical nitrate formulation
(2)
- Used mainly for angina
- Not effective as anti-hypertensive
agent, but may have hypotensive
side effects
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
Hydralazine
Mechanism of action(maybe)
Proposed MOA:
interference with action
of IP3 on calcium release
from sarcoplasmic
reticulum
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
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
Pulmonary Hypertension
* A rare disorder
* Estimated prevalence of — cases per million persons
* Defined by a mean pulmonary artery pressure ≥ — at rest
15-50
25mmHg
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
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
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
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
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
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.)
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
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
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)
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
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
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
Selexipag
Selective prostacyclin IP receptor agonist
(3)
- Monitor vital signs
- High risk patient
- Acute pulmonary hypertension could occur
- Limit or avoid vasoconstrictors
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
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
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
