ANALGESIC DRUGS #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 :

I. Chemical stimuliII. Thermal stimuli III. Mechanical stimuli

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

NociceptorsA 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 to primary afferent nerve fibers.

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 )

e.g. Morphine

Non- narcotic analgesics (non- opioid analgesics)

(non- steroidal anti-inflammatory drugs)

NSAIDs

e.g. Aspirin

Opioid analgesicsOpioid 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 analgesicsThe 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

Prostaglandins Thromboxanes

Prostacyclin

COX

Leukotrienes

Lipoxygenase

LAB WORKObjective :

To show the analgesic effects of different analgesics using different methods.

I. Writhing test.II. Hot plate method.

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.

DrugNo. of

writhing/20 minutes

Control Acetic cid

Test 1Morphine acetic

acid

Test 2 Aspirin acetic

acid

5 min’s

5 min’s

Hot plate methodprinciple:

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.

DrugTime interval

zero 5 10 15 20 25 30

Morphine

aspirin

Conc (g%) Dose mg/Kg

Morphine 0.2% 20

aspirin 3% 300