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Drug Therapy for Hypertension
Drug Therapy for Hypertension
Blood Pressure: HTN
Blood Pressure: HTN

Persistent systolic blood pressure (SBP) of greater than 150 mm Hg and/or a diastolic

blood pressure (DBP) greater than

90 mm Hg for patients 60 years of age or

older and

SBP greater than 140 and DBP greater than 90 for patients younger than 60 years of age

and those who have chronic kidney disease

or diabetes

Blood Pressure
Blood Pressure

BP determined by product of CO [4-8 L/min] and SVR [BP= CO x SVR]

Amount of blood ejected from LV & measured in L/minute

SVR

Resistance to blood flow determined by diameter of blood vessel & vascular

muscultature

Hypertension Drug Classes
Hypertension Drug Classes

Diuretics

Thiazide (low ceiling) diuretics:

hydrochlorothiazide (HCTZ)

Loop (high ceiling) diuretics: furosemide (Lasix)

Potassium-sparing diuretics:spironolactone (Aldactone)

Calcium channel blockers (CCB): verapamil (Calan), amlodipine (Norvasc)

Angiotensin-converting enzyme (ACE) inhibitors:

enalapril (Vasotec), lisinopril (Zestril), quinapril

(Accupril)

Hypertension Drug Classes…
Hypertension Drug Classes…

Beta-adrenergic blockers (Cardioselective & noncardioselective): metoprolol (Lopressor)

Angiotensin II receptor blockers (ARBS):

valsarten (Diovan), losarten (Cozaar),

candesartan (Atacand)

Aldosterone receptor antagonists:

eplerenone (Inspra)

Hypertension Drug Classes…
Hypertension Drug Classes…

Vasodilators: nitrates: nitroglycerin (Nitro- bid), nitroprusside (Nipride, Sodium nitropruside) Renin inhibitors: aliskiren (Tektuma)

ARBS & CCB (dihydrophyridines) (new):

amlodipine (Norvasc) & olmesarten (Azor):

Ace Inhibitors (PRILS)
Ace Inhibitors (PRILS)

Angiotensin-converting enzyme Agents: captopril (Capoten), enalapril (Vasotec), benazepril, lisinopril, quinapril, fosinopril, mexipril, perindopril, quinapril, ramipril, trandolarpil Act as antagonist of the RAAS

Mechanim of action:

Interfere with conversion of angiotensin converting enzyme which is responsible for converting Angiotensin I to angiotensin II (potent vasoconstrictor & inducer of Aldosterone secretion by adrenals) leading to:

_______________

and

reduction in BP

Attack the middle of the RASS

MOA: Prils
MOA: Prils

Primary effects CV

Reduce BP by lowering SVR by preventing breakdown of vasodilating substance bradykinin and substance P & preventing formation of A-II

Decrease afterload or resistance against which LV must pump to eject volume of blood during contraction

Renal Diuresis

ACEI Therapeutic Effects
ACEI Therapeutic Effects

Body Substance

Effect in Body

ACEI Action

Resulting

 

Hemodynamic

Effect

Aldosterone

Na & H2O retention

Prevents its secretion

Diuresis=Decreas e plasma volume = decrease filing pressure = decrease preload

Angiotensin I

Potent

Prevents its

Decrease SVR =

vasoconstrictor

formation

decrease afterload

Bradykinin

Potent

Prevents its

Decrease SVR =

vasoconstrictor

breakdown

decrease afterload

Ace-Inhibitors….
Ace-Inhibitors….

Side effects: DRY, HACKING COUGH, ORTHOSTATIC HYPOTENSION,

agranulocytosis, neutropenia, insomnia, dizziness, tinnitus, photosensitivity (severe:

St. John’s Wort), loss of taste, angioedema,

skin rash Monitor e-lytes

Monitor for hypotension, syncope when used w/diuretics

Monitor BP, pulse, blood studies, hepatic studies

Ace Inhibitors…
Ace Inhibitors…

Tell pt to avoid salt/potassium substitutues, OTC drugs (decongestants:

Pseudoephedrine, phenylephrine)

Tell pt to avoid to avoid pineapple, NSAIDS, ASA(decreases effect); grapefruit/jc:

enhances effect Instruct male pt that impotence may occur

Instruct pt to rise slowly when getting OOB to avoid hypotensive effects esp. during initial use

Captopril
Captopril

Protypical drug Shown clinical efficacy in minimizing or preventing LV dilatation & dysfunction {ventricular modeling] Reduces risk of HF Shortest half-life of all ACEI Dosing: 3-4 times per day Careful with 1 st dosing effect; Safety!!!

Enalapril
Enalapril

Shown to improve survival after an

MI

Reduce incidence of HF Route: PO and Parenteral [enalaprilat]

PO: must have functioning liver to be converted to active form

Adrenergics
Adrenergics

Stimulate the nerves in the body's sympathetic nervous system (SNS).

Interact with these receptors.

They can mimic epinephrine and norepinephrine and bind with the receptors,

causing the fight or flight

Adrenergic Blockers: OLOL
Adrenergic Blockers: OLOL

Beta-Blockers Agents: metoprolol (Lopressor) Site of Action: Beta-1 & Beta-2 receptors Mechanism of Action:

Beta-1: block beta-1 receptors in heart & peripheral vessels, reducing cardiac rate & output

As a result of blocking B-1: Decreases HR (negative chronotropic) and myocardial contractility

Decreases CO & sympathetic vasoconstrictor tone; renin secretion by kidneys

Adrenergic Blockers: Beta-Blockers
Adrenergic Blockers: Beta-Blockers

Noncardioselective: Blocks beta-1&2 adrenergic receptors in bronchial, vascular smooth muscle. DO NOT ADMINISTER TO PTS w/RESPIRATORY DISORDER (Bronchospasm)

DIABETICS: masks s/s HYPOGLYCEMIA

DOC: hypertensive pts with ischemic heart disease (IHD)

SE: SEXUAL DYSFUNCTION, hypotension, bradycardia, depression, fatigue, weakness, Bronchospasm, sore throat, hypoglycemia

Beta-Blockers…
Beta-Blockers…

Instruct pt to avoid grapefruit/jc: enhances effect Caution diabetics: masks s/s hypoglycemia Caution about decrease libido/impotence Monitor BP, P: hospital setting: Parameters:

standard: HOLD SBP <100, HR <60 Monitor apical/radial: < 60: hold & notify HCP

Teach pt to take pulse: hold if < 60 & notify HCP

Instruct pt to avoid OTC decongestants,ETOH, Na intake

Instruct not to suddenly stop: rebound HTN & aggravate symptoms of angina/or ischemic HD

Nevbivolol
Nevbivolol

Released 2008 Beta-1 selective for HTN; HF Besides blocking beta-1, produces vasodilation which lowers SVR Causes less sexual dysfunction

DO NOT STOP APRUPTLY, must be TAPERED over 1-2 weeks

Angiotensin II Receptor Antagonists

Angiotensin II receptor Blockers (ARBS) Agents: valsarten (Diovan), losarten (Cozaar), candesarten (Atacand) Mechanism of Action:

Selectively block the binding of angiotensin II to its receptor in vascular & adrenal tissues by competing directly w/angiotensin II but not inhibiting ACE

Block the hypertensive effect of the mineralcorticosteroid hormone ALDOSTERONE Target the bottom of the RAS cascade

ARBS…

S/E: Hypotension, cough, hyperkalemia, dizziness, headache, drowsiness, diarrhea, metallic or salty taste, rash

Monitor BP, P

• Teach patient: grapefruit/jc & St. John’s

wort: increase chance of adverse effects

Instruct patient not to get up fast; not to drive, climb stairs until familiar w/effects of

drugs

Central Alpha adrenergic agonists
Central Alpha adrenergic agonists

Agent:clonidine (Catapress), methyldopa (Aldoment)

Mechanism of Action: Act on CNS preventing reuptake of norepinephrine (reduces sympathetic outflow) and resulting in lower peripheral vascular resistance and BP; vasodilation, decreases SVR/BP

S/E: sedation, postural hypotension, impotence, dry mouth (hard candy, gum chewing helps), night mares

Available transdermal: Catapres-TTS

Clonidine
Clonidine

Most commonly used Lower BP; manage opioid withdrawal Great safety profile Route: PO, topical [patch]-Catapress TTS

Must remove old patch before placing new one

Do NOT stop abruptly = severe rebound HTN

Alpha-adrenergic antagonists
Alpha-adrenergic antagonists

Agents: prazosin (Minipress), doxazosin (Cardura), terazosin (Hytrin), tamsulosin (Flomax) Alpha-1 blockers Mechanism of action:

Dilate arterioles & veins Block alpha-1 ,produces peripheral vasodilation (lowers SVR/BP) Lower BP quickly Use is limited: frequent & bothersome side effects Cardura & Hytrin: used for benign prostatic hypertrophy (BPH) Tamsulosin: Soley for symptomatic control BPH

Doxazosin
Doxazosin

Alpha-1

Reduces PVR and BP: dilates both arterial and venous vessels

Immediate and extended release

Matrix of capsule is expelled in stool when drug is released from ER form

Combination Alpha & Beta-Blocker

Adrenergic

Carvedilol (Coreg) Labetalol (Trandate) Alpha-1, B-1, B-2 properties Peripheral vasodilation Decreases HR, CO, SVR,BP S/E: dyspepsia, nasal stuffiness, Hepatic toxicity

Available in IV form for hypertensive crisis in hospitalized pt.

Calcium Channel Blockers
Calcium Channel Blockers

Agents: verapamil (Calan), amlodipine (Norvasc)

Mechanism of action:

Interferes with transmembrane flux of calcium ions, resulting in vasodilation leading to decrease BP, SVR, HR, contractility

Work on arterial wall; relax arterial wall thereby decreasing BP

CCB
CCB

S/E: 1 st AV block, gingival hyperplasia, constipation (verapamil)

Caution use in pts with heart failure Contra: 2 nd and 3 rd degree heart block Avoid grapefruit on nifepidine (Cardizem) Do not use sublingual short acting nifedipine in hypertensive emergencies, unsafe

Change peripheral IV infusion site q12 h In hospitalized pt

Renin Inhibitors
Renin Inhibitors

Effective for mild-moderate HTN Agents: aliskiren (Tektuma) Mechanism of action:

Prevent renin from producing vasocontriction, increasing peripheral resistance and increasing CO

Blocks the action of renin at the top of the RAS

Most common side effect: Diarrhea, respiratory distress

Vasodilators
Vasodilators

Nitrates Agents: nitroglycerin (Nitro-bid),nitroprusside (Sodium nitropruside,Nitropress Mechanism of action:

Produce vasodilation by relaxing smooth muscle. Decrease peripheral vascular resistance Reduce S/D BP, preload, afterload Headache, flushing

Hypertensive crisis (emergent) IV form, cardiac monitor

Hydralazine
Hydralazine

Essential HTN PO

IV: who cannot tolerate PO in hospital orfor HTN emergencies

Bidil: adjunct Rx for AA 37.5 mg hydralazine and 20 mg isosorbide dinitrate

Sodium Nitroprusside
Sodium Nitroprusside

Used in ICU setting for severe HTN emergencies

Titrated to effect by IV infusion

IV: onset Less 2 min, half life 2 min, lasts 1-

10 min

Contra: severe HF, inadequate cerebral perfusion

Epleronone: Selective Aldosterone

Blocker

HTN Reduces BP by blocking Aldosterone at its corresponding receptors in kidney, heart, vessels and brain Routine HTN Rx and post MI HF Contra; ELEVATED POTASSIUM >5.5 mEq/L or severe renal impairment and those

using medication that inhibits action of

cytochrome P-450

Bosentan [Tracleer]
Bosentan [Tracleer]

Blocks receptors of hormone endothelin

Soley to treat pulmonary HTN in moderate to severe HF

CONTRA: liver impairment and those receving cyclosporine or glyburide

Treprostinal, iloprost, ambristntan and macitentan

ED Drugs
ED Drugs

Sildenafil {viagra; Revatio], tadalafil known as Cialis { Adcirca]: Pulm. HTN