The document discusses two major classes of analgesics - narcotic analgesics and non-narcotic analgesics (NSAIDs). It describes the classification of NSAIDs, their mechanism of action involving inhibition of cyclooxygenase enzymes, and their therapeutic uses for anti-inflammatory, analgesic, and antipyretic effects. Adverse effects including gastrointestinal issues and renal toxicity are also noted. The mechanisms and effects of opioid analgesics are then outlined, along with their clinical uses, side effects, toxicity, and treatment with naloxone or naltrexone.

1. Dr. AMIR BAHADUR
DIRECTOR, BINOR
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2. Analgesics
Two major classes
NARCOTIC analgesics
Non-Narcotic analgesics (NSAIDs)
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4. Classification
A. Nonselective COX inhibitors (traditional NSAIDs)
1.Salicylates: Aspirin
2.Propionic acid derivatives: Ibuprofen, Naproxen,
Ketoprofen, Flurbiprofen.
3.Anthranilic acid derivative: Mefenamic acid
4.Aryl-acetic acid derivatives: Diclofenac, Aceclofenac.
5.Oxicam derivatives: Piroxicam, Tenoxicam.
6.Pyrrolo-pyrrole derivative: Ketorolac
7.Indole derivative: Indomethacin.
8.Pyrazolone derivative: phenylbutazone,
Oxyphenbutazone
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5. B. Preferential COX-2 inhibitors
Nimesulide, Meloxicam, Nabumeton.
C. Selective COX-2 inhibitors
Celecoxib, Etoricoxib, Parecoxib.
D. Analgesic-antipyratics with poor antiinflammatory
action
1.para aminophenol derivatives: Paracetamol
2.Pyrazolone derivative: Metamizol, Propiphenazone.
3.Benzoxazocine derivative: Nefopam
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6. Mechanism of Action of NSAIDs
NSAIDs blocked PG generation.
Prostaglandins, prostacyclin (PGI2), and
thromboxane A2(TXA2) are produced from
arachidonic acid by the enzyme cyclooxygenase.
Cyclooxygenase (COX) exists in COX-1 and COX-2
isoforms.
COX -3 has recently been identified
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7. Cyclooxygenase (COX) is found bound to the endoplasmatic
reticulum. It exists in 3 isoforms:
• COX-1 (constitutive) acts in physiological conditions.
• COX-2 (inducible) is induced in inflammatory cells by
pathological stimulus.
• COX-3 (in brain).
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8. Actions of NSAIDs
NSAIDs have following main actions:
Analgesic
Anti-pyretic
Anti-inflammatory
Anti-platelets aggregation
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9. 1. Anti-inflammatory effect
 Due to the inhibition of the enzymes that produce
prostaglandin H synthase (cyclooxygenase, or
COX), which converts arachidonic acid to
prostaglandins, and to TXA2 and prostacyclin.
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10. 2. Analgesic effect
A. The analgesic effect of NSAIDs is thought to be
related to:
 the peripheral inhibition of prostaglandin
production
 may also be due to the inhibition of pain stimuli
at a subcortical site.
A. NSAIDs prevent the potentiating action of
prostaglandins on endogenous mediators of
peripheral nerve stimulation (e.g., bradykinin).
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11. 3. Anti-pyretic effect
 The antipyretic effect of NSAIDs is believed to be
related to:
 inhibition of production of prostaglandins induced
by interleukin-1 (IL-1) and interleukin-6 (IL-6) in
the hypothalamus
 the “resetting” of the thermoregulatory system,
leading to vasodilatation and increased heat loss.
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12. Therapeutic uses of NSAIDs
Anti-inflammatory agents
Analgesia agents
Anti-pyretic agents
Anti-platelets aggregation agents
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13. Adverse Effects of NSAIDs
Gastro-intestinal issues
Bleeding tendency
Renal toxicity
Cardiac events: COX 2 inhibitors, rofecoxib
Pregnancy: PDA effect, prolong labor
Toxicity: Salicylism
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15. Strong
Morphine
Methadone
Meperidine
Moderate
Codeine
Oxycodone
Weak
Propoxyphene
Mixed (agonists- antagonists)
Buprenorphine, nalbuphine

16. Antagonists
Naloxone
 Naltrexone

17. Mechanism of Action
Opioids produce analgesia by binding to specific
G protein coupled receptors in brain & spinal
cord
μ,δ, κ receptors.
All 3 subtypes are involved in antinociceptive and
analgesic mechanisms at both spinal and
supraspinal levels.

18. Ionic Mechanisms
Presynaptic level close voltage gated Ca+
channels, and reduce transmission.
Post synpatic level open K+ channels (inhibit post
synaptic neurons).

20. EFFECTS
Analgesia
Most powerful analgesics,
Morphine, methadone, meperidine, fentanyl, heroin
Sedation and euphoria
Respiratory depression
Action at medulla lead to respiratory depression.
Antitussive effects
Suppression of the cough reflex
Nausea & vomiting
Activation of chemoreceptor trigger zone

21. Clinical Uses
Analgesia- Fentanyl, morphine
Cough Supression- Codeine,
Dextromethorphan.
Antidiarrheal- Diphenoxylate, Loperamide
Acute Pulmonary edema- Morphine
Anesthesia- Fentanyl
Opioid Dependence- Methadone

22. Side Effects
Constipation with decreased intestinal peristalsis.
Respiratory depression
Smooth muscle
Cause contraction of billiary billiary tract SM, inc.
ureter and bladder tone, red. Uterine tone (prolong
labor)
Miosis
Tolerence
Dependence

23. Toxicity
Respiratory depression
Miosis
Hypotension
Vomiting
Altered consciouss

24. Treatment of Opioid Poisioning
Along with normal protocol, antidote is
NALOXONE and NALTREXONE

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