Drug Therapy for Hypertension

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
(JNC 8)
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
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
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
Vasodilators: nitrates: nitroglycerin (Nitro-
bid), nitroprusside (Nipride, Sodium
nitropruside)
Renin inhibitors: aliskiren (Tektuma)
ARBS & CCB (dihydrophyridines) (new):
amlodipine (Norvasc) & olmesarten
(Azor):
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
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
Body Substance Effect in Body ACEI Action Resulting
Hemodynamic
Effect

Aldosterone Na & H2O Prevents its Diuresis=Decreas

retention secretion 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.
Side effects: DRY, HACKING COUGH,
ORTHOSTATIC HYPOTENSION,
agranulocytosis, neutropenia, insomnia,
dizziness, tinnitus, photosensitivity (severe:
St. Johns 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
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
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 1st dosing effect; Safety!!!
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
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
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
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
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
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. Johns
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
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
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
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
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
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
S/E: 1st AV block, gingival hyperplasia,
constipation (verapamil)
Caution use in pts with heart failure
Contra: 2nd and 3rd 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
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
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
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
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]
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
Sildenafil {viagra; Revatio], tadalafil known
as Cialis { Adcirca]: Pulm. HTN