Anti Inflamm

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    EVALUATION

    OFANTI-INFLAMMATORY /

    ANALGESIC ACTIVITYOF DRUGS

    Dr. Inas DarwishDr. Dalia Kamal

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    LEARNING OBJECTIVES

    By the end of this practical class you will be able to:

    demonstrate the experimental methods

    of studying analgesia / inflammation

    discuss the analgesic/ anti-inflammatory

    activity of drugs.

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    Introduction:

    What happens afterexposure

    to a noxious

    Stimulus

    http://rds.yahoo.com/_ylt=A9ibyiFL2wZG0gQBUXCJzbkF;_ylu=X3oDMTBkY2IwMGkxBHBvcwMzOARzZWMDc3I-/SIG=1gcjfbjkc/EXP=1174940875/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Danalgesics%2526toggle%253D1%2526cop%253Dmss%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D21%26w=213%26h=165%26imgurl=www.ecrpharma.com%252Fimages%252Fmatrix_analgesics.jpg%26rurl=http%253A%252F%252Fwww.ecrpharma.com%252Fproducts%252Fproducts.html%26size=10.6kB%26name=matrix_analgesics.jpg%26p=analgesics%26type=jpeg%26no=38%26tt=5,524%26oid=55e807f7fe8c3e98%26ei=UTF-8
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    Drugs

    Sensation or

    Perception of pain

    Awareness of pain

    Emotional reaction

    To painful stimuli

    (Reaction to pain)

    http://rds.yahoo.com/_ylt=A9ibyiFL2wZG0gQBUXCJzbkF;_ylu=X3oDMTBkY2IwMGkxBHBvcwMzOARzZWMDc3I-/SIG=1gcjfbjkc/EXP=1174940875/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Danalgesics%2526toggle%253D1%2526cop%253Dmss%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D21%26w=213%26h=165%26imgurl=www.ecrpharma.com%252Fimages%252Fmatrix_analgesics.jpg%26rurl=http%253A%252F%252Fwww.ecrpharma.com%252Fproducts%252Fproducts.html%26size=10.6kB%26name=matrix_analgesics.jpg%26p=analgesics%26type=jpeg%26no=38%26tt=5,524%26oid=55e807f7fe8c3e98%26ei=UTF-8
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    Analgesics

    Narcotic analgesicsNon narcotic analgesicsNon-Steroidal Anti-inflammatory

    drugs NSAIDs'

    Morphine, Codeine, others

    opiate receptors

    severe degree of pain

    respiratory depression,

    physical dependence.

    centrally , peripherally ?

    Salicylates, Oxicams,

    Fenamates, etc

    Anti-inflammatory

    Antipyretic

    mild to moderate pain

    Perceptio

    n of pain

    Reactio

    n topain

    http://rds.yahoo.com/_ylt=A9ibyiFL2wZG0gQBUXCJzbkF;_ylu=X3oDMTBkY2IwMGkxBHBvcwMzOARzZWMDc3I-/SIG=1gcjfbjkc/EXP=1174940875/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Danalgesics%2526toggle%253D1%2526cop%253Dmss%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D21%26w=213%26h=165%26imgurl=www.ecrpharma.com%252Fimages%252Fmatrix_analgesics.jpg%26rurl=http%253A%252F%252Fwww.ecrpharma.com%252Fproducts%252Fproducts.html%26size=10.6kB%26name=matrix_analgesics.jpg%26p=analgesics%26type=jpeg%26no=38%26tt=5,524%26oid=55e807f7fe8c3e98%26ei=UTF-8
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    Assessment of analgesic activity

    Thermal

    methods

    Chemical

    methods

    Induction of pain by

    thermal stimuliInduction of pain by

    irritant chemicals

    Narcotic

    analgesics.

    Non-narcotic

    analgesics.

    http://rds.yahoo.com/_ylt=A9ibyiFL2wZG0gQBUXCJzbkF;_ylu=X3oDMTBkY2IwMGkxBHBvcwMzOARzZWMDc3I-/SIG=1gcjfbjkc/EXP=1174940875/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Danalgesics%2526toggle%253D1%2526cop%253Dmss%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D21%26w=213%26h=165%26imgurl=www.ecrpharma.com%252Fimages%252Fmatrix_analgesics.jpg%26rurl=http%253A%252F%252Fwww.ecrpharma.com%252Fproducts%252Fproducts.html%26size=10.6kB%26name=matrix_analgesics.jpg%26p=analgesics%26type=jpeg%26no=38%26tt=5,524%26oid=55e807f7fe8c3e98%26ei=UTF-8
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    Thermal methods

    Hot Plate

    Tail -Flick

    Tail

    immersion

    Hot water49C

    http://rds.yahoo.com/_ylt=A9ibyiFL2wZG0gQBUXCJzbkF;_ylu=X3oDMTBkY2IwMGkxBHBvcwMzOARzZWMDc3I-/SIG=1gcjfbjkc/EXP=1174940875/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253Danalgesics%2526toggle%253D1%2526cop%253Dmss%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D21%26w=213%26h=165%26imgurl=www.ecrpharma.com%252Fimages%252Fmatrix_analgesics.jpg%26rurl=http%253A%252F%252Fwww.ecrpharma.com%252Fproducts%252Fproducts.html%26size=10.6kB%26name=matrix_analgesics.jpg%26p=analgesics%26type=jpeg%26no=38%26tt=5,524%26oid=55e807f7fe8c3e98%26ei=UTF-8
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    Chemical methods

    Phenyl

    benzequinoneAcetic

    acid

    Irritant

    chemicals

    Carrageenan-

    induced paw edema

    Cotton pellet method

    http://rds.yahoo.com/_ylt=A9iby4IRnQtG4j0AZ1CJzbkF;_ylu=X3oDMTBlcDdzMHMxBHBvcwMxODQEc2VjA3Ny/SIG=1fe875iq3/EXP=1175252625/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253DLaboratory%252Bmice%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D181%26w=520%26h=492%26imgurl=www.all-creatures.org%252Fsaen%252Frat-01a.jpg%26rurl=http%253A%252F%252Fwww.all-creatures.org%252Fwlalw%252Ffact-product.html%26size=19.2kB%26name=rat-01a.jpg%26p=Laboratory%2Bmice%26type=jpeg%26no=184%26tt=672%26oid=58f95c9a095b996c%26ei=UTF-8
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    60 C

    ExperimentalProcedures

    HOT -PlateAcetic acid

    induced writhes

    Selection of animals

    Licking of the paw

    Jumping

    10 sec.

    Nonreactive

    http://rds.yahoo.com/_ylt=A9iby4IRnQtG4j0AZ1CJzbkF;_ylu=X3oDMTBlcDdzMHMxBHBvcwMxODQEc2VjA3Ny/SIG=1fe875iq3/EXP=1175252625/**http%3A//images.search.yahoo.com/search/images/view%3Fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253DLaboratory%252Bmice%2526ei%253DUTF-8%2526fr%253Dyfp-t-501%2526b%253D181%26w=520%26h=492%26imgurl=www.all-creatures.org%252Fsaen%252Frat-01a.jpg%26rurl=http%253A%252F%252Fwww.all-creatures.org%252Fwlalw%252Ffact-product.html%26size=19.2kB%26name=rat-01a.jpg%26p=Laboratory%2Bmice%26type=jpeg%26no=184%26tt=672%26oid=58f95c9a095b996c%26ei=UTF-8
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    JUMPING

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    Analgesic activity of SodiumSalicylate and Morphine

    SedationNo of mice licking/ jumping

    Before after

    30 min. of administration

    No. of animals

    at the start ofthe experiment

    Group

    absent455Na salycilate

    Present

    Straub tail155Morphine

    Selection of animals

    Grouping

    Na salicylate

    (600 mg/kg i.p.)

    Morphine

    (5 mg/kg i.p.)

    Recording the reaction

    30 min after injection

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    Acetic acid-induced writhing in mice:

    Control0.2 ml of

    normal saline I. P.

    Na Salycilatesodium salicylate

    300 mg/kg I.P.

    After 1/2 hour,

    0.2 ml/20g b.wt.

    of 3% acetic acidI.P.

    Writhes ?

    15 min

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    contraction of the

    abdomen

    twisting of the trunk

    extention of the limbs

    Each Writhe consists of

    in thereductionThe percentage

    number of writhesfrom the control group is a

    analgesic activitymeasure of

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    % reduction inNo. of writhes

    from the control

    AverageNo. of

    writhes

    No. of writhes

    in 15 min.Animal No.Group

    26

    23

    27

    30

    1

    2

    3

    ControlGroup

    46%

    14

    17

    15

    9

    1

    2

    3

    NaSalicylate

    (300 mg/kg)

    Analgesic activity of Sodium Salicylate

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    Conclusions

    1.Hot plate method response due toexposure to heat (noxious) stimuluswas inhibited by morphine but not byNa salycilate .

    2.Acetic acid induced writhes arereduced by Na salycilate .

    ..

    ..

    ..

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    Questions

    1.Mentions the two components of pain

    2. Name the important mediators ofinflammation.

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    Questions

    3. What is the mechanism of the anti-inflammatory activity of salicylates?

    4. What is the mechanism of analgesicactivity of morphine?

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    Questions

    5. Why Salicylates did not inhibitmouse hot plate Method response?

    6. Name 2 conditions each where youwill use morphine and Salicylatesas analgesics.

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    Questions

    Hotplate method is used for screening of morphine, whileacetic acid induced writhes is used for screening of NSAIDs.

    Prostaglandins and bradykinin are mediators ofinflammation.

    Acetyl saliycilic acid is an example of NSAIDs.

    Fill in the space:

    ..

    .

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    Questions

    Fill in the space:

    SedationNo. of micelicking/jumping

    before after

    Drug

    absent55Na

    salicylate

    present15Morphine

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    Questions

    Match:

    a. Licking of the paw.

    b. a chemical method.c. mediators of inflammation

    d. an e.g. of narcotic analgesi

    e. writhes

    f. a thermal method

    g. an e.g. of non

    narcotic analgesic

    Morphine is (d )

    Aspirin is (g )

    Acetic acid induces (e )

    Hot plate is ( f )

    Prosaglandins are (c )

    Assessment of NSAIDs

    is by ( b )

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