Therapeutics of HTN Flashcards
Contraindications with ARBs
- history of angioedema on an ARB
- concomitant use of aliskiren in patients w/ DM
- pregnancy/breastfeeding
Why to avoid _________ dihydropyridines?
short-acting
can cause severe tachycardia
ex: IR nifedipine, nicardipine
aliskiren is _____ first line for HTN
NOT
When to avoid nonselective beta blockers
in pts with bronchospastic airway disease (ask pt if they have a history of asthma or COPD)
these meds can be used for tremor or migraine because non selective
monitoring for BBs
heart rate
Contraindications of aldosterone antagonists
E : impaired renal fxn or T2DM or proteinuria
Both (E, S) : concomitant use of K sparing diuretics
What was the PATHWAY-2 trial?
- small group maximized on ACEi or ARB, CCB and thiazide for at least 3 months
- results: spironolactone > placebo/doxazosin/bisoprolol as add-on therapy in resistant HTN
What alpha 2 agonist is preferred in pregnancy?
methyldopa
Dosing frequency of loop diuretics
F : QD or BID
T : QD
B : QD or BID (this has the lower dose)
examples of central alpha 2 agonists
- clonidine
- methyldopa
- guanfacine
Frequency of dosing for aliskiren
QD
When make the switch from spironolactone to eplerenone?
When pt develops gynecomastia (occurs 10% of the time)
dosage forms of central alpha 2 agonists
clonidine: PO (BID - TID) and transdermal weekly patch (lower risk of rebound HTN and improved adherence w/ patch)
methyldopa PO
guanfacine PO
Diuretic monitoring in a basal metabolic panel
- confirm baseline, check in 1 - 2 wks, 6 - 12 mon for electrolytes and renal fxn
- only check loop diuretics and aldosterone antagonists 3 - 4 wks after initiation
What do nondihydropyridines do?
slows AV node conduction and decreases heart rate (negative ionotropic effect)
HTN goals of tx
- decrease morbidity/mortality
- reach BP targets
- select agents with proven CV benefit
clonidine clinical pearls
- titrating off (slow wean-half dose every 2 - 3 days); concomitant use with beta blocker
- oral to transdermal patch (overlap oral regimen for 3 - 4 days)
- patch to oral (consider starting oral no sooner than 8 hours after patch removal)
Adverse effects of ARBs
- angioedema
- hyperkalemia
- acute renal failure w/ severe bilateral renal artery stenosis
DASH diet (reduce BP 11 mmHg)
- vegetables and fruits
- whole grains
- fat-free or low-fat dairy products
- fish, poultry, beans
- nuts and vegetable oils
- foods rich in K, Ca, Mg, fiber, PRT and lower in Na
LIMIT FOODS THAT ARE:
- high in saturated fats
- sugar-sweetened beverages and sweets
What if pt not at goal
- consider QHS dosing of one of the antihypertensives (could be for ACEi, ARBs and CCB - NEVER for diuretics)
- assess adherence (QD vs multiple dosing; combination products)
- educate on diet, exercise and smoking cessation
- rule out white coat HTN
- discontinue interfering substances
- pt may have resistant HTN
ARBs are a good option for ______
PM dosing to ensure nocturnal “BP dipping”
contraindications for beta blockers
- second or third degree heart block
- decompensated heart failure
- post-MI (ISA BBs only)
- severe bradycardia
- sick sinus syndrome
For loop diuretics, is it helpful to switch to another loop diuretic or from PO to IV?
YES
If stage 1 HTN
- if ASCVD >/= 10% or a specific comorbidity:
- Yes: non pharm and med –> reassess in a month
- No: non pharm –> reassess in 3 - 6 months
Normal HTN
S: < 120 AND
D: < 80
Cons of HBPM and ABPM
- user error
- equipment cost
- insurance reimbursement
isolated systolic HTN
systolic BP values are elevated and diastolic BP values are not
examples of direct arterial vasodilators
- hydralazine
- minoxidil
monitoring for ACEi/ARB
BUN/Scr, K
Substances that increase BP
- illicit drugs
- caffeine
- nicotine
- decongestants
- amphetamines
- antidepressants
- atypical antipsychotics
- immunosuppressants
- oral contraceptives
- NSAIDs
- Systemic steroids
- oncology agents
If elevated BP, 120 - 129/< 80
- non pharmacological treatment
- reassess in 3 - 6 months
Potassium-sparing diuretics have ______ BP effects
minimal
used in combo with thiazide to minimize hypokalemia
Patient specific factor: Cerebrovascular Disease
Secondary stroke prevention
- ACEi/ARB
- Thiazide diuretic*
- Combination of the above
Patient Specific factor: Pregnancy
Preferred and contraindicated
Preferred:
- methyldopa
- nifedipine
- labetalol
Contraindicated (meds that impact RAAS system):
- ACEi
- ARB
- Direct renin inhibitor
- hesitate to use thiazide diuretics
Adverse effects of aliskiren
- Extensive
- diarrhea
- musculoskeletal effects
- dizziness
- HA
- hyperkalemia
- renal insufficiency/ARF
- orthostatic hypotension
What do ARBs do?
Blocks effects of angiotensin II by binding to target receptors
beta blockers can mask signs of __________
hypoglycemia
Adverse effects of loop diuretics
- hypokalemia
- hypomagnesemia
- hypocalcemia
- hyperuricemia
- ototoxicity
resistant HTN is a _______ meaning must ________
disease of exclusion ; rule out secondary causes of HTN, nonadherence, whitecoat HTN, etc
BP goals
ACC/AHA: < 130/80 (may consider < 140/90 in elderly frail pts)
ADA: < 140/90 (goal of < 130/80 for CVD or ASCVD > 15%
KDIGE: < 140/90 w/out albuminuria; < 130/80 w/ albuminuria
HTN Stage 2
S: >/= 140 OR
D: >/= 90
ACC/AHA recommendation for choice of initial medication
FIRST-line agents should include thiazide diuretics*, CCBs and ACE inhibitors or ARBs
What to remember with beta blockers?
avoid abrupt cessation
titrate!
When is spironolactone preferred?
With resistant HTN
When to dose K sparing diuretics?
-morning to avoid nocturnal diuresis
Loop diuretics are preferred in _________
heart failure for symptom management
What does ACEi do?
Prevents conversion of angiotensin I to angiotensin II
Pros of HBPM and ABPM
- confirm diagnosis
- aide in medication titration
- identify white coat and masked HTN
- Better predictor of long-term cardiovascular outcomes
Mixed alpha/beta blockers - examples and when to use
- carvedilol (BID), labetalol (BID)
- great for BP because block alpha receptors
Patient specific factor: Ethnicity and Race
In black adults with HTN but without ___ and ___, including those with DM, initial antihypertensive tx should include a _______ or _______
HF ; CKD ; thiazide diuretic ; CCB
ALLHAT Trial
- pts with HTN and 1 additional risk factor
- pts randomized to chlorthalidone, lisinopril-based therapy, amlodipine, doxazosin
- Results: Chlorthalidone > amlodipine and lisinopril based therapy in preventing stroke, heart attacks and heart failure
- Doxazosin stopped early due to increased risk of heart failure
LEARNED THAT thiazide diuretics should be first line therapy
If can’t take diuretic, consider a CCB or ACE-I
MOST pts with high BP need more than one drug
CCB clinical pearls
- no routine lab monitoring
- check for drug interactions
- dihydropyridine CCBs are first line for HTN
- peripheral edema is dose-dependent
- extended release formulations are preferred
- nondihydropyridine CCB formulation are not interchangeable
- if a CCB is needed in the setting of heart failure, choose amlodipine*
Chlorthalidone is ____ than HCTZ. But HCTZ is _____ and _____
1 - 2 x more potent ; more common ; cheaper
Intrinsic sympathomimetic activity (ISA) beta blocker examples and facts
- acebutolol (BID), penbutolol (QD), pindolol (BID)
- not common, avoid in heart failure and IHD
- used in pts who need beta blocker but heart rate too low (blocks heart rate from going up)
____ is the most significant risk factor for cardiovascular disease
HTN
Patient specific factor: Heart Failure (Reduced Ejection Fraction)
Reduced ejection fraction: follow most recent failure guidelines
-avoid non-dihydropyridine CCBs
Examples of aldosterone antagonists
- spironolactone
- eplerenone
Adverse effects of dihydropyridine CCBs
- reflex tachycardia
- flushing
- dizziness
- HA
- peripheral edema (dose-related)
- gingival hyperplasia
ACCORD trial
-pts WITH diabetes age 40 - 79 w/ CVD or multiple CVD risk factors
- -BP goals:
- **Intensive group: < 120 (achieved 119.3)
- **standard group: < 130 - 140 (achieved 133.5)
- reduced risk of stroke 44%
- increased risk of adverse events
Examples of non selective beta blockers
- nadalol
- propanolol IR
- propanolol LA
How do beta blockers work?
-decrease heart rate + decrease force of contraction –> decrease in CO
Examples of loop diuretics
- furosemide
- bumetanide
- torsemide
- ethacrynic acid
BTFE!
Drug interactions of dihydropyridines
- grapefruit juice
- CYP3A4 enzyme inducer/inhibitor
*pay attention to drug interactions with statins
Dosing frequency of nonselective beta blockers
nadalol and propanolol LA are QD but propranolol IR is BID
For loop diuretics, may need ______ doses with _________ or ____________
higher dose ; severely reduced renal fxn ; fluid overload
When will thiazide diuretic not work?
When CrCl < 30 ml/min
Dosing frequency of cardioselective beta blockers
all but short-acting metoprolol tartrate (BID) is QD
ACEi/ARB Monitoring
Monitor K+ and renal fxn at baseline, 1 - 2 wks after initiation (check BMP within 1 week for elderly), 3 - 4 wks after initiation (only if elevated Scr), every 6 - 12 months
Nondihydropyridines CCBs are _____ first line tx for HTN
NOT
HTN Pharmacologic treatment options
- ACE inhibitors
- ARBS
- CCB
- Direct renin inhibitors
- Beta blockers
- Diuretics
- alpha 1 and 2 blockers
- vasodilators
- sympatholytic agents
ACEi is a ________ for HTN
first line
Loop diuretics are ______ first line for HTN
NOT
Most studied thiazide
chlorthalidone
orthostatic HTN
a systolic BP decrease of greater than or equal to 20 mmHg, a diastolic BP decrease of greater than or equal to 10 mmHg within 3 minutes of positional change, and/or increase in heart rate greater than 20 bpm
direct arterial vasodilators are ______therapy for HTN
last line
Pt populations with additional benefit from beta blockers
- tachyarrhythmias
- tremors
- migraines
- thyrotoxicosis
What do renin inhibitors do?
Blocks conversion of angiotensinogen to angiotensin I
When do not initiate aldosterone antagonist?
With potassium > 5mEq/L. ***consider holding dose if K+ > 5.5 mEq/L or Scr increase > 25%
Modifiable HTN risk factors
- high Na intake
- obesity
- low K intake
- excess alcohol intake
Benefit of controlling HTN is worth the risk of ______
increasing blood sugar
Angiotensin Inhibitor Clinical Pearls
- discuss contraceptive methods with women of childbearing age
- do not combine drug classes
- assess pt’s risk for hyperkalemia
- educate pt on dietary sources of K
- ACEi/ARBs often preferred over other first line agents in the presence of other compelling indications
Warnings with dihydropyridine CCBs
increased risk of angina/MI in pts with obstructive coronary disease due to reflex tachycardia
risk factors for resistant HTN
- older age (blood vessels are more stiff)
- obesity
- CKD
- diabetes
- Black
Examples of nondihydropyridines are
- diltiazem ER
- verapamil ER
Use aliskiren when pregnant?
No
Pts with ______ (4) benefit from the use of ACEi
- diabetes w/ proteinuria
- Heart failure
- Post MI
- CKD
use beta blockers with caution in pts with
- peripheral artery disease (carvedilol preferred)
- reactive airway disease (use selective BBs)
Frequency of dosing for aldosterone antagonists
S : QD or BID
E : QD or BID
Diuretic clinical pearls
- DON’T GIVE AT BEDTIME
- Thiazides are first line for most HTN pts
- Spironolactone is first line for pts with resistant HTN
- Don’t use K+ sparing diuretics as monotherapy for HTN
- Pay attention to pt allergies (sulfa)
- Check CrCl when choosing diuretic class
- Important to monitor K (and other electrolytes)
With nondihydropyridines, what formulation are preferred for HTN?
extended-release
Long term consequences of HTN
- left ventricular hypertrophy
- angina or MI
- coronary revascularization
- heart failure
- stroke or TIA
- CKD
- peripheral vascular disease
- retinopathy
How does aliskiren impact bradykinin?
It doesn’t! Therefore, less cough
Adverse effects of beta blockers
- bronchospasms
- bradycardia
- fatigue
- exercise intolerance
- depression
Direct renin inhibitor
aliskiren
Why are dihydropyridine more potent than nondihydropyridines?
- vasodilation –> baroreceptor-mediated tachycardia
- no effect on atrioventricular node conduction
SPRINT trial
-pts without diabetes or prior stroke
- BP goals:
- **Intensive group: < 120 (achieved 121.4)
- **standard group: < 140 (achieved 136.2)
- reduced risk of death 27%
- average of 2.8 medications used
- increased risk of electrolyte abnormalities, hypotension and AKI
Adverse effects of thiazide diuretics
- hypokalemia
- hypomagnesemia
- hypercalcemia
- hyperuricemia
- hyperglycemia
- hyperlipidemia
- sexual dysfunction
Patient specific factor: Heart Failure
Preserved ejection fraction: For fluid overload
Diuretic
Subclasses of CCBs
- dihydropyridines (more vasodilation)
- nondihydropyridines (more inotropic effects)
- similar effect on BP
resistant HTN
fail to attain goal BP while adherent to a regimen that includes at least 3 agents at maximum dose (including a diuretic or when 4 or more agents are needed)
Pt populations that would receive additional benefit from dihydropyridine
- reynaud syndrome (cold extremities)
- elderly pts w/ isolated systolic HTN
HTN Stage 1
S: 130 - 139 OR
D: 80 - 89
Essential HTN pathophysiology
- humoral abnormalities
- neuronal mechanisms
- vascular endothelial mechanisms
- peripheral autoregulation defects
- electrolyte disturbances
ACEi/ARB monitoring: Consider ________ if ________
holding or reducing dose if K+ > 5.5 mEq/L or Scr increase > 30%
Counsel on ways to decrease K+
Patient specific factor: Heart Failure
Preserved ejection fraction: For elevated heart rate
Beta blocker
minoxidil is __________ than hydralazine
more potent
monitoring for aldosterone antagonists
BUN/Scr, K
ARBs impact HTN by ________
- vasodilation
- reduced PVR
- Increased diuresis
it should be noted that with alpha 1 blockers and HTN…
THEY SHOULD NEVER BE USED FIRST LINE FOR HTN
monitoring for CCBs
heart rate (non-dihydropyridine)
alpha 2 agonists are ______ due to _______
last line ; adverse effects
Thiazide diuretics are more effective than ______ with ______
loop diuretics ; CrCl > 30ml/min
Management of resistant HTN
Step 1: maximize lifestyle interventions, optimize 3 drug regimen (ACEi or ARB, CCB and diuretic)
Step 2: substitute optimized thiazide-like diuretic (chlorthalidone, indapamide)
Step 3: add mineralocorticoid receptor antagonist (spironolactone, eplerenone)
Step 4: add BB if heart rate > 70 bpm, consider central alpha 2 agonist (clonidine patch or guanfacine QHS) if BB contraindicated and/or heart rate < 70 bpm
Step 5: add hydralazine
Step 6: substitute minoxidil for hydralazine
Drug interactions with aldosterone antagonists
- ACEi
- ARBs
- Renin inhibitors
- NSAIDs (increase risk of hyperkalemia)
for direct arterial vasodilators, exercise caution when pts have (5)
- CVA
- renal impairment
- CAD
- Liver disease
- SLE
When to dose loop diuretics?
Morning or afternoon to avoid nocturnal diuresis
Frequency of ACEi dosing
Everything QD except captopril is BID
If normal BP, how to address
- promote healthy lifestyle
- reassess in 1 year
Patient Specific factor: Diabetes
All first-line classes are useful and effective
But in the presence of albuminuria: ACEi or ARB
Adverse effects of ACEi
- angioedema
- cough (excess of bradykinin)
- hyperkalemia
- acute renal failure w/ severe bilateral renal artery stenosis
ARBs are considered _____ for HTN but _____
first line ; also kind of a back up
Can use ARBs in pts with ________
history of cough with ACEi
HTN pts at GOAL should have follow up every ______
3 - 6 months
adverse effects of alpha 2 agonists
- CNS depression
- dizziness
- fatigue
- anticholinergic effects
- bradycardia
- reflex tachycardia
- fluid retention
(notice both bradycardia and tachycardia)
When de-escalating therapy…
identify the first and second line therapy options that have the most potential for adverse effects
example 1st line: amlodipine, chlorthalidone
example 2nd line: carvedilol, hydralazine
Diuretics in HTN
Initial anti-hypertensive effects:
-diuresis –> ______ SV –> ______ PVR
reduced ; increase
alpha 1 blockers are associated with ________ especially in the _______
orthostatic HTN ; elderly
Patient specific factor: Heart Failure
Preserved ejection fraction: For elevated BP
ACEi/ARB
Thiazide diuretics should be dosed ________
IN THE MORNING
Nebivolol acts by ____________
nitric oxide induced vasodilation
Contraindications of ACEi
- history of angioedema on an ACEi
- concomitant use of aliskiren in pts w/ DM
- pregnancy/breastfeeding (avoid RAAS system)
How often are thiazides commonly dosed in a day?
ONCE (also higher doses aren’t really a thing)
Gender modifiable risk factor: Which gender is more likely to display HTN and at what age?
Age < 55: M > F
Age 55 - 64: F >/= M
Age > 64: F»_space; M
Patient populations with additional benefit from nondihydropyridines
- supraventricular tachyarrhythmias (Afib)
- pts with angina who can not tolerate a beta blocker
which direct arterial vasodilator has a black box warning and what is it?
minoxidil
may cause pericarditis and pericardial effusion that may progress to tamponade…may increase oxygen demand and exacerbate angina pectoris
maximum dose of a diuretic and two other antihypertensives should be used b4 this drug
Patient specific factor: Stable Ischemic Heart Disease
First line:
- beta blockers
- ACEi/ARBs
Dihydropyridine CCBs can be used if still uncontrolled
secondary HTN
elevated arterial BP due to concurrent medical conditions or medications (identifiable cause)
Secondary HTN Risk Factors
- CKD
- renovascular disease
- primary aldosteronism
- obstructive sleep apnea
- drug-induced
- food/substances (Na, ethanol)
- pheochromocytoma
- cushings syndrome/chronic steroid use
- thyroid or parathyroid disease
- aortic coarctation
Elevated HTN
S: 120 - 129 AND
D: < 80
examples of alpha 1 blockers
- doxazosin
- prazosin
- terazosin
Adverse effects of aldosterone antagonists
- hyperkalemia
- hyponatremia
- gynecomastia (spironolactone)
Frequency of K sparing dosing
A : QD or BID
T : QD or BID
BP measurement techniques
In office (2 readings 5 minutes apart)
Ambulatory BP monitoring (ABPM - indicated for evaluation of “white coat”, “masked” HTN and nighttime BP dipping)
Home BP monitoring (HBPM - indicated for evaluation of “white coat”, “masked” HTN, response to therapy and may improve adherence)
Thiazide diuretics are ______ for most ____ patients
first line ; HTN (ALLHAT)
For HTN patients, most are ____________
asymptomatic
Patient specific factor: CKD
Post kidney transplantation
dihydropyridine CCBs preferred due to improved GFR and kidney survival
definition of resistant HTN
failure to attain goal BP while adherent to a regimen that includes at least 3 agents at maximum dose (including a diuretic) or when 4 or more agents are needed
Non-modifiable HTN risk factors
- age
- ethnicity
- genetic predisposition
- gender
Diuretics in HTN
Chronic anti-hypertensive effects:
-SV returns to ______ –> ______ in PVR
normal ; decrease
adverse effects of vasodilators
- palpitations
- tachycardia
- chest pain
- GI SE
- HA
- hematologic dyscrasias
- hepatotoxicity
- lupus-like syndrome/rash (hydralazine)
- fluid retention
- hair growth (minoxidil)
should avoid ______ with alpha 2 agonists due to ________
abrupt cessation ; rebound HTN
for direct arterial vasodilators concomitant therapy w/ ____________ and ___________ needed
diuretic ; beta blocker
Adverse effects of K sparing diuretics
- hyperkalemia***
- increased uric acid (be cautious in gout pts)
- hyperglycemia
monitoring for other diuretics
BUN/Scr, electrolytes (K, Mg, Na), uric acid (thiazides)
essential HTN
elevated arterial BP with an unknown etiology
What is HTN?
Persistently elevated arterial BP
Thiazide diuretics are contraindicated with _______
- sulfa allergy
- anuria (aren’t producing urine)
How do ACEi work?
- effects vasodilation
- reduced PVR
- increased diuresis
What diuretics are available?
- thiazide
- loop
- aldosterone antagonists
- k-sparing
Contraindications of loop diuretics
sulfa allergy
Name the preferred combinations
Preferred:
- ACEi/CCB
- ARB/CCB
- ACEi/diuretic
- ARB/diuretic
Acceptable:
-CCB/diuretic
***No ACEi/ARB combo
Dihydropyridine CCBs
-first line HTN
If stage 2 HTN
-non pharm + 2 meds –> reassess in a month
Concomitant use of aliskiren with an ACEi or ARB is _________ in pts with ________
contraindicated ; diabetes
alpha 1 blockers can be considered _____ for pts with concomitant _____
second line ; BPH
Frequency of dosing for ARBs
QD (preferably at night)
Nondihydropyridines dosing frequency
QD or BID
Potassium-sparing diuretics
- amiloride
- triamterene
Examples of thiazide diuretics
- Chlorthalidone
- HCTZ
- Indapamide
- Metolazone
nondihydropyridine drug interactions
- concomitant use of beta blockers (increases risk of heart block)
- grapefruit juice
- CYP3A4 enzyme inducer/inhibitors (3A4 substrates)
Patient specific factor: CKD
CKD stage 1 or 2 AND albuminuria
CKD stage 3 or higher (eGFR = 60)
ACEi (or ARB)
What to monitor with aliskiren?
K, BUN, Scr
Loop diuretics are more effective than thiazide diuretics when the CrCl is ______
< 30 ml/min
Since ethacrynic acid is old, use it when ______
people have a sulfa allergy
When to dose aldosterone antagonists?
In the morning or early afternoon to avoid nocturnal diuresis
When to exercise caution when using a K sparing diuretic?
pts with diabetes and CKD (eGFR < 45 ml/min)
Dosing frequency of dihydropyridine CCBs
Most QD except isradipine (BID) and nicardipine LA (BID)
pts sometimes take their dose and cut it in half to make it BID dosing
What do CCBs do?
Inhibit influx of Ca across cardiac and smooth muscle cell membranes –> coronary and peripheral vasodilation
Adverse effects of nondihydropyridines
- bradycardia
- HA
- dizziness
- AV node block
- systolic heart heart failure
- gingival hyperplasia
- constipation (V > D)
Beta blockers are ____ first line unless _____
NOT ; a compelling indication is present
compelling indication = heart failure and CAD
direct arterial vasodilators are reserved for pts w/ ___________ or __________
special indications ; very difficult to control BP (i.e. severe CKD or hemodialysis)
Contraindications of nondihydropyridine use
- heart block
- left ventricular dysfunction
When to dose ACEi?
PM dosing is an option to ensure “BP dipping” overnight
