Cardiology Review: HTN

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Cardiology Review HTN

• Julia Akaah M.D.

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• Of the estimated 50 million Americans that have
  HTN (average BPgt140/90)
• 90 have essential HTN
• Remainder have secondary HTN
• Renal parenchymal disease
• Renovascular disease
• Pheochromocytoma
• Cushings 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

• Help identify patients baseline and any evidence
  of organ damage
• Urinalysis
• Hematocrit
• Electrolytes, BUN, Cr, glucose, Ca
• Uric acid
• Fasting lipid profile
• CXR
• ECG
• echocardiogram

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Initial Management

• 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

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Pharmacologic therapy

• Diuretics
• Beta Blockers
• Alpha1-receptor blockers
• Centrally acting Adrenergic Antagonists
• Calcium channel blockers
• ACE-I/ARBs
• Vasodilators

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Diuretics Mechanism of Action

• 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

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Thiazide diuretics HCTZ, chlorthalidone,
metolazone

• Block sodium reabsorption in distal convoluted
  tubule by inhibition of the thiazide sensitive
  Na/Cl co transporter
• Usually ineffective when creatinine gt2.0mg/dl

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• Side effects
• Weakness
• ms. Cramps
• Impotence
• Hypokalemia
• Hypomagnesemia
• increased LDL and TG

• Hypercalcemia
• Hyperglycemia
• Hyperuricemia
• Hyponatremia
• thiazide induced pancreatitis

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Loop diureticsfurosemide, torsemide, bumetanide

• 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)

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Potassium sparing diureticsspironolactone,
amiloride, triamterene

• 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

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Beta Blockers

• Competitive inhibition of catecholamines at B-
  adrenergic receptors which decreases heart rate,
  cardiac output, and decreases plasma renin
• 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.)
• therefore can be given at low doses, with caution
  in mild COPD, DM and peripheral vascular disease
• At higher doses, selectivity is lost
• Nonselective (nadolol, propranolol, timolol)
• 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
• Very lipid soluble propranolol, metoprolol,
  timolol
• As lipid solubility decreases the drug is renally
  eliminated and less drug enters the brain and
  therefore duration of action is longer
• Least-lipid soluble atenolol, betaxolol, nadolol
• Side effects high degree AV block, HF, Raynauds,
  impotence, insomnia, depression, contraindicated
  in asthma, severe COPD, and DM

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Alpha1-receptor blockersprazosin, terazosin,
doxazosin

• Block alpha receptors, producing arterial and
  venous vasodilation
• Side effects
• First dose effect
• Hypotension
• Syncope
• May decrease total cholesterol and TG levels and
  increase HDL

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Centrally acting Adrenergic Antagonistsmethyldopa
, clonidine

• 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
• acute withdrawal of clonidine can cause rebound
  HTN

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Calcium channel antagonists

• Effective in both blacks and whites
• 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

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Inhibitors of the renin-angiotensin system ACE-I

• 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

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Angiotensin II receptor blockerslosartan,
valsartan, candesartan

• 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

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Vasodilatorshydralazine, minoxidil

• 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
• Dont 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
• 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

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Hypertensive crisis

• Hypertensive Urgency
• DBP gt120-130mmHg
• BP reduction within several hours
• Hypertensive Emergency
• SBP gt210, DBP gt130
• Manifestations of acute organ disease
• Immediate BP reduction by 20-25

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Inservice topics related to HTN

• 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

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