Antihypertensive Drugs

Diuretics
Thiazidess & related drugs Hydrochlorothiazide chlorothalidone Loop diuretics Fu
rosemide Bumetanide Ethacrynic acid K- sparing diuretics spironolactone triametr
ine omiloxide Centrally acting drugs Methyldopa Clonidine Guanfacine Trimethapha
n
Sympatholytic agents
Ganglionic blockers Adrenergic neuron blockers Guanithidine Reserpine Adrenergic
receptor blockers - lockers - propanolol - Metoprolol - Atenolol -blockers -Pr
zo
sin Mixed blockers -L
bet
lol
Direct v
sodil
tors
Arteri
l v
sodil
tors K- ch
nnel
gonists -Hydrol
zine - Minoxidil - Di
zoxide A
rteri
l & venous v
sodil
tor SodiumNitr oPrusside
ACE inhibitors
- C
ptopril - En
l
pril
C
- ch
nnel blockers - ver
p
mil - Nifidipine
H
ss
n J
m
l
M.Hish
m

Diuretics
Diuretics lower BP prim
ry by depleting body N
+ stores. N
+ incre
ses BV & PVR
by: vessel stiffness & neur
l re
ctivity
Thi
zides & rel
ted drugs 1) Initi
l in blood volume & COP 2) After chronic
dmi
nistr
tion (6-8 weeks), COP gr
du
lly returns to norm
l while PVR declines due t
o:
. Loss of N
+ from
rteri
l w
ll b. sensitivity of v
scul
r or smooth muscle
to NE Indic
ted in c
ses of Mild or moder
te hypertension (lowering BP by 10-15
mmHg) In sever hypertension in combin
tion with other
ntihypertensive drugs
Loop diuretics
K- sp
ring diuretics
Mech
nism
1) More potent th
n thi
zides
s diuretics BUT less potent
s
ntihypertensive 2
) The
ntihypertensive effect of loop diuretics is rel
ted BV - Hypertension
ss
oci
ted with reduced glomerul
r filtr
tion r
te ( GFR) Ren
l imp
irment - He
rt f

ilure or liver cirrhosis, where N
retention is m
rked - Hypertension in which
multiple drugs with N
ret
ining properties
re used (Contr
ceptives)
- Avoid excessive K depletion p
rticul
rly in p
tients t
king digit
lis - Enh
nc
e the n
triuretic effects of other duretics
Side effects
1) Hypok
lemi
(Except for K- sp
ring diuretics) 2) Imp
ir glucose toler
nce, di

betes mellitus
nd incre
se serum lipid conc. 3) Impotence loss of libido, di
r
rhe

nd gout

Symp
thetic
gents
Centr
lly
cting drugs Clonidine
1) Centr
l
ction stimul
tes the centr
l presyn
ptic 2-receptors th
t
re inhibit
ory to symp
thetic outflow 2) Peripher
l
ction - Reduces the rele
se of NE from

drenergic nerve - Prevents c
rdi
c responses to postg
nglionic
drenergic nerv
e stimul
tion - H
s
we
k direct peripher
l v
sodil
tion
ction
G
nglionic blockers ( Symp. & p
r
.) Trimeth
ph
n 1) symp
thetic v
soconstrictio
n tone le
ding to:
. Dil
tion of the
rterioles b. Dil
tion of the veins 2) Pro
duces
direct v
sodil
tion
ction & hist
mine like effect
Adrenergic neuron blockers Gu
nethidine It inhibits the rele
se of NE th
t occur
when
norm
l
ction potenti
l re
ches symp
thetic nerve ending thus tend to COP
by br
dyc
rdi

nd rel
x
tion of c
p
cit
nce vessels With chronic ther
py, COP
returns to norm
l while PVR Reserpine - Blocks the
bility of
drenergic tr
nsmi
tter vesicles to upt
ke
nd store biogenic
mines by interfering with upt
ke mec
h
nism, resulting in - Depletion of NE, Dop
mine & serotonin in both centr
l
nd
peripher
l v
scul
r resist
nce
Methyldop
Converted into methyl NE (potent 2
drenergic
gonist) in the CNS, this
would le
d to decre
se in symp
thetic outflow (M Dop

M NE
2
gonist
NE
Symp.)
Mech
nism
Ther
peutic uses
- Moder
te Hypertension - prophyl
ctic tre
tment for m
rgin - Sed
tion & dry mou
th - Postur
l hypotension - Rebound hypertension if clonidine is suddenly withdr

wn Gu
nf
cine ~ clonidine
moder
te & sever forms in hypertension
Side effects
-Sed
tion on long term ther
py - Imp
ired ment
l concentr
tion & ment
l depressi
on - Nightm
res & vertigo
- In m
lign
nt hypertension - Acute pulmon
ry edem
due to hypertensive c
rdi
c
f
ilure - Hypertensive enceph
lop
thy - Postur
l hypotension & T
chyc
rdi
- Con
stip
tion, dry mouth, urin
ry retention - Mydri
sis - Impotence
Little use due to side effects
Little use due to its side effects
- Postur
l hypotension
nd hypotension following exercise - Di
rrhe

nd del
yed
ej
cul
tion
- Postur
l hypotension - Sed
tion, nightm
rs
nd severe ment
l depression - Di
r
rhe

nd incre
se g
stric
cid secretion

Propr
nolol () 1- 1 2 antagonists 2- Depresses renin-angiotensinaldosterone system

y inhi ition of renin production (2 effect)
Mechanism
Adrenergic receptor Blockers Metoprolol & Atenolol () Prazosin () 1- selective loc
kers, oth locking of 1 receptors in h
ve side effects fewer
rterioles
nd ven
ules th
n propr
nolol H
s
v
scul
r smooth muscle rel
x
nt effect
- Lowers BP in mild & moder
te hypertension - Prevent reflex t
chyc
rdi
th
t of
ten results from tre
tment with direct v
sodil
tors in c
se of sever hypertensio
n - M
y incre
se pl
sm
triglycerides
nd decre
se HDL-cholesterol - Nervousness
, Nightm
res, Ment
l depression
nd incre
se intensity of
ngin
- Asthm
, perip
her
l v
scul
r insufficiency
nd di
betes For tre
tment of hypertensive p
tients
who suffer from
sthm
, di
betes or peripher
l v
scul
r dise
se Tre
tment of se
vere hypertension in combin
tion with other
ntihypertensive
gents Ther
peutic uses
- Postur
l hypotension
nd t
chyc
rdi

re observed with 1st dose - Angin
pecto
ris & fluid Simil
r to non-selective Side effects retention lockers - Drowsiness
, headache, GIT distur ance, lurred vision, dry mouth lockers BP y COP. With co
ntinued treatment COP returns to normal ut PVR is reset at lower level and thus
BP remains low Ganglionic Blockers (Trimethaphan) The depolarizing lockers are
not used in hypertension as they cause initial stimulation if the ganglia and t
hus tend to raise BP at first The competitive lockers suffer from the disadvant
age of that they lock oth sympathetic and parasympathetic ganglia, with the ex
ception of trimethaphan, so they have een replaced y drugs which have etter s
elective action an sympathetic tone in the prolonged management of essential hyp
ertension
La etalol (Mixed) It locks & receptors , locking is predominant Reduces the sy
mpathetic vascular resistance without significant alteration in HR or COP reduce
s plasma renin activity Hypertension of pheochromocytoma (adrenal gland tumors t
hat produce xss adrenalin) Hypertensive emergencies

Direct Vasodilators
Arterial vasodilators K+ channel agonists Hydralazine & Minoxidil Diazoxide Rela
xation of smooth Effective in long acting muscle of arterioles, arteriolar dilat
or systemic vascular resistance K+ out, cant Ca+2 in, relaxation Out patients thera
py of hypertension - HR & stroke volume due to compensatory responses mediated
y aroreceptors and sympathetic NS as well as renin and aldosterone leading to C
OP and renal lood fllow - Tachycardia, palpitation and angina - Headache, nause
a, anorexia, sweating and flushing hypertensive emergencies - Excessive hypotens
ion with tachycardia and COP - Hyperglycemia due to the inhi ition of insulin re
lease - Salt & water retention Ca+ Channel lockers Verapamil & Nifidipine Inhi
it Ca+ influx in arterial smooth muscle leading to dilation of peripheral arteri
oles Mild to moderate hypertension, Angina or coronary spasm Slight tachycardia
& in COP Arterial & venous vasodilator Na Nitroprusside Dilates oth arterial &
venous vessels, resulting in PVR and venous return Hypertensive emergencies seve
re cardiac failure Prolonged therapy leads to accumulation of: CN- / SCN1) Cyani
de (meta olic acidosis, arrhythmias, excessive hypotension & death) 2) Thiocyana
te (weakness, psychosis, muscle spasm & cconvulsion Both can e avoided y: Sodi
um thiosulfate as a sulfur donor or hydroxyl co olamin Nausea, vomiting, sweatin
g, restlessness, headache and palpitation
Mechanism
Therapeutic uses
Side effects & toxicity

Angiotensin converting enzyme inhi itors

(Captopril Enalapril)
Action

y renin-angiotensin aldosterol system

Angiotensin

Angiotensin I

Angiotensin II

- Angiotensin II has a vasoconstrictor and Na retaining activity - Booth Angiote

nsin II & Angiotensin III stimulate aldosterone release, which increase Na and w
ater retention and thus the lood pressure increase - Inhi it the ACE and thus i
nhi it the action of renin- angiotensin- aldosterone system - They stimulate Kal
likrein-Kinin system ( radykinin) which has a potent vasodilation effect. - The
hypotensive effect of ACE inhi itor is associated with increasing glomerular fil
tration rate
Mechanism
Therapeutics Side effects
Treatment of: - sever or refractory hypertension -Hypertensive dia etic patients
- Renal insufficiency to increase glomerular filtration rate - Proteinuria - Ne
utropenia or Pancytopenia - Skin rashes, drug fever, taste impairment and dry co
ugh

Management Non pharmacological therapy:

Mild & Moderate - Thiazides - Ca+2 Contraceptives ( drugs with - Clonidine Na re
taining prop.)
Loop - Propranolol diuretics Sever - ACE inh. - Methyl dopa Digit
alis ( K depletion)
- Prazosin (com .) K-sparing diuretics Use propranolol 2 pre
vent reflex tachycardia due 2 Malignant hypertension vasodilators pulmonary edem
a Emergencies hypertensive - Diazoxide encephalopathy
- Sod.Nitroprusside - La i
tolol trimethaphan - Trimethaphan (malignant) Pheochromocytoma
Dia etic la etalo
l - ACE inh. - 1 selective blockers Outpatient
Hydralazine (Metoprolol, Atenolol)
& Minoxidil Impaired GFR - ACE inh. - Loop diuretics Sever cardiac failure
Angi
na / asthma sod.nitroprusside - Ca+2 blockers - 1 selective blockers (Metoprolol,
Atenolol)
Monotherapy therapy:
Diuretics Sympatholytic Vasodilators & Ca channel blockers ACE inhibitors
Low Na diet Weight reduction Stop smoking Exercise Cope with stress
Contraindications Diabetes - Thiazide - Propranolol - Diuretics Asthma / angina
- 2 blockers (Propranolol, labetalol). - Prazosin
K+ channel agonists (Hydralazine, Minoxidil, Diazoxide)
Combination therapy:
Emergencies :
Diuretics & - lockers Diuretics & - lockers & vasodilators Ganglionic locker, loo
p diuretics & vasodilators
Diuretics Vasodilators: Diazoxide i.v, sod.nitroprossside i.v, hydralazine i.m L
o talol, trimethaphan, reserpine, methyldopa Dialysis
Causes lipido / impotence - Diuretics - Trimethphan - Guanthidine (delayed ejacu
lation) Causes fluid retension - Prazosin - diazoxide