1. evalution OF ANALGESIC AGENTS

2. INTRODUCTION
Pain is a complex unpleasant phenomenon composed of sensory experiences that include time, space, intensity, and emotion. .
Analgesics is defined as they are agents which selectively relieve pain by acting in the CNS or by peripheral pain mechanisms without significantly altering consciousness.

3. Narcotics Analgesics are classified as : CLASSIFICATION
Ex. Morphine, Pethadine
Non-narcotics Ex. NSAID
and acetaminophen EX: paracetamol

4. Description
Although pain syndromes may be dissimilar, the common factor is a sensory pathway from the affected organ to the brain.
Analgesics work at the level of the nerves, either by blocking the signal from the peripheral nervous system,
or by distorting the interpretation by the central nervous system.
Selection of an appropriate analgesic is based on
consideration of the risk-benefit factors of each class of drugs,
based on type of pain,
severity of pain,
and risk of adverse effects.
Traditionally, pain has been divided into two classes,
acute and chronic
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5. Acute pain
Acute pain is self - limiting in duration, and includes post-operative pain, pain of injury, and childbirth.
Because pain of these types is expected to be short term, the long-term side effects of analgesic therapy may routinely be ignored.
Thus, these patients may safely be treated with narcotic analgesics without concern about possible addiction, or NSAIDs with only limited concern for the risk of ulcers.
Drugs and doses should be adjusted based on observation of healing rate, switching patients from high to low doses, and from narcotic analgesics to non-narcotics when circumstances permit.
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6. Chronic pain
Chronic pain, pain lasting over three months and severe enough to impair function, is more difficult to treat, since the anticipated side effects of the analgesics are more difficult to manage.
In the case of narcotic analgesics this means the addiction potential, as well as respiratory depression and constipation.
For the NSAIDs, the risk of gastric ulcers limit dose.
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7. Narcotic analgesics
The narcotic analgesics, also termed opioids, are all derived from opium. The class includes morphine, codeine, and a number of semi-synthetics including meperidine (Demerol),
The narcotic analgesics vary in potency, but all are effective in treatment of visceral pain when used in adequate doses.
Adverse effects are dose related. Because these drugs are all addictive, they are controlled under federal and state laws. A variety of dosage forms are available, including oral solids, liquids, intravenous and intrathecal injections, and transcutaneous patches.
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8. NSAIDs
NSAIDs are effective analgesics even at doses too low to have any anti-inflammatory effects.
There are a number of chemical classes, but all have similar therapeutic effects and side effects.
Most are appropriate only for oral administration; however ketorolac (Toradol) is appropriate for injection and may be used in moderate to severe pain for short periods.
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9. Acetaminophen
Acetaminophen is a non-narcotic analgesic with no anti-inflammatory properties. It is appropriate for mild to moderate pain.
Although the drug is well tolerated in normal doses, it may have significant toxicity at high doses.
Because acetaminophen is largely free of side effects at therapeutic doses, it has been considered the first choice for mild pain, including that of osteoarthritis.
Topical analgesics (topical being those that are applied on the skin) have become much more popular in recent years.
Those applied for local effect include methylsalicylate, and transdermal lidocaine. Transdermal fentanyl may be applied for systemic (the entire body in general) effect.
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10. MECHANISM OF ACTION
Analgesic drugs act in various ways on the peripheral and central nervous systems.
Opioids produce analgesia by binding to specific G – protein coupled receptors in brain and spinal cord.
NSAIDs inhibit the activity of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and thereby the synthesis of prostaglandins and thromboxanes.
 Inhibition of COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects.

11. Tramadol
Tramadol is a narcotic-like pain reliever. Tramadol is used to treat moderate to severe pain.
is a centrally acting analgesic with a multimode of action. It acts on serotonergic and noradrenergic nociception.
classified as pain relievers type 2 affects the same receptors as morphine, a competitor on morphine's receptors.
which causes addictive, but to a lesser extent than the rest of narcotic competition on the same receptors.
painkillers of tramadol Considered largest of Many of the analgesia,
but this is advisable to use more caution. It can be used for intravenous, doses used are from 50 to 100 mg. Half-life is from five to seven hours
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12. side effects of tramadol
Include
pruritus,
anxiety,
tremor, agitation
, diarrhea,
constipation,
hallucination,
nausea, vomiting,
and diaphoresis.
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13. Morphine Papaver Somniferous
Naturally occurring substance
Papaver Somniferous
Works on Opioid Receptors µ (mu), δ (delta), and к (kappa)
G-protein coupled receptors, inhibition of adenylate cyclase
↑ opening of Pot. Channels (hyperpolarization of parasympathetic nerve
↓ opening of Cal. Channels.
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14. Pharmacological Action s
Analgesia
Euphoria
Respiratory depression
Cough suppression
Nausea & vomiting
Pupillary constriction
Delay of gastric emptying
Histamine release
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15. Side Effects Sedation Respiratory depression Constipation Itching
Tolerance & dependence
Hypotension
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16. Meloxicam
Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and fever reducer effects.
It is a derivative of  oxicam , closely related to piroxicam,
. Meloxicam starts to relieve pain about 30–60 minutes after administration
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17. Mechanism of action
Meloxicam blocks cyclooxygenase (COX), the enzyme responsible for converting arachidonic acid into prostaglandin H2—
the first step in the synthesis of prostaglandins, which are mediators of inflammation.
Meloxicam has been shown, especially at its low therapeutic doses, selectively to inhibit COX 2 over COX-1
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18. acetylsalicylic acid (ASA)
Aspirin, is a medication, often used to treat pain, fever, and inflammation. Aspirin is also used long-term, at low doses, to help prevent heart attacks, strokes, and blood clot formation in people at high risk of developing blood clots.  
 Aspirin may be effective at preventing certain types of cancer, particularly colorectal cancer
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19. side effects
The main side effects of aspirin are gastric ulcers, stomach bleeding, especially with higher doses.
Aspirin can increase the effect of medicines used to treat diabetes mellitus, resulting in abnormally low blood sugars if blood sugar levels are not monitored.
NSAIDs should be discontinued prior to elective surgery because of a mild tendency to interfere with blood clotting. Aspirin, because of its prolonged effect on platelets, is best discontinued at least ten to fourteen days in advance of the procedure.

20. SCREENING
MODELS

21. Principle:
record the response of animal to a painful stimulus before & after administration of analgesic
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22. Pain - state models using Thermal stimuli.
IN VIVO MODELS
Pain - state models using Thermal stimuli.
* Tail - flick model using radiant heat.
* Hot - plate test.
Pain - state models using Electrical stimuli.
* Electrical stimulation of the tail.
* Grid - shock test.
* Stimulation of the limbs.
Pain - state models using Chemical stimuli.
* Formalin test.
* Acetic acid induced writhing test.

23. HOT – PLATE TEST Purpose and rationale
The paws of mice and rats are sensitive to heat at temperatures which are not damaging to skin.
The responses are jumping, withdrawal of the paws and licking of the paws.
The responses is prolonged after administration of centrally acting analgesics, whereas peripheral analgesics of the acetylsalicylic acid or phenyl-acetic acid type do not generally affect these responses.

24. Procedure
Groups of 10 mice (18-22g) are selected and divided into standard,
test & control group respectively
The temperature of the hot plate is maintained at 55° to 56°C.
The animals are placed on the hot plate & time until either
licking or jumping occurs is recorded.
The latency is recorded before & after 20, 60 and 90 min after the administration of standard or test compound.

25. Evaluation
The prolongation of latency time between the test, standard and control animals are compared.
Using various doses ED50 values can be calculated.