Antihypertensive

Drugs

Thiazidess &
related drugs
Hydrochlorothiazide
chlorothalidone

Loop
diuretics
Furosemide
Bumetanide
Ethacrynic
acid

Direct
vasodilators

Sympatholytic
agents

Diuretics
K- sparing
diuretics
spironolactone
triametrine
omiloxide

Centrally
acting drugs

Ganglionic
blockers

Methyldopa
Clonidine
Guanfacine

Trimethaphan

Adrenergic
neuron
blockers
Guanithidine
Reserpine

Adrenergic
receptor
blockers
-blockers
- propanolol
- Metoprolol
- Atenolol
-blockers
-Prazosin
Mixed
blockers
-Labetalol

Hassan Jamal

Arterial
vasodilators
K- channel
agonists
-Hydrolazine
- Minoxidil
- Diazoxide

Arterial &
venous
vasodilator

ACE
inhibitors
- Captopril
- Enalapril

SodiumNitr
oPrusside

Ca- channel
blockers
- verapamil
- Nifidipine

M.Hisham

Diuretics
Diuretics lower BP primary by depleting body Na+ stores.
Na+ increases BV & PVR by: vessel stiffness & neural reactivity

Thiazides & related drugs

Mechanism

1) Initial in blood volume & COP

2) After chronic administration (6-8
weeks), COP gradually returns to
normal while PVR declines due to:
a. Loss of Na+ from arterial wall
b. sensitivity of vascular or
smooth muscle to NE
-

Indicated in cases of

Side effects

Mild or moderate hypertension

(lowering BP by 10-15 mmHg)
In sever hypertension in
combination with other
antihypertensive drugs

Loop diuretics

K- sparing diuretics

1) More potent than thiazides as

diuretics BUT less potent as
antihypertensive
2) The antihypertensive effect of
loop diuretics is related BV
- Hypertension associated with
reduced glomerular filtration rate
( GFR) Renal impairment
- Heart failure or liver cirrhosis,
where Na retention is marked
- Hypertension in which multiple
drugs with Na retaining properties
are used (Contraceptives)

1) Hypokalemia (Except for K- sparing diuretics)

2) Impair glucose tolerance, diabetes mellitus and increase serum lipid conc.
3) Impotence loss of libido, diarrhea and gout

- Avoid excessive K depletion

particularly in patients taking
digitalis
- Enhance the natriuretic effects
of other duretics

Sympathetic agents
Centrally acting drugs

Mechanism

Therapeutic
uses

Side effects

Ganglionic blockers
( Symp. & para.)

Adrenergic neuron blockers

Clonidine

Methyldopa

Trimethaphan

Guanethidine

Reserpine

1) Central action
stimulates the central
presynaptic 2-receptors
that are inhibitory to
sympathetic outflow
2) Peripheral action
- Reduces the release of NE
from adrenergic nerve
- Prevents cardiac
responses to
postganglionic adrenergic
nerve stimulation
- Has a weak direct
peripheral vasodilation
action

Converted into methyl NE (potent 2adrenergic agonist) in

the CNS, this would
lead to decrease in
sympathetic outflow

1) sympathetic
vasoconstriction tone
leading to:
a. Dilation of the
arterioles
b. Dilation of the
veins

It inhibits the release

of NE that occur when
a normal action
potential reaches
sympathetic nerve
ending thus tend to
COP by bradycardia
and relaxation of
capacitance vessels

- Blocks the ability of

adrenergic
transmitter vesicles
to uptake and store
biogenic amines by
interfering with
uptake mechanism,
resulting in
- Depletion of NE,
Dopamine &
serotonin in both
central and
peripheral vascular
resistance

- Moderate
Hypertension
- prophylactic
treatment for margin
- Sedation & dry mouth
- Postural hypotension
- Rebound hypertension if
clonidine is suddenly
withdrawn
Guanfacine ~ clonidine

(M Dopa M NE
2 agonist NE
Symp.)

moderate & sever

forms in hypertension

-Sedation on long
term therapy
- Impaired mental
concentration &
mental depression
- Nightmares &
vertigo

2) Produces a direct
vasodilation action &
histamine like effect

- In malignant
hypertension
- Acute pulmonary
edema due to
hypertensive cardiac
failure
- Hypertensive
encephalopathy
- Postural hypotension
& Tachycardia
- Constipation, dry
mouth, urinary
retention
- Mydriasis
- Impotence

With chronic
therapy, COP
returns to normal
while PVR

Little use due to side

effects

- Postural
hypotension and
hypotension
following exercise
- Diarrhea and
delayed ejaculation

Little use due to its

side effects

- Postural
hypotension
- Sedation, nightmars
and severe mental
depression
- Diarrhea and
increase gastric acid
secretion

Propranolol ()
1- 1 2 antagonists

Mechanism

2- Depresses renin-angiotensinaldosterone system by

inhibition of renin production
(2 effect)

Adrenergic receptor Blockers

Metoprolol & Atenolol ()
Prazosin ()
1- selective blockers, both blocking of 1 receptors in
have side effects fewer
arterioles and venules
than propranolol
Has a vascular smooth
muscle relaxant effect

Therapeutic uses

- Lowers BP in mild & moderate

hypertension
- Prevent reflex tachycardia
that often results from
treatment with direct
vasodilators in case of sever
hypertension

For treatment of
hypertensive patients who
suffer from asthma,
diabetes or peripheral
vascular disease

Treatment of severe
hypertension in
combination with other
antihypertensive agents

Labetalol (Mixed)
It blocks & receptors
, blocking is
predominant
Reduces the
sympathetic vascular
resistance without
significant alteration in
HR or COP
reduces plasma renin
activity
Hypertension of
pheochromocytoma
(adrenal gland tumors
that produce xss
adrenalin)
Hypertensive
emergencies

- Postural hypotension
and tachycardia are
observed with 1st dose
- Angina pectoris & fluid
Similar to non-selective Side effects
retention
blockers
- Drowsiness, headache,
GIT disturbance,
blurred vision, dry
mouth
blockers BP by COP. With continued treatment COP returns to normal but PVR is reset at lower level and thus BP remains low
- May increase plasma
triglycerides and decrease
HDL-cholesterol
- Nervousness, Nightmares,
Mental depression and
increase intensity of angina
- Asthma, peripheral vascular
insufficiency and diabetes

Ganglionic Blockers (Trimethaphan)

The depolarizing blockers are not used in hypertension as they cause initial stimulation if the ganglia and thus tend to raise BP at first
The competitive blockers suffer from the disadvantage of that they block both sympathetic and parasympathetic ganglia, with the exception of
trimethaphan, so they have been replaced by drugs which have better selective action an sympathetic tone in the prolonged management of
essential hypertension

Direct Vasodilators
Arterial & venous
vasodilator

Arterial vasodilators
K+ channel agonists
Hydralazine & Minoxidil

Mechanism

Therapeutic uses

Side effects & toxicity

Ca+ Channel blockers

Diazoxide

Relaxation of smooth
Effective in long acting
muscle of arterioles,
arteriolar dilator
systemic vascular
resistance
K+ out, cant Ca+2 in, relaxation
Out patients therapy of
hypertension
- HR & stroke volume
due to compensatory
responses mediated by
baroreceptors and
sympathetic NS as well
as renin and
aldosterone leading to
COP and renal blood
fllow
- Tachycardia, palpitation
and angina
- Headache, nausea,
anorexia, sweating and
flushing

hypertensive emergencies
- Excessive hypotension
with tachycardia and
COP
- Hyperglycemia due to
the inhibition of insulin
release
- Salt & water retention

Verapamil & Nifidipine

Na Nitroprusside

Inhibit Ca+ influx in arterial

smooth muscle leading to
dilation of peripheral
arterioles

Dilates both arterial &

venous vessels, resulting in
PVR and venous return

Mild to moderate
hypertension, Angina or
coronary spasm
Slight tachycardia & in
COP

Hypertensive emergencies
severe cardiac failure
Prolonged therapy leads to
accumulation of: CN- / SCN1) Cyanide (metabolic
acidosis, arrhythmias,
excessive hypotension
& death)
2) Thiocyanate
(weakness, psychosis,
muscle spasm &
cconvulsion
Both can be avoided by:
Sodium thiosulfate as a
sulfur donor or hydroxyl
cobolamin
Nausea, vomiting,
sweating, restlessness,
headache and palpitation

Angiotensin converting enzyme inhibitors

(Captopril Enalapril)

Action by renin-angiotensin
aldosterol system

Mechanism

Angiotensin Angiotensin I Angiotensin II Angiotensin III

- Angiotensin II has a vasoconstrictor and Na retaining activity

- Booth Angiotensin II & Angiotensin III stimulate aldosterone release, which increase Na and water retention
and thus the blood pressure increase
- Inhibit the ACE and thus inhibit the action of renin- angiotensin- aldosterone system
- They stimulate Kallikrein-Kinin system (bradykinin) which has a potent vasodilation effect.
- The hypotensive effect of ACE inhibitor is associated with increasing glomerular filtration rate

Therapeutics

Treatment of:
- sever or refractory hypertension
-Hypertensive diabetic patients
- Renal insufficiency to increase glomerular filtration rate

Side effects

- Proteinuria

- Neutropenia or Pancytopenia - Skin rashes, drug fever, taste impairment and dry cough

Management
Non pharmacological
therapy:
-

Low Na diet
Weight reduction
Stop smoking
Exercise
Cope with stress

Diuretics
Sympatholytic
Vasodilators & Ca
channel blockers
ACE inhibitors

Monotherapy therapy:

Combination therapy:
-

Diuretics & -blockers

Diuretics & -blockers &
vasodilators
Ganglionic blocker, loop
diuretics & vasodilators

Emergencies :
-

Diuretics
Vasodilators: Diazoxide
i.v, sod.nitroprossside i.v,
hydralazine i.m
Lobtalol, trimethaphan,
reserpine, methyldopa
Dialysis

Mild & Moderate

- Thiazides
- Ca+2
Contraceptives ( drugs with
- Clonidine
Na retaining prop.) Loop
- Propranolol
diuretics
Sever
- ACE inh.
- Methyl dopa
Digitalis ( K depletion)
- Prazosin (comb.)
K-sparing diuretics
Use propranolol 2 prevent
reflex tachycardia due 2
Malignant hypertension
vasodilators
pulmonary edema
Emergencies
hypertensive
- Diazoxide
encephalopathy
- Sod.Nitroprusside
- Labitolol
trimethaphan
- Trimethaphan
(malignant)
Pheochromocytoma
Diabetic
labetalol
- ACE inh.
- 1 selective blockers
Outpatient Hydralazine
(Metoprolol, Atenolol)
& Minoxidil
Impaired GFR
- ACE inh.
- Loop diuretics
Sever cardiac failure
Angina / asthma
sod.nitroprusside
- Ca+2 blockers
- 1 selective blockers
(Metoprolol, Atenolol)

Contraindications
Diabetes
- Thiazide
- Propranolol
- Diuretics
Asthma / angina
- 2 blockers (Propranolol,
labetalol).
- Prazosin
-

K+ channel agonists
(Hydralazine, Minoxidil,
Diazoxide)

Causes lipido / impotence

- Diuretics
- Trimethphan
- Guanthidine (delayed
ejaculation)
Causes fluid retension
- Prazosin
- diazoxide