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  2. 2. HISTORY OFOPIOIDS Opium is a dark brown, resinous materialextracted from poppy seeds (Papaver somniferum)…. It has been known from the earliest times, since1500 BC…. Opium eating became a social custom in China inthe 18thcentury…. Opium and laudanum (opium combined withalcohol) were used to treat almost all knowndiseases….
  3. 3. HISTORY CONT’D Serturner, a pharmacist isolated theactive principle of opium in 1806… He named it “MORPHINE” after thegreek God of dreams Morpheus…. Invention of the hypodermic needlein 1856 lead to drug abuse… In the last century a large number ofcompounds have been developedwith morphine like, antagonistic andmixed agonistic-antagonisticproperties…
  4. 4. NATURAL OPIOIDSOCCUR IN 2 PLACES: 1) In the juice of the opium poppy (morphineand codeine) 2) As endogenous endorphins All other opioids are prepared from eithermorphine (semisynthetic opioids such asheroin) or they are synthesized from precursorcompounds (synthetic opioids such asfentanyl)
  5. 5. CLASSIFICATION 1. NATURAL OPIUM ALKALOIDS:Morphine, Codeine 2. SEMISYNTHETIC OPIATES:Diacetylmorphine(heroin), Pholcodeine 3. SYNTHETIC OPIOIDS:Pethidine(meperidine), Fentanyl, Methadone,Dextropropoxyphene, Tramadol
  6. 6. CODEINE: It is methyl morphine, less potent andefficacious than Morphine… Subanalgesic doses suppress cough… Has low affinity for opoid receptors, analgesicaction is ascribed to morphine generated by itsdemethylation by CYP2D6… Well absorbed oraly… Constipation is a prominent side effect, madeuse in diarrhoea… Parenteral preparation not available…
  7. 7. PETHIDINE(MEPERIDINE): Synthesized as an atropine substitute in 1939,chemically unrelated to Morphine… Interacts with opioid receptors, actionsblocked by Naloxone… Primarily used as analgesic and in pre-anaesthetic medication, not useful in coughand diarrhoea… Less potent than Morphine, efficacy iscomparable… Side effects similar to that of Morphine, someatropinic effects also seen…
  8. 8. FENTANYL: A pethidine congener, 80-100 times morepotent than Morphine… Produces few cardiovascular effects, has littletendency to release histamine… Rapid onset, short duration of action… In injectable form almost exclusively used inanaesthesia… Transdermal patches are used for cancer andother types of chronic pain…
  9. 9. METHADONE: A synthetic opioid, chemically dissimilar butpharmacologically very similar to Morphine… Almost all properties are similar to morphine,except for the abuse potential… Due to the slow and persistent nature of actionit is probably incapable of giving a ‘kick’… Used primarily as substitution therapy ofopioid dependence… Another technique is methadone maintenancetherapy in opioid addicts- sufficient dose givenorally to produce high degree of tolerance thatpleasurable effects of Morphine or heroin isnot perceived…
  10. 10. DEXTROPROPOXYPHENE: Chemically related to methadone but similar tocodeine in action… As poor antitussive and constipating action… Its demethylated metabolite is cardiotoxic… Marketed only in combination withparacetamol and other drugs… Delirium and convulsions have occurred inoverdose…
  11. 11. TRAMADOL: Relieves pain by opioid as well as additionalmechanisms… Affinity for µ receptor is low, while that for κand δ is very low… Inhibits reuptake of NA and 5-HT, activatesmonoaminergic spinal inhibition of pain… Analgesic action is only partially reversed bynaloxone… Side effects include dizziness, nausea,sleepiness , dry mouth, sweating and loweringof seizure threshold… Indicated for mild to moderate pain due toinjury, surgery etc. and for chronic pain butnot effective in sever pain…
  12. 12. MECHANISM OFACTION Opioids exert their actions by interacting with specificreceptors present on neurons in the CNS and in peripheraltissues… Release of pain-signaling neurotransmitters in peripheralnociceptive fibres is regulated by endogenous endorphinsor by exogenous opioid agonists by acting presynapticallyto inhibit NT release, causing analgesia… Various Morphine-like and other agonistic andantagonistic drugs have been produced, the action ofwhich cannot be explained on the basis of a single opioidreceptor…
  13. 13. OPIOID RECEPTORS There are three types: 1)µ2)κ3)δ These are G-protein coupled receptors… Mostly located on prejunctional neurones… Various monoaminergic, GABA, glutamatepathways are involved in opioid actions
  14. 14.  Characterized by high affinity towards Morphine… Major receptor for mediating action of Morphine… Endogenous ligands:- 1)Endomorphin 12)Endomorphin 2 other opioid peptides:- β-endorphinenkephalinsdynorphins -funaltrexamine:-relatively selective but irreversibleβµ antagonist… Mainly found in Periaqueductal gray, Thalamus,Nucleus tractus solitarious and Nucleus ambiguus…µ-RECEPTORRecently foundin mammalianbrainLow affinitytowards µreceptor
  15. 15. µ-RECEPTOR: TWO TYPES µ-1 Located outsidespinal cord Responsible forcentral interpretationof pain µ-2 Located throughoutCNS Responsible forrespiratorydepression, spinalanalgesia, physicaldependence, andeuphoria
  16. 16. Κ-RECEPTOR Characterized by high affinity for ketocyclazocineand dynorphin A… Dynorphin A is its endogenous ligand… Two subtypes are functionally important:- κ1 - spinal analgesia- κ2 – supraspinal analgesia(low ceiling)
  17. 17. -RECEPTOR Characterized by high affinity for leucine andmethionine enkephalins… These are its endogenous ligands also… Mainly spinal analgesia, but these receptorsalso seen in limbic areas –responsible fordependence and reinforcing actions… Present in myentric plexus neurons –mediatereduced g.i motility… Naltrindole is a selective antagonist…δ
  18. 18. µ κ δAnalgesiaRespiratory depressionReduced g.i motilitySedationPhysical dependenceMiosisEuphoriaAnalgesiaRespiratorydespressionReduced g.i motilitySedationPhysical dependenceMiosisDysphoria,psychotomimeticAnalgesiaRespiratorydespressionReduced g.i motilityAffective behaviourReinforcing actionActions of the receptors
  19. 19. THANK YOU