Quiz #2 Flashcards
How many US adults have HTN?
1 in 3
Of the people who have HTN, how many are in treatment?
76.5%
How many people have their HTN under control?
54%
What are the 3 types of HTN?
Essential (no identifiable cause)
White coat (office): elevated BP in clinical environment - usually 10 mmHg or more difference
Secondary:
What are the 5 most common drugs that cause HTN?
amphetamines corticosteroids (oral) decongestants NSAIDs estrogen-containing oral contraceptives
How and when is HTN staged?
for initiation of therapy normal: less than 120/80 pre hypertensive: 120-139/80-89 stage 1: 140-159/90-99 stage 2: greater than or equal to 160/100
What organs can be damaged by HTN?
brain (stroke, TIA, dementia)
eyes (retinopathy)
Heart (LV hypertrophy, angina, MI, coronary revascularization, heart failure)
Kidney: (chronic kidney disease)
Peripheral vasculature: peripheral arterial disease
goal of treatment
to reduce mortality and morbidity from CV events.
recommended BP goals:
ASH-ISH
less than 140/90 under 80 y.o.
150/90 80 & over w/out diabetes or cod
JNC8
150/90 60 and over
American Diabetes association
SBP less than 130 for certain individuals if achieved w/out undue treatment burden
KDIGO:
less than 130/80 for patients w/CKD who have persistent albumin excretion of more than 30 mg per 24 hrs
what constitutes albuminuria?
albumin excretion > 30 mg per 24 hours - have to have repeated result for it to be persistent.
what are recommended lifestyle modifications?
weight loss: maintain BMI 18.5-24.9
DASH-type diet
reduced salt intake: 1.5 g/day sodium or 3.8 g/ day sodium chloride (less than)
physical activity: 30 minutes/day most days
moderation of alcohol intake: men 2 or fewer/day, women 1 or fewer drink equivalents/day (5 oz wine, 12 oz beer, 1.5 oz distilled spirits)
What are the proven first line agents for most people with HTN?
proven to reduce CV events: - ACEi -ARB -CCB -thiazide diuretics for those without compelling indications
What are the starting doses for thiazide diuretics?
hydrochlorothiazide: 12.5 mg
chlorthalidone: 12.5 mg
indapamide: 1.25 mg
metolazone: 2.5 mg
what are the starting doses for loop diuretics?
bumetanide: 0.5 mg
furosemide: 20 mg bid
torsemide: 5 mg
What are the starting doses for Potassium sparing diuretics?
amiloride: 5 mg
triamterene: 100 mg bid
what are the starting doses for ACE inhibitors?
lisinopril: 10 mg
enalapril: 5 mg
captopril: 25 mg bid
What are the starting doses for ARBs?
Losartan: 50 mg
Candesartan: 8 mg
Valsartan: 80-160 mg
What are the starting doses for dihydropyridine CCBs?
amlopidine: 5 mg
Felodipine: 5 mg
What are the starting doses for non-dihydropyridine CCBs?
Diltiazem ER: 180-250 mg
verapamil ER: 120-360 mg
What are the starting doses for beta blockers?
metoprolol: 25-100 mg
atenolol: 50-100 mg
Propranolol 40-160 mg bid
What are the aldosterone antagonists?
eplerenone
spironolactone
spirono/HCTZ
What is the direct renin inhibitor?
aliskiren
What should your initial drug therapy be for patients under 80, diagnosed with HTN and no compelling indications?
Stage 1: Monotherapy using ACEi, ARB, CCB or thiazide
Black patients: CCB or thiazide
Stage 2: 2 drug combo using thiazide or CCB + ACEi or ARB
how do age & race affect initial drug therapy choice?
blacks and people 60 and over tend to have greater antihypertensive effects with CCBs or thiazides.
What are the compelling indications that affect initial drug therapy choices?
- heart failure with reduced ejection fraction
- post-myocardial infarction
- coronary artery disease
- diabetes mellitus
- chronic kidney disease
- recurrent stroke prevention (history of ischemic stroke)
What are the guidelines for initial treatment for someone w/htn and heart failure with reduced ejection fraction?
Standard: diuretic with ACEi or ARB, then add beta blocker
add-on: aldosterone antagonist
what are the guidelines for initial treatment for someone w/HTN and post-myocardial infarction?
standard: beta blocker first, then add ACEi or ARB
What are guidelines for someone w/HTN and coronary artery disease?
standard: Beta-blocker first, then add ACEi or ARB
Add-on:
2nd tier: CCB
3rd tier: thiazide
What are the guidelines for someone w/HTN and diabetes mellitus?
standard: ACEi or ARB
Add on:
2nd tier: CCB
3rd tier: thiazide diuretic and/or beta-blocker
What are the guidelines for someone w/HTN and chronic kidney disease?
standard: ACEi or ARB
What are the guidelines for someone w/HTN and recurrent stroke (history of ischemic stroke)?
standard: thiazide diuretic or thiazide + ACEi
when should you re-evalute someone after starting HTN drug therapy
2-4 weeks
how is reduced EF defined?
left ventricular dysfunction or systolic heart failure
Justify guidelines for HFrEF
- Diuretic: relieves symptoms of edema (people w/heart failure tend to accumulate fluid)
- ACEi or ARB: reduces risk of CV events & risk of death
- beta blocker: reduces risk of CV events, reduces risk of death, and increases ejection fraction
How should beta blockers be dosed in someone w/HFrEF?
only 3 are FDA approved in HFrEF
Bisoprolol: starting dose 1.25 mg qd: target 10 mg qd
carvedilol: starting: 3.125 mg bid. Target: 25-50 mg bid
Metoprolol XL: starting: 12.5-25 mg qd. Target 200 qd.
ONLY initiate in stable HFrEF (no signs of HF exacerbation) to avoid causing acute decompensation
double dose every 2 weeks but only if HF is stable. Only target dose is proven to provide long-term CV benefits in HFrEF
aldosterone antagonist as add on is proven to further reduce risk of CV events
Justify guidelines for post MI
Beta blocker (should be started first, followed soon thereafter by ACEi): reduces stimulation of myocardium - eases burden to the heart ACEi promotes cardiac remodeling goal is to reduce risk of 2nd heart attack
What are the signs of coronary artery disease?
chronic stable angina, acute MI or unstable angina
similar to post MI, but these patients have symptoms of cardiac ischemia
Justify guidelines for coronary artery disease
Beta blocker reduces stimulation of the myocardium & treats ischemic symptoms (do beta blocker first, then follow w/ACEi or ARB)
ACEi or ARB promotes cardiac remodeling
Add-on therapy has been proven to reduce risk of CV events (in addition to lowering BP), in patients w/coronary artery disease
CCB can treat ischemic symptoms
thiazide only lowers BP
What is bp goal for patient w/diabetes type 1 and type 2
Justify guidelines for Diabetes Mellitus
ACEi or ARB reduces risk of CV events & kidney disease progression (in addition to BP lowering) (some experts think this is not clearly proven in black patients).
Add-on therapy has been proven to reduce risk of CV events & further reduce bp to goal values
Sasses says add-on should be CCB, not a thiazide
Justify CKD guidelines
ACEi or ARB has been proven to reduce rate of kidney disease progression (in addition to lowering BP)
a loop is sometimes preferred over thiazide in severe CKD (eGFR
How is significant CKD defined?
by JNC7:
reduced excretory function with an eGFR 1.5 mg/dL in men or > 1.3 mg/dL in women) and/or persistent urine albumin excretion
Justify recurrent stroke prevention guidelines
thiazide diuretic mono therapy or in combo w/ACEi is proven to reduce risk of recurrent stroke (in addition to BP lowering)
What is pulse pressure and why is it important?
Difference b/t SBP and DBP. Elderly people tend to have elevated SBP but not DBP, so their pulse pressure is greater. The greater the pulse pressure, the more at risk you are for a CV event.
How should elderly patients be treated?
80 and older
more at risk for orthostatic hypotension. overall therapy should be the same as for younger people, BUT you should start with low initial doses & titrations should be gradual to minimize risk
always start one drug at a time.
- diuretic, ACEi and ARB may cause more orthostatic hypotension than other therapy b/c they have higher amounts of circulating renin
how is orthostatic hypotension defined?
change in SBP of > 20 mm Hg from sitting to standing (or > 10 mm Hg DBP)
avoid volume depletion and rapid dose titration in very elderly patients to minimize this risk
What is the BP goal for patients 80 and older
unless they have CKD or diabetes, it is 150/90 (less than)
CKD eGFR /= 30
when should we use loop diuretics?
for patients w/peripheral edema
stage 4 or 5 kidney disease or w/HF
only switch w/edema
What are the subclasses of diuretics?
Thiazides: chlorthalidone, hydrochlorothiazide, indapamide, metolazone
Loop: bumetanide, furosemide, torsemide
Potassium sparing: amiloride, amiloride/hydrochlorothiazide, triamterene, triamterene/hydrochlorothiazide
What are the side effects of diuretics?
all dose dependent:
- electrolyte depletion (hypokalemia except potassium sparing, hyponatremia, hypomagnesemia)
- hyperkalemia can occur w/potassium sparing agents, especially in those with severe CKD
- possible dehydration & orthostatic hypotension
- exacerbation of gout (mostly thiazides)
What are the drug interactions and contraindications for diuretics?
May increase lithium concentrations
CI in gouty arthritis (especially thiazides), hypotension, dehydration, hyponatremia
What are the dosing considerations for diuretics?
HCTZ is most common BUT
chlorthalidone is more potent mg for mg, better studied long term in patients w/HTN
dose dependent side effects (increase glucose and cholesterol) but generally small & not clinically significant in many patients
What are the ACEi?
benazepril captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril
What are the side effects for ACEi?
- dry cough 20-30% of patients
- hyperkalemia (b/c of aldosterone effects)
- potential renal failure in those with renal-artery stenosis
- angioedema
What are the Drug interactions & CI for ACEi?
May increase lithium concentrations
CI in pregnancy, bilateral renal artery stenosis, history of angioedema
What are some considerations when using and ACEi?
can increase SCr due to dilation of the efferent arteriole in the kidney, resulting in an altered GRF. Only stop if SCr increases > 30% from baseline
using ACEi w/potassium sparing diuretic or aldosterone antagonist or ARB in patients w/CKD requires careful monitoring for hyperkalemia
dosing considerations: half the usual starting dose should be selected for those with HFrEF, hyponatremia or volume depletion, and in the very elderly to minimize the first dose hypotension
What are the angiotensin II receptor blockers?
azilsartan candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan
What are the side effects of ARBs?
hyperkalemia
potential renal failure in those with bilateral renal artery stenosis
What are the drug interactions & CI for ARBs?
may increase lithium concentrations
CI in pregnancy, bilateral renal artery stenosis
What are some other considerations for ARBs?
don’t cause dry cough
many (but not all) are available generically
can increase SCr values, same as with ACEi
dosing considerations are the same as with ACEi
same concerns for hyperkalemia and potassium sparing diuretic, aldosterone antagonist, or ACEi in patients w/CKD
What are the calcium channel blockers (dihydropyridines)?
amlodipine felodipine isradipine isradipine SR nicardipine sustained release nifedipine long-acting nisoldipine ***immediate release nifedipine should be avoided*** - causes stroke and heart attack in patients w/HTN
What are the side effects for dihydropyridine CCBs?
headache peripheral edema flushing reflex tachycardia worsening of GERD
When are dihydropyridine CCBs CI?
HFrEF (except amlodipine and felodipine)
What are the non-dihydropyridine CCBs?
diltiazem (sustained release & extended release)
verapamil (sustained release and controlled onset extended release)
What are the side effects for non-dihydropyridine CCBs?
decrease HR and possible heart block
constipation (worse with verapamil)
peripheral edema
worsening of GERD
What are the drug interactions & CIs for non-dihydropyridine CCBs?
DI:
verapamil & diltiazem inhibit hepatic metabolism of drugs that utilize the CYP P450 3A4 isoenzyme system
can increase cyclosporine concentrations
increase risk of heart block with beta blockers or digoxin
CI in 2nd or 3rd degree heart block, HFrEF (can make heart failure worse b/c decreases strength of contraction)
What are additional considerations with CCBs?
- marked pharmacological difference b/t DHP and non-DHP CCBs (non-DHPs not used very frequently & verapamil & diltiazem products are not interchangeable)
- constipation & decreased heart rate are dose-related
- most once daily products are dosed in the morning except cover HS (verapamil) Verelan HS (verapamil) and Cardizem LA (diltiazem) have chronotherapeutic delivery mechanisms which have no clinical benefit.
What are the beta blockers?
Cardioselective: atenolol betaxolol bisoprolol metoprolol tartrate & succinate
Nonselective (can block beta 2's - can exacerbate underlying asthma & cause SOB): nadolol propranolol propranolol long-acting timolol
Intrinsic sympathomimetic activity (no clinical reason to pick one of these) acebutolol carteolol penbutolol pindolol
Mixed alpha & beta blockers:
carvedilol
carvedilol phosphate
labetalol
What are the side effects of beta blockers?
dose dependent & more prominent w/non-selective agents
- exercise intolerance, fatigue
- decreased HR and possible heart block (lower dose or stop if HR
What are drug interactions & CI w/beta blockers?
Drug interactions:
increased angina with cocaine
increased risk of heart block with verapamil, diltiazem or digoxin
CI:
2nd or 3rd degree heart block
acute left ventricular dysfunction (systolic heart failure)
severe bronchospastic disease (e.g. asthma) however a low dose cardioselective beta blocker may be used cautiously if a compelling indication for beta blocker therapy exists
ISA beta blockers in those post MI
more considerations for beta blockers
- cardio-selective agent is generally preferred over others
dosing considerations:
- dose dependent side effects that are more prevalent with non-selective agents
- adverse effects on cholesterol or glucose are small & not clinically significant, & do not occur w/mixed alpha/beta blockers
- rebound HTN w/abrupt discontinuation, if a beta blocker is discontinued should be tapered over 3-7 days
- starting doses that are lower than what is typical in HTN should be VERY low in those with left ventricular dysfunction
- metoprolol tartrate (2-3/day) and metoprolol succinate (long acting) are NOT equipotent on a mg per mg basis
- atenolol should be dosed BID but is almost always dosed QD; it also is the 1 beta blocker that has the LEAST amount of long term beneficial evidence - many clinicians believe atenolol should not be used
What are the aldosterone antagonists?
eplerenone
spironolactone
spironolactone/hydrochlorothiazide
What are the side effects of aldosterone antagonists?
- significant hyperkalemia can occur, especially in CKD
- possible dehydration & orthostatic hypotension
- hyponatremia
- gynecomastia, but only with spironolactone
What are drug interactions & CI for aldosterone antagonists?
may increase lithium concentrations
CI in: Hypotension, dehydration, hyperkalemia
more considerations for aldosterone antagonists
using w/a potassium sparing diuretic or ACEi or ARB or in patients w/CKD requires careful monitoring for hyperkalemia
what are some patient education points?
- we control, not cure HTN
- usually chronic treatment is necessary
- multiple agents are often required
- presence or absence of symptoms are not helpful (unless in crisis)
-don’t discontinue treatment w/out medical consultation - simplify treatments to maximize adherence
- keep therapy inexpensive if possible
collaborate
What should we monitor for?
always monitor for drug efficacy and toxicity
adherence, & disease progression/presence of HTN-associated complications
What monitoring should we do for each class of HTN drug?
diuretic: BP, BUN/SCr, serum potassium, magnesium, sodium, uric acid (thiazides)
aldosterone antagonists: BP; BUN/SCr, serum potassium
ACEi: BP; BUN/SCr, serum potassium
ARB: BP; BUN/SCr, serum potassium
CCB: BP, Heart rate
Beta blocker: BP, heart rate
When should we re-evalute patients?
2-4 weeks in clinically stable patients
1-7 days in unstable patients or those w/very high BP (>/= 200/110 mm Hg)
situations where ACEi are good and bad
potentially favorable effects:
low-normal potassium, pre-diabetes
potentially unfavorable:
high-normal potassium or hyperkalemia
avoid:
pregnancy, bilateral renal artery stenosis, history of angioedema
situations where ARB are good and bad
favorable:
low-normal potassium , pre diabetes
unfavorable:
high-normal potassium or hyperkalemia
avoid:
pregnancy, bilateral renal artery stenosis
situations where CCB dihydropyridines are good & bad
favorable:
Raynaud’s syndrome, cyclosporine induced HTN
unfavorable:
peripheral edema, high-normal heart rate or tachycardia
avoid:
HFrEF (except amlodipine and felodipine)
situations where non-dihydropyridine CCBs are good and bad
favorable:
Raynaud’s syndrome, migraine headache, arrhythmias, high-normal heart rate or tachycardia
unfavorable:
peripheral edema, low-normal heart rate
avoid:
2nd or 3rd degree heart block, HFrEF
situations where diuretics are good and bad
favorable:
osteoporosis (thiazide only), high-normal potassium
unfavorable:
Gout (mostly thiazide), pre diabetes, low-normal potassium
avoid:
acute gout, hyponatremia, hypokalemia
ON-TARGET trial
showed ACEi w/ARB combo should never be used b/c hospitalizations, acute kidney failure, hyperkalemia & life threatening side effects were more present with ACEi + ARB combo.
looked at ACE alone, ACE + ARB and ARB alone - CV events were all the same
ACCOMPLISH trial:
looked at 2 drug combos: half with ACEi + diuretic and half w/ACEi + amlodipine
ACEi + amlodipine had significantly fewer CV events.
supported initial 2 drug antihypertensive regimens in patients w/stage 2 hypertension
definition of resistant hypertension
patients not at their goal BP on 3 or more antihypertensive agents (ideally, at full doses, one of which is a diuretic), or a patient requiring 4 or more antihypertensive agents to treat hypertension, even if they are at goal BP
What are some causes of resistant HTN?
improper BP measurement
volume overload
drug-induced
secondary HTN
what is the pharmacotherapy for resistant HTN?
- assure diuretic therapy: chlorthiadone should be preferentially used instead of hydrochlorothiazide - more potent & has longer half life
- an aldosterone antagonist as an add-on agent is highly effective
- consider loop diuretic in patients w/resistant ht. that have very compromised kidney function (CrCl
What are the alternative antihypertensive agents?
they have NOT been proved to reduce risk of CV events to same extent as 1st line. Should be used in combo w/1st line
alpha 1 blockers: doxazosin, prazosin, terazosin
direct renin inhibitors: aliskiren
central alpha 2 agonists: clonidine, clonidine patch, methyldopa
peripheral adrenergic antagonist: reserpine
direct arterial vasodilators: minoxidil, hydralazine
What’s the deal with alpha -1 blockers?
give 1st dose at bedtime, rise from sitting or lying down slowly to minimize orthostatic hypotension risk, additional benefits in men with bph
doxazosin
prazosin
terazosin
what’s the deal with direct renin inhibitors?
may cause hyperkalemia in patients w/ckd & diabetes or in those receiving potassium sparing diuretic, aldosterone antagonist, ACEi or ARB; may cause acute kidney failure in patients w/severe bilateral renal artery stenosis or severe stenosis in artery to solitary kidney; do not use in pregnancy
aliskiren
what’s the deal with central alpha-2 agonists?
abrupt discontinuation may cause rebound ht.; most effective if used w/a diuretic to diminish fluid retention, clonidine patch is replaced once per week
clonidine, methyldopa
what’s the deal with peripheral adrenergic antagonists?
used in many of the major clinical trials; should be used w/ a diuretic to diminish fluid retention
reserpine
what’s the deal with direct arterial vasodilators?
should be used w/diuretic and beta blocker to diminish fluid retention & reflex tachycardia
minoxidil
hydralazine
what defines hypertensive crises?
urgency: BP >/= 180/110 + no end organ damage
emergency: BP >/= 180/110 + end organ damage
how do you calculate mean arterial pressure?
(CO X SVR) + CVP
2/3 (DBP) + 1/3 (SBP)
what are some causes of htn crises?
essential ht.
endocrine disease (cushing syndrome, renin-secreting tumor, primary hyperaldosteronism, pheochromocytoma)
renovascular disease (renal artery stenosis, polyarteritis nods, takayasu arteritis)
CNS: (cerebral edema, cerebral hemorrhage, brain tumor, spinal cord injury)
coarctation of aorta
pregnancy - eclampsia
pain
burns
What are types of end organ damage associated w/HTN emergency
cerebral infarction (stroke) intracerebral or subarachnoid bleed hypertensive encephalopathy acute pulmonary edema acute congestive heart failure acute myocardial infarction or unstable angina aortic dissection eclampsia
What is the clinical presentation of HTN emergency?
- abrupt to a few hour onset
- funduscopic: retinal hemorrhages, papilledema, blurry vision
- pulmonary: acute pulmonary edema, rales
- neurologic: stroke, loss of consciousness, memory loss
- renal: azotemia, proteinuria, oliguria, acute renal failure
- cardiac: heart attack, aortic dissection, unstable angina
- pregnancy: eclampsia
- prognosis: HTN emergency can be fatal w/in hour if not treated
goals of htn urgency treatment
reduce bp to 160/100 over several hours to a few days
avoid reductions in MAO > 25% in 1st 24 hrs
long term get back to bp goal (w/in 1-2 weeks)
or more aggressive goal based on co-morbidities
hospitalization not generally necessary - usually oral meds okay treatment
how do you manage HTN urgency?
use rapid onset meds
adjust current antihypertensive regimen
add another long acting antihypertensive med (compelling indications?)
monitor patients w/in 7 days
rapid release nifedipine should be avoided
what are drugs used w/htn urgency?
captopril (ACEi) clonidine (central alpha-2 agonist) labetalol (alpha blocker, beta blocker) nicardipine (DHP CCB) minoxidil (arterial & venous dilator)
what are the goals for HTN emergency treatment?
decrease MAP by 10% during 1st hour & another 15% over next 2-3 hours
gradually decrease bp to 160/100 over first 6 hrs from presentation
avoid reducing MAP > 25% during first 2 hours
long term get back to bp goal or more aggressive goal based on co-morbidities
how do you treat HTN emergency?
if too rapid reduction, cerebral hypo perfusion may occur (especially w/stroke) - importance of assessing MAP
if neurologic function deteriorates after reduction of bp, then treatment should be suspended and bp allowed to increase
for aortic dissection, the goal is SBP
drugs used for htn emergency
clevidipine (DHP CCB) enalaprilat (ACEi) esmolol (beta blocker) fenoldopam (dopamine-1 agonist) hydralazine (arterial vasodilator) labetalol ( alpha blocker, beta blocker) nicardipine (DHP CCB) nitroglycerin (arterial & venous dilator) nitroprusside (arterial and venous dilator)
