2. Contents
• Introduction
• Analgesics and its classification
• Use of opium
• Opioid, its comparison and classification
• Opioid receptors and its working
• Classification of opiates
3. Introduction
An analgesic or painkiller is any member of the group of drugs used
to achieve analgesia, relief from pain.
• Analgesic drugs act in various ways on the peripheral and central
nervous systems.
• Analgesics include paracetamol, the nonsteroidal anti-inflammatory
drugs (NSAIDs) such as the salicylates, and opioid drugs such as
morphine and oxycodone.
• Opioids are substances that act on opioid receptors to produce
morphine-like effects. And used for pain relief, including anesthesia.
4. • Morphine and other opioids (e.g., codeine, oxycodone,
hydrocodone, dihydromorphine, pethidine) all exert a similar
influence on the cerebral opioid receptor system.
• Buprenorphine is a partial agonist of the μ-opioid receptor, and
tramadol is a serotonin norepinephrine reuptake inhibitor (SNRI)
with weak μ-opioid receptor agonist properties.
• Dosing of all opioids may be limited by opioid toxicity (confusion,
respiratory depression, myoclonic jerks and pinpoint pupils),
seizures (tramadol), but opioid-tolerant individuals usually have
higher dose ceilings than patients without tolerance.
5. • When used appropriately, opioids and other central
analgesics are safe and effective,
• The effect of tolerance means that frequent use of
the drug may result in its diminished effect. When
safe to do so, the dosage may need to be
increased to maintain effectiveness against
tolerance, which may be of particular concern
regarding patients suffering with chronic pain and
requiring an analgesic over long periods.
• Opioid tolerance is often addressed with opioid
rotation therapy in which a patient is routinely
switched between two or more non-cross-tolerant
opioid medications in order to prevent exceeding
safe dosages in the attempt to achieve an
adequate analgesic effect.
6.
7. Analgesics
• Analgesics are the medications used to relieve pain
without reducing the consciousness of the patient
• They work by reducing the amount of pain felt and
this is generally achieved by interfering with the way
the pain message is transmitted by the nerves.
• Analgesics will not treat the cause of the pain but
they will provide temporary relief from pain symptoms
9. The use of Opium
• Opium was first discovered in pre-biblical
times; derived from the opium poppy
• Opium was widely used from the middle ages
in a medicine known as “tincture of opium” or
Laudanam
11. • Opium, narcotic drug that is obtained from the unripe
seedpods of the opium poppy (Papaver somniferum), a plant
of the family Papaveraceae.
• Opium is obtained by slightly incising the seed capsules of the
poppy after the plant’s flower petals have fallen. The slit
seedpods exude a milky latex that coagulates and changes
colour, turning into a gumlike brown mass upon exposure to
air.
• This raw opium may be ground into a powder, sold as lumps,
cakes, or bricks, or treated further to obtain derivatives such
as morphine, codeine, and heroin.
• Opium and the drugs obtained from it are called opiates.
12. What are Opioids
• All drugs with morphine-like actions are described as Opioids.
• Opioids were originally derived from the opium poppy (papaver somniferum) which has 25 alkaloids
• Only two of the alkaloids have any analgesic action: morphine and codeine
GlaxoSmithKline supplies ~25% of the world's medicinal opiate needs from
opium poppies grown by farmers in Tasmania
• Opioids are often used as medicines because they contain
chemicals that relax the body and can relieve pain.
• Prescription opioids are used mostly to treat moderate to severe pain,
though some opioids can be used to treat coughing and diarrhea.
• Opioids can be highly addictive, and overdoses and death are common.
• Heroin is one of the world's most dangerous opioids, and is never used
as a medicine in the United States.
13. • All of these drugs work by impersonating brain chemicals
known as endorphins (En-DOR-fins). Endorphins serve as
messengers between nerve cells. As such, they are
neurotransmitters.
• When one brain cell releases endorphin molecules, they
float across a gap to another cell. There they bind to
receptor molecules. These sit on the outside of the target
cell. The endorphin’s shape fits into the receptor like a key
into a lock. When they connect, the receptor now can turn
on — or off — activities inside its host cell.
• Receptors for endorphins exist in the brain’s pleasure center
and on nerve cells that relay pain signals. So when the body
releases its natural endorphins, they not only fight pain but
also contribute to a feeling of pleasure.
14. How opioid works?
• Opioid drugs work by binding to opioid
receptors in the brain, spinal cord, and other
areas of the body.
• They reduce the sending of pain messages
to the brain and reduce feelings of pain.
• Opioids are used to treat moderate to
severe pain that may not respond well to
other pain medications.
15. • Heroin and other opioid drugs flood the brain’s
opioid receptors, creating a high or euphoric
feeling.
• When a person uses these kinds of drugs regularly,
the number of opioid receptors in his or her brain
increases to the point where natural endorphins are
no longer capable of stimulating them.
• The more opioid receptors a person has, the more
opioid drugs are needed to get high and, eventually,
to simply feel normal.
• This is called building a tolerance.
16. • When not all opioid receptors are
activated, it can create feelings of
anxiety, depression and physical
pain or illness — what’s called
withdrawal.
• Once someone has developed a
tolerance for opioids, he or she
requires an increasing amount of
drugs to avoid the sensation of
withdrawal.
17. • One of the effects of opioid drugs on
the body is respiratory depression, or
slowed breathing.
• Overdosing on opioids can be fatal
because too much of the drug can
reduce the number of breaths a person
takes, to the point that he or she stops
breathing altogether.
18. • Analgesics are for anyone with pain, and
that includes almost everyone with arthritis
or a related condition.
• Opioids have been increasingly prescribed
for chronic pain, but unlike NSAIDS, opioids
don’t cause gastrointestinal bleeding.
• But opioid use for chronic (non-cancer) pain
is controversial because they’re associated
with a high risk of abuse, addiction and
accidental overdose.
• Certain factors predict the suitability of long-
term opioid use for individuals with chronic
pain.
19. A tool called DIRE
(Diagnosis, Intractability, Risk and
Efficacy)
- helps doctors to assess those factors –
including the patient’s cause of pain,
psychological health, chemical health and
social support.
22. Opioid or Narcotic?
OPIOID
• Natural, semi-synthetic and synthetic drugs that relieve pain by binding to opioid receptors in
the nervous system
• While synthetic opioids are manufactured chemically, semi-synthetic opioids are a hybrid
resulting from chemical modifications to natural opiates.
• Examples of synthetic opioids include fentanyl and methadone, while oxycodone and
hydrocodone are examples of semi-synthetic opioids.
NARCOTIC
• The narcotic definition pertains to an agent that produces insensibility or narcosis.
• However, due to the negative association the term narcotic has with illegal drugs, it has fallen
out of use in medical settings. (Obsolete term for opioid) including opioids, cocaine and other
substances
23. OPIATE:
• An opiate is a drug naturally derived from the flowering opium poppy plant.
• Examples of opiates include heroin, morphine and codeine (thus excluding synthetic
opioids such as fentanyl)
OPIOID:
• An opioid is a broader term that includes opiates and refers to any substance,
natural or synthetic, that binds to the brain’s opioid receptors – the parts of the brain
responsible for controlling pain, reward and addictive behaviors.
• Some examples of synthetic opioids include the prescription painkillers hydrocodone
(Vicodin) and oxycodone (OxyContin), as well as fentanyl and methadone.
Opiate or Opioid? ”All opiates are opioids, not all opioids are opiates.”
24.
25. OPIOID • Compound with morphine-like activity
OPIATE • Substance extracted from opium
• Exudate of unripe seed capsule of Papaver
somniferum
• Contain 2 types of alkaloids
PHENANTHRENE
DERIVATIVES
• Morphine (10% in opium)
• Codeine (0.5% in opium)
• Thebaine (0.2% in opium), (Nonanalgesic)
BENZOISOQUINOLINE
DERIVATIVES
• Papaverine (1%)
• Non anaIgeslic
• Noscapine (6%)
26. Classification of opiates ( Classification of Opioids According to Source )
NATURAL OPIATES • Are the alkaloids contained in the latex of opium : morphine,
codeine, papaverine and thebaine;
SEMI- SYNTHETIC
OPIATES
• Created from the natural opiates, and are derived from
morphine, codeine etc. :
• hydromorphone, hydrocodone, oxycodone, oxymorphone,
desomorphine, diacetylmorphine (Heroin), nicomorphine,
dipropanoylmorphine, benzylmorphine and ethylmorphine;
FULLY SYNTHETIC
OPIATES
• fentanyl, pethidine, methadone, tramadol and propoxyphene;
ENDOGENOUS OPIOID
PEPTIDES
• endorphins, enkephalins, dynorphins, and endomorphins.
27. Classification of Opioids According to Chemical structure:
Phenanthrenes • morphine, codeine, heroin, hydromorphone, and
oxycodone
Benzomorphans • pentazocine and phenazocine
Diphenylpropylamines • propoxyphene, methadone, levo-α-acetylmethadol,
loperamide
Phenylpiperidines • meperidine, also known as pethidine
Anilidopiperidines • fentanyl, alfentanil, and sufentanil
Oripavine derivatives • etorphine, dihydroetorphine, and buprenorphine
Morphinan derivatives • levorphanol and butorphanol
28. WEAK OPIOIDS STRONG OPIOIDS
• codeine
• dihydrocodeine
• tramadol
•morphine
•oxycodone
•methadone
•fentanyl
•pethidine
Opioids are divided into 2 groups:
These opioids are available in different formulations such as a liquid or syrup, quick-acting
tablets and capsules, slow-release tablets and capsules, patches to put on your skin, or
injections, which may be under your skin, into a vein or into a muscle.
Classification of Opioids According to Strength:
29. • The opioid receptors are named μ, κ, δ, σ, and ε.
• Opioids can act as agonists, antagonists, agonists/antagonists, or partial agonists
Classification of Opioids According to their effects on opioid receptors:
30.
31. Opioid Antagonists
1) Pure antagonists: Naloxone, Naltrexone and Nalmefene
• Affinity for all receptors
• Can displace opioids bound to a-receptors
• No action on normal person but reverses poisoning and withdrawl symptoms in
addicts
I) Mixed agonists and anti-agonists: Nalorphine, Pentazocine, Butorphanol and
Nalbuphine
II) Partial/ weak u-agonists and k-antagonists: Buprenorphine
36. Morphine
• Morphine is a pain medication of the opiate variety which is found
naturally in a number of plants and animals
• It acts directly on the central nervous system (CNS) to decrease the
feeling of pain and can be taken for both acute and chronic pain
• It is frequently used for pain from myocardial infarction and during
labour.
• Maximum effect is around 20 minutes when given intravenously and
60 minutes when given by mouth, while duration of effect is 3–7 hours.
• Potentially serious side effects include a decreased respiratory effort and
low blood pressure. Morphine has a high potential for addiction and
abuse. If the dose is reduced after long-term use, withdrawal may occur.
• Common side effects include drowsiness, vomiting, and constipation
37. Morphine (Pharmalogical actions) - CNS
ANALGESIA:
• Strong analgesic
• Visceral pain is relieved better than somatic pain
• Degree of analgesia increases with dose
• Nociceptive pain is better relieved than Neurotic pain
• Associated reactions to pain are also relieved –
apprehension, fear and autonomic effects
• Tolerance to pain is better
38. Morphine – Analgesia action
• Two components – Spinal and supraspinal
• Inhibits release of excitatory transmitters from
primary afferents – At Substantia gelatinosa of
dorsal horn
• Exerted through Interneurons – gating of pain
• At super-spinal level in cortex, midbrain and
medulla – alter processing and interpretation and
send inhibitory impulses through descending
pathway
39. • The first pain modulatory
mechanism called the
"Gate Control" theory was
proposed by Melzack and
Wall in the mid 1960s.
• The concept of the gate
control theory is that non-
painful input closes the
gates to painful input, which
results in prevention of the
pain sensation from
traveling to the CNS (i.e.,
non-noxious input
[stimulation] suppresses
pain).
40. • Gate control theory of pain is the idea that
physical pain is not a direct result of activation
of pain receptor neurons, but rather, its
perception is modulated by interaction between
different neurons
• Nerve fibers (A delta (fast channels)) and C
fibers (slow channels) transmit pain impulses
from the periphery
• Impulses are intercepted in the dorsal horns of
the spinal cord, the substantia gelatinosa
• In this region, cells can be inhibited or facilitated
to the T-cells (trigger cells)
41. Reducing pain with morphine
• Most painkillers have an upper threshold – at
a certain point, they are ineffective. However,
morphine is able to block more and more
pain with increasing doses.
• Morphine reduces pain and is often given to
patients in hospitals and the wounded on
battle fields for this purpose.
• The morphine molecule has a similar shape
as the neurotransmitters in the neurons
transmitting pain signals, but the morphine
molecule will not carry the electrical charge
forward to the next neuron once it is in the
receptor, thus blocking the pain signal.
• When morphine binds to opioid receptors, it
activates a series of events in which the GPCR
activates its corresponding g-protein and
triggers an increased conduction through
potassium channels, decreased conduction
through calcium channels, and an inhibition of
adenylyl cyclase, also known as adenylate
cyclase.
• Together, these changes in our nervous system
reduce the effect of our body’s signaling
systems that transmit pain.
42. • Codeine is an opioid (methylmorphine) with
a relatively limited analgesic effect.
• It doesn’t cause significant respiratory
depressions but has good antitussive
properties
• Codeine raises the stimulus threshold of the
cough center and thus has a cough
suppressing effect
• It has less potent analgesic properties
Codeine
Antitussives are drugs that suppress coughing, possibly by reducing the
activity of the cough center in the brain. Antitussive agents are used to
relieve dry cough.
43. • In most humans 10% of a codeine dose is transformed to morphine through
demethylation in the liver. This explains the analgesic effect that is absent in
individuals with the respective genetic traits.
• Codeine sulfate is an opioid analgesic, related to morphine, but with less potent
analgesic properties. Codeine is selective for the mu receptor, but with a much
weaker affinity than morphine.
• The analgesic properties of codeine have been speculated to come from its
conversion to morphine, although the exact mechanism of analgesic action remains
unknown.
44. Pethidine (Meperidine)
Morphine vs Pethidine:
• 1/10th as potent as Morphine, but efficacy is
similar
• Produces as much sedation, euphoria and
respiratory depression equianalgesic dose and
similar abuse potential
• Less spasmodic action in smooth muscles – less
miosis, constipation and urinary retention
• Rapid but short duration of action (2-3 hours)
• Vagolytic effect – Tachycardia
• Devoid of antitussive action
• Less histamine release – safer in asthmatics
• Better oral absorption
45. Pethidine – contd.
Pharmacokinetics
• Well absorbed orally, bioavailability 50%
• Effects appear in 10-15 min after oral absorption
• On parental administration actions last for 2-3 hours
• Metabolized in liver – mepiridinic acid norpathedine
• Norpathedine accumulates on chronic use
• Excreted in urine
46. Pethidine – contd.
Adverse effects:
• Similar to Morphine
• Atropine like effects – dry mouth, blurred vision, tachycardia
• Overdose – tremors, mydriasis, delirium and convulsion due to
norpethidine accumulation
Uses:
• Analgesic as substitute of Morphine
• Preanesthetic medication
• As analgesic during labour – less fatal respiratory depression
• Dose 50-100 mg IM/SC, oral – 50-100 mg tabs
47. Methadone
• Chemically dissimilar but similar in most of
pharmacological actions – analgesic, respiratory depression
etc.
• High action orally as well as parenterally
• Single dose effect is – same with Morphine including the
duration of action
• Cumulation – on repeated administration (t1/2 24-36 hours)
• Highly bound to plasma protein (80-90%)
• Metabolized in liver by – demethylation and cyclization
• Excreted in urine
• Used as substitution therapy as opioid dependence: 1:4 mg
and 1:20 mg of Morphine and Pethidine
• Codeine is used as substitution in Methadone addiction
48. Tramadol
• Centrally acting analgesics
• Very low action on opioid receptors
• Other mechanisms involved in analgesic action - spinal inhibition
of pain
• Effective both orally and I V (100 mg = 10 mg Morphine)
• Side effects are similar to Morphine but less prominent
• Well tolerated and low abuse potential
• Only partially reversed by Naloxone
• Used in chronic neuropathic pain and short diagnostic procedures
• Dose: 50-100 mg IM/IV/Oral
49.
50.
51. Medicated assisted treatment for Opioid use
disorder
• Medication-assisted treatment (MAT)—a combination of
psychosocial therapy and U.S. Food and Drug
Administration-approved medication—is the most effective
intervention to treat opioid use disorder (OUD)
• OUD is a chronic brain disease caused by the recurrent use of
opioids, including prescription drugs, such as oxycodone and
hydrocodone, and illicit substances such as heroin.
• OUD includes dysfunction of the brain reward system,
motivation, memory, and related circuitry and is reflected in
individuals “pathologically pursuing reward and/or relief by
substance use and other behaviors.”
52. What is MAT?
• MAT pairs nondrug therapies, such as counseling or cognitive behavioral
therapy, with an FDA-approved medication to treat OUD. These drugs—
methadone, buprenorphine, and naltrexone—are available in various product
formulations and doses.
53. Mechanisms of action
• Receptors, which are found on
human cells, are places where a
drug or substance made by the body
binds to either cause or block an
effect. Methadone and
buprenorphine are opioid agonists,
meaning they activate or occupy the
mu-opioid receptor, the same one
activated by heroin.
54. • Methadone is a full agonist. By fully occupying the mu-opioid receptor,
methadone lessens the painful symptoms of opiate withdrawal and blocks the
euphoric effects of other opioid drugs.
• Buprenorphine is a partial agonist, meaning it does not completely bind to the
mu-opioid receptor. As a result, buprenorphine has a ceiling effect, meaning that
its effects will plateau and will not increase even with repeated dosing.
Buprenorphine does not produce euphoria and does not have some of the
dangerous side effects associated with other opioids.
• Naltrexone is an opioid antagonist, meaning that it covers, rather than activates,
the mu-opioid receptor, effectively blocking the effects of opioids if they are
used. Opioid antagonists do not produce any euphoric effects, so no physical
dependence is associated with their use.
