Part 1

1: Systtemic hy
ypertens
sion and
d antihy
ypertens
sive dru
ugs

█ Bas
sic inform
mation

▌Vasc
cular smo
ooth musc
cle contrraction an
nd relaxation

Vasoco n is initiated by ope

onstriction ening of vooltage gateed L-type Ca2+ chan nnels in
2+
the meembrane off vascular smooth m muscle cellss. Increase
ed intracel lular Ca triggers
osphorylation of myo
the pho osin light ch e which iniitiates conttraction.
hain kinase

Vasodiilation is in
nitiated by
y either:
 Activation of guanylyl cyclase → ↑cGMP → dephosp phorylationn of myos
sin light
ain kinase → smooth ms
cha m relaxatiion.
 Ope +
ening of K chann nels in thee vasculaar smooth muscle ccell memb brane →
smoooth ms sttabilization (hyperpolarization) → relaxation.

▌The v
vascular endothellium and local vas
somotor control
c

Besidee the neu ural contrrol of blo ood vesssels through the ssympathettic and
parasympathetic systems, the vascu helium pro
ular endoth oduces vaarious compounds
that he
elp controlling the vas
scular tone
e:

Nitric o
oxide It is a diffusible gaas with very
v short half-life. It causes VD by
(NO; orr EDRF) increasing
g intracellu
ular cGMP P. It protec
cts againsst atheroscclerosis,
high blood
d pressure e, heart failure and th
hrombosis..
PGI2 It is synergistic to NO. It cause
es VD via specific
s reeceptors
Endoth
helin Is a 21-a
amino-acid
d peptide. By its action on ETA recepptors, it
causes se
evere VC a
and vascula
ar smooth muscle hyypertrophy
y.

149
 Angiotensin- Located on the endothelial cell membrane and converts circulating
converting angiotensin-I (synthesized by the action of renin on
enzyme (ACE) angiotensinogen) to angiotensin-II. By its action on AT1 receptors,
Ang-II causes VC and stimulates aldosterone release.
Other factors Histamine causes VD, bradykinin (synthesized from kininogen)
causes VD, and serotonin (released by platelets) causes VC.

█ Management of systemic hypertension

Systemic hypertension is persistent elevation of BP above 140/90.

Classification of hypertension:
■ According to etiology: primary (= essential, 90%) or secondary.
■ According to type: systolic, diastolic, or mixed.
■ According to degree: see table.

Classification of blood pressure levels of the British Hypertension Society

Category Systolic BP (mmHg) Diastolic BP (mmHg)

Normal blood pressure <140 <90
Hypertension
Stage 1 (mild) 140–159 90–99
Stage 2 (moderate) 160–179 100–109
Stage 3 (severe) ≥180 ≥110
Isolated systolic hypertension >140 <90
N.B. If systolic and diastolic BP fall into different categories, the higher value should be
taken for classification.

Target BP:

 For most patients, the goal of therapy is to maintain BP < 140/90 mm Hg.
 In patients with DM or chronic kidney disease, BP should be < 130/80 mm Hg.

▌Non-drug therapy = life style modification:

 Dietary sodium restriction and potassium and magnesium supplementation.
 Stop smoking and avoid stress.
 Weight reduction alone can correct hypertension in 75% of obese patients.
 Daily physical exercise (~30 min/day): it lowers serum cholesterol, improves
endothelial functions, and enhances tissue oxygenation.

150
 Control of risk factors: e.g. diabetes mellitus, hyperlipidemia, and obesity.
 Avoid drugs that ↑ BP e.g. sympathomimetics, sodium-containing drugs, oral
contraceptive pills, corticosteroids.

N.B. Patients failing to normalize BP after 2 weeks of non-pharmacological therapy

should be considered for drug therapy.

▌Drug therapy (antihypertensive drugs):

First choice groups Second choice groups

(commonly used drugs) (used in special cases):

■ A ngiotensin-converting ■ α1- blockers: prazosin and doxasosin.

enzyme inhibitors (ACEIs) ■ Combined α and β-blockers: labetalol.
■ B eta-blockers ■ Adrenergic neuron blockers: α-
methyldopa and reserpine.
■ C alcium channel blockers
■ Vasodilators: e.g. hydralazine.
■ D iuretics
■ Central α2 stimulants: clonidine.
■ Endothelin blockers: Bosentan.
■ Dopamine agonists: fenoldopam.

█ Beta-blockers

For detailed mechanism and pharmacology: see chapter 2.

Indications of beta-blockers in hypertension:

 Hypertension associated with cardiac problems e.g. IHD, cardiac arrhythmia,
aortic dissection, etc.
 Hypertension associated with thyrotoxicosis.
 Hypertenstion associated with increased sympathetic overactivity.

█ Diuretics

For detailed mechanism and pharmacology: see chapter 3.

Indications of diuretics in hypertension:

 Thiazides are given as initial therapy in most cases of mild, non-complicated
essential hypertension.
 Hypertension associated with volume overload (salt and water retention): e.g.
CHF, liver cirrhosis, primary hyperaldosteronism, pulmonary edema, etc.

151
 █ Angiotensin--convertin
ng enzym
me inhibittors (ACE
EIs)

▌Back
kground

▌The rrenin-angiotensin-aldosteron
ne (RAAS) system

 Whe ccurs, therre is ↓ RBF and ↓ GFR. This m

en renal isschemia oc may lead to acute
olig
guria that may
m develo op to acutee tubular necrosis.
 As a compensatory me echanism, rrenin is re
eleased fro
om the juxttaglomerular cells
of the kidney as a rescu
ue messag e to initiate
e stimulation of RAA
AS as follow
ws:

 Ang
g-II acts on
n AT1 rece
eptors in th
he efferent arterioles
s of the kid
dney causing their
VC and thus maintains
m adequate
a GFR in spiite of the ↓ RBF.
G
 Unffortunatelyy, Ang-II ac 1 receptorrs in other vascular beds and tissues
cts on AT1
cau
using systemic VC, cell hyp pertrophy, and apoptosis ((i.e. degen nerative
cha
anges).

152
Should we inhibit the RAAS?!
Inhibitors of RAAS
 Inhibition of the RAAS will  Inhibitors of renin release: β-blockers,
correct the hypertension but α-methyldopa, and clonidine.
also will ↓ GFR and aggravate  Inhibitors of plasma renin activity:
RF if renal ischemia was grave. aliskiren.
 Normal S. creatinine is 0.3-1.2  Inhibitors of Ang-2 formation: ACEIs
mg/dl. If S. creatinine is up to 3  AT1 receptor blockers (ARBs) e.g.
mg/dl (i.e. mild renal impairm- losartan, valsartan
ent) → you can block RAAS.
 If S. creatinine >3 mg/dl (i.e. severe renal impairment) → blocking the RAAS is
dangerous and will aggravate RF.

█ Angiotensin converting enzyme inhibitors

Classification
 SH-containing drugs: Captopril, zofenopril, alacepril
 Non SH-containing drugs: Enalarpril, fosinopril, lisinopril, benazepril, ramipril

Pharmacological properties of some ACEIs

Captopril Fosinopril Enalapril Lisinopril Benazepril

SH group + – – – –
Immune S/E + – – – –
Prodrug – + + – +
Metabolism Liver, Liver, Liver No Liver,
kidney kidney metabolism kidney
Onset 1–4h
Frequency of
/8 h /12 h /12 h /24 h /24 h
administration
SL dose 25 mg None None None None

Mechanism of action
They inhibit Ang-converting enzyme (ACE) in the vascular endothelium leading to:
– Inhibition of both Ang-II formation and aldosterone release (→ ↓ both VC
and salt & water retention).
– Prevent degradation of bradykinin which is a potent VD.
– Most ACEIs have direct VD action to both arteries (i.e. ↓ afterload) and
veins (i.e. ↓ preload).

153
 Pharm
macologica
al effects

CVS
S:  They ↓ BP mainly by decreasin
T ng peripheral resistannce but no
o reflex
t
tachycard ia or channges in th
he COP ca an occur. This may be due
t either (1) resettting of barorecepto
to b ors; and/o or (2) ennhanced
p
parasympaathetic actiivity.
 They ↑ CO
T OP (only inn presence of CHF)) due to rreduction of both
v
venous retu
urn (preloa
ad), and sy
ystemic BP
P (afterload
d).
 They ↓ myocardia
T m l changes complic cating accute myoocardial
infarction (ventricu lar hyperttrophy, and densee collagen
n scar)
b
because they
t preve
ent myoc cyte cell hypertrophhy and collagen
c
s
synthesis (i.e. preven
nt cardiac
c remodeliing).
Otheer  They ↓ ap
T poptosis, ↓ cell hypertrophy, & ↓
tissu
ue c
collagen synthesiss (i.e. they
t reduce
d
degenerative change es caused by the action
o Ang-II on
of n AT1 receeptors).

peutic use
Therap es

■ Sys
stemic hyp
pertension
n:
– Hyperrenin
nemic hype
ertension.
– Normoreninemic hyppertension :
because th
hey are dirrect VDs.

■ Con
ngestive heart
h failurre (CHF):
– T
To ↓ afte
erload and
d preload through
reduction of both systemic vascular
resistancee, and aldo osterone rrelease (↓
Na and H2O retention n).
– T
To ↓ myyocardial hypertrop phy and
d
dilatation (i.e.
( ↓ remo
odeling).

■ To prevent LV
L hypertrrophy (rem
modeling)
er acute MI
afte M through
h:
– ↓ arterial BP (↓ myoca
ardial strain
n).
– ↓ myocytee cell hyperrtrophy, ap poptosis, and
a collage
en synthessis.

■ Diabetic neph
hropathy & microalb
buminuria
a:
– T
They ↓ re
enal chang
ges compl icating dia ephropathyy (mesang
abetic ne gial cell
a
apoptosis,, proliferration, aand colla agen syn nthesis), thus re
educing
m
microalbuuminuria (pprovided th
hat renal im
mpairmentt is not gra
ave).

154
Advers
se effects::
C : Dry Coug gh (the moost commo on): inhibittion of ACE leads too accumula
ation of
bradykinin
n and PGs, which caause bronchial irritatioon and spaasm.
Treatmentt: stop ACE
EIs. Cough
h will resolv
ve after a fe
ew days.
A : Angioede ema (edem ma of the e face, to ongue and
d
throat): du
ue to accuumulation of bradykinin or duee
to immune e reaction. It may be
e life threatening.
P : Aggravatio on of Proteinuria
P a in patients with
h
significantt renal failu
ure.
T : anges: tem
Taste cha mporary lo
oss of tastte (ageusia
a
and dysge
eusia).
O : Orthostattic (First dose)
d hyppotension:: especially
y
in sodium depleted (hypovolem mic) patien
nts.
Prevention
n: start by small at b edtime the
en increase
e graduallyy.
P : cy: teratoge
Pregnanc enesis (feta
al pulmonarry hypoplas
sia and rennal dysfunc
ction)
R : skin Rash
h
I : Increased erkalemia)) due to ↓ aldosteron
d K+ (hype a e release.
L : nia (neutro
Leukopen openia): esp
pecially in patients with
w impaireed renal fu
unction.

N.B. Th
he sulfhydryl group (-SH)
( pres ent in cap
ptopril may be responnsible parttially for
the im
mmunologic cal side effects
e e.g
g. angioe edema, ta aste chan nges, skin n rash,
leukop
penia.

Contra
aindication
ns
■ Hyp
potension: when sys
stolic BP iss less than 95 mm Hg
g.
■ Sev
vere renal failure or bilateral rrenal artery stenosiis (SCr > 3 mg/dl). Why?
W
– In these conditions, the use off ACEIs is dangerous becausee they ↓ An
ng-II → ↓
VC of the efferent arterioles
a → ↓ glomerular filtrattion pressuure and ↓ GFR →
on of renal failure in b
aggravatio both kidne
eys.
– Dangerouss hyperkalemia may occur.
– Dangerouss neutropeenia may o occur.
■ Pre
egnancy and
a lactattion: theyy may cau
use fetal pulmonary
p y hypoplas
sia and
grow
wth retardation.
■ Hyp
perkalemia
a.
■ Neu
utropenia,, thrombo a, or seve
ocytopenia ere anemia (ACEIs may caus
se bone
marrrow depre
ession).
■ Imm
mune prooblems: whether due to autoimmune diseaases or due
d to
imm
munosupprressive dru
ugs.

155
 Precautions
– Initial dose should be small and at bedtime to avoid 1st dose hypotension.
– Frequent monitoring of kidney functions (S. creatinine) and potassium levels
one week after treatment and then every 3 months.
– Avoid use of K+ sparing diuretics to avoid severe hyperkalemia.
– Remember all other contraindications…

█ Angiotensin II receptor blockers (ARBs)

(Losartan- Valsartan- Candesartan- Telmisartan)

 They selectively block AT1 receptors and they exert most of the pharmacological
effects seen with ACEIs.
 They have no effect on bradykinin metabolism.
 They have the potential for more complete inhibition of Ang-II action compared
with ACE inhibitors because there are non-ACE enzymes (cathepsin and
chymase) that can convert Ang-I into Ang-II.
 The adverse effects and contraindications are similar to those of ACE
inhibitors but cough and angioedema are less common than with ACE
inhibitors.

ACE inhibitors ARBs

Class Angiotensin converting enzyme Angiotensin receptor blocker
inhibitor (ACEI) (ARB)
Mechanism Inhibition of ACE leading to: ↓ Blocking of AT-1 receptors
VC effect of Ang-II leading to ↓ VC effect of Ang-II
↑ VD bradykinins

Efficacy in Less effective because other More effective because it blocks

inhibition of enzymes rather than ACE can AT-1 receptor, the final station
RAAS convert Ang-I into Ang-II responsible for Ang-II effects.
Cough and Frequent due to ↑ bradykinins Less frequent (they do not ↑
angioedema bradykinins)

█ Direct renin inhibitors: aliskiren

 Activation of angiotensinogen into Ang-I by renin is the rate limiting step in

formation of RAAS.
 Aliskiren is a recently approved drug for treatment of hyperreninemic
hypertension. It inhibits renin activity and consequently the RAAS.
 The efficacy and side effects of aliskiren are comparable to ACEIs and ARBs.

156
█ Calc
cium chan
nnel bloc
ckers (CC
CBs)

These a
are drugs that
t block voltage-g
gated
2+
Ca ch hannels.

Classiffication off CCBs ac

ccording to
o
tissue selectivityy
■ CCBB with mainly cardiaac effects:
vera
apamil, diiltiazem.
■ CCB B with mainly vascular effectss
(dih
hydropyridiines): nifed
dipine,
amlodipine, nimodipin
n pine
e, nicardip
■ CCBB with main effect on
n other tis
ssue:
flun
narizine, cinnarizine
c e

Pharm
macologica
al effects

CVS Nifedip
pine Diltiazem
D Vera
apamil
Heart:
- Neggative inotrropic effec
ct — ++ +++
- A-VV conductioon — ↓↓ ↓↓↓
- HR ↑ (refle
ex) ↓ ↓↓
↓

Blood vessels:
- Corronary VD +++
+ ++ ++
+
- Peripheral VDD +++
+ ++ ++
+
- Bloood pressurre ↓↓↓
↓ ↓ ↓

Other e
effects
 Theey relax all smooth muscles (v (vascular, bronchial,
b GIT, uterin ne, etc.).
 Theey ↓ Ca - mediated
2+
m cell
c necro osis and ap poptosis.
 Verrapamil ↓ in ase from pa
nsulin relea ancreatic beta
b cells bu
ut of little cllinical significance.

Therap
peutic use
es

▌Cardiio-selectiv
ve CCBs (v
verapamill & diltiaze
em):

■ Isch
hemic hea
art disease
e (IHD):
– They ↓↓ myocardial contractilit
c ty and myoocardial O2 demand.
– They prod
duce coronnary VD and d ↑ corona
ary blood flow.
– They ↓ Ca - mediate
2
2+
ed myocytte cell necrrosis.

157
 B. vasculosselective CCBs
N.B C (dihyydropyridinnes) e.g niifedipine aare also be
eneficial
in IIHD but they cause e conside erable peripheral VD D, so the dose sho ould be
adju
usted to avvoid hypotension andd reflex tac
chycardia.

■ Carrdiac arrhy
ythmias: supravent
s ricular tac
chycardia (SVT):
– SVT includ
de atrial flu
utter, fibrilla
ation, paro
oxysmal atrial tachyccardia, etc.
– Verapamil ↓ AV cond duction, so o it protec
cts the ven
ntricles fro
om the rappid atrial
rate (also β-blockers
β s have the same effect).

B. Nifedipine is contraindicated a
N.B as it causes
s hypotens
sion and refflex tachyc
cardia.

■ Hyp
pertrophic
c obstructive cardio
omyopathy
y (HOCM)::
– In hypertrophic obsstructive caardiomyop
pathy, the wall of
the left ventricle
v and interve entricular septum is s much
thickened leading to o narrowin ng of the aortic outtlet and
on of blood
obstructio d flow.
– Increasing
g contracttility worse ens the obstruction
o n while
decreasingg contracttility reduc es resistan
nce to blood flow
through the aortic ou
utlet and im
mprove exerrcise tolera
ance.

B. Nifedipin
N.B ne is contra
aindicatedd because it produce es reflex
hycardia → worsening
tach g of the ou
utflow obsttruction.

■ Arte
erial hypertension:
– They ↓ myyocardial contractilityy and COP.
– They causse periphe eral VD d ue to ↓ CaC 2+ influx
x in the
vascular smooth
s ms
s.

▌Vascu
ulo-selecttive CCBs (Nifedipin
ne and am
mlodipine)::

 Arteerial hyperttension.
 Perripheral vascular
v disease (e.g. Ray ynaud’s disease
d aand intermittent
udication): to improve peripherral microcirrculation.
clau
 Nife
edipine is sometimes used to rrelax the uterus
u and delay pretterm labor..
 Nim
modipine has
h high afffinity for c
cerebral BV
V. It is use
ed for preveention of cerebral
c
vasospasm an
nd ischemia complic
cating sub
barachnoid hemorrhaage.

Advers
se effects
Verrapamil & diltiazem::
– Bradycard dia and hea
art block.
– Worsening g of CHF (d
due to theiir –ve inotrropic effectt).
– Constipatiion due to ↓ GIT mottility.

158
 Nife
edipine:
– Hypotension and refflex tachyccardia.
– Gingival (g gum) hyperrplasia.
– Salt & watter retentio
on (=ankle edema;
more com mmon than with verappamil due
to significa
ant VD and
d hypotenssion).

Contra
aindication
ns & preca
autions

Verapa
amil & diltiazem:
– Con
ngestive he
eart failure
e.
– Braadycardia and
a heart block.
b
– Wolff-Pakinso
on-White syndrome:
s
 In WPW syndrom me, there e is
accessoryy conducting path hway
between atria
a and ventricles
v o
other
tthan the e normal AV sysstem
causing a uniqu ue type of
atrioventric
cular re-en
ntry tachyc
cardia.
 A
As a rule, most druggs that ↓ A
AV nodal co onduction (Adenosinne; Beta-bllockers;
CCBs; Dig goxin) can paradoxic cally ↑ the conduction in the ab
bnormal pathway
p
leading to worseningg of the tac
chycardia.
 W
WPW syndrome can be man naged by amiodaro
a ne but deefinitive tre
eatment
aser ablatio
includes la on of the a
accessory pathway (s
see later).
– Veraapamil sh
hould not be comb h digitalis or β-blo
bined with ockers as it may
agg
gravate bra
adycardia caused
c byy these dru
ugs (nifedip
pine is the drug of ch
hoice to
be u
used with β-blockers
β s because it doesn't cause braddycardia).

Nifedip
pine:
– Hyp
potension.
– Hyp
pertrophic obstructiv ve cardiom yopathy (H HOCM) Wh
hy?
– Unsstable angina (risk off reflex tachhycardia).
– Sup
praventricuular tachyccardia (SVT T) Why?

159
 █ Vaso
odilators

Classiffication

■ Arte
erio-dilato
ors: Nifedipine – Hyddralazine – Minoxid
dil – Diazoxxide
– TThey dilate a ↓↓ BP (→ ↓ afterlo
e arteries and oad)
– TThey are used
u in sevvere system
mic hypertension.

■ Ven
nodilators: Nitrates
– TThey dilate eins →↓ ven
e mainly ve n (→ ↓ preload)
nous return
– TThey are used
u in acuute pulmonnary edema.

■ Mix
xed dilatorrs: Sodium
m nitropru sside – Prrazosin – ACEIs
A – Trrimetapha
an
– TThey ↓ pre
eload & afte
erload so tthey are us
sed in CHF
F.

Genera
al conside
erations
 Vassodilators relax
r ular smootth ms and ↓ peripheral resistannce.
vascu
 Theey usually cause reflex sympaathetic stiimulation (e.g. reflexex tachycardia) so
theyy can be combined
c with
w beta-b blockers.
 Theey usually cause sa alt and wwater rete ention (du
ue to refleex stimula ation of
aldo
osterone reelease) so they shou
uld be combined withh diureticss.
 Thee use of vasodilators
v s is declin
ning as a result of newer mo odalities, such
s as
ACEEIs and CCCBs, which h are more
e effective with
w fewerr adverse eeffects.

Hydralazine

 It is a direcct arterio
olodilator by uncle
ear
mec chanism.
 It iis used in severe e hyperte ension an nd
rd
hyppertension in pregna ancy (3 c choice aftter
α-mmethyldopa a and nifed
dipine).
 It is usually combine ed with d diuretics to
couunteract sa alt and waater retenttion, and β-
blocckers to counteract
c reflex tachhycardia.
 It m
may cause systemic lupus eryythematos sis
(SLEE)-like syyndrome especiallyy in slo ow
aceetylators. Th
he patient develops mild form of arthritis, renal imp
pairment, and
a skin
rashh that usua
ally disappe
ear upon sttopping of the drug.

Minox
xidil

 It iss a direct arteriolodilator byy opening

g K+ channels → hyyperpolarizzation →
rela
axation of the
t vascula
ar smooth ms.

160
 It is given orally for chronic hypertension but its use as antihypertensive is
declining; however, it should be combined with diuretics and β-blockers.
 It was found to stimulate hair growth (hypertrichosis) (by unclear mechanism),
so it is now used topically to prevent hair loss in both males and females.

Diazoxide

 Structurally related to thiazides but it is not diuretic

 It is a direct arteriolodilator by opening K+ channels → hyperpolarization →
relaxation of the vascular smooth ms.
 It is given parenterally in hypertensive emergencies but its use is declining.

Sodium nitroprusside

 It liberates nitric oxide (NO) → ↑ cGMP → dilatation of both arteries and veins →
↓ both preload and afterload.
 It is given by i.v. infusion in hypertensive emergencies and acute heart failure
because it has rapid action
 It can be converted to cyanide and thiocyanate. The accumulation of cyanide
and risk of toxicity are minimized by concomitant administration of sodium
thiosulfate (see angina) or hydroxocobalamin (vitamin B12).
 Sodium nitroprusside in aqueous solution is sensitive to light and must be
made up fresh before each administration and covered with opaque foil.

Fenoldopam

 It stimulates peripheral dopamine (D1) receptors in renal and mesenteric arteries,

leading to VD and decrease peripheral resistance.
 It is used parenterally as a rapid-acting vasodilator to treat emergency
hypertension in hospitalized patients.

█ Endothelin-1 receptor antagonists

 Endothelin-1 is 21 amino acid peptide. It is the predominant endothelin secreted

by the vascular endothelium. It is elevated in patients with pulmonary
hypertension and coronary artery disease.
 It acts on two types of receptors, ETA and ETB. ETA receptors is the main
subtype in smooth ms and mediates VC and vascular smooth ms hypertrophy.
 Bosentan is orally active nonselective blocker of ETA and ETB receptors, while
ambrisentan is a selective ETA blocker.
 Both drugs are approved for treatment of primary pulmonary hypertension.

161
 █ Specialized vasodilators
Drugs used for erectile dysfunction: Sildenafil, tadalafil

 These drugs inhibit phosphodiesterase (PDE) type 5 the enzyme responsible for
breakdown of cGMP in erectile tissue (and lung) → ↑ cGMP → VD of the corpus
cavernosum.
 They are very effective for treatment of erectile dysfunction in men. The effect
of the drug appears after 30 min of oral administration and lasts for 4-5 hours.
 Sildenafil is also approved for treatment of pulmonary hypertension.
 Side effects include blue discloration of vision, headache, and optic neuropathy.
 These drugs are contraindicated in patients taking nitrates or nicorandil for
treatment of angina because nitrates also act by ↑ cGMP leading to severe VD,
hypotension, and reflex tachycardia → aggravation of angina and development of
arrhythmia.

▌Choice of the antihypertensive drugs:

Clinical condition Best choice

Starting therapy for non-complicated Patient <55 years old: ACE inhibitors
essential hypertension Patient >55 years old: CCBs
If not adequate, add thiazide or beta
blockers.
Hypertension of pregnancy α-methyldopa
Labetalol – Nifedipine - Hydralazine
Hypertension in a diabetic patient with ACE inhibitors
diabetic nephropathy (proteinuria)
Hypertension with chronic kidney disease S. creatinine <3 mg/dl: ACEIs
S. creatinine >3 mg/dl: CCBs
Hypertension with CHF ACE inhibitors - diuretics
Hypertension with bronchial asthma CCBs
Hypertension with angina CCBs - beta-blockers
Hypertension with thyrotoxicosis, Beta-blockers
sympathetic overactivity, arrhythmia,
or, HOCM
Hypertension with BPH α1 blockers
Primary pulmonary hypertension Endothelin receptor antagonists

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▌Management of hypertensive emergencies:

Hypertensive emergencies are clinical Hypertensive

situations associated with one or more of the encephalopathy
following:
Is a clinical presentation
 BP > 180/120mmHg. consists of severe headache,
 Target organ damage e.g. cerebral mental confusion, blurred
stroke, encephalopathy, heart failure, vision, and focal neurologic
aortic dissection, edema of the optic disc signs. If untreated it may
(papilledema). progress over a period of 12–
48 hours to convulsions,
Management: coma, and even death.

– Hospitalization and start parenteral

therapy to lower BP rapidly (within a few hours not minutes).
– Chronic hypertension is associated with autoregulatory changes in cerebral,
myocardial, and renal blood flow; so if sudden lowering of BP is done,
cerebral, renal, and myocardial ischemic events can develop.
– The initial target in the first 1-2 hrs is to lower systolic BP by no more than
25%, maintaining diastolic BP at no less than 100 mmHg.
– Drugs commonly used: sodium nitroprusside, labetalol, fenoldopam, all
are given by slow i.v. infusion.
– Recent guidelines state that the following drugs are not recommended:
 Nifedipine, nitroglycerin, and hydralazine: because these agents can
cause sudden, uncontrolled, and severe reductions in BP that may
precipitate cerebral, renal, and myocardial ischemic events with fatal
outcomes.
 Furosemide can lead to significant volume depletion and should be used
only if there is associated volume overload as in case of pulmonary edema
and acute heart failure.

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