Cardiology Review: HTN Julia Akaah M.D.. Of the estimated 50 million Americans that have HTN (average BP>140/90): Of the estimated 50 million Americans.

Cardiology Review: HTNCardiology Review: HTN

Julia Akaah M.D.Julia Akaah M.D.

Of the estimated 50 million Americans Of the estimated 50 million Americans that have HTN (average BP>140/90):that have HTN (average BP>140/90): 90% have essential HTN90% have essential HTN Remainder have secondary HTNRemainder have secondary HTN

Renal parenchymal diseaseRenal parenchymal disease Renovascular diseaseRenovascular disease PheochromocytomaPheochromocytoma Cushing’s syndromeCushing’s syndrome Primary hyperaldosteronismPrimary hyperaldosteronism Coarctation of the aortaCoarctation of the aorta Autosomal dominant or recessive diseases of Autosomal dominant or recessive diseases of

the adrenal-renal axis that result in salt the adrenal-renal axis that result in salt retentionretention

Laboratory EvaluationLaboratory Evaluation Help identify patient’s baseline and any Help identify patient’s baseline and any

evidence of organ damage evidence of organ damage UrinalysisUrinalysis HematocritHematocrit Electrolytes, BUN, Cr, glucose, CaElectrolytes, BUN, Cr, glucose, Ca Uric acidUric acid Fasting lipid profileFasting lipid profile CXRCXR ECGECG echocardiogramechocardiogram

Initial ManagementInitial Management

Goal of treatment is to prevent long Goal of treatment is to prevent long term sequelaeterm sequelae

Most patients should be given a 3-6 Most patients should be given a 3-6 month opportunity to reduce BP by month opportunity to reduce BP by nonpharmacologic meansnonpharmacologic means

Pharmacologic therapyPharmacologic therapy

DiureticsDiuretics Beta BlockersBeta Blockers Alpha1-receptor blockersAlpha1-receptor blockers Centrally acting Adrenergic AntagonistsCentrally acting Adrenergic Antagonists Calcium channel blockersCalcium channel blockers ACE-I/ARBsACE-I/ARBs VasodilatorsVasodilators

Diuretics: Mechanism of ActionDiuretics: Mechanism of Action

Initiate natriuresis and decrease Initiate natriuresis and decrease intravascular volumeintravascular volume

May initially increase peripheral May initially increase peripheral resistance and decrease cardiac resistance and decrease cardiac outputoutput

May produce mild vasodilation by May produce mild vasodilation by inhibiting Na entry into vascular inhibiting Na entry into vascular smooth muscle cellssmooth muscle cells

Thiazide diureticsThiazide diuretics HCTZ, chlorthalidone, HCTZ, chlorthalidone,

metolazonemetolazone Block sodium reabsorption in distal Block sodium reabsorption in distal

convoluted tubule by inhibition of the convoluted tubule by inhibition of the thiazide sensitive Na/Cl co thiazide sensitive Na/Cl co transportertransporter

Usually ineffective when creatinine Usually ineffective when creatinine >2.0mg/dl>2.0mg/dl

Side effects:Side effects: WeaknessWeakness ms. Crampsms. Cramps ImpotenceImpotence HypokalemiaHypokalemia HypomagnesemiHypomagnesemi

aa increased LDL increased LDL

and TGand TG

HypercalcemiaHypercalcemia HyperglycemiaHyperglycemia HyperuricemiaHyperuricemia HyponatremiaHyponatremia thiazide induced thiazide induced

pancreatitispancreatitis

Loop diureticsLoop diureticsfurosemide, torsemide, furosemide, torsemide,

bumetanidebumetanide Block Na reabsorption in the thick Block Na reabsorption in the thick

ascending loop of Henle by inhibiting the ascending loop of Henle by inhibiting the Na/K/2Cl cotransporterNa/K/2Cl cotransporter

Most effective in patients with associated Most effective in patients with associated renal insufficiencyrenal insufficiency

Can cause hypomagnesemia, Can cause hypomagnesemia, hypocalcemia, hypokalemia, increase hypocalcemia, hypokalemia, increase fasting glucose, postural hypotension and fasting glucose, postural hypotension and reversible ototoxicity (dose related)reversible ototoxicity (dose related)

Spironolactone competitively inhibits Spironolactone competitively inhibits the action of aldosterone the action of aldosterone

Triamterene and amiloride inhibit the Triamterene and amiloride inhibit the reabsorption of Na and secretion of Kreabsorption of Na and secretion of K

Weak agents when used alone Weak agents when used alone therefore combined with thiazide for therefore combined with thiazide for added potencyadded potency

Hyperkalemia, gynecomastia, renal Hyperkalemia, gynecomastia, renal tubular damage and renal calculi with tubular damage and renal calculi with combination of triamterene and HCTZcombination of triamterene and HCTZ

Potassium sparing diureticsPotassium sparing diureticsspironolactone, amiloride, spironolactone, amiloride,

triamterenetriamterene

Beta BlockersBeta Blockers

Competitive inhibition of Competitive inhibition of catecholamines at B- adrenergic catecholamines at B- adrenergic receptors which decreases heart receptors which decreases heart rate, cardiac output, and decreases rate, cardiac output, and decreases plasma reninplasma renin Advantageous in patients with increased Advantageous in patients with increased

adrenergic drive, LVH and previous MI adrenergic drive, LVH and previous MI and stable HFand stable HF

Cardioselective beta blockers have primarily Cardioselective beta blockers have primarily beta-1 blocking effects (atenolol, metoprolol, beta-1 blocking effects (atenolol, metoprolol, bisoprolol, etc.)bisoprolol, etc.)

therefore can be given at low doses, with caution therefore can be given at low doses, with caution in mild COPD, DM and peripheral vascular diseasein mild COPD, DM and peripheral vascular disease

At higher doses, selectivity is lostAt higher doses, selectivity is lost

Nonselective (nadolol, propranolol, timolol)Nonselective (nadolol, propranolol, timolol)

Alpha and beta antagonists (labetolol, Alpha and beta antagonists (labetolol, carvedilol)carvedilol)

As lipid solubility increases, the liver As lipid solubility increases, the liver metabolizes more of the drug and more metabolizes more of the drug and more enters the brain, and therefore duration of enters the brain, and therefore duration of action is shorteraction is shorter Very lipid soluble: propranolol, metoprolol, timololVery lipid soluble: propranolol, metoprolol, timolol

As lipid solubility decreases the drug is As lipid solubility decreases the drug is renally eliminated and less drug enters the renally eliminated and less drug enters the brain and therefore duration of action is brain and therefore duration of action is longerlonger Least-lipid soluble: atenolol, betaxolol, nadololLeast-lipid soluble: atenolol, betaxolol, nadolol

Side effects: high degree AV block, HF, Side effects: high degree AV block, HF, Raynauds, impotence, insomnia, depression, Raynauds, impotence, insomnia, depression, contraindicated in asthma, severe COPD, and contraindicated in asthma, severe COPD, and DMDM

Alpha1-receptor blockersAlpha1-receptor blockersprazosin, terazosin, doxazosinprazosin, terazosin, doxazosin

Block alpha receptors, producing Block alpha receptors, producing arterial and venous vasodilationarterial and venous vasodilation

Side effectsSide effects First dose effectFirst dose effect HypotensionHypotension SyncopeSyncope May decrease total cholesterol and TG May decrease total cholesterol and TG

levels and increase HDLlevels and increase HDL

Centrally acting Adrenergic Centrally acting Adrenergic AntagonistsAntagonists

methyldopa, clonidinemethyldopa, clonidine Stimulate presynaptic alpha 2-adrenergic Stimulate presynaptic alpha 2-adrenergic

receptors leading to decrease in peripheral receptors leading to decrease in peripheral sympathetic tone and systemic vascular sympathetic tone and systemic vascular resistanceresistance

Side effects: bradycardia, drowsiness, dry Side effects: bradycardia, drowsiness, dry mouth, orthostatic hypotension, mouth, orthostatic hypotension, galactorrhea and sexual dysfunctiongalactorrhea and sexual dysfunction acute withdrawal of clonidine can cause acute withdrawal of clonidine can cause

rebound HTNrebound HTN

Calcium channel Calcium channel antagonistsantagonists

Effective in both blacks and whitesEffective in both blacks and whites

Dihydropyridines (nifedipine, felodipine, Dihydropyridines (nifedipine, felodipine, amlodipine etc.)amlodipine etc.)

Nondihydropyridines (verapamil, Nondihydropyridines (verapamil, diltiazem)diltiazem)

Cause arteriolar vasodilation by Cause arteriolar vasodilation by selective blockade of the slow inward selective blockade of the slow inward calcium channels in vascular smooth calcium channels in vascular smooth muscle cells. May cause initial muscle cells. May cause initial natriuresesnatriureses

Side effects: constipation, nausea, Side effects: constipation, nausea, HA, orthostatic hypotension, lower HA, orthostatic hypotension, lower extremity edemaextremity edema

Inhibitors of the renin-angiotensin Inhibitors of the renin-angiotensin system: ACE-Isystem: ACE-I

Inhibition of ACE leads to arteriolar Inhibition of ACE leads to arteriolar and venous vasodilation and to and venous vasodilation and to natriuresisnatriuresis

beneficial in pts. with associated beneficial in pts. with associated heart failure or kidney diseaseheart failure or kidney disease

Retard progression of nephropathy Retard progression of nephropathy and proteinuriaand proteinuria

ACE-I prevent recurrent MI and the ACE-I prevent recurrent MI and the development of CHF in persons who development of CHF in persons who have had an MI complicated by have had an MI complicated by reduced LV functionreduced LV function

Dose reduction in renal insufficiency Dose reduction in renal insufficiency and contraindicated in pregnancyand contraindicated in pregnancy

Side effects: orthostatic hypotension, Side effects: orthostatic hypotension, hyperkalemia, cough, angioedema, hyperkalemia, cough, angioedema, and loss of renal functionand loss of renal function

Angiotensin II receptor Angiotensin II receptor blockersblockers

losartan, valsartan, losartan, valsartan, candesartancandesartan Cause decreased peripheral Cause decreased peripheral

resistance by by inhibiting the actions resistance by by inhibiting the actions of angiotensin II at its cell surface of angiotensin II at its cell surface receptorreceptor

Side effect profile similar to ACE-I but Side effect profile similar to ACE-I but decreased likelihood of coughdecreased likelihood of cough

Avoid in pregnancyAvoid in pregnancy

VasodilatorsVasodilatorshydralazine, minoxidilhydralazine, minoxidil

Direct dilatation of arteriolesDirect dilatation of arterioles Dose should not exceed 200mg/d Dose should not exceed 200mg/d

because of the increased risk of because of the increased risk of lupus like syndromelupus like syndrome

Side effects: headache, palpitations, Side effects: headache, palpitations, tachycardia, fluid retention, lupus tachycardia, fluid retention, lupus like syndrome, and peripheral like syndrome, and peripheral neuropathy with hydralazineneuropathy with hydralazine

Side effects: weight gain, hirsutism Side effects: weight gain, hirsutism and pericardial effusions with and pericardial effusions with minoxidilminoxidil

Don’t use in ischemic heart disease, Don’t use in ischemic heart disease, dissecting aneurysm, or cerebral dissecting aneurysm, or cerebral hemorrhage because it can increase hemorrhage because it can increase cardiac output and cerebral blood cardiac output and cerebral blood flowflow

Drugs for monotherapy: diuretics, B Drugs for monotherapy: diuretics, B blockers, CCBs, ACEI, alpha-beta blockers, CCBs, ACEI, alpha-beta blockers, and ARBsblockers, and ARBs Diuretics and calcium antagonists are Diuretics and calcium antagonists are

more effective in blacks and elderlymore effective in blacks and elderly Centrally acting alpha agonists are Centrally acting alpha agonists are

not used as monotherapy but are not used as monotherapy but are appropriate in combination with appropriate in combination with diureticsdiuretics

Vasodilators are best used as third Vasodilators are best used as third drug in combination with diuretics drug in combination with diuretics and adrenergic inhibitorsand adrenergic inhibitors

Hypertensive crisisHypertensive crisis

Hypertensive UrgencyHypertensive Urgency DBP >120-130mmHgDBP >120-130mmHg BP reduction within several hoursBP reduction within several hours

Hypertensive EmergencyHypertensive Emergency SBP >210, DBP >130SBP >210, DBP >130 Manifestations of acute organ diseaseManifestations of acute organ disease Immediate BP reduction by 20-25%Immediate BP reduction by 20-25%

Inservice topics related to HTN:Inservice topics related to HTN:

Antihypertensive monotherapy for Antihypertensive monotherapy for elderly black patientelderly black patient

Rebound hypertension with clonidineRebound hypertension with clonidine Identify drugs that can unmask Identify drugs that can unmask

hyporeninemic hypoaldosteronismhyporeninemic hypoaldosteronism Hypertension in DM with proteinuriaHypertension in DM with proteinuria Hypertensive crisisHypertensive crisis

In several office visits, a 33 yr old woman has an In several office visits, a 33 yr old woman has an average BP of 150/105 mmHg. She has a strong average BP of 150/105 mmHg. She has a strong family history of HTN. She is asymptomatic. family history of HTN. She is asymptomatic. Except for mild obesity, the physical examination Except for mild obesity, the physical examination is normal. The results of routine laboratory is normal. The results of routine laboratory studies are also normal. She is a nonsmoker. studies are also normal. She is a nonsmoker. She states that she recently married and is trying She states that she recently married and is trying to get pregnant. In addition to lifestyle to get pregnant. In addition to lifestyle recommendations, what is the most appropriate recommendations, what is the most appropriate drug to consider for BP reduction?drug to consider for BP reduction?

a. Atenolola. Atenololb. Methyldopab. Methyldopac. Lisinoprilc. Lisinoprild. HCTZd. HCTZe. Losartan e. Losartan