Transcript LAB 3 Analgesics

# Lab
3#
Introduction
- Pain:
an unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or
described in terms of such damage
- Analgesics :
Drugs used to relief or suppress the pain.
 pain is associated with electrical activity in small
diameter primary afferent fibers of peripheral nerves .
 These nerves have sensory ending in the peripheral
tissues and activated by noxious stimuli of various
kinds :
Chemical stimuli
II. Thermal stimuli
III. Mechanical stimuli
I.
 Types of afferent sensory nerve fibers :
C- fibers
A - fibers
Non- myelinated
Myelinated
Low conducting
velocity
High conduction
velocity
Cause a dull burning
and non-localized pain
Cause a sharp and
localized pain
Nociceptors
A Sensory receptor that sends signals that cause
the perception of pain in response to a potentially
damaging stimulus.
These receptors are activated by mechanical,
thermal and chemical stimulants.
 Provide information about the location,
intensity
and duration of a noxious stimulus to the body
 Nociceptors are connected
nerve fibers.
to primary afferent
Pain Mediators
 pain mediators include :
bradykinin, leukotriene, substance P, histamine, Ach,
5-HT and prostaglandins
 they increase the sensitivity of the nerve ending to
other pain mediators
Pain Mediators
 Mechanism of action of the paim mediators to cause
pain :
I.
Direct : stimulate of the nerve ending directly via
nocieceptors.
II. Indirect : increase the sensitivity of nerve ending to
other pain mediators.
Analgesics are divided into
Narcortic analgesics
( opioid analgesics )
Non- narcotic analgesics
( non- opioid analgesics )
( non- steroidal
anti-inflammatory drugs )
NSAIDs
e.g. Morphine
e.g. Aspirin
Opioid analgesics
Opioid include natural (Morphine), semisynthetic
(Heroin) and synthetic (Fentanyl).
They reduce moderate to severe pain without loss
of consciousness.
They act by binding to specific receptors located
primarily in the brain and spinal cord.
Opioid analgesics
The major classes of opioid receptors are(μ, κ, δ)
mu, delta and kappa.
Each receptor type has subtypes: mu1, mu2, delta1,
delta2, kappa1, kappa2 and kappa3.
Most of the currently available opioid analgesics
act primarily at the mu receptor.
Mechansim of action :
 All opioid recptors are linked through G-proiten by
inhibition of adenylate cyclase i.e facilitate opening of K
channels ( causing hyperpolarization ) and inhibit opening
of Ca channels ( inhibiting transmitters release )
 They stimulate the release of endogenous opiod peptide (
endorphins and enkephalins) which cause decresing in
release of pain mediators.
Side effects:
 Dependency and tolerance
 Nausea and constipation
 CNS: drowsiness, lightheadedness, euphoria or dysphoria, or
confusion.
 Urinary retention
 Respiratory depression, particularly in elderly or debilitated patients
 Miosis ( constriction of the pupil )
Non opioid analgesics (NSAIDs)
 Aspirin and other NSAIDs are useful for the treatment of
pain from injury ( mild to moderate )
 Examples for NSAIDs :
I.
Cox ( cyclooxygenase) non selective : Aspirin,
Ibuprofen, Diclofenac …etc
II. Cox2 selective : Celecoxib and Rofecoxib.
Phospholipids
Phospholipase A2
Arachidonic Acid
COX
Prostaglandins
Lipoxygenase
Leukotrienes
Thromboxanes
Prostacyclin
LAB WORK
Objective :
 To show the analgesic effects of different
analgesics using different methods.
Writhing test.
II. Hot plate method.
I.
Writhing test
Principle:
 Pain is induced by injection of noxious chemical as
Acetic acid 0.1% at volume 0.3 ml.
 Writhing means stretching behavior of the
abdominal and at least one hind limb.
Procedure:
1.First inject the mouse with acetic acid and calculate
the number of writhing/20 minutes and this will be
control test.
2.Inject the second animal with aspirin and inject the
third one with morphine.
3.After 5 minutes inject the animals with acetic acid
then calculate the number of writhing/20 minutes.
Procedure:
4.Compare the number of writhing for each drug and
comment on the results (a drug has more number of
writhing >>> more potency as analgesic.
No. of writhing/20
minutes
Drug
Control
Acetic cid
Test 1
Morphine
Test 2
Aspirin
5 min’s acetic acid
5 min’s
acetic acid
Hot plate method
principle:
 The paws of the mouse are very sensitive to heat at
temperature which are not damaging the skin .
 At temperature of 55 C the mouse will jump and licking
the paws.
 The time till these response occur is calculated and is
prolonged after administration of analgesics.
Procedure:
1.
Put the mouse on the hot plate and record the time taken in
order to jump or licking the fore paws.
2.
Record the time in seconds this is the control time.
3.
Weight the animal and calculate the dose of Morphine and
Aspirin
4.
At 5 min’s interval ( for 30 min’s ) place the animal on the hot
plate and record the time to see the response .
5.
Compare the time need to see the response the drug with
longer time is more potent as analgesic.
Drug
Morphine
aspirin
Time interval
zero
5
10
15
20
25
30
Conc (g%)
Dose mg/Kg
Morphine
0.2%
20
aspirin
3%
300