Cardiovascular/HTN Flashcards
How prevalent is HTN in the USA?
30% or more (1/3 of Americans have HTN)
What is HTN?
BP 140/90
What causes HTN
idiopathic
CO increases and peripheral vascular resistance increases
Why is HTN bad?
if untreated for a long time can cause:
outcome is
not good for t heart untreated for a long time can cause: ♣ CHF ♣ Aneurysm ♣ Vision issues ♣ Renal failure
poor
A person who is normotensive at age 55 has up to a ___% chance of developing HTN
90
HTN is the #1 reason for
office visits
a decrease in BP of 2mmHg can
lower risk of cardiovascular events by 10%
JNC 8 (JNC - Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) says that the following types of pts should start pharmacotherapy at what BP?
- Patients <60 years of age
-Pts with diabetes start tx at
with CKD
60+ years old
Patients <60 years of age = 140/90
patients with diabetes= 140/90
Patients with CKD= 140/90
Patients 60 years of age or greater =150/90
why would patients 60+ years of age start tx at a higher BP?
Systolic is high but diastolic is okay this is called isolated systolic HTN and a lot of old people get this (usually like 170/70)
Arteries get stiffer with age so BP goes up
Don’t start tx until later because their BP is normally higher
What do we tx HTN with?
thiazide Diuretics, ACE inhibitors, ARBs, CCBs
How do diuretics work?
Diuretics work by depleting sodium (sodium wasting)
“Where sodium goes, so goes water” (if you get rid of Na+, water will also leave and BP will decrease
Only class of diuretics recommended in HTN
thiazides
as you move through the nephron less and less ____ happens
explain
reabsorption
near the glomerulus 60-70% of absorption occurs there
but as you get down passed the loop of henle it drops down to 25% and then in the distal convoluted tubules it drops to 5%
Loop diuretics—bad because they decrease
tons of fluid
Hydrochlorothiazide (HCTZ) (thiazide diuretic)
- ____ derivative so need to watch out for
- MOA=
-sulfonamide, allergies (people with sulfa allergies)
-decrease reabsorption in distal convoluted tubules
by Blocking Na+-CL- symporter on luminal membrane
**this is where 5% of reabsorption takes place and HCTZ blocks it
HCTZ =hydrochlorotiazide
effects
Na+ and Cl- loss K+ loss Mg2+ loss (mechanism unknown) Decreased Ca2+ excretion Decreased peripheral vascular resistance (mechanism unknown)
• HCTZ =hydrochlorotiazide has to be secreted into lumen so kidney has to be
functioning and working very well. So that means glomerulus has to be perfused and still be filtering (fluid has to be coming out of the glomerulus)
• How does the glomerulus work
in order for thiazides to work, glomerulus has to be very
They work on hydrostatic pressure so they are like balloons with a bunch of holes in it
o Not a lot of water is going to come out of holes if you have just a little fluid inside deflated balloon
o If you have a lot of fluid (very perfused) lots of fluid can come out of the holes
o So in order for thiazides to work, glomeruli have to be very perfused
can pts kidney dysfxn take hydrochlorothiazide?
no they will not take these drugs –doesn’t work because their kidneys are not perfused
with HCTZ how long does it take to see consistent decrease in BP?
Effective with renal failure?
Takes up to 3 weeks to see consistent decrease in BP (it will take a little while)
• Not effective if you have renal failure (ineffective if GFR is below 30ml/min)
HCTZ is called ceiling drugs—because
if you Increase dose beyond a certain point does not increase diuresis
adverse affects of HCTZ
o adverse affects ♣ hypokalemia ♣ hyponatremia ♣ hyperuricemia—gout ♣ hypercalcemia ♣ hyperglycemia if pt has high blood sugar, or is diabetic, this drug could push them up so diabetic can use it, but you need to monitor their blood sugar and put them on some other drug to help blood sugar ♣ volume depletion
Drugs that are just like Thiazides (“Thiazide-like” Diuretics)
name 3
which do we prefer, these or HCTZ?
chlorthalidone
indapeamide (lozol)
Matolazone (Zaroxolyn)
We prefer to use the first 2 (chlorothalidone and indapeamide) over hydrochlorothiazide
we use to use HCTZ a lot but now we are seeing more chlorthalidone and indapamide
Drug Interactions with Thiazide-Like Diuretics
1) Uricosuric agents (namely, probenecid) → compete for secretion into proximal tubule and thiazides interfere with uric acid excretion
2) Sulfonylureas and insulin → decreased effectiveness in maintaining blood sugar
3) **Quinidine → increased risk of QT prolongation; potentially fatal
4) Drugs that potentiate orthostatic hypotension
5) Hypokalemia may increase digitalis toxicity
6) NSAIDs
7) Beta-blockers → hyperglycemia/hyperlipidemia
8) Corticosteroids → hypokalemia
Hypokalemia is an issue with THiazides/Thiazide like diuretics, how can we tx this?
diet
Loop Diuretics fxn + names
Bumetanide (Bumex)
Furosemide (Lasix)
Torsemide (Demadex)
MOA: Inhibit Na+-K+-2Cl- cotransporter in thick ascending limb of loop of Henle
Knowing that loop diuretics Inhibit Na+-K+-2Cl- cotransporter in thick ascending limb of loop of Henle, do you expect loops to be more potent, less potent, or equipotent to thiazides?
More potent!!! Because that act where 25% of Na+ reabsorption occurs and so they are blocking a lot of water from coming back in
Loop Diuretics used for HTN?
NO
Loop Diuretics half life? onset? capable of increasing Ca2+ loss?
Short half-life, rapid onset
Capable of increasing renal blood flow
Ca2+ is lost but reabsorbed in Distal Convoluted Tubule so hypocalcemia is rare in patients with normal Ca2+ regulation
Loop Diuretics produces a ton of _____
and even effective when
urine (pts pee a lot)
pt has very decreased renal function
if pt is old and on Lasix, tell them to take this medicine when?
take Lasix in morning so they are not getting up all night and peeing (also because a lot of old pts are on Lasix, and getting up at night a lot can cause injury/fall risk)
Are loop diuretics safe?
side effects?
very
o Ototoxicity (hearing loss/vestibular dysfxn)
o Hyperuricemia
o Hypovolemia ** more potent than with thiazides**
o Hypokalemia ** very profound with these drugs**
hypomagnesemia
Loop Diuretics– if you put someone on a loop diuretic you must also give them
must give them a a Rx for K+
–> don’t ever forget to give someone potassium if you give them Lasix/loop diuretics **
Drug Interactions with Loop Diuretics
Drug interactions
Lithium → increased lithium levels (lithium toxicity)
Aminoglycosides → risk of ototoxicity
NSAIDs → decrease effectiveness of loop diuretics
Hypokalemia may increase digitalis toxicity
Corticosteroids → hypokalemia
Potassium sparing diuretics– not used for
MOA
HTN (same with loop diuretics)
• MOA: inhibit sodium reabsorption and potassium excretion in collecting tubule
Potassium sparing diuretics: good diuretics?
use for pt with renal failure?
not awesome
Use in renal failure? not sure how effective they are in renal failure
Adverse effects of K+ sparing diuretics
Hyperkalemia (because they spare potassium)
Gynecomastia (men with boobs), menstrual irregularities (spironolactone)
photosensitivity
If you wanted to, can you tx HTN with Potassium sparing diuretics? +
yes but needs to be in conjunction with a thiazide diuretic –all it does Is make sure you are not loosing K+
Not part of JNC 8 because you don’t need a loop diuretic to give you K+, you can just have pt change diet, or give them K+
K+ sparing diuretics: Drug interactions
Drug interactions–main thing is risk of hyperkalemia—avoid things with more K+
Strong CYP3A4 inhibitors (eplerenone only)
**Potassium– they are already going to be hyperkalemic–don’t give them more potassium
ACEIs, ARBs, β-blockers increase risk of hyperkalemia
Trimethoprim (hyperkalemia)
NSAIDs
Lithium
Digoxin (increased t1/2 of digoxin)
• What about using K+ sparing diuretics with a loop diuretic?
Won’t make a difference because you lose so much K+ in loop diuretics the K+ sparing won’t make up for it
Potassium Sparing : Aldosterone Antagonists (ends with one)
name a couple drugs
MOA:
Spironolactone (Aldactone), eplerenone (Inspra)
MOA: Prevent aldosterone from binding to target receptors
when would you use potassium sparing: aldosterone antagonists
Uses In combo with K+ wasting diuretics Secondary hyperaldosteronism (cirrhosis, nephrotic syndrome) Heart failure Resistant hypertension Ascites PCOS (polycystic ovary syndrome)
Potassium-sparing: Sodium Channel Blockers
MOA
drugs
dp not require the presence of _____ to be effective
MOA: directly inhibit Na+ influx into collecting duct
Triamterene (Dyrenium), amiloride (Midamor)
aldosterone
Angiotensin-Converting Enzyme Inhibitors (ACEIs)
MOA
also prevent the degradation of
end in
MOA: Block conversion of angiotensin I to angiotensin II
angiotensin I ——-\/—–> angiotensin II
/\
(so increases)bradykinin (a potent endothelial vasodilator)–> causes the cough
pril
Uses of ACE inhibitors
Uses:
- HTN– Both primary and that caused by renal artery stenosis
- Heart failure- specifically LV systolic dysfxn (loss of inotropy) “baggy heart”
- Post MI (prevents remodeling of Heart muscles)
- Patients at high risk of cardiovascular events
- Pts with diabetes—protects your kidneys from further damage
ACEIs are less effective in what population
Less effective in African American patients
Still works but not as well
Some ACEIs list:
all end in
does it matter which you use?
"pril"--doesn't matter which you use because they are equally efficacious at equivalent doses Benazepril (Lotension) Captopril (Capoten) Enalapril (Vasotec) Enalaprilat (Vasotec Injection) Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik)
Side effects of ACEIs
1) First-dose hypotension – watch patients who are salt depleted, CHF, those on multiple antihypertensives, dehydration (Initial dose should be low to minimize side effects )
2) Cough (5-20%) – switch to ARB or another class
3) Hyperkalemia (in presence of other causes)
4) Angioedema-less prevalent than the cough but very prevalent still (swelling of lips, mouth, tongue)
One really big side effect of ACEIs
how? _____ presents a problem when given with ACEIs
explain
acute renal failure
NSAIDs
ACEIs prevent constriction of efferent arteriole
Normally angiotension II would vasoconstrict at your efferent arteriole (normal)
–but we are blocking this action with the ACEI so we are not getting vasoconstriction at efferent arteriole so stuff flows into the glomerulus and its wide open to flow out
-Prostaglandins normally dilate the AFFerent arterioles
however NSAIDs inhibit formation of prostaglandins so they will not dilate the afferent arterioles
• net effect of thse two drugs: glomerulus doesn’t get fluid –> what fluid is does get can flow right out– damage of glomerulus –> acute renal failure
ACEIs prevent constriction of
efferent arteriole
Prostaglandins normally dilate the
Afferent arterioles
ACEI contraindications
- Pregnancy- black box warning ** pregnant women do not get ACE inhibitors (anything with pril—get them off of it
- —–ACEIs must be stopped at the first sign of pregnancy
- —–Fetal hypotension, renal failure, and death will occur
- DO not use in hypoperfused state (eg. Dehydration,etc)
- ->Because of issue of hydrostatic pressure in glomerulus
-Use catuion with drugs that increase potassium or or decrease perfusion
ARBs-
fxn:
where does this happen in chain compared to ACEI
bradykinin?
angiotensin receptor blockers
Block type 1 angiotensin II (AT1) receptors (prevents angtiotensin II from going to AT1)
Effect is occurring further down the cascade
No disruption in bradykinin degradation != less cough/angioedema
ARBs do a little less ______ but better at
can At2 receptors still be activated?
A little less vasodilation however better at inhibiting the effects of angiotensin
AT2 receptors can still be activated because angiotensin II is still circulating
Fxn of ARB
Dilate arteries and veins → decreased preload and afterload
Inhibit cardiac remodeling
Promote Na+ and water excretion
Inhibit aldosterone secretion
Down regulate sympathetic adrenergic activity
ARB drugs end in “ “
artan Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan)
All ARBs are approved to tx
then certain ones are also approved to tx
**HTN
diabetic neuropathy (I's) --->irbesartan, iosartan Stroke prophylaxis -->Losartan Heart failure and post-MI w/LVF ---> Valsartan
Calcium Channel Blockers
MOA:
MOA: Block calcium influx by binding of L-type (L for long-lasting) calcium channels in the heart and vascular smooth muscle cells
–> normally: Ca2+ influx stimulates contraction (so without it, more relaxation (Relaxation of arterial smooth muscle)
normally In the SA node of the heart, L-type channels allow increased Ca++ entry to hyperpolarize pacemaker channels leading to conduction —> cardiac effects
What diuretic can we use according to JNC 8
Thiazides (2 good classes)
Chlorothalidone and idampemide
End result of CCBs
Can use in some heart conditions like
get relaxation of arterial smooth mm—no effect on venous system ***
HTN, angina, antiarrythmics Hypertension (systemic and pulmonary) A-flutter A-fib Paroxysmal SVT
CCBs effects
Main effects :
Decrease contractility (negative inotrope)
Decrease heart rate (negative chronotrope)
Decrease conduction velocity
Vasodilation
CCBs are in 3 classes what are they?
Dihydropyridines- Amlodipine and Norvasc are most popular
phenylalkylamines–> just one Verapamil (not even used for BP)
(nonydropyridne)
benzothiazepines –> just one Diltiazem (not even used for BP)
(nonydropiridine)
Are all CCBs created equal?
NO
each does different things and has different characteristics
Dihydropiridines
characteristics
type of CCB
1) High vascular selectivity - Periph.VascularResistance
2) Potent arteriolar vasodilators
3) Minimal effect on heart**
4) Most useful for the tx of HTN alone
5) Longer t1/2 preparations are better tolerated and are the standard
Dihydropyridines (what kind of drug?) and which has the longest half life
what do they bind to?
CCB
Amlodipine has longest t1/2
Bind to N binding site of L-type channel
Amlodipine…what is it?
what is it a fantastic drug for besides just regular HTN?
used as a CCB best choice for HTN when using a dihydropyridine
Because of its affects on arteries specifically, amlodipine (CCB) is a fantastic drug for people with isolated systolic HTN (old people where systolic is high but diastolic is normal)
–> Because you drop the top # without dropping the bottom #
Verapimil and Diltizaem—are they used for HTN/BP?
no not really, not used for BP –used for arrhythmias
Verapamil Binds to the Essentially cardioselective Less potent\_\_\_\_\_\_\_\_ than dihydropyridines Used for stable Inhibits
V binding site of L-type calcium channels
vasodilator
angina and arrhythmias
P-glycoprotein
Diltiazem
Binds to the
Something in between
Inhibits
D binding site of L-type calcium channels
dihydropyridine and verapamil
P-glycoprotein
Verapamil and diltiazem are class IV _____ drugs because of their impact on myocardial function
antiarrhythmic
Verapamil and diltiazem have ______ half-lives and require tid-qid dosing.
Newer formulations are available that are slow or delayed release allowing less frequent dosing. Pay attention to names with CR, XR, CD.
short
Which has more side effects dihydropyridines or diltiazem and verapamil
_______ is a big deal in terms of side effect with dihydropirines
dihydropyridines
peripheral edema
If a pt cannot tolerate amlodipine can we switch them to verapamil/diltizem?
NO
amlodopine is a dihydropiridine and it treats HTN, whereas verapamil and dilitzem do not tx blood pressure!!!! Option is to switch to another drug class
Dihydropirines, along with verapamil and dilitizem all kind of do the same things on the chart until you get to:
Heart Rate and AV conduction
dihydropyridines actually increase HR while diltizaem and verapamil decrease it
dihydropyridine actually does nothing for AV conduction while diltizaem and verapamil decrease it
Of dihydropyridines, diltizaem and verapamil, which ones do you have to be careful with if pt is on B-blockers
diltizaem and verapamil–need to be careful
dihydropyridines it doesn’t matter
CCBS are a Good option specifically in some patients such as
Diabetes – no effect on glucose
Airway disease – no effect on bronchial dilation
Depression – does not exacerbate illness
African-American – no angioedema
Migraine – ____ &______may decrease migraine frequency by 50%;
verapamil and amlodipine
Some CCBs inhibit _____ – must watch for drug interactions
cytochromes
JNC drug choices :
thiazide, CCB, ACEI, ARB
Preferred thiazides: chlorthalidone, indapamide
how does JNC say to use these drugs?
also need to modify
Options
1) Titrate to maximum dose of one drug before adding second drug
OR
2) Start one drug then add a second before maximizing dose of first
OR
3) Start two at the same time
–>Recommended if BP is greater than 20/10 mmHg above goal
Lifestyle
o Lifestyle Modifications along with these drug treatments?
healthy lifestyle o Low salt o Exercise o Stop smoking (hardens your arteries) o Low fat
pts with CKD should always get an _____except for
Do not combine an ace and an arb because
ACEI or an arb
pregnant people!!
very similar, no benefit and increased risk of hyperkalemia
African Americans/blacks should be treated with ____ why?
African Americans have higher ____ risk; so therefore use ____to provide best protection and are more effective than ACEI/ARB
African Americans are more “____ sensitive”
thiazide, CCB
ACEI and ARB do not work as well with them–works but not very effectively.
CCB
salt
Pts with CKD: tx should include
ACEI or ARB (including African Americans/black)
ways to improve compliance of these drugs/ efficacy
Simplify with once-daily or combo products to improve adherence
Wait 2-3 weeks before increasing dose or adding new drug
home blood pressure reporting
______ are more effective at decreasing systolic BP than diastolic
thiazides and CCBs
do Pts with CKD or CAD benefit from having lower blood pressure targets?
no
use normal BP targets
correct procedure for measuring BP
–> Blood pressure should be measured after the patient has emptied their bladder and has been seated for five minutes with back supported and legs resting on the ground (not crossed).
–>Arm used for measurement should rest on a table, at heart-level.
–>Use a sphygmomanometer/stethoscope or automated electronic device (preferred) with the correct size arm cuff.
–>Take two readings one to two minutes apart, and average the readings (preferred).
–>Measure blood pressure in both arms at initial evaluation. Use the higher reading for measurements thereafter.
