HTN-1 Flashcards
Normal BP
<120/80 mmHg
Elevated BP
120-129 mmHg / ≤ 80 mmHG
Stage 1 Hypertension BP
≥ 130 mmHg systolic
OR
≥ 80 mmHf diastolic
Stage 2 Hypertension BP
≥ 140 mmHg systolic
OR
≥ 90 mmHg diastolic
Hypertensive Urgency / Emergency BP
≥ 180 mmHg systolic
OR
≥ 120 mmHg diastolic
What are the hypertension risk factors
Age
FH
Smoking
Obesity
Metabolic Syndrome
High alcohol intake
Diabetes
High sodium intake
Dyslipidemia
What are the two major processes that regulate BP
-baroreceptors and the sympathetic nervous system
-renin-angiotensin aldosterone system
Pathophysiology of decreased BP on alpha and beta receptors
decrease BP
decrease signal to brain
increase sympathetic nervous system
increase catecholamines
alpha increase peripheral resistance
beta effects heart
Pathophysiology of decreased BP in blood volume
decrease BP
decrease signal to kidneys
renin -> angio -> angio II vasoconstrictor
aldosterone increases sodium and water
results in higher blood volume
What are the secondary causes of hypertension
renal disease
Cushing’s disease
pheochromocytoma
pregnancy
sleep apnea
contraceptives
sympathomimetics
NSAIDs
steroids
SSRIs/SNRIs
cocaine
nicotine
amphetamines
licorice
What is the primary goal of treating hypertension
reduce morbidity and mortality by decreasing the risk of target organ damage
What are the best practices for checking BP
sit for 5 minutes
no caffeine
arm placement
correct cuff size
check both arms
feet flat on floor
not talking
clothing removed from where cuff placed
Higher CVD risk = more important to have a ______ goal and assure we get there ________
tighter
quickly
What is the CV risk for stage 1 hypertension and ASCVD or 10 year CVD risk ≥ 10%
high CV risk
What is the CV risk for stage 1 hypertension and no ASCVD and 10-year CVD risk < 10%
Low CV risk
What are the ASCVD risks
ACS (acute coronary syndrome) CAD (coronary artery syndrome)
PAD (peripheral artery disease)
TIA (transient ischemic attack)
Stroke
MI (myocardial infarction)
Angina (stable or unstable)
CABG or PCI/stent (coronary/arterial revascularization)
What calculation can you use for a patient between the ages of 40-79 to estimate risk of CV event in the next 10 years
American College of Cardiology Risk Calculator
If a patient is less than 40 and has 2 or more risk factors included in calculation (smoking, african american, HLD, DM) they are considered what kind of CV risk
High CV risk
If a patient has an elevated BP (120-129/<80) what is their recommendations
Start with nonpharmacologic therapy, reassess BP in 3-6 months
If a patient has stage 1 hypertension and a high CV risk what is their recommendation
-Start with nonpharmacologic and pharmacologic therapy
-Reassess BP in 1 month
-If at goal reassess 3-6 months
-Not at goal reassess for adherence and intensification of therapy
If a patient has stage 1 hypertension and a low CV risk what is their recommendation
-Start with nonpharmacologic therapy
-Reassess BP in 3-6 months
-Not at goal consider pharmacologic therapy
If a patient has stage 2 hypertension what is their recommendation
-Start with nonpharmacologic and pharmacologic therapy
-Reassess BP in 1 month
-At goal reassess 3-6 months
-Not at goal asses for adherence and consider intensification of therapy
Food considerations for improving BP
Na+ restriction
High-fiber and natural foods
Limit high saturated fats
Low-fat dairy products
Lifestyle consideration for improving BP
Exercise
Aerobic activity
Dynamic resistance
Isometric resistance
Moderate alcohol
Smoking cessation
cardiac output times peripheral resistance equals
blood pressure
What two things effect cardiac output
cardiac (heart rate, heart contraction)
volume control (renal renin-angiotension, aldosterone)
What two things effect peripheral resistance
sympathetic control (vasoconstrictor, vasodilator)
humoral (catecholamines, prostagandins)
What part of the renal system is not permeable to water
distal convoluted tubule
What part of the renal system is not permeable to salt
thin descending tubule
Where are thiazide agents located
distal convoluted tubule
Where are loop diuretics located
thick ascending tubule
Where are potassium sparing agents located
collecting tubule
What are diuretics mechanism of action
decreases extracellular volume, enhancing sodium excretion in the urine, leading to a decrease in cardiac output
What is the most frequent used class of antihypertensive agents in the US
thiazide diuretics
Results of thiazide diuretics
high K+ secretion causing hypokalemic because K+ is not reabsorbed
What drug class do these belong to:
hydrochlorothiazide (hydrodiuril)
chlorthalidone (hygroton)
Indapamide
Metolazone
thiazide diuretics
What is the GFR goal of kidneys
<30 ml/min
ACE and ARBs will ________ diuretic induced loss of K+
counteract
Hydrochlorothiazide primary and secondary site
primary: kidney
secondary: vascular smooth muscle cells
What drug class do these belong to:
furosemide (lasix)
bumetanide (bumex)
ethacrynic acid (edecrin)
torsemide (demadex)
Loop diuretic
(block Na/K/Cl
What diuretics is the highest capacity especially if renal function is not normal and has the highest capacity Na/Cl/K pump
loop diuretics (twice a day medications for hypertension, heart failure, and ascites)
Loop diuretics increase the urinary secretion of what ions
na
cl
ca
mg
K+
What drug class do these belong to:
amiloride (midamor)
triamterene (dyrenium)
potassium sparing channel blockers
What drug class do these belong to:
spironolactone (aldactone)
eplerenone (inspra)
potassium sparing receptor blockers
What class of diuretic can you not use with ACE and ARBs
potassium sparing
What is the function of potassium sparing channel blockers
block pore of the epithelial sodium channel
(decrease volume, hyperkalemic)
What is the function of potassium sparing receptor blockers
steroid hormone produced by adrenal gland
regulate Na+, K+, and acid/base balance in blood
Potassium sparing diuretics ________ transepithelial _____ transport
enhances
NaCl
ACE inhibition
-BP is decreased due to decrease in blood volume, peripheral resistance and cardiac load
-inhibit vasoconstriction and release of aldosterone which inhibits the retention of sodium and water
What does ACE inhibition do to bradykinin
increases it
What do all ACE inhibitors end in
“-pril”
What do ACE-I treat
chronic renal disease
aldosterone (they tend to enhance the efficacy of diuretic drugs)
young middle-aged Caucasians
Adverse effects of ACE-I
-rise in serum K+
-caution with K+-sparing diuretics, K+ supplements, NSAIDs, beta-blockers
-bradykinin: dry cough, angioedema
-dysgeusia
-contradicted with pregnancy
ARBs do not inhibit ACE-mediated degradation of ___________
bradykinin
What do all AT1 receptor blockers end in
“-sartan”
What do AT1 and AT2 do
AT1: vascular, myocardial tissue, kidney, brain, and adrenal glomerulosa cells
AT2: adrenal medulla, kidney, CNS
What are the three steps of AT1 receptor activation
Altered Peripheral Resistance (direct vasoconstriction, enhance sympathetic discharge)
Altered Renal Function (increase Na+ reabsorption in the proximal tubule and distal tubule)
Altered Cardiac Function (relax smooth muscle to promote vasodilation, increase salt and water secretion, reduce plasma volume decreasing cellular hypertrophy)
AT1 receptor blockers treatment
high angiotenstion II: volume depketion, renovascular hypertension, cardiac function, cirrhosis
no bradykinin
not effective in old, blacks, low-renin patients
Adverse effects of AT1 receptors
insignificant rise in serum K+ (hyperkalemia)
contraindicated in pregnancy
Aliskiren hemifuramate (tekturna)
-inhibits the catalytic activity of renin producing Ang1, Ang2, aldosterone which decreases BP
-systolic and diastolyic
-monotherapy and combo therapy
-contraindicated in pregnancy
When do you start two medicines for hypertension
> 30 mmHg above systolic or >20 mmHg diastolic
African American: >20mmHg above systolic or >10mmHG diastolic
What numbers of BP is a hypertension emergency
> 180 systolic or >120 diastolic
What medicine to use for systolic heart failure (SHF/CHF)
ACE and beta blocker
What medicine to use for post-MI
ACE-I and beta blocker
What medicine to use for diabetes with albuminuria
ACE-I or ARB
What medicine to use for CKD with albuminuria
ACE-I or ARB
What medicine to use for stroke
ACE-I or ARB
If there are no compelling indications for hypertension what are the trifecta of choices to use
thiazide diuretics (-pine)
ACE-I and ARBs
Calcium Channel Blockers
If patients are over 60 or black what is the recommended medication class to use
thiazide or calcium channel blocker
(beta blocker NOT recommended)
What do alpha blockers cause
orthostatic hypotension
(important to titrate slow and start low)
Central alpha 2 agonists
Only for resistant hypertension or hypertensive emergency
ADRs don’t go away (adverse drug reaction)
Avoid in HF
Alcohol dependence
ADHD ER formulation
Methyldopa used in pregnancy
Vasodilators
Resistant HTN (systolic)
Use with diuretic to decrease fluid retention
Moderate dose of 2 or more medications are _____ effective than high doses of one medication
more
Thiazides and CCBs cause ____ excretion and vasodilation
Na+
ACE-I and ARBs improve ____-induced edema by causing venule dilations
CCB (calcium channel blocker)
ACE and ARBs may improve ___________ from thiazides
hypokalemia
When should a follow-up be after starting/changing therapy
2-4 weeks
When should a follow-up be if BP is stable and controlled
3-6 months
Diuretics increase the excretion of electrolytes and water from the body ______ affecting protein, vitamin, glucose, or amino acid reabsorption
without
Diuretics are used to treat _____ and hypertension
edema
What is the primary target organ of diuretics where they interfere with reabsorption of ions
kindey
What are osmotics site of action and mechanism of action
Site: proximal tubule
mechanism: osmotic effects decrease sodium and water reabsorption
What are carbonic anhydrase inhibitors site of action and mechanism of action
site: proximal convoluted tubule
mechanism: inhibition of renal carbonic anhydrase decreases sodium bicarbonate reabsorption
What are thiazides site of action and mechanism of action
site: thick ascending loop and distal tubule
mechanism: inhibit na/cl symporter
What are loop or high ceiling site of action and mechanism of action
site: thick ascending limb
mechanism: inhibit na/k/cl transport system
What are potassium-sparing site of action and mechanism of action
site: distal tubule and collecting duct
mechanism: inhibit sodium and water reabsorption by competitive inhibition of aldosterone or blockage of sodium channels
What are osmotics MOA
decrease na and h2o reabsorption
Osmotics are ______ polar and have a ______ molecular weight
highly
low
Are osmotics secreted as charged or uncharged parent drugs
uncharged
Carbonic anhydrase inhibitors MOA
inhibit carbonic anhydrase which decreases H+ exchange for Na+ ion in the kidney. Lose Na, HCO3, and H2O
Carbonic anhydrase inhibitors treat what
glaucoma and acidify urine (result in metabolic acidiosis)
Sulfonamides are ______ and are common with all CAIs
acidic
Methyls improve ________
lipophilicity
Secondary aliphatic amines _______ water solubility
increase
An ionizable amino group cause ______ water solubility
higher
MOA of thiazides
compete for Cl- binding of Na/Cl symport which inhibits reabsorption of Na and Cl ions -> hyponatremia, hypokalemia, hypomagnesia
In thiazides what group is important at position 6
EWG
In thiazides what is present at position 3 and 4
double bond to make them more active
In thiazides what is at position 3 to increase a longer duration of action
alkyls to increase lipid solubility
What is the duration of action of loops or high ceiling diuretics
short duration of action to cause excretions of ions
What is the only loop without sulfur
ethacrynic
MOA of loops
Inhibit Na/K/Cl symporter, may alter warfarin, ototoxicity with ethacrynic acid
Potassium Sparing side effects
do not use with ACE-I or ARBs
sexual side effects due to nonselective binding receptors
What is present at position 9 or 11 in potassium sparing
epoxide
What is replaced at position 7 in potassium sparing diuretics
thioester with ester
What is present at position 17 in potassium-sparing diuretics
gamma lactone ring
What is MOA of potassium-sparing diuretics
bind to negatively charged regions of Na channel (weak bases)
What do ACE-I’s cut
dipeptides
ACE needs zinc in order to do what
bind by ionic bond with amines then zinc helps dipeptide cleavage, hydrogen bond between substrate and ACE
ACE-I have _____ bioavailability and undergo phase 1 metabolism by ________
low
esterases
What ring minics the C-terminal in ACE-I
N-ring
Large hydrophobic rings ______ potency
increase
___________ group is best for zinc binding in ACE-I because they shorten duration of action
sulfhydryl
Esterification produces orally bioavailable prodrugs in ACE-I because zinc binding to which two groups is optimal
carboxylate
phosphinate
ACE-I are usually acidic excepts for which two drugs because they contain amines
captopril
fosinopril
In ARBs esters need to be _______ in order to produce a free acid
hydrolyzed
ARBs need an _______ group
acidic and it has to be ortho
The tetrazole ring in ARBs need to be ______
ionized
Incomplete absorption in ARBs results in _____ lipid solubility and _____ bioavailability because the drug is unchanged
low
low
Renin Inhibitors MOA
enzyme secreted by kidneys to decrease glomerular filtration rate resulting in low BP
What functional group do you want in renin inhibitors to mimic their sites
isopropyl
