Cilnidipine

What Is Blood Pressure ?

Blood

pressure is the amount of

force on the walls of the arteries as
the blood circulates around the body.

Blood Pressure
BP = pressure exerted on the vessel wall by
blood
BP = cardiac output ( CO) x PVR
where CO is
CO = stroke volume x Heart rate
BP = ( SV X HR ) X PVR

BLOOD PRESSURE
Peripheral Vascular Resistance depends on :
- Lumen diameter of peripheral
arterioles
- dilatation of peripheral arterioles
decreases PVR & lowers BP
- Contraction of peripheral arterioles
increases PVR & BP

Hypertension

JNC-7

Causes of Hypertension

Primary / Essential hypertension:

- No identifiable cause
Most common cause
Accounts for 93 % of cases

Secondary Hypertension:
(Due to other diseases)
Renal Hypertension
Endocrine Hypertension etc.

Harmful effects of High Blood Pressure

Hardening of the arteriesatherosclerosis

Stroke

Heart attack

Kidney damage-kidney failure

Blindness

Benefits of lowering BP

Condition

Stroke
MI
Heart Failure

Percent reduction

34-40%
20-25 %
50%

Goals of therapy
BP

< 140/90 mmHg

In

diabetics or in patients with

chronic renal disease:
<140/80 mmHg

ISH : SBP in persons>50 years:

<140 mmHg

Ideal Antihypertensive drug

Good efficacy-should provide 24-hr control

of BP with once daily dose

Minimal or no serum glucose imbalance

Minimal or no electrolyte imbalance

Minimal or no lipid profile imbalance

Improve quality of life

- Physical activity, sleep, sexual
functions.

Dosage compliance

Major Antihypertensives
1. Diuretics: Hydrochlorothiazide
2. Beta blockers : Atenolol, nebivolol, metoprolol
3.

ACE inhibitors :
- Enalapril, Lisinopril, Ramipril etc

4. AT1 receptor antagonists:

- Losartan, valsartan, telmisartan etc
5.

Calcium antagonists :
- Cilnidipine, Amlodipine, Nifedipine, Diltiazem

6.

Alpha blockers :

- Prazosin,terazosin,doxazosin

Calcium Antagonists

Also called calcium channel blockers-Dilate

arterioles- decrease PVR & BP
3 groups:

1.Dihydropyridine derivatives:
Nifedipine, felodipine, amlodipine, cilnidipine
etc
2.Benzothiazepines: Diltiazem
3.Phenylalkylamines: Verapamil

Calcium Antagonists

CCBs block the L type calcium channels

present within blood vessels- prevent entry of
calcium ions into vascular smooth muscle
fibers
relaxing large and small arteries and
reducing peripheral resistance( PVR )
Reduce force of contraction of myocardium

Calcium Channel Blockers

Indications

Hypertension
Angina

Calcium antagonists
CCBs are commonly used to treat hypertension
because:
Very well tolerated,compliance is high,
They dont have any adverse effect on quality
of life
Do not alter carbohydrate or lipid Metabolism
often used in combination with beta-blocker
therapy

Calcium antagonists
Averse

Drug Reactions:

Flushing
Headache
Ankle oedema
Reflex tachycardia

Renin Angiotensin Aldosterone

System (RAAS)

Plays an essential role in regulation of

blood pressure, blood volume,
electrolyte balance and glomerular
filtration rate (GFR)

RAAS
Angiotensinogen
Renin(kidney)

Angiotensin I
Non ACE
Pathway

ACE
Angiotensin II

AT1 receptors
Vasoconstriction
growth
(PVR)

Aldosterone
release
salt & water
retention
(preload)

AT2 receptors
Stimulation
of SNS

Cell

RAAS

AT1 receptors:
Responsible for virtually all the known actions
of Angiotensin II

AT1 receptors are present in the

blood vessels
adrenal gland
heart
kidney
brain &
liver

RAAS

Vasoconstriction:
Angiotensin II is the most potent
vasoconstrictor in the body
Produces constriction of arterioles as
well as veins
Constriction of peripheral arterioles
results in increased Peripheral
Vascular Resistance (PVR)

RAAS

Inappropriately elevated levels of angiotensin II have

following adverse effects:
Constriction of peripheral arterioles leads to
increased PVR (afterload)
Angiotensin II leads to aldosterone secretion from
adrenal cortex
Aldosterone causes sodium & water retention in the
body, thus increasing blood volume (preload)

RAAS
All these actions of angiotensin II
are seen after it has combined
with AT1 receptors

RAAS - Inhibition
Two

different groups of drugs that

inhibit the RAAS are:

ACE inhibitors e.g. Enalapril, Lisinopril,
Ramipril
AT1 receptor blockers (ARBs) e.g.
Losartan, Valsartan, Telmisartan

Angiotensin-II Receptor Blockers

Block the AT1 receptors

Reduce afterload & preload

e.g. Losartan, candesartan, valsartan,
telmisartan etc

Better tolerated than ACE inhibitors-

- do not produce dry cough

Beta Blockers

Mode of action
Block

Beta receptors present in heart :

Decrease

CO-decrease heart rate & force of

contraction-negative chronotropic & negative
inotropic effects

Decrease

Central

tone

in Renin release from the Kidneys

action - reduction in Sympathetic

Beta blockers
Classification :
1.Non-selective:
Block both beta1 & beta2 receptors
(Propranolol )
2.Cardio-selective:
Block only beta1 receptors
(Atenolol, Metoprolol, Nebivolol )
3. Combined beta & alpha blocker:
Block both beta1 & beta2 + alpha1 receptors
( carvedilol )

Beta Blockers
Indications

Hypertension
Angina
Post-MI

Beta Blockers

Side effects
Bradycardia
AV block- not safe in heart block
Fatigue
Bronchospasm- not safe in
asthma
Loss of Libido
Impotence
Dyslipidemia

Algorithm for Treatment of Hypertension

Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg)

(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Stage 2 Hypertension
Without Compelling
Indications

With Compelling
Indications

(SBP >160Stage
or 2DBP
>100 mmHg)
Hypertension
(SBP >160 or DBP >100 mmHg)
Drug(s) for the compelling
Stage 1 Hypertension
Stage 2 Hypertension
2-drug combination
2-drug combination for mostfor most
indications

(SBP 140159 or DBP 9099

mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.

(SBP >160 or DBP >100 mmHg)

(usually
thiazide-type
2-drug
combination diuretic
for most and
(usuallyorthiazide-type
diuretic
and
ACEI,
ARB, or BB,
or CCB)

Other antihypertensive drugs

(diuretics, ACEI, ARB, BB, CCB)
as needed.

(usually thiazide-type diuretic and

ACEI, or ARB,
Not ator
Goal BB, or CCB)
ACEI, or ARB, or BB, or CCB)

Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.

Cilnidipine

Cilnidipine was administered orally once daily at an initial

dose of 10 mg for 4 weeks

Treatment: 10 mg Cilnidipine for 7 days

Cilnidipine is effective as a once-daily antihypertensive agent and causes

little infuence on heart rate and the autonomic nervous system in patients with mild to
moderate essential hypertension

Study designed to compare the effects of 12-month blood pressure (BP)

control using cilnidipine and telmisartan on vascular damage in untreated
hypertensive patients
One hundred patients were randomly assigned to either a cilnidipine
group or a telmisartan group
The extent of vascular damage was assessed before and after treatment
by measuring
urinary albumin excretion (UAE)
pulse wave velocity (PWV)
intima-media thickness (IMT) of the carotid arteries
Both drugs similarly decreased BP
Both UAE and PWV were significantly improved in both groups, but
IMT was significantly reduced only in the cilnidipine group.

Study compared cilnidipine and amlodipine with respect to their effects

on renal function and proteinuria
Twenty-eight proteinuric hypertensive outpatients (13 men and 15
women, aged 62.2 years) who had been maintained on CCBs
for more than 3 months were randomly assigned to a group receiving
amlodipine besilate (14 patients) or a group receiving cilnidipine (14
patients)
Before and at 6 and 12 months after randomization, the concentrations
of urine protein, urine albumin, serum and urine creatinine (Cr), and
serum 2-microglobulin were determine
Amlodipine group showed a significant increase in proteinuria, while the
increase was suppressed in the cilnidipine group

Conclusion: cilnidipine results in a greater suppression of the

increase in proteinuria and greater reduction in glomerular
filtration rate than amlodipine, and that these effects are similar
between cilnidipine and RA inhibitors

The study was a prospective, randomized, open label comparison

45 patients received 5-10mg Amlodipine and other 55 patients of same age
groups received 10-20mg Cilnidipine.
Both the drug significantly reduced both systolic (SBP) and diastolic blood
pressure (DSP)
Amlodipine group the pulse rate (PR) after treatment tended to be higher than
those before treatment
Cilnidipine group there was decrease in PR after treatment
Unlike Amlodipine, Cilnidipine decreased urinary protein excretion and in
diabetic patients reduced serum triglyceride
Unlike Amlodipine, Cilnidipine which inhibits L-and N-type calcium channels will
be useful for patients with hypertension and cardiovascular disease, diabetes
mellitus or renal disease and proves to be a better alternative to existing calcium
channel blockers

Evaluated the antialbuminuric advantage of cilnidipine,L/N type Calcium channel blocker (CCB),
compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria.
Participants were 90 type 2 diabetic patients exhibiting either normo- or microalbuminuria, and
undergoing CCB treatment for 6 months prior to study entry.
The CCB at the time of entry was continued for the first 6 months (Period 1).
Treatment was subsequently switched from cilnidipine to an L-type CCB, or vice versa, for the
second 6-month observation period (Period 2).
During Period 1, the L-type CCB group showed a significant increase of urinary albumin excretion
(UAE) over time, while the cilnidipine group showed no significant elevation.
During Period 2, switching of the treatment from the L-type CCB to cilnidipine resulted in
significant reduction of the UAE, whereas switching from cilnidipine to the L-type CCB resulted in
no significant change in the UAE.
This study demonstrated that the antialbuminuric effect of Cilnidipine, but not the L-type CCBs,
was sustained even in patients treated for a long time.
In addition, the antialbuminuric effect can be anticipated after switching from an L-type CCB to
cilnidipine, but not vice versa.

Conclusion:
In Treatment Period of L-type CCB there was increase in Urinary
Protein Excretion while in Treatment Period of Cilnidipine there
was reduction in Urinary Protein Excretion.
Cilnidipine offers Reno-protection

Hypertens Res 2006; 29: 339-44

Fifty-eight subjects diagnosed with both essential
hypertension and morning hypertension (43 currently being
treated, 15 new patients) were prescribed cilnidipine at a
dosage of 1020 mg per day for 8 weeks
After addition of or a change to cilnidipine, the morning
systolic blood pressure (SBP) was controlled to less than 135
mmHg in 25 (58%) out of the 43 patients currently
receiving antihypertensive medication
Office SBP in 24 out of those 25 patients was also
maintained under 140 mmHg
In the 15 newly treated patients, the morning SBP of 12
patients (80%) was controlled to less than 135 mmHg after
administration of cilnidipine

J Clin Hypertens 2013; 15: 133

The authors examined 2319 patients treated with cilnidipine for 12
weeks
Clinic systolic BP (SBP) decreased by 19.6 mm Hg from 155.0 mm Hg,
whereas morning SBP decreased by 17.0 mm Hg from 152.9 mm Hg
after 12-week cilnidipine treatment
Cilnidipine significantly reduced BP and Pulse Rate (PR) in hypertensive
patients at the clinic and at home, especially with higher BP and PR in
the morning

J Hyper 2007; 25: 2178- 2183

50 patients with untreated essential hypertension were randomized to
receive 5mg of amlodipine (n=25) or 10mg of cilnidipine (n=25)
once daily in the morning for 24 weeks
Patients were evaluated before and after the therapy to assess
changes in renal function, flow-mediated vasodilation (a parameter of
vascular endothelial function), and brachial-ankle pulse wave velocity (a
parameter of arterial stiffness)
After treatment, urinary albumin excretion was decreased significantly
in the cilnidipine group compared with the amlodipine group, and
the decrease of brachial-ankle pulse wave velocity was significantly
larger in the cilnidipine group than in the amlodipine group
Conclusion:
These results suggest that cilnidipine is more effective than amlodipine
at improving renal function and arterial stiffness in patients with
essential hypertension

Kidney International 2007; 72:1543-49

339 patients, already receiving reninangiotensin system inhibitor

treatment, were randomly assigned to cilnidipine or amlodipine
Primary endpoint was a decrease in the urinary protein to creatinine
ratio
After 1-year of treatment, systolic and diastolic blood pressures were
significantly reduced in both groups which did not differ between them
The urinary protein to creatinine ratio significantly decreased in the
cilnidipine compared to the amlodipine group
Cilnidipine exerted a greater antiproteinuric effect than amlodipine
even in the subgroup whose blood pressure fell below the target level.
Study suggests that cilnidipine is superior to amlodipine in
preventing the progression of proteinuria in hypertensive patients
when coupled with a reninangiotensin system inhibitor

Excellent Tolerability of Cilnidipine in Patients with

Amlodipine induced Edema
27

patients with Amlodipine induced

edema
Treatment with Cilnidipine 10 mg for
4 weeks
Edema resolved in all patients
Significant decrease in bilateral ankle
circumference and body weight (p<
0.001)

Before
Treatment

After
Treatment

Ankle
Circumference
Rt (cm)

26

23.7

-2.3

p<0.001

Ankle
Circumference
Lft (cm)

26.3

23.9

-2.4

p<0.001

Body Weight
(Kg)

67.8

67.3

-0.5

p<0.001