BLOOD PRESSURE

arterial blood pressure

HYDRAULIC EQUATION ABP directly proportionate to CO and
PVR
BP= CO x PVR
Systolic BP
cardiac contraction
affected by cardiac
output (CO)
CO= volume of blood
pumped by the left
ventricle per
contraction

Diastolic BP
blood filling of cardiac chambers
affected by TPR/SVR/PVR
-total peripheral resistance/ systemic
vascular resistance/ peripheral vascular
resistance
TPR= resistance to passage of blood
through precapillary arterioles

MAJOR FACTORS INFLUENCING BP

Cardiovascular System

Hydraulic equation (BP= CO x TPR)

-3 anatomic sites where CO and TPR are maintained (both
normotensive and hypertensive):
1) arterioles (resistance vessels)
2) postcapillary venules (capacitance vessels)
3) heart
4) kidney contributes to maintenance of blood pressure by
regulating the volume of intravascular fluid
Postural baroreflex - mediated by autonomic nerves
-responsible for rapid, moment-to-moment adjustments in blood
pressure, such as in transition from a reclining to an upright
posture vasomotor area of the medulla
Carotid baroreceptors: stimulated by the stretch of the vessel
walls brought about by ABP
Baroreceptor activation inhibits central sympathetic discharge
Transition to upright posture baroreceptors sense the
reduction in arterial pressure as reduced wall stretch
sympathetic discharge is disinhibited increase in sympathetic
outflow PVR (constriction of arterioles) and CO (direct
stimulation of the heart and constriction of capacitance vessels,
which increases venous return to the heart) normal BP
RAAS - humoral mechanism
Vasoactive substances
- local release from vascular endothelium may also be involved in
the regulation of vascular resistance
- endothelin-1 constricts BVs
-nitric oxide dilates blood BVs
*Baroreflex + humoral mech (RAAS) = contribute to maintain
normal BP at the 4 anatomic sites

-both normotensive and hypertensive indls

-hypertensive set at higher level
Venous tone: degree of constriction; net capillary filtration,
TPR, BP
NORMAL REGULATION OF BLOOD PRESSURE

* Hypertensive px differs in that the baroreceptors and the renal

blood volume-pressure control systems appear to be "set" at a
higher level of blood pressure.

Physiology
Blood flow: volume of blood that flows through any tissue in a given time period (in mL/min)
Cardiac output: volume of blood that circulates through systemic (or pulmonary) blood vessels each minute; SV x HR
Stroke volume: volume of blood pumped by the ventricles per contraction
Vascular Resistance: opposition to blood flow bet. Blood and the walls of the bvs
Venous return: volume of blood flowing back to the heart through systemic veins; due to pressure generated by contraction of left ventricle
Determinants of arterial pressure:
cardiac output- determined by SV and HR
vascular resistance- determined by functional and anatomic changes in small arteries
Cardiac Output
Stroke volume
Preload: degree of stretching of heart muscles
-proportional to EDV high heart rate, short vent. diastole, low EDV, low SV
-high venous return, high EDV high SV, high CO, high BP
Myocardial contractility: positive inotropic agents (ANS stimulation; E/NE; increased Ca2+; digitalis); negative inotropic agents
(inhibition of ANS; anoxia, acidosis, increased K+)
Afterload: higher pressure, lower stroke volume, low CO lower BP
Heart Rate
Autonomic Regulation
-CV center in medulla increase/decrease frequency of nerve impulses in sympathetic and parasympathetic branches of ANS
-proprioceptors; chemoreceptors; baroreceptors
Chemical regulation
-Hormones E/NE increase both heart rate and contractility
-Cations Elevated blood levels of K+ or Na+ decrease heart rate and contractility; Excess Na_ blocks Ca2+ inflow during cardiac
action potentials, thereby decreasing the force of contraction; whereas excess K+ blocks generation of action potentials; moderate
increase in interstitial Ca2+ level speeds heart rate and strengthens the heartbeat
Age, gender, physical fitness, and body temperature
Vascular Resistance
size of the lumen- smaller lumen greater resistance to blood flow BP increases (vasoconstriction)
blood viscosity- depends on ratio of RBCs to plasma volume (polycythemia, dehydration); higher viscosity higher resistance higher BP
-anemia, hemorrhage low viscosity low BP
total blood vessel length: longer bv, higher resistance; obese have addl bvs in their adipose tissues higher bv length higher BP
Venous Return
skeletal muscle pump: contraction, pushes blood upward more blood returned to heart higher BP
respiratory pump: inhalation, blood pushed upward more blood returned higher BP

Total Blood Volume

Renin-angiotensin-aldosterone system
Decrease in blood volume decreased blood pressure juxtaglomerular cells secrete renin converts angiotensinogen, a plasma
protein produced by the liver, into angiotensin I (lungs) the enzyme ACE converts angiotensin I into the hormone angiotensin II Blood
level of angiotensin II increases Ang II stimulates the adrenal cortex to secrete aldosterone ( kidneys) aldosterone increases reabsorption
of Na and water so that less is lost in the urine; Ald also stimulates the kidneys to increase secretion of K+ and H+ into the urine increased
water reabsorption by the kidneys, blood volume increases blood pressure increases to normal
--Ang II vasoconstriction of the arterioles increases blood pressure raise blood pressure to normal

HYPERTENSION
Most common CV disease
Increasing prevalence with advanced age
Other factors: psychological stress, environmental and dietary
factors ( salt and potassium or calcium intake) as contributing to
the development of HTN
Elevated arterial pressure, pathological changes in vasculature
and hypertrophy of LV
Principal cause of stroke
Major risk factor for CAD and its attendant complications, MI
and sudden cardiac death
Major contributor to cardiac failure, renal insufficiency, and
dissecting aneurysm of the aorta
ETIOLOGY OF HYPERTENSION
Primary/ Essential/Idiopathic HTN
- Familial and is likely to be the consequence of an interaction
between environmental and genetic factors
-With unknown cause (~90%)
Secondary HTN
-With known cause (~10-15%)

-e.g. renal artery constriction, coarctation of the aorta,

pheochromocytoma, Cushing's disease, and primary
aldosteronism
GESTATIONAL HYPERTENSION
during pregnancy
predisposes a patient to pre- eclampsia and eclampsia
-Preeclampsia abnormal condition of pregnancy characterized
by sudden hypertension (140/90mmHg), proteinuria
(300mg/24hr) and generalized edema that typically appears after
the 20th week of pregnancy
-Other signs and symptoms are generalized edema, blurred
vision, and headaches
-Preeclampsia might be related to an autoimmune or allergic
reaction resulting from the presence of a fetus (1st pregnancy)
-Eclampsia: more life threatening (with seizures)
Drugs:
methyldopa (DOC)
hydralazine
labetalol

Classification of Blood Pressure for Adults (Age >18)a

JNC 7 (7th report of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure)
-based on the average of two or more properly measured, seated BP readings on each of two or more office visits
-if SBP and DBP values yield different classifications, the highest category is used for the purpose of determining a classification
BP
Classification

Normal
Prehypertension

SBP
mmHg

DBP
mmHg

Lifestyle
Modification

<120
120-139

and <80
or 80-89

Encourage
Yes

Stage 1
Hypertension

140-159

or 90-99

Yes

Stage 2
Hypertension

> 160

or >100

Yes

Initial Drug Therapy

W/o compelling
indication

With compelling
indication

No antihypertensive
drug indicated

Drug(s) for
compelling
indicationd
Drug(s) for
compelling
indicationsd
Other hypertensive
drugs (diuretics,
ACEI, ARB, BB, CCB
as needed)

Thiazide-type
diuretics; consider
ACEI, ARB, BB, CCB,
or combination
Two-drug
combinationc for
most (thiazide and
ACEI/ARB/BB/CCB)

for px w/ DM of CKD, values > 130/80mmHg are considered above goal

initial combined therapy should be used cautiously in those at risk for orthostatic hypotension
d
Tx px w/ CKD or DM to BP goal of 130/80 mmHg
c

COMPELLING INDICATIONS
are co-morbid conditions where specific drug therapies have been shown in outcome trials to provide unique long-term benefits

* A diagnosis cannot be made based on one elevated BP measurement. An elevated value from the average of two or more measurements on
two or more clinical encounters is needed to diagnose hypertension.

 Parenteral (Sodium nitroprusside, Diazoxide,

Fenoldopam)
Calcium channel blockers

Hypertensive Crises
180/120 mm Hg
2 categories:
Hypertensive emergencies
with acute target-organ
damage
immediate treatment with IV
drugs
goal: DBP < 110

Hypertensive urgencies
without damage
managed with oral drugs for
hours or days

Overall Goal of Therapy

to reduce hypertension-related morbidity & mortality
goal BP values based on JNC 7:
most patients: <140/90
patients with DM & CKD: <130/80
* Most patients require combination therapy to achieve goal BP
values. But lifestyle modifications should be prescribed in ALL
patients with pre-hypertension & hypertension.

ANTI-HYPERTENSIVES
Primary
Diuretics
ACE inhibitors
Angiotensin-receptor
blockers (ARBs)
-blockers
Calcium-channel blockers

Secondary
1-blockers
Central 2-agonists
Peripheral adrenergic
antagonists
Direct arterial vasodilators

Classification of Anti-HTN
*based on principal regulatory site or mechanism on which they
act
A. Diuretics
- lower blood pressure by depleting sodium and
other electrolytes in the body and reducing
blood volume
1. Carbonic anhydrase inhibitors
2. Loop diuretics
3. Thiazide diuretics
4. Potassium-sparing diuretics
5. Osmotic diuretics
B. Sympathoplegics
act on the sympathetic system
reduce PVR
inhibit cardiac function
increase venous pooling
subtypes:
1. Centrally-acting
Methyldopa, Clonidine, Guanfacine,
Guanabenz
2 . Peripherally-acting
Trimethaphan, Reserpine, Guanethidine,
Guanadrel
2. Alpha blockers
Phentolamine, Phenoxybenzamine
3. Beta blockers (-olol)
C.

Direct vasodilators
-reduce pressure by relaxing vascular smooth
muscle dilating resistance vessels andto
varying degreesincreasing capacitance as well
Oral (Hydralazine, Minoxidil)

D.

Angiotensin antagonists
-reduce peripheral vascular resistance and (potentially)
blood volume
1. ACE inhibitors (-pril)
2. Angiotensin II receptor blockers/ ARBs (-sartan)
E. Aliskiren selective rennin inhibitor
Monotherapy vs. Polypharmacy
Monotherapy
Polypharmacy
Better compliance
Most
patients
with
Lower cost
hypertension require two or
Fewer adverse effects(in more
some cases
drugs, each acting by a
different mechanism
Each of the drugs acts on
one of a set of interacting,
mutually
compensatory
regulatory mechanisms for
maintaining blood pressure

A. DIURETICS
B. SYMPATHOPLEGICS
I. Centrally-acting Sympathoplegics
sympathetic outflow from vasopressor centers in the brainstem but retain or increase sensitivity to baroreceptor control
Antihypertensive and toxic actions are generally less dependent on posture
Drug
Properties
Pharmacologic
Dosage/Administration/
Side effects
Effect/ Mechanism
Pharmacodynamics
of Action
Methyldopa
PRODRUG
Agonist at
Maximal anti HTN effect in
overt sedation at onset of
(Aldomet)
presynaptic
46 hours
tx
Analog of L-dopa;
a2receptors in the
Persists for up to 24 hours
chronic use: persistent
converted to brainstem
mental lassitude (slow)
methyldopamine and REDUCES TPR
SAFE FOR PREGNANT
and impaired mental
methylnorepinephrine
WOMEN
concentration
inhibits
lactation
dopaminergic
positive Coombs test
mechanism in the
-presence of antigens in the
hypothalamus
RBC hemolytic anemia
prolactin
lactation
Clonidine
Lipid-soluble and rapidly Agonist at a2 Relatively short half-life
WITHDRAWAL-INDUCED
(Catapres)
enters the brain from
receptors
Effect is directly related
REBOUND HYPERTENSION
the circulation
to blood concentration =
Tx:
75mcg / 150mcg
2-imidazoline derivative Partial agonist at
PO bid (or as a patch) to
phentolamine+propranolol
(originally tested as nasal a- receptors
maintain smooth blood
decongestant)
inhibits pressor
pressure control
Dry mouth and sedation -->
effects of other acentrally-acting and doseagonists
Transdermal: reduces blood dependent coincide
pressure for 7 days after a
temporally w/ the drugs anti Direct stimulation
single application
HTN effect
of a-adrenoceptors
in arterioles
Increasing doses are more
Hypertensive crisis
effective (but also
(>1mg/day) nervousness,
sympathetic and
more toxic)
tachycardia, headache,
parasympathetic
sweating after omitting 1 or 2
tone
Tapering of dose with
doses
BP , TPR and
simultaneous administration
TX: reinstitute clonidine OR
bradycardia
of alternative anti-HTN drug
admin of mixed /adrenoceptor-blockers
renal vascular
resistance
CI: mental depression
DI: Tricyclic antidepressants
Produces a brief
(TCAs) a-adrenoceptorrise in blood
blocking action
pressure followed
by more prolonged
hypotension (IV)
Guanfacine (Tenex)
adjunct drugs
share the central
avoided unless
adrenoceptorGuanabenz (Wytensin)
unresponsive to other
stimulating
meds
effects of clonidine
do not appear to
offer
any advantages over
clonidine

II.Peripherally-acting sympathoplegics
Trimethaphan

Ganglionic receptor
blocker
-competitively blocks
nicotinic
cholinoceptors on
postganglionic

IV infusion for hypertensive

emergencies

adverse effects of ganglion

blockers:
-sympathoplegia (excessive
orthostatic hypotension and
sexual dysfunction)
-parasympathoplegia

Reserpine

Guanethidine

Guanadrel

Alkaloid from
Rauwolfia serpentina

Very polar drug

neurons in both
sympathetic and
parasympathetic
ganglia
Inhibits catecholamine
storage by blocking the
ability of aminergic
transmitter vesicles to
take up and store
biogenic amines (VMAT)
Parkinsonism
dopamine depletion in
the corpus striatum
Inhibits NE release at
nerve endings
-concentrated in
transmitter vesicles
where it replaces
norepinephrine
causes a gradual
depletion of
norepinephrine
stores in the nerve
ending

(constipation, urinary
retention, precipitation of
glaucoma, blurred vision, dry
mouth)
CNS: sedation, mental
depression, and parkinsonism
symptoms readily enters
the brain
GI: mild diarrhea, GI cramps
and increased gastric acid
secretion

Long half-life (5 days)

Gradual onset of
sympathoplegia (maximal
effect in 12 weeks)
and persists for a
comparable period after
cessation of therapy

guanethidine-like
drug

CI: peptic ulcer, mental

depression
Profound sympathoplegia
Marked postural
hypotension, diarrhea, and
impaired
Ejaculation
No CNS effects vs. other
anti-HTN drugs too polar!
Diarrhea
parasympathetic dominance
DI: cocaine, amphetamine,
TCS, phenothiazines,
phenoxybenzamine (block CA
uptake or displaces amines)
-nasal decongestant
CI: pheochromocytoma
Orthostatic hypotension
Impaired sexual function in
males

III. Alpha-1 blockers

reduce arteriolar resistance
increase venous capacitance
cause vasodilation
Prazosin (Minipress)
essential hypertension
CHF
Terazosin (Hytrin)
BPH
Doxazosin (Cardura)

FIRST-DOSE PHENOMENON (highest in prazosin)

-sudden fall in BP when abruptly changing from lying to standing position
Postural hypotension related to first dose or when
drug is resumed after several months off
Syncope in 1% with prazosin > 2 mg
Self-limiting
Best started on a low dose and taken at night (hs)

Nonselective Alpha-Adrenoceptor Receptor Blockers

Phentolamine
Phenoxybenzamine

Diagnosis and treatment of pheochromocytoma and in other clinical situations associated with exaggerated
release of catecholamines

IV. Beta-blockers
competitive inhibitors of catecholamines at betaadrenoreceptor sites (B1, B2, B3)
B2- bronchial & peripheral BVs (brocho & vasodilation)
B3- adipose tissues (CA-induced thermogenesis, cardiac
contractility)
act to reduce the effect of the catecholamine agonist on
sensitive tissues
heart contractility
heart rate
cardiac output
renin secretion
Cardiac Effects
Decrease contractility negative inotropy)

mask hypoglycemia
CI: COPD, bronchial asthma
SI: withdrawal syndrome
severe bradycardia and heartblock
Cardioselectivity: ability of a drug to preferentially bind to one type of
B-receptor
Tx for angina but higher doses lowers cardioselectivity

Decrease relaxation rate (negative lusitropy)

Decrease heart rate (negative chronotropy)
Decrease conduction velocity (negative dromotropy)
Vascular Effects
Smooth muscle contraction (mild vasoconstriction)

Nonselective

Selective

Mixed a-& -blockers

Propranolol (Inderal)
Nadolol (Corgard)
Timolol (Blocadren)
Pindolol (Visken)

Betaxolol (Betaoptic)
Bisoprolol (Zebeta)
Esmolol (Brevibloc)
Acebutolol (Sectral)
Atenolol (Tenormin)
Metoprolol (Lopressor)

Labetalol (Normodyne)
Carvedilol (Coreg)

With intrinsic sympathomimetic

activity (ISA)

With membrane-stabilizing activity

For chronic open-angle glaucoma

Pindolol
Acebutolol

Carteolol (Ocupress)
Betaxolol (Betaoptic)
Levobunolol (Betagan)
Metipranolol (Optipranolol)
Timolol (Timoptic)
Levobetaxolol (Betaxon)

Acebutolol
Pindolol
Penbutolol

Class/Drug
HTN
Non-selective B1/B2
Carteolol
X
Carvedilol
X
Labetalol
X
Nadolol
X
Penbutolol
X
Pindolol
X
Propranolol
X
Sotalol
Timolol
X
B1 selective
Acebutolol
X
Atenolol
X
Betaxolol
X
Bisoprolol
X
Esmolol
X
Metoprolol
X
Nebivolol
x

Angina

Arrhy

MI

CHF

x
X
X
X
X
X
X
X
X
X
X
x

X
X
X

X
X
X
X
X
X

Comments
ISA; long-acting; also for glaucoma
a-blocking acitivity
ISA; a-blocking acitivity
long-acting
ISA
ISA; MSA
MSA; prototype
Several other significant mech
Primarily for glaucoma
ISA

X
MSA

Ultra short acting; intra/ postoperative HTN

MSA
Rel. selective in most pxl vasodilationg (NO rel)

C. VASODILATORS
relax smooth muscles of blood vessels
TPR and mean ABP compensatory responses mediated by baroreceptors and the sympathetic nervous system, as well as renin,
angiotensin, and aldosterone because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual
dysfunction (kaya dapat polypharmacy)

Oral
(long-term outpx therapy)
Hydralazine
Minoxidil
Drug

Hydralazine
(Apresoline)

Indication

Treatment of
gestational HTN
Combination of
hydralazine with nitrates
is effective in heart
failure

Minoxidil
(Loniten)

PRODRUG
AM: Minoxidil sulfate

Topical: Rogaine
stimulant to hair
growth for
correction of
baldness

Very efficacious orally

active vasodilator

Sodium nitroprusside
(Nitropress)
Complex of iron,
cyanide(CN) groups,
and a
nitroso moiety
Na2[Fe(CN)5NO)]

Must be used in
combination with a ablocker and a loop
diuretic
Should replace
hydralazine when
maximal doses of the
latter are not effective or
in patients with renal
failure and severe
hypertension, who do not
respond well to
hydralazine
Useful in hypertensive
emergencies and severe
HF
Rapidly lowers BP;
effects disappear within
1-10 mins after
discontinuation

Parenteral
Calcium channel blockers
(hypertensive emergencies)
(both)
Sodium nitroprusside
Diazoxide
Fenoldopam
Pharmacologic
Dosage/Administration/
Side effects
Effect/
Pharmacodynamics
Mechanism of
Action
Direct
Well absorbed
SLE-like effects: myalgia,
relaxation of
Rapid first-pass
arthralgia, rashes, fever (>
arteriolar (but
metabolism
400mg/d) not assoc. w/ renal
not veins)
(~25% bioavailability)
damage; reversible
smooth muscle
rapid acetylators have
= SVR
first-pass metabolism,
IHD: reflex tachycardia &
blood levels, and antiHTN
sympathetic stimulation
benefit from a given dose
angina
than do slow acetylators
tachyphylaxis to its
t1/2 = 1.5-3 h
antihypertensive effects
bid-tid for smooth BP
developed rapidly
control
SLE-like syndrome
Toxicity: headache, nausea,
(=400mg/day)
anorexia, palpitations, sweating,
and flushing
Opening of K+
t1/2 = 4h
Associated with reflex
channels in
90% bioavailability
sympathetic stimulation
smooth muscle
40 mg/d
and sodium and fluid retention
membranes by
(compensatory mechanism)
minoxidil sulfate
stabilizes
Hypertrichosis, headache,
membrane at
sweating
resting potential
no contraction
Dilates
arterioles but not
veins

Activation of
guanylyl cyclase
(either via release
of NO or by direct
stimulation of the
enzyme)
intracellular
cGMP
relaxation of
vascular smooth
muscle
Dilates BOTH
arteries & veins =
PVR, venous
return

Parenterally administered
(IV infusion)
Freshly prepared, covered
w/ opaque foil (light
sensitive)
Begins at 0.5 mcg/kg /min
and may be increased up to
10 mcg/kg/min as necessary
Rapidly metabolized by
uptake into RBCs w/
liberation of CN
CN metabolized by
mitochondrial enzyme,
rhodanase, in the presence
of a sulfur donor, to the less
toxic thiocyanate
CN- + sulfur (rhodanase)
SCN-

CN toxicity: metabolic acidosis,

arrhythmias, excessive
hypotension, death
Low dose toxicity: defect in CN
metabolism
ANTIDOTE: Sodium thiosulfate
(sulfur donor) and
hydroxocobalamin (combine w/
CN0 to form cyanocobalamin/B12
Accumulation of thiocyanate in
renal insufficiency
SCN- toxicity: weakness,
disorientation, psychosis, muscle
spasms, and convulsions (> 10
mg/dL)

Diazoxide
(Hyperstat IV)

Long-acting arteriolar
dilator
Occasionally used to
treat HTN emergencies
PO Proglycem: used
to manage hypoglycemia
secondary to insulinoma

Fenoldopam
(Corlopam)

Peripheral arteriolar
dilator used for
hypertensive
emergencies and
postoperative
hypertension

Prevents
vascular smooth
muscle
contractions
by opening K+
channels and
stabilizing
membrane
potential at
resting level
Inhibits insulin
release from the
pancreas
(probably by
opening K+
channels in the cell membrane)
Agonist of
dopamine D1
receptors
dilation of
peripheral
arteries +
natriuresis

Thiocyanate is distributed
in ECF
Slowly eliminated by the
kidney
Dose gradually increase (50
150mg)
Effect post rapid injection
(within 5 mins) and lasts for
4-12 h
Bound extensively to
serum albumin and to
vascular tissue reduce
dose in renal px
Partially metabolized

Delayed hypothyroidism inhibition of I- uptake by the

thyroid (rare)

Rapidly metabolized by
conjugation
t1/2 = 10 minutes
Administered by continuous
IV infusion
Initiated at a low dosage
(0.1 mcg/kg/ min) titrated
upward every 15 or 20
minutes to a maximum dose
of 1.6 mcg/kg/min

Reflex tachycardia, headache,

and flushing;
increased IOP (CI: glaucoma)

Rapid fall in TPR and mean

ABP associated with substantial
tachycardia and increased CO
hypotensive effects when
patients are pretreated with ablockers to prevent the reflex
tachycardia and associated
increase in CO

Calcium Channel Blockers

Anti-anginal & anti-arrhythmic effects
Reduce PVR and BP by inhibiting Ca+2influx into arterial smooth
muscle cells

Dihydropyridine type
block Ca+2channel in blood vessels
- cardiac depressant effect, more selective vs non-DHP
Amlodipine (Norvasc)
Felodipine (Plendil)
Isradipine (DynaCirc)
Nicardipine (Cardene)
Nifedipine (Adalat)
Nisoldipine (Sular)

Pharmacologic Effects
peripheral edema
reflex tachycardia (DHP)
bradycardia (Non-DHP)
heart block (Non-DHP + Beta Blocker)
Non-dihydropyridine type
-depresses both heart and BVs
Verapamil (Isoptin)
Greatest depressant effect on heart HR and CO
Diltiazem (Cardizem)
Intermediate actions
block Ca+2channels in heart & blood vessels

D. Angiotensin Antagonists
ACE inhibitors
Angiotensin II Receptor blockers
ACE inhibitors
Inhibit Angiotensin Converting Enzyme (ACE), thereby preventing
the conversion of Angiotensin I (decapeptide) into the active
Angiotensin II (octapeptide)
ACE inhibits:
Peptidyl dipeptidase converting enzyme peptidyl dipeptidase
that hydrolyzes angiotensin I to angiotensin II
Plasma kininase: inactivates bradykinin (potent vasodilator) w/c
works by stimulating release of nitric oxide and prostacyclin
ACE Inhibitors
BP principally by TPR
CO and HR are not significantly changed

Angiotensin II Receptor blockers

Angiotensin II Receptor Blockers
provide similar benefits as with ACEIs
less occurrence of angioedema & dry cough

 Do not result in reflex sympathetic activation and can be used safely in persons with ischemic heart disease vs vasodilators
-absence of reflex tachycardia may be due to downward resetting of the baroreceptors or to enhanced parasympathetic activity
Drug
Captopril (Capoten)

Enalapril (Vasotec)

Indication
CKD: diminish proteinuria
and stabilize renal function
(even in the absence of
lowering of
blood pressure)

IV only
Probably result from
improved intrarenal
hemodynamics, with
decreased glomerular
efferent arteriolar resistance
and a resulting reduction of
intraglomerular capillary
pressure

Mechanism of
Action
Inhibit peptidyl
dipeptidase &
plasma kininase
oral prodrug
that is
converted by
hydrolysis to a
converting
enzyme
inhibitor,
enalaprilat, with
effects similar to
those of
captopril

Lisinopril (Prinivil)
lysine derivative of
enalaprilat

Perindopril (Aceon)

Dosage/Administration/
Pharmacodynamics
Short-acting
BID/TID
Peak concn of
enalaprilat occurs after 34 hrs
BID/TID

HF and MI

All are prodrugs

Quinapril (Accupril)
Ramipril (Altace)

Idiosyncratic dry cough

(accompanied by wheezing)
Angioedema
Hyperkalemia more likely in
px assoc. w/ DM or renal
insufficiency
Cough + Angioedema due to
bradykinin and substance P

1080 mg once daily

Reduce incidence of
diabetes in patients with
high cardiovascular risk

Side effects

Converted to the active

agents by hydrolysis,
primarily in the liver

DI: potassium supplements or

potassium-sparing diuretics,
which can result in hyperkalemia
CI: second and third trimesters of
pregnancy because of the risk of
fetal hypotension, anuria, and
renal failure, sometimes
associated with fetal
malformations or death

All ACEIs except

fosinopril and moexipril
are eliminated via the
kidney (lower dose)

Benazepril, fosinopril,
moexipril trandolapril

Angiotensin II Receptor blockers

Candesartan (Atacand)
no effect on bradykinin metabolism more selective blockers of angiotensin effects than ACE inhibitors
Irbesartan (Avapro)

have the potential for more complete inhibition of angiotensin action vs ACEIs because there are enzymes
other than ACE that are capable of generating angiotensin II

Losartan (Cozaar)
provide benefits similar to those of ACEIs in px w/ HF or CKD
Telmisartan (Micardis)
Valdesartan (Diovan)

SI: similar to ACEIs including the hazard of use during pregnancy

Cough and angioedema can less common
Selective rennin inhibitor

Aliskiren

Directly inhibits
renin(acts earlier in
RAAS vs.
ACEIs or ARBs)

Same effectiveness in
lowering BP as ACEIs, ARBs,
and thiazides

SE: diarrhea (higher doses),

cough and angioedema
(less than ACEIs)

Metabolized by CYP 3A4

CI in pregnancy

Available as a FDC (fixed

dose concn.) with
valsartanas well as HCTZ

Hyperkalemia significantly
more common with
aliskiren+valsartan