The Vascular System Flashcards
what is renin released by
the kidneys in response to perfusion
angiotensinogen is released by:
the liver
angiotensinogen is converted to angiotensin I by:
renin
angiotensin II causes:
vasoconstriction, salt retention, vascular growth
angiotensin II stimulates:
release of aldosterone
what is the MOA of direct renin inhibitor
blocks renin activity on angioteninsogen
what is the MOA of ACE inhibitors
prevents ACE from converting angiotensin I to angiotensin II
what is the MOA of angiotensin receptor blockers
blocks angiotensin II activity at the AT1 receptor
what is the MOA of aldosterone antagonists
blocks the activity of aldosterone in the kidneys and other tissues
what is the use for direct renin inhibitor and MOA and drug to drug interactions and ADRs
- prevent conversion of angiotensinogen to angiotensin I
- use: HTN
- increased levels when combined with CYP3A4 inhibitors like macrolide ABs
- ADRs: diarrhea, dyspepsia, hypotension*
what are the dental considerations with direct renin inhibitors
- monitor vital signs
- after supine positioning, have patient sit upright for at least 2 minutes before standing to avoid orthostatic hypotension
what does angiotensin cause
- aldosterone release
= vasoppressin release - sympathetic
- vasoconstriction
what else do ACE inhibitors act on
kininase II which inhibits bradykinin which results in cough and vasodilation
what are the ACE inhibitors
- the “prils”
what is the mneumonic for adverse drug reactions to ACEi
- CAPTOPRIL
- Angioedema/agranulocytosis
- potassium excess/proteinuria
- taste changes
- orthostatic hypotension
- pregnancy - contraindication
- renal artery stenosis- bilateral - contraindication
- increased serum creatinine
- leukopenia/liver toxicity
what is the MOA, use, ADRs, and drug-drug itneractions dor ACEi
- inhibits the angiotensin converting enzyme blocking the conversion of angiotensin I to angiotensin II
- HTN, HF, post MI, kidney disease
- ADRs: cough, angioedema, hypotension, acute renal insufficiency, hyperkalemia, taste distrubances,
- drug interactions: NSAIDs, alcohol, general anesthesia
what are the dental implications for ACEi
- orthostatic hypotension
- minotr vital signs
- ACEi cough may make dental procedures difficult
- if dental surgery is anticipated evaluate risk of hypotensive episode
what is the MOA of angiotensin II receptor blockers
-angiotensinogen -> angiotensin I -> angiotensin II -> works on AT1 and AT2 receptors
- AT1 receptors cause vasoconstriction and proliferative action
- AT2 receptors cause vasodilation and antiproliferative action
what are the drugs that are angiotensin receptor blockers
the “sartans”
what are the adverse drug reactions for angiotensin receptor blockers and how do we remember this
- Halt Dangerous Hypertension
- Headache/hypotension
- dizziness
- hyperkalemia
what is the MOA, use, ADRs, and drug interactions with angiotensin receptor blockers
- MOA: blocks the AT1 receptor of angiotensin II
- use: HTN, HF, kidney disease
- ADRs: hypotension, dizziness and hyperkalemia
- drug interactions: sedative meds, NSAIDs, general anesthesia
what are the dental implications for angiotensin receptor blockers
- orthostatic hypotension
- monitor vital signs
- if dental surgery is anticipated evaluate risk of hypotensive episode
what is the MOA for angiotensin recpetor Neprilsyn inhibitor
Sacubitril inhibits nepryilysin resulting in evaluated levels of B-type natriuretic peptide
- valsartan blocks the angiotensin II AT1 receptor
what is the use, ADRs and drug interactions of Sacubritril/valsartan
- USE: HF reduced ejectin fraction
- ADRs; hypotension, hyperkalemia, angioedema
- drug interactions: increased risk of angioedme
- dental implications: watch to hypotension upon rising
what is the MOA of aldosterone antagonists
competitive antagonist of the aldosterone receptor (myocardium, arterial walls and kidneys)
what is the result of aldosterone antagonists
- retention of Na+ and H2O -> edema
- exceretion K+ and Mg2+ -> arrythmias
- collagen deposition -> fibrosis of myocardium and vessels
what is an example of aldosterone antagonist, use, ADRs, and drug interactions
- spironolactone
- use: HTN, HF, liver failure*, edmea, primary hyperaldosteronism
- ADRs: hyperkalemia, renal insufficiency, gynecomastia, dry mouth
- drug interactions: NSAIDS
what are the dental implications of aldosterone antagonists
- monitor vital signs
- assess salivary flow as a factor in caries, perio disease and candidiasis from dry mouth effect
what are the key mediators that cause vasoconstrictions
- angiotensin II
- endothelin 1
what are the key mediators in vasodilation
- NO
- prostaglandin
how do you increase contraction in vascular smooth muscle cells
- increased calcium activates myosin light chain kinase through:
- phosphorylation of myosin
- sensitization of the myofilaments to calcium
- inhibition of myosin phosphatase
decreased intracellular calcium leads to ____ in SM
relaxation
where is endothelin 1 produced
vascular tissue, smooth muscle, brain, kidney, intestines and adrenal gland
where is endothelin 2 produced
kidney and intestines
where is endothelin 3 produced
brain, kidney, intestine, adrenal gland
what are the the endothelin receptor types and what do each cause
- ETA: vasoconstriction, bronchoconstriction, aldosterone secretion
- ETB: vasodilation, inhibition of platelet aggregation
what does NO do
activates guanylyl cylase resulting in increase in cGMP -> reduction in calcium in cell
what are the prostaglandins and what do each do
- PGI2: prostacyline, binds to IP receptor and activates adenylyl cyclase -> cAMP leading to relaxation. also inhibits platelet aggregation
- PGG2 and PGH2 - prostaglandin endoperoxide intermediates: have some constricting activity
what are the direct acting vasodilators
- calcium channel blockers
- minoxidil
- nitroprusside
- hydralazine
- ethanol
what are the two types of calcium channel blockerd
- dihydropyridine: end in “dipine”
- non- dihydropyridine: eirhter dilitiazem and verapamil
describe the dihydropryridine CCBs
- more selective for calcium channels in peripheral vasculature
- more effective for HTN
describe the non-dihydropyridine
m-more selective for calcium channels in myocardium
- more effective for arrhythmias
what is the MOA, ADRs, and drug interactions for calcium channel blockers
- blocks L type channels in vascular smooth muscle
- ADRs: edema, gingival hyperplasia
- hypotension with sedatives, opiods, anesthetics, NSAIDs
what are the dental implications for calcium channel blockers
- gingival hyperplasia up to 10%
- monitor vital signs
- orthostatic hypotension
- use vasoconstrictions and anestheics with caution
what is the MOA of minoxidil
- opening KATP channels
- resulting in hyperpolarization of cells
- turns off voltage dependent Ca2+ channels
- lowering the intracellular Ca2+ concentration
- resulting in vascular smooth muscle relaxation
what is the use, ADRs, and drug interactions with minoxidil
- use: severe resistant hypertension
-ADRs: hair growth, edema, photosensitive - drug: NSAIDs, sedatives
what are the dental implications with minoxidil
- monitor vital signs
- orthostatic hypotension - worst drug for this
- avoid or limit vasoconstrictor
what is the MOA for sodium nitroprusside
only available for IV administration
- used for acute control of hypertension
what is the oral/topical nitrate formulation for sodium nitroprusside used for
- angina
- not effective as anti HTN agent, but may have hypotension SE
what is the use, ADRs, drug interactions and dental implications for sodium nitroprusside
- use: hypertensive crisis
- ADRs: methemoglobinemia, hypotension, dizziness, thiocyanate toxicity
- drug interactions: PDE-5 inhibitors
- dental implications; none
what is the MOA of hyrdralazine
- interference with action of IP3 on calcium release from SR
what is the use, ADRs, drug interactions for hydralazine
- use:HTN, HF- acute use
- ADRs: headache, palpitations, GI disturbances, flushed face
- drug interactions: reduced anti-hypertensive effect with NSAIDs and sympathomimetic
what are the dental implications of hydralazine
- monitor vital signs
- orthostatic hypotension
avoid or limit dose of vasoconstrictor
describe pulmonary hypertension
- a rare disorder: 15-50 cases per million people
- defined by a mean pulmonary artery pressure greater than 25mmHg at rest
what are the groups of pulmonary hypertension and describe each
- 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
- group V: pulmonary HTN with unclear mechanism
what are the world health organizations functional classes for pulmonary hypertension
- class 1: no limitation
- class II: slight limitation
- class III: marked limitation of physical activity
- class IV: inability to carry out any physical activity without symptoms
what are the oral medications for PAH
- endothelin receptor antagonists
- PDE5 inhibitors
- prostacyclin analogue
- soluble guanylate cyclase stimulator
- selective prostacyclin IP receptor agonist
what are the parenteral medications for PAH
- inhaled options: ilprost, treprostinil
- IV options: treprostinil, epoprostenol
- subcutaneous options: treprostinil
what is the MOA of endothelin recepotr antagonist
- block the ETA receptor
- decreasing the formation of IP3
- lowering the intracellular Ca2+ concentration
- resulting in vascular smooth muscle relaxation
most ERAs block both _______ but have a high affinity for ______
ETA and ETB; ETA
what is an exampleo of ERA, use, ADRs, drug interactions
- bosentan
- use: PAH WHO FC III and IV
- ADRs: headache, flushed face, dyspepsia, liver dysfunction*
- drug interactions: increased levels when used with ketoconazole
- pregnancy category X
what are the dental implications for bosentan
- monitor vital signs
- high risk pts- acute pulmonary HTN could occur
- bleeding gums
- limit or avoid vasoconstrictors
- low risk for orthostatic hypotension
what is the MOA of PDE5 inhibitors
- inhibit action of PDE5
- increase intracellular cGMP concentration
- lowering the intracellular Ca2+ concentration
- resulting in vascular smooth muscle relaxation
PDE5 inhibitors are also used to treat:
erectile dysfunction
what is an example of PDE5 inhibitors, use, ADRs, drug to drug interactions
- sildenafil
- use: PAH, erectile dysfunction and BPH
- ADRs: headache, flushed face, dyspepsia, rash
- drug interactions: sodium nitroprusside- avoid combo bc severe hypotension. increased levels with CYP 3A4 inhibition
what are the dental implications with sildenafil
- monitor vital signs
- high risk pateint if using for PAH
- limit or avoid vasoconstrictors
- avoid use of nitroglycerin of nitroprusside
- low risk of orthostatic hypotension
what i the MOA for prostacylcin analogues
- bind to prostacyclin receptor (IP)
- stimulate activity of adenylate cyclase
- increase intracellular cyclic AMP levels
- lowering the intracellular Ca2+ concentration
- resulting in vascular smooth muscle relaxation
what is the example, use, ADRs and drug interactions of prostacyclin analogue
- treprostinil
- use: PAH
- ADRs: headache, flushing, hypotension, infusion site pain, jaw pain, inhibition of platelelt aggregation
- drug interactions; other drugs that increase risk of bleeding
describe jaw pain as a SE of prostacyclin therapy, the cause and management
- prostacyclin is a mediator in inflammation and pain - may produce hyperalgesia
- often occurs with 1st bite of meal
- not dose limiting
- management: taking slow bites, sucking on a saltine cracker or hard candy or chewing gum before eating
what are the dental implications of prostacyclin analogues
- monitor vital signs
- limit or avoid vasoconstrictors
- high risk pt- acute PAH could occur, continuous infusion could be interrupted
- increased risk of bleeding because it inhibitrs platelet aggregation
what is the MOA of selexipag
- selective prostacylin IP receptor agonist
- stimulate activity of adenylate cyclase
- increase intracellular cyclic AMP levels
- lowering the intracellular Calcium concentration
- resulting in vascular smooth muscle relaxation
what is the example, use, ADR and drug interaction of selective prostacyclin IP receptor agonist
- selexipag
- use: PAH group I
- ADRs: flushing, headache (65%), diarrhea (42%) and jaw pain (26%)
- drug interactions: none
what are the dental implications of selexipag
- monitor vital sings
- high risk pt: acute PAH can occur
- limit or avoid vasoconstrictors
what is the MOA of soluble guanylate cyclase stimulator
- sensitizes guanylyl cyclase to NO but also directly activates guanylyl cyclase
- increase intracellular cGMP concentration
- lowering the intracellular Caclium concentration
- resulting in vascular smooth muscle relaxation
what is the example, use, ADRs, drug interactions of soluble guanylate cyclase stimulator
- riociguat
- use: PAH group 1 and 4
- ADRs: hypotension, dyspepsai, headahce, edema
- drug interactions: pregnancy category X, avoid PDE5 inhibitors, decrease effects with CYP3A4/2C8 inducers
what are the dental implications of riociguat
- monitor vital signs
- High risk pt- acute PAH can occur
- avoid or limit vasoconstrictors
- increased risk of bleeding
