Cardiology Review: HTN
Julia Akaah M.D.
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Of the estimated 50 million Americans that
have HTN (average BP>140/90):
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90% have essential HTN
Remainder have secondary HTN
Renal parenchymal disease
 Renovascular disease
 Pheochromocytoma
 Cushing’s syndrome
 Primary hyperaldosteronism
 Coarctation of the aorta
 Autosomal dominant or recessive diseases of the
adrenal-renal axis that result in salt retention
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Laboratory Evaluation
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Help identify patient’s baseline and any
evidence of organ damage
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Urinalysis
Hematocrit
Electrolytes, BUN, Cr, glucose, Ca
Uric acid
Fasting lipid profile
CXR
ECG
echocardiogram
Initial Management
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Goal of treatment is to prevent long term
sequelae
Most patients should be given a 3-6 month
opportunity to reduce BP by
nonpharmacologic means
Pharmacologic therapy
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Diuretics
Beta Blockers
Alpha1-receptor blockers
Centrally acting Adrenergic Antagonists
Calcium channel blockers
ACE-I/ARBs
Vasodilators
Diuretics: Mechanism of Action
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Initiate natriuresis and decrease
intravascular volume
May initially increase peripheral
resistance and decrease cardiac output
May produce mild vasodilation by
inhibiting Na entry into vascular smooth
muscle cells
Thiazide diuretics
HCTZ, chlorthalidone, metolazone
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Block sodium reabsorption in distal
convoluted tubule by inhibition of the
thiazide sensitive Na/Cl co transporter
Usually ineffective when creatinine
>2.0mg/dl
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Side effects:
 Weakness
 ms. Cramps
 Impotence
 Hypokalemia
 Hypomagnesemia
 increased LDL and
TG
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Hypercalcemia
Hyperglycemia
Hyperuricemia
Hyponatremia
thiazide induced
pancreatitis
Loop diuretics
furosemide, torsemide, bumetanide
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Block Na reabsorption in the thick ascending
loop of Henle by inhibiting the Na/K/2Cl
cotransporter
Most effective in patients with associated renal
insufficiency
Can cause hypomagnesemia, hypocalcemia,
hypokalemia, increase fasting glucose, postural
hypotension and reversible ototoxicity (dose
related)
Potassium sparing diuretics
spironolactone, amiloride,
triamterene
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Spironolactone competitively inhibits the
action of aldosterone
Triamterene and amiloride inhibit the
reabsorption of Na and secretion of K
Weak agents when used alone therefore
combined with thiazide for added potency
Hyperkalemia, gynecomastia, renal tubular
damage and renal calculi with combination
of triamterene and HCTZ
Beta Blockers
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Competitive inhibition of catecholamines
at B- adrenergic receptors which
decreases heart rate, cardiac output, and
decreases plasma renin
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Advantageous in patients with increased
adrenergic drive, LVH and previous MI and
stable HF
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Cardioselective beta blockers have primarily
beta-1 blocking effects (atenolol, metoprolol,
bisoprolol, etc.)
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therefore can be given at low doses, with caution in
mild COPD, DM and peripheral vascular disease
At higher doses, selectivity is lost
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Nonselective (nadolol, propranolol, timolol)
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Alpha and beta antagonists (labetolol, carvedilol)
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As lipid solubility increases, the liver metabolizes
more of the drug and more enters the brain, and
therefore duration of action is shorter
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As lipid solubility decreases the drug is renally
eliminated and less drug enters the brain and
therefore duration of action is longer
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Very lipid soluble: propranolol, metoprolol, timolol
Least-lipid soluble: atenolol, betaxolol, nadolol
Side effects: high degree AV block, HF,
Raynauds, impotence, insomnia, depression,
contraindicated in asthma, severe COPD, and
DM
Alpha1-receptor blockers
prazosin, terazosin, doxazosin
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Block alpha receptors, producing arterial
and venous vasodilation
Side effects
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First dose effect
Hypotension
Syncope
May decrease total cholesterol and TG levels
and increase HDL
Centrally acting Adrenergic Antagonists
methyldopa, clonidine
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Stimulate presynaptic alpha 2-adrenergic
receptors leading to decrease in peripheral
sympathetic tone and systemic vascular
resistance
Side effects: bradycardia, drowsiness, dry
mouth, orthostatic hypotension, galactorrhea
and sexual dysfunction
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acute withdrawal of clonidine can cause rebound HTN
Calcium channel antagonists
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Effective in both blacks and whites
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Dihydropyridines (nifedipine, felodipine,
amlodipine etc.)
Nondihydropyridines (verapamil, diltiazem)
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Cause arteriolar vasodilation by selective
blockade of the slow inward calcium
channels in vascular smooth muscle cells.
May cause initial natriureses
Side effects: constipation, nausea, HA,
orthostatic hypotension, lower extremity
edema
Inhibitors of the renin-angiotensin
system: ACE-I
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Inhibition of ACE leads to arteriolar and
venous vasodilation and to natriuresis
beneficial in pts. with associated heart
failure or kidney disease
Retard progression of nephropathy and
proteinuria
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ACE-I prevent recurrent MI and the
development of CHF in persons who have
had an MI complicated by reduced LV
function
Dose reduction in renal insufficiency and
contraindicated in pregnancy
Side effects: orthostatic hypotension,
hyperkalemia, cough, angioedema, and
loss of renal function
Angiotensin II receptor blockers
losartan, valsartan, candesartan
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Cause decreased peripheral resistance by
by inhibiting the actions of angiotensin II
at its cell surface receptor
Side effect profile similar to ACE-I but
decreased likelihood of cough
Avoid in pregnancy
Vasodilators
hydralazine, minoxidil
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Direct dilatation of arterioles
Dose should not exceed 200mg/d because
of the increased risk of lupus like
syndrome
Side effects: headache, palpitations,
tachycardia, fluid retention, lupus like
syndrome, and peripheral neuropathy with
hydralazine
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Side effects: weight gain, hirsutism and
pericardial effusions with minoxidil
Don’t use in ischemic heart disease,
dissecting aneurysm, or cerebral
hemorrhage because it can increase
cardiac output and cerebral blood flow
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Drugs for monotherapy: diuretics, B
blockers, CCBs, ACEI, alpha-beta blockers,
and ARBs
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Diuretics and calcium antagonists are more
effective in blacks and elderly
Centrally acting alpha agonists are not
used as monotherapy but are appropriate
in combination with diuretics
Vasodilators are best used as third drug in
combination with diuretics and adrenergic
inhibitors
Hypertensive crisis
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Hypertensive Urgency
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DBP >120-130mmHg
BP reduction within several hours
Hypertensive Emergency
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SBP >210, DBP >130
Manifestations of acute organ disease
Immediate BP reduction by 20-25%
Inservice topics related to HTN:
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Antihypertensive monotherapy for elderly
black patient
Rebound hypertension with clonidine
Identify drugs that can unmask
hyporeninemic hypoaldosteronism
Hypertension in DM with proteinuria
Hypertensive crisis
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In several office visits, a 33 yr old woman has an
average BP of 150/105 mmHg. She has a strong
family history of HTN. She is asymptomatic. Except
for mild obesity, the physical examination is normal.
The results of routine laboratory studies are also
normal. She is a nonsmoker. She states that she
recently married and is trying to get pregnant. In
addition to lifestyle recommendations, what is the
most appropriate drug to consider for BP reduction?
a. Atenolol
b. Methyldopa
c. Lisinopril
d. HCTZ
e. Losartan