Hypertension: Harrison's & Saseen Flashcards
Most contemporary guidelines endorse what kind of blood pressure goals for most patients?
< 140/90
Most contemporary guidelines endorse what kind of blood pressure goals for patients with diabetes or chronic kidney disease?
< 130/80
Some controversy exists about certain groups of patients & blood pressure goals? What patient groups?
Patients with CAD, vascular disease (stroke, PAD), & those with a 10 year risk of CAD
What should the clinician’s first consideration be in selecting anti-hypertensive drug therapy?
Is there a compelling indication for a SPECIFIC drug therapy?
What are some comorbidities that create compelling indications for specific anti-hypertensive drugs?
#Diabetes #Chronic kidney disease #Coronary artery disease #Left ventricular dysfunction #Previous ischemic stroke
First line regimen for patients with DIABETES?
Add-on therapy?
1st line: ACE-inhibitor or ARB
Add-on: Thiazide, then beta-blocker &/or CCB
First line regimen for patients with CHRONIC KIDNEY DISEASE:
ACE-inhibitor or ARB
First line regimen for patients with CORONARY ARTERY DISEASE?
Add-on therapy?
1st line: beta-blocker & ACE-inhibitor or ARB
Add-on: Aldosterone antagonist, CCB, and/or thiazide diuretic
First line regimen for patients with LEFT VENTRICULAR DYSFUNCTION?
Add-on therapy?
1st line: Diuretic, ACE-inhibitor or ARB, & Beta-blocker
Add-on: Aldosterone antagonist &/or hydralazine with isosorbide dinitrate
First line regimen for patients with PREVIOUS ISCHEMIC STROKE:
#ACE-inhibitor with or without #Thiazide diuretic
True or false: most diabetics with hypertension can be controlled on a single drug.
False. Most require 2-3 drugs to attain control.
Why are ACE or ARBs recommended as 1st line therapy for diabetics with hypertension?
Both have been proven to reduce the risk of CV events & kidney disease progression in diabetic patients.
Why are calcium-channel blockers particularly useful in diabetics with hypertension?
They do not affect glycemic control.
How does estimated glomerular filtration rate affect the selection of diuretic in a hypertensive diabetic patient?
eGFR > 30: thiazide diuretic
eGFR < 30: loop diuretic
What is the thiazide diuretic used in clinical trials regarding hypertensive diabetic patients?
Chlorthalidone
Beta-blockers are considered 3rd or 4th line add-on for diabetic patients with hypertension. Why?
Risk of hyperglycemia with beta-blocker therapy
True or false: all beta-blockers carry the same risk for hyperglycemia in diabetic patients.
False: in the GEMINI trial, carvedilol had no significant effect on glucose, but metoprolol did.
How does the clinician identify CKD in a hypertensive patient for the purposes of drug therapy?
CKD in Stage 3 or higher:
1) eGFR < 60 (serum creatinine > 1.3 in women or 1.5 in men)
2) Albuminuria > 300 mg/day
Diuretics can serve 2 purposes in the hypertensive CKD patient. What are they?
1) BP control
2) volume regulation
When should the clinician choose a thiazide diuretic for a CKD patient? A loop diuretic?
Thiazide: eGFR > 30
Loop: eGFR < 30, or patient in volume overload/edema
Why are beta-blockers the cornerstone of anti-hypertension therapy in patients with CAD?
Proven long term benefits: reduces risk of death by more than 20%. Effects: #reduces stimulation of myocardium #balances myocardium oxygen supply vs. demand #treats ischemic symptoms
How does an ACE or ARB benefit the hypertensive CAD patient?
Preventing adverse cardiac remodeling
In addition to the first line of beta-blocker & ACE/ARB, how can a CCB benefit a hypertensive CAD patient?
Treat ischemic symptoms
When should the clinician select a dihydropyridine CCB vs. a non-dihydropyridine CCB?
If added to beta-blocker, select the DIHYDROPYRIDINE CCB (to avoid excessive bradycardia). If beta-blocker is contraindicated, select the NON-DIHYDROPYRIDINE CCB, because of ability to lower heart rate & reduce myocardial oxygen demand (i.e. what the beta-blocker WOULD be doing if they could take it).
In addition to lower BP, diuretic therapy has what other purpose in the patient with hypertension & LV dysfunction?
Treating or preventing fluid overload
Use of beta-blockers in addition to ACE/ARB for patients with LV dysfunction has an additional benefit. What is it?
Increased ejection fraction
What rule should the clinician remember when starting beta-blocker therapy on a hypertensive patient with LV dysfunction?
Start low, go slow!
[Start at a low dose & titrate up to a target dose.]
For African-American patients in particular, what 3rd or 4th line therapy has been shown to reduce CV events in hypertensive patients with LV dysfunction?
Hydralazine in combo with isosorbide dinitrate
History of a CVA, especially ischemic, is a compelling indication for use of…
a diuretic!
Certain drug combinations have been shown in trials to reduce risk of recurrent stroke, MI, & CV events in patients with prior stroke. What are they?
#Diuretics alone #Diuretics in combination with ACE-inhibitors
True or false: ARB therapy has been shown to reduce risk of recurrent stroke in hypertensive patients.
False. It has not been shown to reduce CVA risk either as first or second line therapy.
How do ACE-inhibitors work?
By inhibiting ACE, resulting in decreased angiotensin II. This causes decreased vasoconstriction, decreased aldosterone secretion, & sodium/water retention.
How do ARBs work?
Blockade of angiotensin II type 1 receptor. Decreases the effects of angiotensin II, causing decreased vasoconstriction, decreased aldosterone secretion, & sodium/water retention.
How do CCBs: Dihydropyridines work?
Blocking cellular calcium entry through L-type channel. Results in reduced total peripheral resistance through arterial vasodilation.
How do CCBs: Non-dihydropyridines work?
Blocking cellular calcium entry through L-type channel. Results in reduced total peripheral resistance through arterial vasodilation. ADDITIONALLY: decreased myocardial contractility results in negative inotropic effect, blocked AV nodal conduction results in decreased HR.
How do thiazide diuretics work?
#Short term: natriuresis, resulting in reductions in cardiac output & decreased blood volume #Longer term: decreased peripheral vascular resistance
How do beta-blockers work?
Blockade of beta-1 receptors. Results in reduced cardiac output & reduced HR. Inhibit renin release, decreases adrenergic CNS effects, reduces catecholamine release/response.
How do aldosterone antagonists work?
Blockade of aldosterone receptors. Decreased vasoconstriction & decreased sodium/water retention.
Volume loss (intentional or unintentional) while on ACE-inhibitor therapy may result in…
…major decreases in BP and deterioration in renal function to the point of acute renal failure.
ACE-inhibitors as monotherapy may not be as effective in what type of hypertension? This can be overcome by…
Salt-sensitive, low-renin forms of hypertension (as often found in African-American, diabetic, and elderly hypertensive patients). This can be overcome by administering in higher-than-usual doses.
What is a very distinct adverse effect of ACE-inhibitors? Will switching to a different ACEI help?
A dry cough. Switching to another ACEI does not seem to help, as it is a class effect.
If a patient develops angioedema on an ACE-inhibitor, should they ever take one again?
That would be a NOPE! You’re gonna have to go with an ARB on that one.
ACE-inhibitor use during pregnancy?
NEVER. NOPE. DO NOT.
ARBs use during pregnancy?
NOPE. DON’T EVEN TRY IT.
True or false: ARBs also cause “The Cough.”
False. Also, patients who have angioedema on an ACE can use ARB without that effect.
What are the 2 classes of CCBs?
#Dihydropyridines #Non-dihydropyridines
Other uses for dihydropyridine CCBs?
#Cyclosporine-induced hypertension #Raynaud phenomenon
Other uses for non-dihydropyridine CCBs?
#Atrial fibrillation #Migraine headache prevention
What is an advantage of 2nd-generation dihydropyridines?
They are highly selective for vasculature, so they avoid the affects on cardiac contractility that 1st-generation ones had.
Side effects common to ALL CCBs:
#GERD #Constipation (almost ALWAYS happens with verapamil)
Side effects of dihydropyridine CCBs:
#Flushing #Headache #Peripheral Edema
What can be done to avoid the peripheral edema side effect of dihydropyridines?
#reduce the dihydropyridine dose #add an ACE or ARB #encourage pt to elevate lower extremities
Non-dihydropyridines are contraindicated in what group?
Patients with LV dysfunction. Can cause CHF exacerbation!
What are the 2 CCBs that inhibit the CYP450 3A4 system?
Verapamil & diltiazem
CCBs are more effective than ACE/ARB in what group?
African-Americans & those with low-renin, salt-sensitive HTN
True or false: the BP reducing effects of thiazide diuretics are mainly due to decreased circulating volume.
False. They are due to the short-term, long-term, & chronic effects of the diuretic on the body.
What are the short-term effects of thiazide diuretics? How long are we talking?
First 2-4 weeks: reductions in BP are related to decreases in cardiac output & plasma volume. There’s also an increase in plasma renin activity & a transient increase in peripheral vascular resistance.
What are the long-term effects of thiazide diuretics? How long are we talking?
After 4 weeks: cardiac output & plasma volume return to normal levels, but BP stays low because of persistent DECREASE in peripheral vascular resistance.
What are the chronic effects of thiazide diuretics? How long are we talking?
Persistent reduction in total peripheral resistance
Four subclasses of beta-blockers
#Cardioselective beta-blockers #Non-selective beta-blockers #Beta-blockers with intrinsic sympathomimetic activity #Mixed alpha-/beta-blockers
Why should patients be taught never to abruptly discontinue their beta-blocker?
Rebound hypertension time!
What side effect might you get if you combine verapamil or diltiazem with a beta-blocker?
Sharp reduction in heart rate and risk of heart block! Fancy!
True or false: the newest guidelines consider beta-blockers first line therapy for uncomplicated hypertension?
False! That’s old school thinking. Newer information tells us that beta-blockers should not supplant ACEs/ARBs.
What are the 2 clinically available aldosterone antagonists?
#spironolactone #eplerenone
What are potential side effects of spironolactone?
#painful gynecomastia (in men) #erectile dysfunction #menstrual irregularities
Can spironolactone-induced gynecomastia be reversed?
Yes but it takes a while
What effect might aldosterone antagonists have on potassium levels?
Hyperkalemia can be a problem! Mostly it happens when AAs are given to people with CKD or in combination with ACE/ARBs (which are known to increase serum potassium).
Two special groups for whom hydralazine (an arterial vasodilator) is recommended:
#pregnant women #African-American patients with CHF (in combo with isosorbide dinitrate!)
The most widely used alpha-agonist?
Clonidine! Congratulations!
Methyldopa is used almost exclusively for…
…gestational hypertension or management of chronic hypertension in pregnant patients. It has a very long history of safety! (It ain’t broke we we ain’t trying to fix it.)
What is an advantage of fixed-dose combination drugs?
Decreasing the number of pills increases adherence to therapy.
What’s a positive Osler sign?
Inflating the cuff above systolic BP, but finding the brachial or radial artery is still palpable. A component of pseudohypertension.
What is “essential” hypertension, aka “idiopathic” or “primary” hypertension?
HTN without a clear etiology
What is “secondary” hypertension?
HTN with an apparent reason for the BP elevation
What might cause secondary hypertension with wide pulse pressure?
#Decreased vascular compliance (arteriosclerosis) #Increased cardiac output (aortic regurg, thyrotoxicosis, hyperkinetic heart syndrome, fever, AV fistula, patent ductus)
What might cause secondary hypertension with both systolic & diastolic increases?
#Renal: parenchymal disease, cysts, tumors, obstructive uropathy #Renovascular: arteriosclerosis, fibromuscular dysplasia #Adrenal: Primary aldosteronism, Cushing's, 17 alpha-hydroxylase or 11 beta-hydroxylase deficiencies, pheochromocytoma #Aortic coarctation #Obstructive sleep apnea #Pre-eclampsia, eclampsia #Neurogenic: psychogenic, diencephalic syndrome, familial dysautonomia, polyneuritis, acute increased ICP, acute spinal cord section #Endocrine: Hypothyroid, hyperthyroid, hypercalcemia, acromegaly #Meds: Estrogens, adrenal steroids, decongestants, appetite suppressants, cyclosporine, TCAs, MAOIs, erythropoetin, NSAIDs, cocaine
AND A PARTRIDGE IN A PEAR TREE. GEEZ.
What is the etiology of essential hypertension?
We don’t freakin’ know, honestly.
Tends to be familial & likely is consequence of interaction between environment & genetic factors.
What are the major “end organs” damaged by hypertension?
#Heart #Brain #Kidneys #Peripheral arteries
How does chronic hypertension damage the heart?
**Heart disease is the most common cause of death in hypertensive patients** #Left ventricular hypertrophy #CHF #CAD #Cardiac arrythmias
How does chronic hypertension damage the brain?
#CVA (high BP is highest risk factor for CVA) #HTN is associated with impaired cognition with aging #Malignant hypertension: hypertensive encephalopathy
How does chronic hypertension damage the kidneys?
#Both a target organ AND a potential cause #Loss of autoregulation leads to renal injury & CKD
How does chronic hypertension damage the peripheral arteries?
Peripheral arterial disease (intermittent claudication)
Non-pharmacological HTN Management
#Weight reduction (BMI < 25 kg/m2) #Dietary salt reduction ( < 6 g NaCl daily) #DASH diet (rich in fruits/veggies, low fat dairy with reduced saturated & total fat) #Moderation of ETOH consumption (≤ 2 drinks daily for men, ≤ 1 for women) #Physical activity
Hypertensive Urgency
#Situation in which BP must be controlled within a few hours #Asymptomatic HTN ≥ 220/125 #Patient with optic disc edema, target organ damage/complications, dangerous perioperative HTN
Hypertensive Emergency
#Situations in which BP must be controlled within 1 hour to avoid morbidity or death #Generally DBP ≥ 130 #Hypertensive encephalopathy or nephropathy #Other emergencies: intracranial hemmorhage, MI, aortic dissection, pulmonary edema, preeclampsia/eclampsia, malignant HTN
Examples of thiazide diuretics
#chlorthalidone #hydrochlorothiazide #indapamide #metolazone
Examples of loop diuretics
#furosemide #bumetanide
Examples of potassium sparing diuretics
#amiloride #spironolactone #triamterene
