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Journal Club

This document summarizes a study that compared the effects of the ACE inhibitor captopril and the ARB losartan on pain sensitivity in mice. The study found that both drugs increased pain sensitivity in hot plate and acetic acid writhing tests, indicating a hyperalgesic effect. Captopril produced more pronounced and longer-lasting hyperalgesia than losartan at equivalent doses. The hyperalgesic effects are thought to be due to the drugs' actions on the renin-angiotensin-aldosterone system and their effects on substances involved in pain perception like bradykinin and prostaglandins. The findings suggest patients on these drugs may experience higher sensitivity to painful stimuli.

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120 views19 pages

Journal Club

This document summarizes a study that compared the effects of the ACE inhibitor captopril and the ARB losartan on pain sensitivity in mice. The study found that both drugs increased pain sensitivity in hot plate and acetic acid writhing tests, indicating a hyperalgesic effect. Captopril produced more pronounced and longer-lasting hyperalgesia than losartan at equivalent doses. The hyperalgesic effects are thought to be due to the drugs' actions on the renin-angiotensin-aldosterone system and their effects on substances involved in pain perception like bradykinin and prostaglandins. The findings suggest patients on these drugs may experience higher sensitivity to painful stimuli.

Uploaded by

DrPallavi D
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPT, PDF, TXT or read online on Scribd
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Journal club

Dr.Hitesh

ROHIT, CHAKRADHAR RAO , GOPALA KRISHNA


Department of Pharmacology,
Kasturba Medical College,
Mangalore 575 001

IJPP;2006; vol 50; Issue 2;page 169174

INTRODUCTION

ACEIs & ARAs are widely used compounds in


various cardiovascular disorders.

ACE(carboxy - dipeptidylpeptidase), converts


angiotensin - I to angiotensin - II .

Degrade the kinins like bradykinin and substance P.

Intro..

ACEI`s

angiotensin II level in plasma & tissue kinins.

Bradykinin is a potent mediator of inflammation and pain.

Angiotensin II has pro-nocioceptive activity and has antiopioid activity.

Why captopril and losartan ?

Hyperalgesic effect of ACEIs but limited for losartan.

Enalapril and losartan increases pain sensitivity during


treatment.

The antinocioceptive effect of ACEI`s (but not enalapril) & ARA

These conflicting results tempted us to evaluate and compare


the effects of captopril and losartan .

Material and
methods
Animals :

Swiss albino mice weighing between 2530 g of either


sex

clean polypropylene cages and maintained at


temperature between 2731C .

Animals were divided into two sets.

Material

Each set consisting of 7 groups with 6 animals in


each group.
Group I
Groups II to IV
Groups V to VII

normal saline (vehicle),


captopril 0.5, 1 and 2 mg/kg
losartan 0.5, 1 and 2 mg/kg

The study was approved by the institutional animal


ethical committee.

Material.
Drugs:

Captopril and losartan (Wokhardt Ltd.,Mumbai) were


dissolved in normal saline

Injected intraperitoneally.

10 ml/kg body weight.

Methods
Hot

plate method:

Heat is used as a source of pain.

Eddy`s hot plate (techno instruments,India)

Constant temperature 55C

Reaction time is noted (licking the paw or jumping or


raising the limbs)

Animals having Basal reaction time not exceeding


15 sec were included in study.

Reaction time was noted.


Writhing

test:

Freshly prepared 0.6% acetic acid , 10ml/kg,


intraperitoneally to each group.

The time for onset of writhing and the number of


contractions in following 15 mins were recorded.

one-way ANOVA , Turkey-Kramer multiple comparison


test.
P values < 0.05.

Effects of captropril and losartan on basal reaction time of mice in hot plate method.
Drug(n)

Dose/kg

Reaction
time
before
drug
adm

15 min

30 min

60 min

90 min

120 min

Control
normal
saline

10ml/kg

3.090.31

2.630.34

3.210.26

4.401.18

3.150.52

3.790.79

captopril

0.5mg/kg

3.350.24

1.520.13

1.680.29

1.510.40

1.630.47

1.040.14

captopril

1 mg/kg

2.660.42

0.840.10

1.270.20

1.480.36

1.150.11

0.900.09

captopril

2mg/kg

3.240.14

0.780.12

0.860.09

0.930.10

0.900.03

0.900.08

losartan

0.5mg/kg

3.320.22

1.380.17

1.250.13

1.410.19

1.480.02

2.260.24

losartan

1 mg/kg

3.170.31

1.390.15

1.280.13

1.390.25

1.200.11

1.750.11

losartan

2 mg/kg

2.610.37

1.350.10

1.260.08

1.300.19

1.090.05

1.250.10

Effects of captropril and losartan on 0.6% acetic acid induced abdominal writhings in mice.
Drugs

Dose/kg

Time for onset of


writhing( in min)

Total number of writhing


in 15 min

Control normal saline

10 ml/kg

3.780.54

28.8336.590

captopril

0.5mg/kg

0.820.11

Sustained
abdominal
contraction

captopril

1mg/kg

0.790.14

Sustained
abdominal
contraction

captopril

2mg/kg

0.390.03

Sustained
abdominal
contraction

losartan

0.5mg/kg

1.250.09

56.662.45

losartan

1mg/kg

0.930.30

73.162.78

losartan

2mg/kg

0.410.017

93.662.33

Discussion:

Hyperalgesic effect of captopril and losartan.

Captopril exhibited higher and long lasting


hyperalgesic effect than losartan.

Modulation of pain with ACE inhibitors suggest that


there is interplay between RAS and pain perception.

Discussion:

Kinins and prostaglandins are important chemical


substances involved in inflammation and pain
perception.
The hyperalgesia produced by ACE inhibitors like
Captopril might be due to
1) decreased angiotensin II concentration.
2) increased bradykinin and
3) enhanced prostaglandin level

Experimental studies show that increasedb renal


bradykinin concentration following AT1 receptor
blockade, due to unopposed action of AII on AT2
receptor hence possibility of involvement of
bradykinin and PGs in hyperalgesic effect of ARAs.

Patient on these drugs may show higher sensitivity


to various noxious stimuli hence care should be
taken while prescribing these drugs to patients in
the presence of pain.

Hyperalgesic effect of these drugs may be helpful by


facilitating the perception of painful stimuli, at least
in hypertensive patients with coronary artery
disease, may possibly interfere with silent episodes.

Conclusion:

Captopril and losartan showed hyperalgesic effect in


both experimental models, thermal and chemical
induced pain in mice.

Captopril produce more hyperalgesia than losartan


on dose to dose basis.

Thank you

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