Analgesics Part 2

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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