INTRODUCTION

 The term opioid refers to all compounds

related to “opium” i.e.; natural product
derived from “poppy”.
 Opiates are drugs derived from opium and
include the natural products and many
semi- synthetic derivatives.
 Opioid analgesics are also known as
“NARCOTICS”.
 The term “NARCOTIC”, is derived from
Greek word, for “stupor”, it originally
refers to any drug that induce sleep but
now it is associated with opioids.
• Opioids are a class of central acting
analgesics that provide powerful dose
dependant relief of moderate to severe
pain.
• They include compounds having no
cardiac or hepato-renal toxic effects and
are approved for various routes of
administration.
 ENDOGENOUS OPIOID
PEPTIDES

Opioids produce analgesia through actions

at receptors in the CNS that contains
peptides with opioid like pharmacologic
properties.
The term used for these substances is
“endogenous opioid peptides”.
“FAMILIES OF ENDOGENOUS
PEPTIDES”
a. Endorphins
b. Enkephalins (met-enkephalins ,leu-
enkephalins)
c. Dynorphins
“LOCATION OF PEPTIDES”

CNS
Adrenal medulla
Gastric glands
Intestine
The peptides have multiple roles:-
• Pain modulation
• Neurohumoral Transmission
• Neurohormonal Effects
 “PRECURSORS”

i. POMC
ii. Preproenkephalin
iii. Preprodynorphins
 POMC:-
 (Pro-opiomelanocortin (POMC) is a
precursor polypeptide with 241 amino acid residues
It contains met-enkephalin sequence, β-endorphins
and several non-opioid peptides.
 Preproenkephalin:-
It contains six copies of met-enkephalin and single
copy o leu-enkephalin.
 Preprodynorphin:-
It contains three peptides of different lengths that begin
with leu-enkephalin sequence i.e.; dynorphin A,
dynorphin B and neodorphin.
“OPIOIDS RECEPTORS”
1. μ (mu)
2. ĸ (kappa )
3. δ (delta)
These receptors are found in CNS, GIT and
to a lesser degree in peripheral tissues.
 OPIOID RECEPTORS
AFFINITY
RECEPTORS FUNCTIONS OPIOID PEPTIDE
AFFINITY
μ Supra-spinal and spinal Endorphins >
analgesia, sedation, Enkephalins >
respiratory inhibition… dynorphins.

ĸ Supra-spinal and spinal Enkephalins >

analgesia, modulation Endorphins and
of hormones and Dynorphins.
neurotransmitter
release.

δ Supra-spinal and spinal Dynorphins >>

analgesia, Endorphins and
psychotomimetic Enkephalins.
effects, slowed GI
transit.
 RECEPOR SUB-TYPES:-

(a) μ1 μ2
(b) δ1 δ2
(c) ĸ1 ĸ2
Genes encoding only one subtype from
each of the μ,δ and ĸ receptor families have
been isolated and characterized thus far.
“MECHANISM OF ACTION”

• All opioid receptors are G protein-coupled

receptors. Their stimulation inhibits adenylyl
cyclase resulting in decrease intra cellular cAMP.
• They also facilitate the opening of K+ channels,
causing efflux of K+, leading to hyper
polarization.
• In addition, they inhibit opening of Ca+ channels
which in turns decreases the release of
neurotransmission and thus relief pain. Various
neurotransmitters include Dopamine, glutamate,
GABA ,NA, 5HT and substance P are involved in
transmission of pain impulses.
PHARMACOKINETICS:-

 ROUTES OF ADMINISTRATION:-
Most opioids analgesics can be given by
different routes such as:
o Oral
o Subcutaneous
o Intra muscular
o Nasal
o Oral Mucosa via lozenges
o Transdermal
• ABSORPTION:-
Most opioid analgesics are well
absorbed when given by subcutaneous,
intramuscular and oral route.
They mostly undergo first pass metabolism.
• DISTRIBUTION:-
All the opioids bind to plasma protiens
with varying affinity.
the drugs rapidly leave the blood
compartment
And localize in high conc. in tissues that are highly
perfused such as brain, lungs, liver, kidneys &
spleen.
• METABOLISM:-
The opioids are converted into large parts
to polar metabolites mostly glucoronides which
are then readily excreted by the kidneys.
• EXCRETION:-
Polar metabolites, including glucoronide
conjugates of opioid analgesics are excreted
mainly in urine. Sometimes it may also be
found in bile.
 “CLASSIFICATION”
 Natural opium alkaloids:
A) Phenanthrene group:
Morphine
Codeine
Thebaine
B) Benzyl isoquinoline group:
Papaverine
Noscapine
Semi Synthetic derivatives:
(a)Morphine derivative:
Diamorphine
Ethylmorphine
Heroin(diacetylmorphine)
(b) Codeine derivatives:
Dihydrocodiene
Pholcodiene
Nalbuphine
Hydromorphone
Oxymorphone
Hydrocodone
(c)thebaine derivatives:-
Buprenorphine
 Synthetic compounds:
(a) Phenylpiperidine group:-
Pethidine
Alphaprodine
Fentanyl
Ethoheptazine
Diphenoxylate
Loperamide

(b) Diphenylheptane group:-

Dextropropoxyphene
Methadone
(c) Morphinan group:-
Levorphanol
Dextromethorphan
Levomethorphan
Butorphanol
(d) Benzomorphan group:-
Pentazocine
Phenazocine
(e) Miscellaneous groups:-
Dextromoramide
Dipipanone
 THERAPEUTIC
CLASSIFICATION OF OPIOID
I. HIGH EFFICAY ANALGESICS FOR PAIN:
Morphine Methadone
Pethidine Phenazocine
Buprenorphine Levorphanol
Dextromoramide Dipipanone
II. LOW EFFICACY ANALGESICS FOR MILD
AND MODERATE PAIN:
Codeine Dihydrocodiene
Dextropropoxyphene Pentazocine
Nalbuphine
 III. HIGH EFFICACY OPIOIDS FOR SURGERY/
ANESTHESIA:-
Fentanyl Alfentanil
Phenoperidine Piritamide
IV. ANTITUSSIVE OPIOIDS:-
(a) relatively less addictive:
Codeine Dihydrocodiene
Pholcodiene
(b) non addictive:
Dextromethorphan
Noscapine
V. ANTI DIARRHEAL OPIOIDS:
Loperamide Diphenoxylate
 OPIOID ANTAGONISTS
 Naloxone
Nalmefene
Naltrexone
Nalorphine
Diprenorphine
 “SYSTEMIC EFFECTS OF
OPIOIDS”
ANALGESIA:-
Opioids are used primarily for analgesia.
This analgesia occurs without loss of
consciousness.
Continuous dull pain is relived more effectively
than sharp intermittent pain.
Sufficient amounts of opioids can also relive
the severe pain.
EFFECT ON HYPOTHALAMUS:-
Opioids alter the equilibrium point on the
hypothalamic heat regulatory mechanism such that
body temperature usually falls slightly.
However, chronic high dosage may increase body
temperature.
MIOSIS:-
Opioid analgesics cause constriction of pupil.
Therapeutic doses of morphine increase
accommodation & lowers intra ocular
pressure in normal & glaucomatous eyes.
RESPIRATORY DEPRESSION:-
Opioids depress respiration at least partly by
direct effect on the brain stem respiratory centers.
Therapeutic doses of opioids depresses all phases
of respiratory activity & also may produce irregular
& periodic breathing.
Combination of opioids with other medicines such
as general anesthetics, alcohol, or sedative,
hypnotics may increase the risk of respiratory
depression.
COUGH:-
Opioids also suppress the cough reflex partly
by their direct action on cough center in
medulla.
NAUSEA AND VOMITING:-
OPIOD analgesics can activate the brainstem
chemoreceptor trigger zone to produce nausea
& vomiting.
CVS EFFECTS:-
Most opioids have no direct effect on heart but
sometimes bradycardia.
Opioids are also observed to well maintain
blood pressure in patients receiving them.
GIT EFFECTS:-
Constipation has long been recognized as an
effect of opioids.
UTERUS:-
They also may prolong labor.

PRURITIS:-
Therapeutic uses of opioid analgesics
produce flushing and warming of the skin
accompanied by sweating and itching.