The Vascular system Flashcards
• released by the kidneys in response to decreased perfusion
-Converts angiotensinogen to angiotensin 1
Renin
- released by liver
* converted to angiotensin I by renin
Angiotensinogen
- no known activity
* converted to angiotensin II by ACE
Angiotensin I
- causes vasoconstriction, salt retention, vascular growth
* stimulates release of aldosterone
Angiotensin II
Blocks renin activity on angiotensinogen
Direct renin inhibitor
aliskiren
Prevents ACE from converting angiotensin I to
angiotensin II
ACE inhibitors
captopril, enalapril, etc..
Blocks angiotensin II activity at the AT1 receptor
Angiotensin receptor blockers
candesartan, valsartan, etc..
Blocks the activity of aldosterone in the kidneys
and other tissues (i.e. heart, smooth muscle)
Aldosterone antagonists (eplerenone and spironolactone)
• MOA: Direct renin inhibitor- prevent conversion of angiotensinogen to angiotensin I
• Use: Hypertension
• ADRs: Diarrhea(frequent), dyspepsia(occasional), Hypotension
• Drug-Drug interactions:• Increased levels when combined with CYP3A4 inhibitors like macrolide antibiotics
-Not commonly prescribed
Aliskerin
• Brand name: Tekturna®
Most all drugs that target the RAAS system have what side effect?
Hypotensin
What 2 things do ace inhibitors decrease?
ACE
Kininase II
What is the affect of ACE inhibitor decreasing Kininase II?
Increased bradykinin leading to cough and possible angioedema
If the drug ends in -pril, what type of drug is it?
ACE inhibitor
What are adverse drug rxns to ACE inhibitors?
Captopril
C Cough (up to 10%)
A Angioedema (<1%) / Agranulocytosis (rare)
P Potassium excess (hyperkalemia 1-10%)/Proteinuria (rare)
T Taste change (2-4%)
O Orthostatic hypotension (~5%)
P Pregnancy (contraindication)
R Renal artery stenosis- bilateral (contraindication)
I Increased serum creatinine (1-10%- transient)
L Leukopenia (rare) / Liver Toxicity (rare)
• MOA: inhibits the angiotensin converting enzyme blocking the conversion of angiotensin I to angiotensin II
• Use: Hypertension, heart failure, post-MI, kidney disease
• ADRs: Cough, angioedema, hypotension, acute renal insufficiency, hyperkalemia, taste disturbances/dry mouth(rare)
• Drug-Drug interactions:• NSAIDs- reduced anti-hypertensive effect
• Alcohol- increased anti-hypertensive effect
• General anesthesia- increased anti-hypertensive effect
• 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
Lisinopril
• Brand name: Prinivil® or Zestril®
If the drug ends in -sartan, what type of drug is it?
ARB
Angiotensin Receptor Blocker
What are the 3 adverse drug reactions of ARB?
HDH
Headache / Hypotension
Dizziness
Hyperkalemia
• MOA: Blocks the AT1 receptor of angiotensin II
• Use: Hypertension, heart failure, kidney disease
• ADRs: Hypotension, dizziness, and hyperkalemia
• Drug-Drug interactions:• Sedative medications- increased anti-hypotensive effects
• NSAIDs- reduced anti-hypertensive effect
• General anesthesia- increased anti-hypertensive effect
• 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
Candesartan
• Brand name: Atacand®
- MOA: Sacubitril inhibits neprilysin resulting in elevated levels of B-type natriuretic peptide (BNP) and valsartan blocks the angiotensin II AT1 receptor
- Use: Heart Failure reduced ejection fraction (HFrEF)
- ADRs: Hypotension (18%), hyperkalemia (12%), angioedema (1-2%)
- Drug-Drug interactions:• ACE inhibitors- increased risk of angioedema
- Dental implications: Watch to hypotension upon rising
Angiotensin Receptor Neprilsyn Inhibitor (ARNI)
• Brand name: Entresto®
Is there more or less hypotension with ARNI?
More
What are the 2 aldosterone antagonists?
spironolactone
eplerenone
• MOA: Competitively inhibits the action of aldosterone• May also be referred to as a potassium-sparing diuretic
• Use: Hypertension, heart failure, liver failure, edema, primary hyperaldosteronism
• ADRs: Hyperkalemia, renal insufficiency, gynecomastia(males), dry mouth
• Drug-Drug interactions:• NSAIDs
• reduced anti-hypertensive effect
• Increased risk of nephrotoxicity
• Monitor vital signs
• Assess salivary flow as a factor in caries,
periodontal disease, and candidiasis secondary to
dry mouth from diuretic effect
Spironolactone
• Brand name: Aldactone®
___ is responsible for myosin and actin muscle contraction of smooth muscle
Ca
• Produced in vascular tissue, smooth muscle, brain,
kidney, intestines, and adrenal gland
Endothelin-1
• Produced in kidney and intestines
Endothelin-2
• Produced in brain, kidney, intestine, adrenal gland
Endothelin-3
Endothelin Rc
vasoconstriction, bronchoconstriction, Increased
aldosterone secretion
ETA-
Endothelin Rc
- vasodilation, inhibition of platelet aggregation
• ETB
• Activates guanylyl cyclase
resulting in Increases cGMP [Ca++]
leading to relaxation
Nitric Oxide
• Binds to I prostanoid receptor (IP) • Activates adenylyl cyclase resulting in Increase cAMP leading to less [Ca++] leading to relaxation • Also inhibit platelet aggregation • PGG2 and PGH2- prostaglandin endoperoxide intermediates • Have some constricting activity
• PGI2- prostacyclin
Drugs ending in -dipines, what type of drug is it?
Dihydropyridine (Ca channel blocker)
\_\_\_\_\_\_\_ CCB • More selective for calcium channels in peripheral vasculature • More effective for hypertension
Dihydropyridine
\_\_\_\_\_\_\_\_\_ CCB • More selective for calcium channels in myocardium • More effective for arrhythmias
Non-Dihydropyridine
• MOA: Blocks L-type calcium channel in the vascular
smooth muscle (Dihydropyridine type)
• Use: Hypertension, and angina
• ADRs:
• Edema (common), dizziness, lightheadedness, hypotension, flushing,
gingival enlargement (rare- more common with DHP type)
• Drug-Drug interactions:
• Hypotension with sedatives, opioids, general and inhaled anesthetics
• NSAIDS reduce blood pressure lowering effect
• 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
Amlodipine
• Brand name: Norvasc®
Mechanism of action: • 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
- MOA: causes smooth muscle relaxation by opening KATP channels
- Use: Severe resistant hypertension
- ADRs: Hair growth, edema, photosensitivity(rare)
- Drug-Drug interactions:• Reduced anti-hypertensive effect with NSAIDs and sympathomimetic
- Increased anti-hypertensive effect with sedatives and other drugs used for conscious sedation
Minoxidil
• Brand name: Loniten®
- MOA: causes smooth muscle relaxation by increasing intracellular nitric oxide concentrations
- Use: Hypertensive crisis
- ADRs: Methemoglobinemia, hypotension, dizziness, thiocyanate toxicity
- Drug-Drug interactions: • PDE-5 inhibitors (i.e. sildenafil)
- Dental implications:• none
Sodium Nitroprusside
• Brand name: Nitropress®
Proposed MOA: interference with action of IP3 on calcium release from sarcoplasmic reticulum
Hydrazaline
\_\_\_\_ MOA: Donates a NO which increases cGMP then causing vasodilation -• Only available for intravenous administration • Used for acute control of hypertension
Sodium nitroprusside
• MOA: Direct acting vasodilator thru interference with action of
IP3 on calcium release from sarcoplasmic reticulum
• Use: Hypertension, and heart failure
• ADRs:
• Headache, palpitations, GI disturbances, flushed face(rare)
• Drug-Drug interactions:
• Reduced anti-hypertensive effect with NSAIDs and
sympathomimetic
Hydralazine
• Brand name: Apresoline®
Defined by a mean pulmonary artery pressure ≥ 25mmHg at rest
Pulmonary hypertension
Group ___ pulmonary hypertension:
Pulmonary arterial HTN (PAH) – primary pulmonary HTN
Group 1
Group ___ pulmonary hypertension:
Pulmonary HTN due to left heart disease
Group 2
Group ___ pulmonary hypertension:
Pulmonary HTN due to lung disease
Group 3
Group ___ pulmonary hypertension:
Chronic thromboembolic pulmonary HTN (CTEPH)
Group 4
Group ___ pulmonary hypertension:
Pulmonary HTN with unclear mechanism
Group 5
What type of pulmonary hypertension med is offered both orally or parenterally?
Prostcyclin analouges
Treprostinil
Mechanism of action: • Block the ETA receptor • Decreasing the formation of IP3 • Lowering the intracellular Ca++ concentration • Resulting in vascular smooth muscle relaxation Most block both ETA and ETB - but have a high affinity for ETA
ERAs Endothelin receptor antagonist
• MOA: Endothelin 1 receptor antagonist
• Use: Pulmonary hypertension WHO FC III and IV
• ADRs:
• Headache, flushed face, dyspepsia, liver dysfunction
• Drug-Drug interactions:
• Increased levels when used with ketoconazole
• Pregnancy category- X aka DON’T USE
• 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
Bosentan
• Brand name: Tracleer®
Mechanism of action: • Inhibit action of PDE5 • Increase intracellular cGMP concentration • Lowering the intracellular Ca++ concentration • Resulting in vascular smooth muscle relaxation They are also used (more commonly) to treat erectile dysfunction
PDE5 inhibitors
• MOA: Phosphodiesterase 5 inhibitor
• Use: Pulmonary hypertension, erectile dysfunction, and BPH
• ADRs:
• Headache, flushed face, dyspepsia, rash
• Drug-Drug interactions:
• Sodium Nitroprusside- avoid combination- severe hypotension
• Increased levels with CYP 3A4 inhibition (i.e. erythromycin,
clarithromycin, etc.)
• 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
Sildenafil
• Brand name: Revatio™(PAH) or Viagra®(ED)
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
Prostacyclin analogues
- MOA: Prostacyclin analogue
- Use: Pulmonary hypertension
- ADRs:
- Headache, flushing, hypotension, infusion site pain
- jaw pain, inhibition of platelet aggregation (Increased r/o bleeding)
- Drug-Drug interactions:
- Other drugs that increased r/o bleeding (i.e. NSAIDS)
- 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
Treprostinil
• Brand name: Orenitram®(PO), Tyvaso™(INH), Remodulin™(IV/SQ)
- MOA: IP receptor agonist
- Use: Pulmonary hypertension Group I
- ADRs:
- Flushing, Headache(65%), diarrhea (42%)
- Jaw pain (26%)
- Drug-Drug interactions:
- None noted
- Monitor vital signs
- High risk patient
- Acute pulmonary hypertension could occur
- Limit or avoid vasoconstrictors
Selexipag
• Brand name: Uptravi®
Mechanism of action: • 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
Soluble guanylate cyclase stimulator
Soluble guanylate cyclase stimulator
- MOA: Soluble guanylate cyclase stimulator
- Use: Pulmonary hypertension group 1 and 4 (CTEPH)
- ADRs:
- Hypotension, dyspepsia, headache, edema
- Drug-Drug interactions:
- Avoid combination with PDE5 inhibitors
- Decrease effects with CYP 3A4/2C8 inducers
- Pregnancy category- X
- 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
Riociguat
• Brand name: Adempas®
