Analgesic Non Steridal Anti Inflammatory Drugs Narcotic Opioid Analgesia Opioid Receptor Salol Principle

Unpleasant sensation evoked by internal or external noxious stimuli, called analgesia. Analgesic are the drugs that relives the pain (Pain killer) by acting on the peripheral and in CNS pain mechanism.

These classification broadly divided into two parts-

 1) Non Opioid / Non- narcotic / aspirin like Analgesics-

1.     These drugs act on CNS as well as peripheral site.
2.     Do not depress CNS.
3.     Do not produce physical dependence 
4.     No abuse liability. 

2) Opioid / narcotic Analgesics-

1.     These drugs act on CNS but not in Peripheral Site.  
2.     CNS depress.  
3.     Abuse.   
4.     Physical Dependence. 

Screening Methods Of Analgesic Activity On Animal Model

Non Opioid/Non- narcotic/Aspirin like Analgesics

These analgesic possess anti inflammatory activity , also known as Non Steroidal anti inflammatory drugs (NSAID's). These drugs also possess anti-pyretic activity.

Classification of Non-Steroidal Anti-inflammatory Drugs- 

1) Non-selective Cox Inhibitors- 

       a) Salicylates :                               Aspirin 

       b) Proionic acid derivative :         Ibuprofen, ketoprofen, flurbiprofen, naproxen

       c) Aryl acetic acid derivative :     Diclofenac, Aceclofenac

       d) N-antranilic acid derivative :   Mephenamic acid, meclofenamate sodium

       e) Pyrrolo-pyrole derivatives :    Ketorolac

       f) Oxicam derivative :                  Piroxicam, Tenoxicam

       g) Indol derivative :                     Indomethacin, sulindac

       h) Pyrazolone derivatives :        Phenylbutazone, oxyphenbutazone    

2) Selective Cox-2 Inhibitors : Celecoxib, rofecoxib, parecoxib, Etoricoxib  

3) Preferential Cox-2 inhibitors : Nimesulide, meloxicam, nabumetone

4) Analgesics with antipyretic inhibitors 

• a) Para-aminophenol derivatives : paracetamol ( acetaminophen), phenacetin, acetanilide
• b)  Benzoxacine derivatives : Nefopan
• c) Pyrazolone derivatives : Propiphenazone, metamizole

Epithelial Tissue - Types, Structure, Location & Function

Mechanism Of Action Of Non Opioid/Non Narcotic Analgesic (NSAID's)

During Pain, fever and inflammation arachidonic acid is secreted  form phopholipid fraction of cell membrane. This arachidonic acid is converted into prostaglandins via the help of cyclooxygenase (COX 1 and COX- 2). Prostaglandins release other mediators such as Histamine, 5HT and bradykinins.

Mechanism Of Action Of Non Opioid  Non Narcotic Analgesic (NSAID's)

Serotonin - Types, Function, Receptors, Pharmacology, Agonist, Antagonist & uses

Mechanism Of action Of Aspirin: 

Aspirin inhibit the biosynthesis of prostaglandins at cyclooxygenase stage. Aspirin in the only NSAIDs that covalently modifies cyclooxygenase by acetylating Ser-530 of COX-1 and Ser-516 of COX-2. Aspirin is 10 to 100 times more potent against COX-1 prevent both 15-peroxidation and endoperoxide.

Mechanism Of Action Of Non Opioid / Non Narcotic Analgesic (NSAID's)

Mechanism Of action Of Ibuprofen: 

Ibuprofen inhibiting the enzyme cyclooxygenase which converts arachidonic acid to prostaglandins. ibuprofen. Mainly suppressed the formation of cyclic endoperoxides. Cyclic endoperoxide release the many prostaglandins and thromboxane A2 which cause inflammation, vasodilation, platelet aggregation etc.

Respiratory System - Organs, Structure & Function

NSAID's Drugs, Dose Pharmacological Uses And Side Effect

Drug	Dose	Uses	Side effect
Aspirin	0.3-1 gm	Analgesic, antipyretic, acute rheumatism	Nausea, epigastric, gastric mucosal damage & peptic ulceration
Mefenamic acid	500 mg, TDS, oral	Relief of moderately server pain, postoperative pain, primarily dysmenorrhoea	Diarrhea, epigastric distress, rare haemolytic anemia
Meclofenamate sodium	200 -300 mg, oral	Acute and chronic rheumatic arthritis
Ibuprofen	0.6 - 1.2 gm/day, oral	Moderate pain such as : migraine, postoperative pain & dysmenorrhoea. Rheumatic disorder and management of sprains	Gastric discomfort, nausea and vomiting
Flurbiprofen	150 - 200 mg/day oral	Ankylosing spondylytis, osteoarthritis, rheumatoid arthritis	Gastric side effect more than ibuprofen
Naproxen	250 mg - 1 gm, oral	Relief pain in dysmenorrhoea & migraine. also used in musculoskeletal disorder and gout	Gastric discomfort, nausea and vomiting
Ketoprofen	100 - 200 mg oral	Relief pain in dysmenorrhoea & migraine. also used in musculoskeletal disorder and gout	Gastric discomfort, nausea and vomiting
Fenoprofen	800 mg - 2.5 gm, oral	Rheumatic disorder and mild to moderate pain
Diclofenac	50 - 150 mg, oral	Renal colic, gout, rheumatoid arthritis, Ankylosing spondylytis, osteoarthritis etc	Epigastric pain, nausea, headache & dizziness
Tolmetin	400 - 600 mg, TDS, oral	Arthritis & soft tissue inflammation
Piroxicam	20 mg, OD, oral	rheumatoid arthritis & osteoarthritis	Heart burn, nausea, anorexia
Indomethacin	75 - 150 mg, oral	Used in management of mild to moderate pain, rheumatoid arthritis & gout	Gastric irritation, nausea, anorexia, gastric bleeding & diarrhea
Sulindac	100 - 200 mg, TDS, oral	Rheumatoid arthritis, gout, musculoskeletal disorder & bursitis	Side effect less than indomethacin
Ketorolac	50 - 150 mg, oral	used in management in mild to moderate pain, dysmenorrhoea & osteoarthritis	Nausea, abdominal pain, dyspepsia, ulceration, loose stools, pruritus & pain at injection site
Nimesulide	100 mg BD	Used as primarily for short lasting painful inflammatory  condition such as - sports, injuries, sinusitis & other ear - nose - throat disorders, dental surgery, low backache & dysmenorrhoea	Gastrointestinal (epigastric, heart burn, nausea & loose motion)
Meloxicam	7.5 - 15 mg/day	Osteoarthritis and rheumatic arthritis	ulcer complication (Bleeding & perforation)
Nabumetone	500 mg OD	Osteoarthritis, rheumatic arthritis & soft tissue injury	Lower incidence of gastric erosion, ulcer & bleeding
Celecoxib	100 - 200 mg, BD	Osteoarthritis, rheumatic arthritis & acute musculoskeletal pain	Abdominal pain, dyspepsia & mild diarrhea
Rofecoxib	12.5 - 25 mg, OD	Osteoarthritis, rheumatic arthritis, dysmenorrhoea, dental, postoperative and acute musculoskeletal pain	Mild gastrointestinal complications

Opioid/Narcotics Analgesics

Narcotic / opioid analgesics have been developed with morphine like property. Morphine is an alkaloid isolated from Papaver somniferum (Opium).

Classification Of Opioid/Narcotics Analgesics

Papaver somniferum (Opium) contain two types of alkaloids:

1) Phenanthrene Derivatives (Act On CNS) : Morphine, codeine, thebaine

2) Benzisoquinoline Derivatives (Act On Smooth Muscles such as antispamodic action): Papavarine, noscapine (narcotine)

Classification Of Narcotic Analgesic

1) Narcotic agonist analgesic:

      a) Phenanthrene 

             i) Natural opium alkaloids :  Morphine, codeine

            ii) Semi-synthetic derivatives

                   A) Codeine derivatives :    Hydrocodone, oxycodone                   

                   B) Morphine Derivatives : Hydroxymorphone, oxymorphone 

      b) Methadones : Methadone, Propoxyphene

      c) Morphinan : Levorphenol

      d) Phenyl piperidens (meperidine) : Pethidine, Fentanyl, Alfentanil, Sufentanil

2) Narcotic Angonist-Antagonist Analgesics:

      a) Phenanthrenes :  Buprenorphine, Nalbuphine

      b) Morphinan :         Butorphanol

      c) Benzomorphan : Phenazocine, Pentazocine

3) Narcotic antagonist : Naloxone, Naltraxone

Mechanism Of Action Of Narcotic/Opioid Analgesic

Opioids excites neurons from periaqueductal gray matter (PAG) and nucleus reticularis paragigantocellularis (NRPG) which comes to retroventral medulla which contain nucleus raphe magnus (NRM). 5-HT and enkephalin containing neurons runs towards dorsal horn and exert inhibitory influence on transmission (substance P).

Mechanism Of Action Of NarcoticOpioid Analgesic

Opioids directly work on dorsal horn as well as peripheral terminal of nociceptive afferent neurons.

Mechanism Of Action Of µ and δ Receptors: 

Activated µ and δ receptors decrease cAMP formation and open potassium channels than hyperpolarisation take place, that decrease the release of substance P (Neurotransmitter).

Mechanism Of Action Of µ and δ Receptors

Mechanism Of Action Of κ Receptor

Activated κ receptor block the N type calcium ion channel that inhibit the calcium influx and hyperpolarization occur. 

Mechanism Of Action Of κ Receptor

Narcotic / Opioid Analgesic Drugs, Dose Pharmacological Uses And Side Effect

Salol Principle

Nencki introduced salol in 1886.

Salol: Two toxic substance (salicylic acid & phenol) were combined into an ester that goes internally slowly hydrolyzes into intestine and give antiseptic action.

Salol divided into two Category : 

1) True salols: When both component of the ester are active compounds. 

Example- Guaiacol Benzoate, Betol, Salol.

2) Partial salols: Ester in which only the alcohol or the acid is the toxic, active or corrosive portion called partial salol. 

Example- Ethyl salicylate, Methyl salicylate, Creosote carbonate, Thymol carbonate.