Hypertension Flashcards
Clinically, when we talk about ‘hypertension’ or BP, we are talking about _________ pressures
arterial
venous pressures only account for a small fraction of arterial pressure
Normal BP, when correctly measure is
< 120/80 mmHg
really should be < 115 mmHg systolic
HTN is defined by
sustained (repeated measures) of BP > 140/90 mmHg
Stage 1 HTN
systolic BP 140-159 and diastolic BP in the 90’s
Stage 2 HTN
systolic BP 160-179 and diastolic BP in the 100-109 range
Stage 3 HTN
systolic BP >/= 180 and diastolic BP >/= 110
aka malignant HTN
Recommendation in pt. 60 y/o or older, is to initiate pharmacologic tx at SBP ______ or DBP ______…and treat to a goal of SBP _____ and DBP _______.
1) >/= 150 mmHg
2) >/= 90 mmHg
3) < 150 mmHg
4) < 90 mmHg
Recommendation in pt. younger than 60 y/o is to initiate pharmacologic tx at ________, and treat to a goal of ________.
1) SBP >/= 140 mmHg
2) SBP < 140 mmHg
(however, Dr. Williams usu. tries to get to < 140 using lifestyle interventions)
Newer evidence is showing that SBP should actually be _________ to lower rates of fatal and nonfatal major CV events
< 120 mmHg
instead of < 140 mmHg
What is the best way to avoid stroke?
controlling HTN
What other major organ sx besides heart is most threatened by high BP?
kidneys
(sustained, elevated BP can chronically damage KD and lead to need for dialysis…#2 cz of dialysis in this country is HTN)
Gold Std is to treat high BP pharmacologically when systolic is
> 150 mmHg
Known complications of untx, sustained elevation in BP
atherosclerosis (MI, stoke), heart failure, kidney damage
The biggest genetic contribution to HTN involves
sodium handling
What are primary non-pharmacolgic interventions for HTN
SODIUM RESTRICTION
wt. loss, smoking cessation, stress management
High-output HTN , usu. seen in younger pt. with essential HTN, is best tx with
beta-antagonists
b/c these drugs will decrease rate and force of contraction
Vascular resistance-based HTN, usu. seen in elderly, is best tx with
thiazide diuretics
What are the four main classes of anti-hypertensive drugs?
1) Diuretics
2) Beta-blockers
3) Calcium channel blockers
4) ACE/ARB
Which type(s) of drug(s) will reduce intravascular volume with concomitant vasodilation
diuretics
Which type(s) of drug(s) will down-regulate sympathetic tone
beta-antagonists
alpha-1-antagonists
central sympatholytics
Which type(s) of drug(s) will modulate vascular smooth muscle tone
CCB
K+ channel openers
Which type(s) of drug(s) will inhibit neurohumoral regulators of the circulation
renin inhibitors
ACE inhibitors
AT-1 antagonists (angiotensin II type 1 receptor antag.)
Diuretics best work on
renal sodium retention
Beta-blockers best work on
sympathetic nervous over-excitability (thus reducing CO of heart)
ACE-I/ARB best work on
renin-angiotensin excess (the reduce angiotensin II, leading to vasodilation)
CCBs best work on
endothelium derived factors to directly relax smooth mm.
Which anti-hypertensive drug class should you start with?
It doesn’t seem to matter
Which of the 4 major drug classes have better outcomes data?
Diuretics, ACE-I/ARB, and CCB
How long does it take to see maximal effect of each of the four major classes?
1 wk: ACE-I/ARB, CCB, B-blockers
2 wks: diuretics
Where do thiazide diuretics act?
distal convoluted tubule
Where do loop diuretics act?
ascending limb of Henle
What are the MC used thiazide diuretics?
1) Chlorothiazide (prototype)
2) Hydrochlorothiazide
3) Chlorothalidone
4) Metolazone
Thiazide diuretic MOA
inhibits sodium and chloride reabsorption in the distal tubule –> increased Na+, Cl-, K+, and Mg ++ excretion –> increased urine output and decreased GFR
(also decreases Ca++ excretion)
Thiazide distinguishing characteristics
1) orally administered
2) generally poorly absorbed
3) onset of action 1-2 hr, but BP effect takes severals days
4) wide-range of half-lifes (generally longer than loop diuretics and can be dosed just once daily)
5) free drug enters tubules by filtration and organic acid secretion
Thiazide predictable characteristics
1) ideal starting agent for HTN, chronic edema, and idiopathic hypercalcuria
2) Better choice of drug for AA pt.
3) MC s/e = hypokalemia and hyponatremia
4) incr. toxicity of digitalis or lithium
Thiazide side effects
*Hypokalemia
*Hyponatremia
hyperglycemia
decr. insulin secretion
incr. plasma lipids
hyperuricemia
hypercalcemia (can be good if pt. have hx KD stones)
Impt. labs when using thiazide diuretics
CMP - should do a couple times in the 1st yr of using thiazide diuretics; the first CMP should be done w/in 6 mo. of starting meds
MC loop diuretics
1) Furosemide (prototype)
2) Bumetanide
3) Torsemide
4) Ethacrynic acid
Which type of diuretics is more potent?
Loop
Loop diuretic MOA
1) enters proximal tubule via organic acid transporter
2) inhibits apical Na-K-2Cl transporter in thick ascending loop of henle (really need to pee!!!)
3) competes with Cl- binding
4) enhances Mg++ and Ca++ excretion
5) incr. K+ and H+ excretion in cortical collecting duct
6) inhibits reabsorption of ~25% of glomerular filtrate
Loop diuretic distinguishing characteristics
1) orally administered
2) rapidly absorbed
3) rapid onset of action for diuresis and BP
4) increases toxicity lithium
5) may have additive toxicity w/ other ototoxic drugs at high doses (IV)
Loop diuretic predictable characteristics
1) preferred diuretic in pt. w/ moderate-severe chronic renal dz (rapid absorption)
2) Preferred when eGFR < 30 (rapid onset of action)
3) Preferred in malignant HTN
3) potency decreased by inhibitors of organic acid ion transport (NSAID’s)
4) MC s/e = hypokalemia and hyponatremia
Side effects of loop diuretics
*Hypokalemia
*Hyponatremia
hyperuricemia
metabolic alkalosis
ototoxicity
Mg++ depletion
What labs need to be done with loop diuretics?
CMP - make sure to do w/in one month of starting drugs
What is the use of “Dual RAS blockade”
It’s now contraindicated (more hypotension, accelerated renal decline, cz more hyperkalemia)
ppl used to use ACE-I + ARB or Aliskiren + ACE-I/ARB
What does ACE-I stand for?
angiotensin converting enzyme inhibitors
MC used ACE-I
1) Lisinopril
2) Enalapril
3) Captopril
4) Ramipril
ACE-I MOA
inhibits angiotensin converting enzyme in the lung –> reduces synthesis of angiotensin II (potent vasoconstrictor)
suppresses aldosterone –> natriuresis
potentiates other VASODILATORS
ACE-I distinguishable characteristics
1) Esp. useful in high-renin HTN
2) Preferred drug for HTN pt. with diabetic nephropathy (doesn’t affect glucose levels)
4) First dose hypotension
5) C/I pregnancy
ACE-I predictable characteristics
1) tx HTN
2) Common s/e: dry cough (MC in AA pt. and even MC in Asian pt.), angioedema (MC in AA), hyperkalemia
What does ARB stand for?
Angiotensin Receptor Blockers
ARB category
Vasodilator
ACE-I category
Vasodilator
MC used ARB
1) Losartan
2) Irbesartan
3) Valsartan
4) Candesartan
ARB MOA
antagonist at angiotensin II receptor of vascular muscles
ARB distinguishing characteristics
1) Best tolerated of anti-HTN drugs (even better tolerated than ACE-I)
2) Less cough and risk for angioedema than ACE-I
3) C/I in pregnancy
ARB predictable characteristics
1) tx HTN
2) s/e: hypotension, dizziness, hyperkalemia
What is paradoxical regarding ACE-I and ARB use in pt. with renal dz?
They both can cz small reductions in kidney fn (usu. transient), however, they are the drugs of choice in pt. with HTN and chronic kidney dz and actually improve kd fn many of these pt.
What lab(s) do you want to do with ACE-I and ARB?
Run a CMP w/in 30 days of starting these drugs
If a cough develops in a pt. taking an ACE-I who needs RAS blockage, what should you do?
substitute with an ARB
What are the three classes of CCBs?
1) Phenylakylamines
2) Benzothiazepines
3) 1, 4 - Dihydropyridines
Verapamil (Isopten) category
CCB - phenylalkylamine
Verapamil (Isopten) MOA
blocks Ca++ influx, dilates peripheral arterioles, slows AV node, and has alpha adrenergic blocking activity
Verapamil (Isopten) distinguishing characteristics
1) Reduces frequency of angina and need for nitrates
2) Preferred drug for paroxysmal SVT
3) Slows ventricular response to afib
4) Well absorbed, 80% metabolized in 1st pass
5) 90% protein bound and metabolites are acitve, T1/2 = 5hr (up to 20hr in pt. w/ cirrhosis)
Verapamil (Isopten) predictable characteristics
1) tx HTN
2) C/I: hypotension, sinus bradycardia, *AV conduction defects, *severe cardiac failure
Diltiazem (Cardizem) category
CCB - benzothiazepine
Diltiazem (Cardizem) MOA
dilates peripheral arteries –> reduces afterload
incr. oxygen supply to myocardium by preventing sympathetic-induced coronary a. spasm
Diltiazem (Cardizem) distinguishing characteristics
1) Less pronounced HR reduction
2) reduces angina episodes and incr. exercise tolerance in stable angina
3) 50% bioavailability after oral dose
4) 75% protein bound and metabolites are active, T1/2 - 3 hr
Diltiazem (Cardizem) predictable uses
1) tx HTN
2) C/I: hypotension, sinus bradycardia, *AV conduction defects, *severe cardiac failure
Nifedipine (Procardia) category
CCB - 1,4-dihydropyridines
other drugs in this category all end in -dipine
Nifedipine (Procardia) MOA
- potent peripheral vasodilation
- little depression of nodes
- fails to dilate coronary aa.
- cz reflux incr. in HR and output
Nifedipine (Procardia) distinguishing characteristics
1) No longer used as a single agent d/t toxicity
2) rapid-complete absorption of sublingual dose
3) 98% protein bound and metabolites are inactive, T1/2 = 3 hr
4) May cz MI, peripheral edema, pulmonary edema
Nifedipine (Procardia) predictable characteristics
1) C/I: *hypotension and severe cardiac failure
Which CCB(s) bind to cardiac cells? Which CCB(s) bind to vascular smooth muscle?
1) Diltiazem and Verapamil
2) Nifedipine
The principal s/e in dihydropyridines is
dose-dependent ankle edema
edema appears to be vasogenic d/t vasodilation
What is a rare s/e that all CCBs cz?
gingival hyperplasia, which is reversible if detected
Which CCBs can impair cardiac conduction?
verapamil and diltiazem
*esp. in older pt. receiving digoxin, B-blockers, or central sympatholytic agents
What is a rare s/e of long-acting dihydropyridine CCBs?
flushing and HA
Beta-blockers MOA
competitive antagonists
generally, they antagonize effects of catecholamines on the heart
Beta-blockers distinguishing characteristics
1) decrease myocardial oxygen consumption d/t reduced rate and contractility
2) reduce CO and maybe cz a little vasodilation
Beta-blockers predictable characteristics
1) tx angina
2) hypotensive effect
MC cardioselective beta-blocker(s)
relative selectivity for B1 receptor
Metaprolol Esmolol Acebutolol Atenolol Betaxolol
What happens to MOA of cardioselective beta-blockers at high doses?
You lose the selective effects and they can cz bronchoconstriction (bind to B2 receptors)
Of the MC cardioselective beta-blockers, only _________ is markedly hydrophilic
atenolol
*thus, it’s less preferred in practice
MC non-cardioselective beta blocker(s)
bind to B1 and B2 receptors
Carvedilol
Adverse effects of beta-blockers
1) CNS effects - sedation, depression, hallucination
2) May lead to or worsen heart failure when initiated (start low dose)
3) Agg. of bronchospasm (non-selective)
4) Hypoglycemia unawareness in DM (d/t block of adrenergic warning signs)
5) impotence
What is the preferred first-line tx for HTN?
ACE-I/ARB, CCB, or thiazide diuretics
