8. Diuretics Flashcards
The issue in brief
• The sodium concentration in normal people is 154 mEq/L (140 mEq in plasma)
• In health, the kidneys filter ____ mL of plasma per minute
• Doing the math, each minute the kidneys filter 18 mEq of sodium; each hour (6018=) 1080 mEq; and each day (24*1080=) more than ____ mEq of asodium. The normal human has less than ____ mEq sodium in their entire body.
* Na is important to the human body - principle cation that keeps plasma vol where it is * Reason why it's 140 > draw blood tube and measure it on that > measuring it in 930 mL of blood, but 7% of blood is \_\_\_\_> then brings you to 154
120
25000
2200
The average American
- Consumes 3400 mg of sodium per day (that’s about 150 mEq)
- This is (150/25000) about ____% of what the kidneys filter each day• Kidneys need to be ____% efficient in recovery of Na
- 6
99. 4
• Everyday you retain 1 meq of Na > for a year, at the end of the year you’ll have 360+ extra meq of Na > 2+ L of normal saline
○ 1 meq = <1% of daily intake
1
- Kidney do a balancing job of keeping us at straight and narrow at what we take in
- When something throws hormones out of whack > ____ retention becomes a problem
- Na loss - ____ loss, don’t live to adulthood
Na
pediatric
• Diuretic ○ Running through \_\_\_\_ish • Natruresis ○ Running through \_\_\_\_ • Kaliuresis ○ Running through \_\_\_\_ • Chloruresis ○ Running through \_\_\_\_ • Aquaresis ○ Running through \_\_\_\_ • Natruietic diuretic > more \_\_\_\_ loss • Kalireutic diuretic > more \_\_\_\_ loss
water sodium potassium chloride water sodium potassium
Therapeutic Uses of Diuretics • Volume excess states* – \_\_\_\_ – Cirrhosis – \_\_\_\_ • \_\_\_\_ • Electrolyte disorders • Glaucoma, Kidney stones, Altitude sickness
• Most common is in HTN ○ Avg 20-30: 5% prevlence ○ 70: 70% ○ Most common drug to maintain HTN are \_\_\_\_ § Cheap (costs more for pharmacist to put label on bottle) • Kidney stones ○ Some diuretics are good, and some are bad ○ Some diuretics affect urine \_\_\_\_ in a good way, and some in a bad way
HF edema HTN diuretics calcium
• Kidney has a cortex and medulla
○ Cortex = ____ of blood
§ And for diuretic to work - has to get into the ____
§ If it doesn’t get into the urine, it won’t block Na reabsorption
§ Most diuretics are targeted towards sodium
filtration
urine
• Everything starts at BC
• Glomerulus allows ____ of water, some electrolytes/AA/glucose, but not proteins or cells
• 200k-2m nephrons per kidney
○ Thought one of casues of HTN is a ____ number of nephrons, so they work harder and wear out more quickly
○ ____ of numbers among population
filitration
low
variation
- After plasma is filtered and ultrafiltrate begins in bowman’s space > proximal section, and a loop of henle, and distal segment (each one ____ to input and output of input and output of glomerulus so it can adjust the filtration based on that); then urine joins other segments from many collecting ducts
- Na, H2O absorbed with a variety of pumps
feedsback
• Proximal tubule ○ Responsible for \_\_\_\_% of reabsorbing what was filtered ○ Biggest structure in \_\_\_\_ of the kidney • Loop of henle ○ Urine is cxn or diluted ○ \_\_\_\_% of Na reabsorbed • DT ○ \_\_\_\_ what comes out • CD ○ Everything goes ○ \_\_\_\_ diuretics work here
70 cortex 20-25 fine tune water
Mechanism of Diuretic Action
• Active
• Passive
• Most diuretics are \_\_\_\_ ○ Sit and block
passive
Diuretic Basics
• highly ____ bound
• interact with specific ____
• inhibit ____+ transport
• most receptors are on the ____ of the tubule (luminal or apical)
• delivery to active site is by two pathways – ____ and secretion
• Highly protein bound ○ Issue: has to get it in the urine, has to get past glomerulus, but if highly protein bound and the glom is picky (doesn't let albumin through) then diuretics go to liver to be metabolized ○ There's another mechanism! ○ Limits delivery by filtration • Specific receptors ○ Typically on luminal side of tubule (not \_\_\_\_, that's the blood side)
protein receptor Na inside filtration basolateral
• Secretion
○ Past glom and in the blood through the kidney, once the blood comes back up along tubule cells > ____ is able to strip a loop diuretic or a DCT diuretic from the protein and slip it into the cell > ____ transfers the diuretic into the lumen > travels along the nephron
○ A lot of delivery is through here
○ ____ tubule cells > harder to get the diuretics in the urine
OAT
MRP
sick
Size of Urine Volume Response 1
• The magnitude of the response (as measured by increase in urine volume and sodium loss) is determined by
– ____ transported by that segment
– “____” the site has to the drug
• How much urine you make for how much drug you expose the research participant
sodium
exposure
• PT > 70% of Na reabsorption
○ Lousy diuretics > if block on that scale person will disappear into urine
• LH > 25% during the thick limb
○ Loop diuretics are most ____ > bc they can block a portion of 25% recovered Na
• DCT > thiazides; 5%
• Gonna see a bigger response effect on blocking the ____
potent
LH
• FENa
○ Fractional excretion of Na
○ Can do a FE of ____ (anything that can filter and measure)
○ If kidney is filtering plasma > and you know the kidney filters 100 ml of urine (via creatinine measurement) > base filtration, and then the ____ of Na > can tell how much you excreted
○ Can calc what portion of Na that was filtered actually makes it into the urine
○ When drug works on active part of the nephron > 20% of what is excreted is in a short amount of time
• Thiazide
○ 5% excretion rate
○ Wimpier drug - but more useful bc get into less ____ with them on the long haul (volume depltion, etc.)
• Only shows magnitude - loop diuretics is very ____
anything
plasma cxn
trouble
potent
• HF > diurese quickly > IV loop diuretics, but don’t know how much Bumex to give
○ IV push (6 now and 6 later)
○ Or 12 mg and drip continuously
○ Depends on how to do it > continuous > more ____ but durable response compared to the mountaintop of the bolus
○ Measure area under curve > colelct urine > measure the Na that came out > you get more than 1 1/4 times the amount of Na excreted > get it closer with ____ infusion
§ Continuous infusion > straight amount of drug to the ____
§ Bolus > ____ more quickly
§ Actual exposure of drug to nephron is greater when infuse ____ versus giving as a bolus
blunted continuous kidney cleared continuously
Size of Urine Volume Response 2
• Delivery of the drug – \_\_\_\_ – GFR – \_\_\_\_ secretion • Nature of volume excess (if present) – \_\_\_\_ – Abdominal ascites • Braking phenomena
• Use drug that's oral; most diuretics are PO (esp thiazides) ○ Must be able to absorb via \_\_\_\_ ○ A lot of people have swollen intestine • A lot of problems can be bc they didn't absorb it bc of \_\_\_\_ • GFR falls > marker of how well kidney works ○ If it's 1/5 of normal > amount you filter is 1/5 compared to a normal person • Tubulointerstitial diseases ○ Damages the ability of the tubules to do \_\_\_\_ so tubular secretion is impaired ○ May give drugs that \_\_\_\_ with the OAT > and if get there first > diuretic goes right by • Ascites > no blood supply, just a wall of fluid • Braking phenomena ○ When give diuretics and threaten volume > \_\_\_\_ back
absorption tubular peripheral edema intestines edema OAT compete pushes
• When have diseases > shifts everything down
• FENa in a healthy individual, and one with disease
○ In HF > the ____ is low
§ Or wall of gut is impaired
○ Cirrhosis
§ Aldo ____
○ Nephrotic syndrome
§ Little ____
§ Affects the secretion across cells via ____ side
GFR
excess
albumin
basolateral
• If use multiple diuretics:
○ More sense to use diuretic that works on a diff ____ then it gives to a larger dose of diuretic on same segment
○ Treat with furoesmide and give them more > you don’t get more in terms of urine Na excretion
○ Have furosemide and give a thiazide > more ____
segement
effect
• Proximal tubule
○ Can absorb bc it has a huge ____ > bc of all the villi
○ Have some ____
○ A lot of reabsorption
surface area
mito
• Most important pump in PCT: ____
○ Highest michaelis menton numbers in human physiology
○ Speaks with forked tongue
§ When filter blood > Na, K, Cl and bicarb > you have no mechanism to recover filtered bicarb > we recover via secreting ____ (Na H antiporter) from proximal tubule cell lumen where there’s a little bit of H ion courtesy of CA in the cell and cytoplasm > makes this available > shot out, Na gets resorbed of the Na-bicarb that we filter > H+ attacks the carbonic anion until it sits to CA > breaks into H2O and CO2 > easily absorb these, and diffuse down equilibrium into the cell > CA in cell picks up > strips ____ and creates carbonic anion and that with Na is jettisoned into the basolateral side
§ No ____ in healthy urine
• Inhibit the Ca > bicarb comes out in the urine
carbonic anhydrase
H+
H+
bicarb
Carbonic Anhydrase Inhibitor
• CO2+H2O H2CO3 H++HCO3- • Reduces luminal \_\_\_\_ production • Reduces \_\_\_\_ in the cytosol • Reduces HCO3- extrusion in \_\_\_\_ space • What’s lost in urine: – \_\_\_\_, \_\_\_\_, \_\_\_\_ • Serum Consequences: Low HCO3-, Low \_\_\_\_
• Reduce bicarb reabsorption • Bicarbonatruei, natureitic, and kalioretic • CA inhibitors - only class of diuretics that'll elevate urine bicarb cxn chronically ○ Consequence: if keep losing bicarb > liver will try to generate more but it can't keep up > develop low bicarb > \_\_\_\_ • Lose a cation with this ○ Bicarb out in urine, the thing that's in cell that's jettisoned to match is K (lots of K+ in cell, little sodium in cell) ○ Cause \_\_\_\_ § Low K+ levels in cardiac disease > determines potential on membrane; small fall outside cell > depolarizes cell > don't repoloraize well > \_\_\_\_ fibrillation
CO2 HCO3- basolateral Na+ HCO3- K+ K+
metabolic acidosis
hypokalemia
vent
Carbonic Anhydrase Inhibitors
• Clinical uses of acetazolamide (DIAMOX):
– Treating states of HCO3- excess (____ )
– **Treating ____
– ____
• Generating too much bicarb • Glaucoma ○ CA is important for forces that cause filtration of fluid in chambers of eye ○ Reduce \_\_\_\_ pressure • Altitude sickness ○ Climb quickly > O2 fall > breather harder > generate an acidosis in response to the respiratory alkalosis > brain \_\_\_\_ and get sick ○ But if know going into that environment, and prep them and reduce bicarb before they begin the climb > generate \_\_\_\_ that they need to generate on the fly (3 days naturally vs \_\_\_\_ day chemically)
alkalosis
glaucoma
altitude sickness
ocular
swelling
metabolic acidosis
1
Toxicity of CAI
• Metabolic Acidosis
– (Low serum ____ level)
• Hypokalemia
– (Reduced ____ levels)
• Hypokalemia ○ Muscle weakness ○ But with vent tachy or v fib > lethal
bicarbonate
potassium
Loop Diuretics
• Mechanism of action:
– Inhibition of the Na+:K+::Cl-:Cl- transporter
– This pump is very active, located in the LOOP of Henle (many ____)
– Depends on ____ cycling
– Depends on ____ extrusion
• Block \_\_\_\_ ○ Active pump ○ Passive way to block • Characteristc of LH > lots of mitochondria • Reason loop diuretics continue to work is bc of K cycling
mitochondria
K+
Cl-
NKCC2
Thick Ascending Limb Loop
Of Henle Cell:
Lotsa ____ very little ____
• All organelles are mito • Takes a lot of energy > absorption of Na in PT is \_\_\_\_ ○ Here in LH > pumping sodium against a gradient > need a lot of \_\_\_\_
mitochondria
brush border
passive
energy
• When filter blood > 154meq of Na and 5meq of K, and 120 meq of Cl and 20-25 bicarb
○ In the normal plasma > 30x as much Na as there is K, and whens tart to proces urine > recover in proximal it’s ____ (Na comes back at same cxn as it was filtered, and K comes back) > ratio of Na and K stays same but volume shrinks > when get to limb of LH and spin pump 5 times > and ot’s gone
§ Spin it 5 times, but if you don’t replenish the ____ in the lumenthe pump will stop working instantly
§ Done via K recycling
§ The K goes back out when it comes in
□ Failure to do this > ____ syndrome
□ The other parts of neprhon cannot cover completely
• Furosemide, fuminenide, torsamide and ethacrinic acid > block this pump
○ Every time this pump is blocked > 2 Cl, 1 Na and 1 K going past segement
isotonic
K
barter’s
CONSEQUNCES OF LOOP BLOCK
• Increase in urine excretion of – \_\_\_\_ –K – \_\_\_\_ – \_\_\_\_ – \_\_\_\_ • Retention of \_\_\_\_
• Promote loss of Ca ○ Some people make calcium containing kidney stones > don't outgrow that > disorder where you lose more calcium in urine than is healthy ○ Gives drug that increase Ca urine excretion it can potentiate stone formation § Don’t want to use a loop in someone with a history \_\_\_\_ • Retains bicarb ○ PCT picks up a little bit \_\_\_\_
Na Cl Mg Ca HCo3- kdiney stones more
• NKCC
○ Some calcium, but the amount extruded is not trivial, it icnreases bc the pumps that are blocked potentiate the loss of both ____ and magnesium
• DCT
○ Stimulate calcium ____ significantly proximally
○ Characterized by low ____++
calcium
reabsorption
Ca
• Give a LD: ○ \_\_\_\_ goes up ○ \_\_\_\_ goes up § 15 fold ○ And K, and Cl ○ \_\_\_\_goes up ○ \_\_\_\_ small increase
volume
Na
Mg
Ca
CLINICAL USE OF LOOPS
• Volume excess states – \_\_\_\_ – Renal failure and edema (swelling) – \_\_\_\_ (ascites) • Occasionally in hypertension, but \_\_\_\_ are usually better
• Used in heavy duty sodium push ○ HF ○ Kidney failure ○ Liver failure • Rarely used in HTN > but bad kidney function > hard to get any effect from thaizides; so use loops here
heart failure
liver failure
thiazides
Toxicity of LOOPS
- ____
- Volume Depletion
- ____ disorder (hypoK+, alkalosis)
- Activation of Renin-angiotensin- aldosterone system
- Impaired ____
- Uric acid retention (gout)• Excessive volume deption > fall; cannot defend a BP bc no ____
• Hypokalemia
○ All diuretics with exception of ____and ____ cause hypokalemia; potentiate excessive bicarb reabsorption ____
• Activates aldo > ____ > facilitates exchange of K for Na in the distal portions of kidney
• Retain uric acid
○ Potentiate ____
vasodilatory
electrolyte
urinary concentration
blood bolume mineralocorticoid antagonist na blockers proximally hypokalemia gout
• DCT
○ 5% of sodium reabsorption
○ Most ____ usage of diuretics occurs here
§ Bc treating ____ > disorder of minimal but definite Na retention in most people
common
HTN
Thiazide diuretics
- chlorothiazide
- hydrochlorothiazide
- polythiazide
- metolazone• ____ group
○ Key to thiazide class; they all share them
○ More than 30 of these across the world
• Chlorothiazide
○ ____ in group
• Work on ____
• Most commonly used: ____
○ Much more ____ > take smaller amounts
sulfamyl first DCT hydrocholorhizde potent
Thiazides
• Sulfamyl group derivatives
• Block ____ in the distal convoluted tubule (“diluting segment”
* Block NaCl, not \_\_\_\_ * A different \_\_\_\_ in the DCT (compared to NKCC in LH)
NaCl co-transporter
K
transporter
Thiazide Effects • Some volume depletion (< \_\_\_\_) • Increased loss in urine of - \_\_\_\_, \_\_\_\_, \_\_\_\_ • Reduced urinary \_\_\_\_ • Impaired urinary \_\_\_\_ • \_\_\_\_
• Working on smaller amount of filtered sodium in this segement • Reduce urinary Ca ○ Patients with \_\_\_\_ this is used ○ Even if don't even have high\_\_\_\_ ○ Anti-calciureic > useful in reducing urinary calcium bc the amount of calium and oxalate in urine have a saturation phenommenon > saturation of either > crystal formation
LOOPs Na K Cl Ca dilution vasodilatory kidney stones BP
• Braking phenomenon
○ Key concept for all diuretics
○ Best studied with the ____
○ Body adjusts when volume is threatened
• Top line > BP (150/100 - high BP)
○ Measure plasma volume > and measure total PR and CO > baseline values, look at changes
○ Plasma-renin activity
§ Renin is the thermostat for Na intake; if you reduce Na intake it goes up and vice versa
§ Baseline renin > reduce Na balance > renin will ____; it’s reflection of sodium balance
• With thiazides:
○ BP goes down
§ First reducing plasma volume > losing more Na a day; lose a pound of two bc peeing off extra salt water you accumulated
○ CO falls
§ Bc the ____ falls
○ Renin goes ____
○ ____ actvity goes up
○ ____ cxn goes up
§ CO stops fall and reaches new low despite contiuing the diuretic > now it ____ the Na deficit (no further loss) by the first period of time it was used, then over time > the plasma volume increases, and CO adjust (____ , etc.) and PR comes back up and then stop diuretics and system reverts
• Relationship of increasing renin, seeing resistance fall and CO return to normal bc of the braking adjustments made by the body > braking phenomenon
○ Important for ____ usage, when treat with thiazide it’s generally chronic
thiazides increase plasma volume up symp aldo maintains baroreceptors chronic
CLINICAL USES THIAZIDES
- ____
- Modest ____ states
- Calcium containing ____• A lot of swelling > use a ____
○ Idiopathic edema uses thiazides
• Anticalciureic
HTN
edema
kidney stones
loop
Toxicity of thiazides
- Volume ____
- Hyperglycemia
- ____ (older thin women)
- Increased uric acid levels (____)• Every diuretic has a risk of ____
• Increase in blood glucose cxn
○ 1-2% of people treated with thiazide get a ____ bump
• Impair ability of kidney to excrete water > water retention > lower the relative cxn of Na in solution and produces > ____
○ Older ____ women are more prone
• Like loops, also increases uric acid levels
○ Uric aid secretion/reabsorption occurs in ____ tubule, when you rid Na distally, and enhance proximal reabsorption you will enhance uric acid recovery and increase the level or ____ > predisposes to gout
depletion
hyponatremia
gout
volume depletion glucose hyponatremia thin proximal urate
Calcium and Magnesium
• SGLT2 inhibitors ○ -\_\_\_\_ ○ Popular among the \_\_\_\_, but they act like a diuretic because they cause \_\_\_\_ in the urine ○ Predispose to volume \_\_\_\_ • Healthy people don't excrete glucose ○ How reabsorb ○ Bind with \_\_\_\_
flozins diabetes Na depletion Na+
What was given?
• PretreatmentUrine: – Na+ 44 mEq/L – K+ 22 mEq/L – Mg++ 8 mEq/L – Ca++ 49 mEq/L
• Post-treatmentUrine – Na+ 64 mEq/L – K+ 39 mEq/L – Mg++ 10 mEq/L – Ca++ 21 mEq/L
• If see this set of chemistries in urine ○ Drug that is naturetic, kaliretuic, magneciruic, but Ca went \_\_\_\_ > this would be a DCT diuretic (\_\_\_\_)
down
thiazide
K-SPARING DIURETICS
• Mineralocorticoid Antagonist – ____
– eplerenone
• Sodium Channel Blocker
– ____
– triamterene
• Importance: when gave thiazides in large doses > fair amount of \_\_\_\_ ○ When older and taking digitalis/CV active drug > problem • This class developed as antidote to potassium loss from loops and thiazides ○ Block \_\_\_\_ that’s stimulated by loops and thiazides § Causes Na reabsorption and \_\_\_\_ loss in urine § Part of hypokalemia is bc of this • Mineralocorticoid antagonist ○ Antagonists of \_\_\_\_ • Can also block \_\_\_\_
spirnolactone amiloride hypokalemia aldosterone K aldosterone ENaC
- Aldo binds mineralcortiocid receptor in cell > nucleus > tranlates in ____ > increases the number of epi ____ channels and ____ pumps
- Absorbing selectively Na > negative outside > send out ____ to balance the charge
protein
sodium
NaK ATPase
K
K-SPARING MECHANISMS
• MR-____ (requires aldosterone)
• Blockade of ____ reabsorption
• Exchange of Na for K ____, preserving K stores
antagonism
Na+
reduced
• Amiloride is a ____ channel blocker selectively
○ Works from ____ the urine on the epi Na channel
○ Standard diuretic
• MCR antagonist gets into ____ and into cell; doesn’t ____ which side
Na epi
insdie
blood
care
• Spirnolactone resembles ____
○ Derivative ____-based hormone
○ Blocks MCR
○ Such analogy to test > also blocks the ____ receptor
testosterone
cholesterol
androgen
CLINICAL USES OF K-SPARING
- Add on if/when ____ occurs
- ____ (spironolactone)
- Hypertension/additional control
- ____ (spironolactone/eplerenone)/survival
• Cirrhosis ○ High \_\_\_\_ effect • \_\_\_\_-resistant for HTN ○ Additional BP control • Addition of MCR antagonist to a \_\_\_\_/ACE inhibitor adds additional survival benefit ○ Used in HF
hypokalemia cirrhosis heart failure aldo drug beta-blocker
OXICITY OF K-SPARERS
• ____
• ____
• Block men hormone > estradiol effect goes unopposed > breast enlargement ○ \_\_\_\_, and isn't always\_\_\_\_ ○ \_\_\_\_ > doesn't block androgen receptor § Spironolactone suffers from this problem • Limited room for K excess > excede ability to store potassium > rises rapidly > stop heart with \_\_\_\_
gynecomastia hyperkalemia painful reversible epelerone hyperkalemia
Aquaretics
• Known as the “-____”
• Several are available – ____ (IV) and ____ (PO) are the best known
• Indication is low ____ level in blood (hyponatremia)
• Tolvaptan > \_\_\_\_ kidney disease • More water than Na in the body > dilution of Na stores ○ Brain doesn't work well in hyponatremia > fuzzy, seize, \_\_\_\_ impairments
vaptans conivaptan tolvaptan sodium polycystic cognitive
TAKE A LOOK AT TABLE 1
V2 receptors
Localization:
- ____ membrane collecting tubule
- vascular ____
- vascular ____
Functions:
- insertion of AQP2 water channels into apical membrane, induction of ____ synthesis
- ____ and factor ____ release
- ____
basolateral
endothelium
muscle
AQP2
vWF
8
vasodilation
• Aqueratics work on ____ receptors
• V1 receptors
○ Best known: give ____ to human > raises BP; but also causes water retention bc you’re excreted a concentrated urine; V2 receptor ____
V2
arginine/vasopressin
agonism
• When arg/vaso sits on V2 receptor > inserts ____ into urine flow > ____ reabsorption of water
○ Urine osmol gets worse > reabsorb water > have a r elative reducitno in ____ concn in body bc you’re over abosrbing water
○ Aqueratics are used when the serum Aa cxn has fallen bc of water ____; most common reason: inappropiate ____ effect on human (common in HF)
aqueporins selective Na retention vaso
blocking V2 receptors produces a ____,
but without either natriuresis or kaliuresis
* Look at amount of na in urine; these drugs don't change rate of excretion over time, they cahnge amount of \_\_\_\_ excreted over time * 1000 meq of Na and certain amount of water; and want to raise relative cxn of sodium to water > excrete the water > selectively excreting more water than soidum > \_\_\_\_ the individual
diureisis
water
concentrate
• Take someone with bad sodium cxn and give them conavaptan (2x a day, IV) and measure: ○ Pee off water, and Na cxn rises ○ Keep it up for a number of days ○ Lose some \_\_\_\_ ○ Once take away > reverts to\_\_\_\_
weight
baseline
TAKE A LOOK AT TABLE 2!
ya
SPRINT
* Resulted in a change in the \_\_\_\_ guidelines * Funded by \_\_\_\_ NIH institutes
HTN
4
Background
• Observational studies identify strong association between BP and risk of CVD, with no evidence of threshold for the relationship
• High BP very common
• High SBP leading risk factor for mortality and disability-adjusted life years
• Worldwide, >1 billion adults have hypertension
• Clinical trials demonstrate antihypertensive drug therapy reduces risk of CVD
• However, optimal target for SBP lowering uncertain
• Don't known optimum upper level number to treat to • Didn't know optimum systolic BP should be • Enrolled people with high \_\_\_\_ risk ○ 50 years of age ○ Framingham score of \_\_\_\_% over next 10 years ○ 130-180 BP ○ Excluded \_\_\_\_ ○ Excluded people with \_\_\_\_ in urine ○ Excluded people with \_\_\_\_ failure • Compared standard goal of <140 to a more intense one requiring more drug of \_\_\_\_
CVD 10 diabetics protein kidney 120
SPRINT Research Question
Examine effect of more intensive high BP treatment than is currently recommended
Randomized controlled trial target systolic BP
- intensive treatment
Goal SBP < ____ mmHg - standard treatment
Goal SBP < ____ mmHg
120
140
Major Inclusion Criteria
• ≥50 years old
• Systolic blood pressure : ____ – ____ mm Hg (treated or untreated)
- Additional cardiovascular disease (CVD) risk
- Clinical or subclinical ____ (excluding stroke)
- ____ (CKD), defined as eGFR 20 – <60 ml/min/1.73m2 • Framingham Risk Score for 10-year CVD risk ≥ ____%
- Age≥____years
130 180 CVD chronic kidney 15 75
Demographic and baseline characteristics
• Framingham CVD risk = \_\_\_\_% ○ If take 100 of these people and watch for 10 years, \_\_\_\_ will have a heart attack/stroke/die ○ Event rate was \_\_\_\_% per year in the study • Imbalance in \_\_\_\_ bc VA was involved • Good representation of \_\_\_\_ and hispanic • \_\_\_\_ population
20.1 20 2.1 women black older
systolic BP during follow up
• Target of <140 • 135-140 was range • <120 was the goal ○ Came close, but about half were ○ \_\_\_\_mm difference in systolic BP § Very large difference in overall BP control § Intervention \_\_\_\_!
15
worked
Medication classes by treatment group
• How to get 15mm difference ○ Used more \_\_\_\_ blockers (ACE inhibitors, angiotensin inhibitors) and used more \_\_\_\_
RAS
diuretics
SPRINT primary outcome
• Fewer events in more intesnsely treated group ○ \_\_\_\_% reduction
25
SAE during follow-up
• Price to pay: ○ \_\_\_\_ abnormalities
electrolyte
Number (%) of Participants with a Monitored Clinical Measure During Follow-up
* More evidence of low \_\_\_\_ values in intense compared to standard group * Will have to do more labs
K
