2. HISTORY OF
OPIOIDS
Opium is a dark brown, resinous material
extracted from poppy seeds (Papaver somniferum)
….
It has been known from the earliest times, since
1500 BC….
Opium eating became a social custom in China in
the 18th
century….
Opium and laudanum (opium combined with
alcohol) were used to treat almost all known
diseases….
3. HISTORY CONT’D
Serturner, a pharmacist isolated the
active principle of opium in 1806…
He named it “MORPHINE” after the
greek God of dreams Morpheus….
Invention of the hypodermic needle
in 1856 lead to drug abuse…
In the last century a large number of
compounds have been developed
with morphine like, antagonistic and
mixed agonistic-antagonistic
properties…
4. NATURAL OPIOIDS
OCCUR IN 2 PLACES:
1) In the juice of the opium poppy (morphine
and codeine)
2) As endogenous endorphins
All other opioids are prepared from either
morphine (semisynthetic opioids such as
heroin) or they are synthesized from precursor
compounds (synthetic opioids such as
fentanyl)
6. CODEINE:
It is methyl morphine, less potent and
efficacious than Morphine…
Subanalgesic doses suppress cough…
Has low affinity for opoid receptors, analgesic
action is ascribed to morphine generated by its
demethylation by CYP2D6…
Well absorbed oraly…
Constipation is a prominent side effect, made
use in diarrhoea…
Parenteral preparation not available…
7. PETHIDINE(MEPERIDINE):
Synthesized as an atropine substitute in 1939,
chemically unrelated to Morphine…
Interacts with opioid receptors, actions
blocked by Naloxone…
Primarily used as analgesic and in pre-
anaesthetic medication, not useful in cough
and diarrhoea…
Less potent than Morphine, efficacy is
comparable…
Side effects similar to that of Morphine, some
atropinic effects also seen…
8. FENTANYL:
A pethidine congener, 80-100 times more
potent than Morphine…
Produces few cardiovascular effects, has little
tendency to release histamine…
Rapid onset, short duration of action…
In injectable form almost exclusively used in
anaesthesia…
Transdermal patches are used for cancer and
other types of chronic pain…
9. METHADONE:
A synthetic opioid, chemically dissimilar but
pharmacologically very similar to Morphine…
Almost all properties are similar to morphine,
except for the abuse potential…
Due to the slow and persistent nature of action
it is probably incapable of giving a ‘kick’…
Used primarily as substitution therapy of
opioid dependence…
Another technique is methadone maintenance
therapy in opioid addicts- sufficient dose given
orally to produce high degree of tolerance that
pleasurable effects of Morphine or heroin is
not perceived…
10. DEXTROPROPOXYPHENE:
Chemically related to methadone but similar to
codeine in action…
As poor antitussive and constipating action…
Its demethylated metabolite is cardiotoxic…
Marketed only in combination with
paracetamol and other drugs…
Delirium and convulsions have occurred in
overdose…
11. TRAMADOL:
Relieves pain by opioid as well as additional
mechanisms…
Affinity for µ receptor is low, while that for κ
and δ is very low…
Inhibits reuptake of NA and 5-HT, activates
monoaminergic spinal inhibition of pain…
Analgesic action is only partially reversed by
naloxone…
Side effects include dizziness, nausea,
sleepiness , dry mouth, sweating and lowering
of seizure threshold…
Indicated for mild to moderate pain due to
injury, surgery etc. and for chronic pain but
not effective in sever pain…
12. MECHANISM OF
ACTION
Opioids exert their actions by interacting with specific
receptors present on neurons in the CNS and in peripheral
tissues…
Release of pain-signaling neurotransmitters in peripheral
nociceptive fibres is regulated by endogenous endorphins
or by exogenous opioid agonists by acting presynaptically
to inhibit NT release, causing analgesia…
Various Morphine-like and other agonistic and
antagonistic drugs have been produced, the action of
which cannot be explained on the basis of a single opioid
receptor…
13. OPIOID RECEPTORS
There are three types: 1)µ
2)κ
3)δ
These are G-protein coupled receptors…
Mostly located on prejunctional neurones…
Various monoaminergic, GABA, glutamate
pathways are involved in opioid actions
14. Characterized by high affinity towards Morphine…
Major receptor for mediating action of Morphine…
Endogenous ligands:- 1)Endomorphin 1
2)Endomorphin 2
other opioid peptides:- β-endorphin
enkephalins
dynorphins
-funaltrexamine:-relatively selective but irreversibleβ
µ antagonist…
Mainly found in Periaqueductal gray, Thalamus,
Nucleus tractus solitarious and Nucleus ambiguus…
µ-RECEPTOR
Recently found
in mammalian
brain
Low affinity
towards µ
receptor
15. µ-RECEPTOR: TWO TYPES
µ-1
Located outside
spinal cord
Responsible for
central interpretation
of pain
µ-2
Located throughout
CNS
Responsible for
respiratory
depression, spinal
analgesia, physical
dependence, and
euphoria
16. Κ-RECEPTOR
Characterized by high affinity for ketocyclazocine
and dynorphin A…
Dynorphin A is its endogenous ligand…
Two subtypes are functionally important:
- κ1 - spinal analgesia
- κ2 – supraspinal analgesia(low ceiling)
17. -RECEPTOR
Characterized by high affinity for leucine and
methionine enkephalins…
These are its endogenous ligands also…
Mainly spinal analgesia, but these receptors
also seen in limbic areas –responsible for
dependence and reinforcing actions…
Present in myentric plexus neurons –mediate
reduced g.i motility…
Naltrindole is a selective antagonist…
δ
