The Vascular system Flashcards by Michael McMahan

• released by the kidneys in response to decreased perfusion

-Converts angiotensinogen to angiotensin 1

Renin

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released by liver

* converted to angiotensin I by renin

Angiotensinogen

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no known activity

* converted to angiotensin II by ACE

Angiotensin I

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causes vasoconstriction, salt retention, vascular growth

* stimulates release of aldosterone

Angiotensin II

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Blocks renin activity on angiotensinogen

Direct renin inhibitor

aliskiren

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Prevents ACE from converting angiotensin I to

angiotensin II

ACE inhibitors

captopril, enalapril, etc..

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Blocks angiotensin II activity at the AT1 receptor

Angiotensin receptor blockers

candesartan, valsartan, etc..

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Blocks the activity of aldosterone in the kidneys

and other tissues (i.e. heart, smooth muscle)

Aldosterone antagonists 
(eplerenone and spironolactone)

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• 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®

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Most all drugs that target the RAAS system have what side effect?

Hypotensin

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What 2 things do ace inhibitors decrease?

ACE

Kininase II

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What is the affect of ACE inhibitor decreasing Kininase II?

Increased bradykinin leading to cough and possible angioedema

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If the drug ends in -pril, what type of drug is it?

ACE inhibitor

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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)

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• 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®

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If the drug ends in -sartan, what type of drug is it?

ARB

Angiotensin Receptor Blocker

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What are the 3 adverse drug reactions of ARB?

HDH

Headache / Hypotension
Dizziness
Hyperkalemia

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• 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®

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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®

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Is there more or less hypotension with ARNI?

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What are the 2 aldosterone antagonists?

spironolactone

eplerenone

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• 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®

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___ is responsible for myosin and actin muscle contraction of smooth muscle

• 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®