Therapeutics of Hypertension Flashcards
Define essential hypertension.
Elevated blood pressure with an unknown etiology.
Define secondary hypertension.
Elevated arterial blood pressure due to concurrent medical conditions or medications (definable cause).
Define isolated systolic hypertension.
Systolic blood pressure values are elevated and diastolic blood pressure values are not.
Define resistant hypertension.
Failure to attain goal blood pressure 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.
Define orthostatic hypotension.
A systolic blood pressure decrease of ≥20 mmHg, a diastolic blood pressure decrease of ≥10 mmHg within 3 minutes of positional change, and/or increase in heart rate >20 BPM
What 5 factors contribute to essential hypertension pathophysiology?
- Humoral abnormalities
- Neuronal mechanisms
- Vascular endothelial mechanisms
- Peripheral autoregulation defects
- Electrolyte disturbances
How do you calculate blood pressure?
CO x TPR
How do you calculate cardiac output?
CO = SV x HR
List some examples of modifiable hypertension risk factors.
- High sodium intake
- Obesity
- Low potassium intake
- Excess alcohol intake
List some examples of non-modifiable hypertension risk factors.
- Age
- Ethnicity
- Genetic predisposition
Who is more at risk for developing hypertension in the <55 age group: males or females?
Males
Who is more at risk for developing hypertension in the 55-64 age group: males or females?
Females (slightly)
Who is more at risk for developing hypertension in the >64 age group: males or females?
Females
List some possible causes of secondary hypertension.
- Chronic kidney disease
- Renovascular disease
- Primary aldosteronism
- Obstructive sleep apnea
- Drug-induced
- Food/substances (sodium, ethanol)
- Pheochromocytoma
- Cushing’s syndrome/chronic steroid use
- Thyroid or parathyroid disease
- Aortic coarctation
List some examples of substances that can increase blood pressure.
- Illicit drugs (cocaine, ecstasy)
- Caffeine
- Nicotine
- Decongestants (pseudoephedrine, phenylephrine)
- Amphetamines (methylphenidate, dextroamphetamine, amphetamine)
- Antidepressants (MAO-Is, SNRIs, TCAs)
- Atypical antipsychotics (clozapine, olanzapine)
- Immunosuppressants (cyclosporine)
- Oral contraceptives (estrogens, androgens, progesterone)
- NSAIDs
- Systemic steroids (methylprednisolone, prednisone, prednisolone, dexamethasone)
- Oncology agents (angiogenesis inhibitors, tyrosine kinase inhibitors)
How do you conduct an in-office blood pressure reading?
Take two readings 5 minutes apart and sitting in a chair; confirm elevated readings in an opposite arm
When would ambulatory blood pressure monitoring (ABPM) be indicated?
For the evaluation of white-coat hypertension, masked hypertension, and nighttime blood pressure dipping.
When is home blood pressure monitoring (HBPM) indicated?
For the evaluation of white-coat and masked hypertension, response to therapy, and to (possibly) improve adherence.
What is the range for normal blood pressure?
<120/80
What is the range for elevated blood pressure?
120-129 and <80
What is the range for Stage 1 hypertension?
130-139 OR 80-89
What is the range for Stage 2 hypertension?
≥140 OR ≥90
According to the ACC/AHA, what blood pressure management strategy should be initiated in patients with elevated (120-129/<80) blood pressure?
Non-pharmacologic treatment, then reassess in 3-6 months
According to the ACC/AHA, what blood pressure strategies should be initiated in patients with Stage 1 hypertension (130-139/80-89) and an ASCVD risk of ≥10% or a specific comorbidity?
Initiate non-pharmacologic treatment AND medication, reassess in 1 month
According to the ACC/AHA, what blood pressure strategies should be initiated in patients with Stage 1 hypertension (130-139/80-89) and without an ASCVD risk of ≥10% or a specific comorbidity?
Initiate non-pharmacologic treatment, reassess in 3-6 months
According to the ACC/AHA, what blood pressure management strategies should be utilized in patients with Stage 2 hypertenion (≥140/90)?
Initiate non-pharmacologic treatment AND 2 medications, reassess in 1 month
How often should follow-ups take place for hypertension patients at goal?
Every 3-6 months
What is the ACC/AHA blood pressure threshold for treatment initiation in patients with clinical CVD or a 10-year ASCVD ≥10%?
≥130/80
What is the ACC/AHA blood pressure threshold for treatment initiation in patients with no clinical CVD and a 10-year ASCVD <10%?
≥140/90
What is the ACC/AHA blood pressure threshold for treatment initiation in non-institutionalized, ambulatory, community-living adults 65 and older?
Which specific comorbidity has a blood pressure threshold for treatment initiation of ≥140/90?
Secondary stroke prevention
What is the most commonly-used blood pressure goal according to the ACC/AHA?
<130/80
What is the ADA-accepted blood pressure goal for patients without CVD and an ASCVD <15%?
<140/90
What is the ADA-accepted blood pressure goal for patients with CVD or an ASCVD ≥15%?
<130/80
What is the KDIGO-accepted blood pressure goal for patients without albuminuria?
<140/90
What is the KDIGO-accepted blood pressure goal for patients with albuminuria (>30 mg/24 hours)?
<130/80
Explain the SPRINT trial.
Involved partipants without diabetes/prior stroke, and demonstrated that 2.8 medications are needed on average to approach blood pressure goals (<120 mmHg) in an intensive group.
Explain the ACCORD trial.
In participants with T2DM age 40-79 with CVD or multiple risk factors, there was no benefit in primary composite outcome despite meeting blood pressure goals.
List some non-pharmacologic treatment options for hypertension/elevated blood pressure.
- Weight loss
- DASH diet
- Decreased sodium intake (<1500 mg/day or 1000 mg reduction per day)
- Enhanced potassium intake (3500-5000 mg/day)
- Physical activity
- Moderation in alcohol intake
What foods should be limited in the DASH diet?
- High saturated fat foods (fatty meats, full-fat dairy, tropical oils)
- Sugar-sweetened beverages and sweets
What are the four classes of first-line agents for antihypertensive therapy?
- Thiazide diuretics
- Calcium channel blockers
- ACE inhibitors
- ARBs
Explain the ALLHAT trial.
Patients >55 with HTN and 1 additional CV risk factor were randomized to 4 different drugs
- Thiazides are first-line
- Chlorthalidone was better than amlodipine and lisinopril-based therapy in preventing stroke, heart attacks, and heart failure
- Patients who cannot take a diuretic should be prescribed a calcium channel blocker or ACE inhibitor
- Most patients with high blood pressure need more than 1 drug
What are the three first-line treatments that can be used in patients with stable ischemic heart disease?
- Beta blockers
- ACE inhibitors
- ARBs
If first-line treatments have already been initiated for hypertension with stable ischemic heart disease and blood pressure goals still aren’t being met, what medication class can be considered?
Dihydropyridine calcium channel blockers
What medication class should be avoided in patients with heart failure with reduced ejection fraction?
Non-dihydropyridine calcium channel blockers
What drug class should be first-line in heart failure patients with preserved ejection fraction and fluid overload?
Diuretics
What two drug classes should be first-line for patients with heart failure and preserved ejection fraction with elevated blood pressure?
ACE inhibitors and ARBs
What drug class is first-line for patients with heart failure with preserved ejection fraction and elevated heart rate?
Beta blockers
What medication classes are first-line for hypertension patients with CKD stage 1/2 AND albuminuria?
ACE inhibitors or ARBs
What medication classes are first-line for patients with hypertension and CKD Stage 3 or higher?
ACE inhibitors or ARBs
What medication class is first-line in hypertension patients who are post-kidney transplant?
Dihydropyridine calcium channel blockers
What three medication classes are first-line in hypertension patients requiring secondary stroke prevention (cerebrovascular disease)?
- Thiazide diuretics
- ACE inhibitors
- ARBs
What medication classes are first-line in hypertension patients with diabetes?
All first-line classes are useful and effective
What medication classes are first-line in hypertension patients with diabetets in the presence of albuminuria?
- ACE inhibitors
- ARBs
What three agents are preferred in pregnant hypertensive patients?
- Methyldopa
- Nifedipine
- Labetalol
What three medication classes are contraindicated in pregnant hypertensive patients?
- ACE inhibitors
- ARBs
- Direct renin inhibitors
What medication classes are first-line in black adults with hypertension but without HF or CKD?
- Thiazide diuretics
- Calcium channel blockers
List the four thiazide diuretics.
- Chlorthalidone
- Hydrochlorothiazide
- Indapamide
- Metolazane
List the four loop diuretics.
- Furosemide
- Torsemide
- Bumetanide
- Ethacrynic acid
List the two aldosterone antagonist diuretics.
- Spironolactone
- Eplerenone
List the two potassium-sparing diuretics.
- Amiloride
- Triamterene
Explain the initial antihypertensive effects of diuretics.
- Diuresis
- Reduced stroke volume
- Increase in PVR
Explain the chronic antihypertensive effects of diuretics.
- Stroke volume returns to normal
- Decrease in PVR (below pretreatment)
Which thiazide diuretic is most potent?
Chlorthalidone
Which trial determined that thiazide diuretics are first-line for most hypertension patients?
ALLHAT
When are thiazidide diuretics more effective than loop diuretics in hypertensive patients?
When CrCl >30 ml/min
How should thiazide diuretics be administered (frequency and time of day)?
Once daily in the morning to avoid nocturnal diuresis
What adverse effects are associated with thiazide diuretics?
- Hypokalemia
- Hypomagnesemia
- Hypercalcemia
- Hyperuricemia
- Hyperglycemia
- Hyperlipidemia
- Sexual dysfunction
- Increase in TGs/cholesterol
What drug class interacts with thiazide diuretics?
Lithium (toxicity with concurrent use)
What are the two contraindications for thiazide diuretics?
- Sulfa allergy
- Anuria
When are loop diuretics more effective than thiazides?
- Heart failure symptom management
- CrCl <30 ml/min
What can help with the high-ceiling dose response curve in loop diuretics?
- May need higher doses with severely reduced renal function/fluid overload
- Switch to another loop diuretic
- Switch from PO to IV
How should loop diuretics be administered (frequency and time of day)?
Once or twice daily in the morning/afternoon to avoid nocturnal diuresis.
What adverse effects are associated with loop diuretics?
- Hypokalemia
- Hypomagnesemia
- Hypocalcemia
- Hyperuricemia
- Ototoxicity
When are loop diuretics contraindicated?
Sulta allergy
What trial demonstrated that spironolactone is preferred with resistant hypertension?
PATHWAY-2
How should aldosterone antagonists be administered (frequency and time of day)?
Once or twice daily in the morning/afternoon to avoid noctural diuresis
When should you consider holding/reducing aldosterone antagonist doses?
- Potassium >5.5 mEq/L
- SCr increase >25%
What adverse effects are associated with aldosterone antagonists?
- Gynecomastia (spironolactone only)
- Hyperkalemia
- Hyponatremia
When is eplerenone contraindicated?
- Impaired renal function (CrCl <50 or SCr >2 (male) or >1.8 (female))
- T2DM and proteinuria
- Concomitant use of potassium sparing diuretics
When is spironolactone contraindicated?
Concomitant use of potassium-sparing diuretics
Since potassium-sparing diuretics have minimal effect on blood pressure alone, how are they commonly used?
In combination with thiazides to minimize hypokalemia
How should potassium-sparing diuretics be administered?
Once or twice daily in the morning to avoid nocturnal diuresis
When should caution be used with potassium-sparing diuretics?
- Diabetics
- CKD (GFR <45 ml/min)
- Gout
What adverse effects are associated with potassium-sparing diuretics?
- Hyperkalemia
- Increased uric acid
- Hyperglycemia
When should electrolytes and renal function be monitored in patients taking thiazide and potassium-sparing diuretics?
- Baseline
- 1-2 weeks after initiation
- Every 6-12 months
When should electrolytes and renal function be monitored in patients taking loop diuretics and aldosterone antagonists?
- Baseline
- 1-2 weeks after initiation
- 3-4 weeks after initiation
- Every 6-12 months
How do ACE inhibitors work?
Inhibit conversion of angiotensin I to angiotensin II
How do angiotensin II receptor blockers (ARBs) work?
Block the effects of angiotensin II by binding to target receptors
How do renin inhibitors work?
Inhibit the conversion of angiotensinogen to angiotensin I
ACE inhibitors are drugs with what suffix?
“-pril”
ACE inhibitors have additional benefit in patients with a history of what?
- Diabetes with proteinuria
- Heart failure
- Post-MI
- CKD
Why are ACE inhibitors a good option for PM dosing?
To ensure blood pressure dipping overnight
How do ACE inhibitors provide antihypertensive effects?
- Vasodilation
- Reduced PVR
- Increased diuresis
What is the only ACE inhibitor that is dosed 2-3 times daily?
Captopril
All ACE inhibitors (except for captopril) are dosed at what frequency?
Minimum once daily
What adverse effects are associated with ACE inhibitors?
- Angioedema
- Cough
- Hyperkalemia
- Acute renal failure with severe bilateral renal artery stenosis
When are ACE inhibitors contraindicated?
- History of angioedema on an ACE inhibitor
- Concomitant use of aliskiren in patients with diabetes
- Pregnancy/breastfeeding
ARB drugs have what suffix?
“-sartan”
Why is there a smaller risk of cough with ARBs?
They don’t block bradykinin breakdown
Why are ARBs a good option for PM dosing?
To ensure blood pressure dipping overnight
Explain the antihypertensive effect of ARBs.
- Vasodilation
- Reduced PVR
- Increased diuresis
How are ARBs administered (frequency and time of day)?
Once to twice daily at bedtime
What adverse effects are associated with ARBs?
- Angioedema (less than ACEi)
- Hyperkalemia
- Acute renal failure/severe bilateral renal artery stenosis
When are ARBs contraindicated?
- History of angioedema on an ARB
- Concomitant use of aliskiren in patients with diabetes
- Pregnancy/breastfeeding
What drug is a direct renin inhibitor?
Aliskiren
When is aliskiren contraindicated?
- Concomitant use with an ACEi/ARB in diabetes patients
- Pregnancy
How is aliskiren administered?
Once daily
What three categories should be monitored in patients taking aliskiren?
- Potassium
- BUN
- SCr
(same as ACEi/ARBs)
What adverse effects are associated with aliskiren?
- Diarrhea
- Musculoskeletal effects (CK increase)
- Dizziness
- Headache
- Hyperkalemia
- Renal insufficiency (ARF)
- Orthostatic hypotension
How do calcium channel blockers work?
They cause coronary and peripheral vasodilation by inhibiting calcium influx across cardiac and smooth muscle cell membranes
What class of calcium channel blockers causes more vasodilation?
Dihydropyridines
What class of calcium channel blockers causes more inotropic effects?
Non-dihydropyridines
Dihydropyridine CCBs have what suffix?
“-pine”
Which two dihydropyridine CCBs have no negative inotropic effects?
Amlodipine and felodipine
Dihydropyridine CCBs have additional benefit in which patient populations?
- Reynaud’s syndrome
- Elderly patients with isolated systolic hypertension
What can result given that dihydropyridine CCBs are more potent vasodilators?
Baroreceptor-mediated tachycardia
Which type of dihydropyridine CCBs are preferred in treating hypertension?
Long-acting dihydropyridines
How are dihydropyridine CCBs administered?
Once or twice daily
(Twice = isradipine and nicardipine DR)
What adverse effects are associated with dihydropyridine CCBs?
- Peripheral edema (dose-related)
- Reflex tachycardia
- Flushing
- Dizziness
- Headache
- Gingival hyperplasia
What warning is associated with dihydropyridine CCBs?
Increased risk of angina/MI in patients with obstructive coronary disease due to reflex tachycardia (for short-acting, immediate release)
What do dihydropyridine CCBs interact with?
- Grapefruit juice
- CYP3A4 inducers/inhibitors (i.e. statins)
What are the two non-dihydropyridine CCBs?
Diltiazem and verapamil
Non-dihydropyridine CCBs are shown to have additional benefit in which patient populations?
- Supraventricular tachyarrhythmias (atrial fibrilation)
- Angina patients who can’t tolerate beta blockers
Explain the antihypertensive effect of non-dihydopyridine CCBs.
Slows AV node conduction and decreases heart rate (negative inotopic effects)
How are non-dihydropyridine CCBs administered?
Once or twice daily
What adverse effects are associated with non-dihydropyridine CCBs?
- Bradycardia
- Headache
- Dizziness
- AV node block
- Systolic heart failure
- Gingival hyperplasia
- Constipation (verapamil > diltiazem)
What drug interactions exist with non-dihydropyridine CCBs?
- Concomitant use of beta blockers (increased risk of heart block)
- Grapefruit juice
- CYP3A4 inducers/inhibitors
When are non-dihydropyridine CCBs contraindicated?
- Heart block
- Left ventricular dysfunction
Which calcium channel blocker should be used in heart failure patients?
Amlodipine
List the cardioselective beta blockers.
- Atenolol
- Betaxolol
- Bisoprolol
- Metoprolol tartrate
- Metoprolol succinate
- Nebivolol
List the nonselective beta blockers.
- Nadolol
- Propranolol IR
- Propranolol LA
When should nonselective beta blockers be avoided?
In bronchospastic airway disease
List the intrinsic sympathomimetic activity beta blockers.
- Acebutolol
- Penbutolol
- Pindolol
When should intrinsic sympathomimetic activity beta blockers be avoided?
Heart failure and IHD.
List the mixed alpha/beta blockers.
- Carvedilol
- Labetalol
What are the two compelling indications that would make beta blockers first-line for hypertension?
Heart failure and CAD
Beta blockers are shown to have additional benefit in which patient populations?
- Tachyarrhythmias
- Tremors
- Migraines
- Thyrotoxicosis