OPIOID AGONIST and ANTAGONIST
PAIN
- Pain is a physiological and emotional experience
characterized by unpleasant feelings, usually
associated with trauma or disease.
- Pain can be classified as either Acute or Chronic
Pain
- Pain can also be classified according to its
source: Nociceptor Pain and Neuropathic Pain
GENERAL PRINCIPLES OF PAIN MANAGEMENT
- The immediate goal of pain management is to
reduce pain to a level that allows the client to
perform reasonable activities of daily living
(ADLs) such as sleeping, eating, and normal
physical activities.
➢ The client should be considered the
expert on his or her own pain;
➢ Pain management is a client right and
should be based on the client’s goals.
Nonpharmacological interventions
such as massage or the application of
heat or cold should be encouraged in
pain management.
➢ Dosing should be individualized and
Adverse effects from pain
medications should be anticipated
and prevented whenever possible.
➢ Around-the-clock dosing for
moderate to severe pain should be
implemented
PAIN PHYSIOLOGY
ANALGESICS
- medications used to relieve pain.
- The two basic categories of analgesics are the
opioids and the non-opioids.
- An opioid analgesic is a natural or synthetic
morphine-like substance capable of reducing
severe pain.
- Opioids are narcotic substances, meaning that
they produce numbness and stupor-like
symptoms.
OPIODS
- Natural opiates and semi-synthetic alkaloids
➢ derived from the opium poppy
- Pharmacologically similar synthetic surrogates,
and endogenous peptides.
- Classified on the basis of their interaction with
opioid receptors;
1. Agonists
2. Mixed agonist-antagonists
3. Antagonists
MECHANISM OF ACTIONS
- Pharmacologic actions of opiates and synthetic
opioid drugs are effected via their interactions
with endogenous opioid peptide receptors.
➢ The opioid analgesic effects occur
through their interactions with specific
receptors for endogenous peptides in
the CNS and peripheral tissues.
OPIOID RECEPTORS
- The major effects of the opioids are mediated
by three receptor families, which are commonly
designated as μ (mu), κ (kappa), and δ (delta).
➢ The analgesic properties of the opioids
are primarily mediated by the μ
receptors that modulate responses to
thermal, mechanical, and chemical
nociception.
➢ The κ receptors in the dorsal horn also
contribute to analgesia by modulating
the response to chemical and thermal
nociception.
➢ The enkephalins interact more
selectively with δ receptors in the
periphery.
ENDOGENOUS OPIOID PEPTIDES
- Three distinct families of peptides have been
identified: the enkephalins, the endorphins, and
the dynorphins.
- These precursors are now designated as
proenkephalin (also proenkephalin A),
proopiomelanocortin (POMC), and
prodynorphin (also proenkephalin B)
THREE DISTINCT FAMILIES OF PEPTIDES
1. ENKEPHALINS
- 5 amino acids long
- Also have met enkephalin (methionine at 5'
position) and leu enkephalin (leucine at 5'
position)
- Neuromodulators since they are small
peptides, it was found that they came from
larger peptides (pro enkephalins)
- Proenkephalin gene codes for peptide 276
amino acid in length
- Cleavage of proenkephalin gives 4 to 5
pieces of activated enkephalins
2. ENDORPHIN
- 30 amino acid peptide
- last 5 amino acids are the same sequence
as enkephalins
- Neurohormones
- Conservation between species
- Little difference in humans
3. DYNORPHIN
- Prodynorphin yields more than seven
peptides that contain leuenkephalin,
including dynorphin A(1-17), which can be
cleaved further to dynorphin A(1-8),
dynorphin B(1-13), and a- and b-
neoendorphin, which differ from each
other by only one amino acid.
- Dynorphin A is also found in the dorsal
horn of the spinal cord.
- Increased levels of dynorphin occur in the
dorsal horn after tissue injury and
inflammation. This elevated dynorphin level
is proposed to increase pain and induce a
state of long-lasting sensitization and
hyperalgesia
➢ -Receptors → analgesia, sedation, miosis,
euphoria, respiratory depression, GI motility
depression & dependence
➢ -Receptors → analgesia, sedation, miosis &
dysphoria
➢ -Receptors, more important in the periphery,
may contribute to analgesia
STRONG AGONISTS
1. MORPHINE
- The gold standard of analgesics used to
relieve severe or agonizing pain & suffering
- Acts directly on the CNS
- A high potential for addiction; tolerance
and both physical and psychological
dependence develop rapidly
• MECHANISM OF ACTIONS
- Interaction with opioid receptors in the CNS
& GIT →
1) hyperpolarization of nerve cells → --
nerve firing
2) presynaptic inhibition of transmitter
release
➢ At -receptors →  release of
substance P which modulates pain
perception -- release of many
excitatory transmitters from nerve
terminals carrying painful stimuli
• PHARMACOLOGICAL EFFECTS
1. CNS:
a. Analgesia & sedation
b. Euphoria
c. Respiratory depression
d. Depression of cough reflex (antitussive)
e. Nausea & vomiting
f. Miosis
2. Smooth muscles (GIT, urinary T., bronchi &
uterus)
3. Cardiovascular & cerebral b.v.
4. Histamine release
5. Hormonal actions
6. Straub tail reaction
 • TOLERANCE and DEPENDENCE
- Repeated administration → tolerance to
the analgesic, sedative, euphoric &
respiratory depressant effects.
- Tolerance DOES NOT develop to the
pupillary constriction & constipation.
- Repeated administration → tolerance to
the analgesic, sedative, euphoric &
respiratory depressant effects.
- Tolerance DOES NOT develop to the
pupillary constriction & constipation.
- Morphine rapidly enters all body tissues,
including the fetus of pregnant women.
- ✓ Infants born of addicted mothers show
physical dependence on opiates and exhibit
withdrawal symptoms if opioids are not
administered.
- Morphine is the least lipophilic opioid →
only a small % crosses the BBB
• ADVERSE EFFECTS
1. Severe respiratory depression
2. Other effects: vomiting, dysphoria &
allergy-enhanced hypotensive effects
3. Elevation of intracranial pressure,
particularly in head injury, can be serious.
Morphine should be used with caution in
patients with asthma, liver disease, or renal
dysfunction
• TOLERANCE and PHYSICAL DEPENDENCE
- Repeated use produces tolerance to the
respiratory depressant, analgesic, euphoric,
and sedative effects of morphine.
- Tolerance usually does not develop to the
pupil-constricting and constipating effects
of the drug.
- Physical and psychological dependence can
occur with morphine and with some of the
other agonists.
- Withdrawal produces a series of
autonomic, motor, and psychological
responses that incapacitate the individual
and cause serious symptoms, although it is
rare that the effects cause death.
• DRUG INTERACTIONS
- Drug interactions with morphine are rare,
although the depressant actions of
morphine are enhanced by phenothiazines,
monoamine oxidase inhibitors (MAOIs),
and tricyclic antidepressants
ADVERSE EFFECTS OBSERVED IN INDIVIDUALS TREATED
WITH OPIOIDS
2. DIAMORPHINE (HEROIN; DIACETYLMORPHINE)
- →Morphine in the body
➢ More potent than morphine (2-4)
➢ A greater lipid solubility →
1) Crosses BBB more readily than morphine
2) Smaller doses can be given orally
➢ A shorter duration of action than
morphine
3. MEPERIDINE (PETHIDINE)
- 1ST synthetic opioid (1939) with additional
antimuscarinic properties
- Similar to morphine in pharmacological
effects except that it tends to cause
RESTLESSNESS rather than SEDATION.
- A faster onset & a shorter duration of
action
- A similar euphoric effect & equally liable to
cause dependence
- Used in moderate to severe pain:
✓ Pethidine is superior to morphine in
Rx pain associated with biliary spasm
or renal colic due to its antispasmodic
effects.
✓ It is preferred for analgesia during
labor (due to its shorter duration of
action (120-150 min) → less resp.
depression than morphine)
- Concurrent administration of pethidine
with MAOIs → severe reactions;
excitement, hyperthermia & convulsions →
death (serotonin syndrome)
4. METHADONE
- A synthetic, orally effective opioid that is 
equal analgesia in potency to morphine
- Less euphoria & sedative actions →
blockade of euphoric effects of heroin,
morphine & similar drugs
- A long duration of action due to long
plasma t1/2 ( 24 h) & duration of action 
with repeated use
➢ 1, 2 & 3 → use in controlled
withdrawal of addicts from heroin &
morphine (anti-addictive)
 5. FENTANYL and SUFENTANIL and ALFENTANYL
- Highly potent phenylpiperidine derivatives,
with actions similar to morphine, but short-
lasting, particularly sufentanil
- Fentanyl is 80-100 more potent than
morphine
- Sufentanil is a highly potent analgesic (5-
10 more potent than fentanyl) used in
heart surgery.
- Alfentanil is an ultra-short acting (5-10
minutes) opioid.
- Fentanyl is extensively used for anesthesia
& analgesia, most often in the operating
room and intensive care unit.
- Fentanyl is sometimes given intrathecally as
part of spinal anesthesia or epidurally for
epidural anesthesia & analgesia.
➢ Fentanyl is available as a patch & as
an oral slow-release device
6. ETORPHINE
- A semi-synthetic morphine analogue with
an analgesic potency 1000-3000 that of
morphine (but otherwise very similar in its
actions)
- Used to immobilize wild large animals, like
elephants, for trapping & research
purposes.
7. TRAMADOL
- Opioid receptor agonist
- A low affinity for  receptors and a very low
affinity for  & 
- NE & 5-HT reuptake blocker
(antidepressant) & α2 adrenoceptor agonist
- These 2 actions are synergistic for analgesia
- Analgesic action is partially reversed by
naloxone
- Used in mild-to-moderate short-lasting pain
& chronic pain
MIXED AGONISTS-ANTAGONISTS
1. PENTAZOCINE ( PARTIAL AGONIST AND  & 
AGONIST)
- At low doses, its potency & effects are very
similar to morphine.
-  Dose  a corresponding  in produced
effects & at high doses, pentazocine →
slight resp. dep. ()
- → marked dysphoria, with nightmares &
hallucinations (), rather than euphoria
- Used in moderate to severe pain
2. NALORPHINE
- In low doses, it competitively antagonizes
(blocks) most actions of morphine.
- In high doses, it is analgesic, and mimic the
effects of morphine.
➢ These effects reflect an antagonist
action on -receptors, coupled with a
partial agonist action on - and -
receptors, the latter causing
dysphoria.
3. BUPRENORPHINE
- It acts like morphine in patients, but it can
also precipitate withdrawal in users of
morphine or other full opioid agonists
- A major use is in opioid detoxification,
because it has shorter and less severe
withdrawal symptoms compared to
methadone
- Buprenorphine tablets are indicated for the
treatment of opioid dependence and are
also available in a combination product
containing buprenorphine and naloxone.
- Naloxone was added to prevent the abuse
of buprenorphine via IV administration.

MODERATE AGONISTS

1. CODEINE
- More oral absorption than morphine (due
to its higher lipid solubility)
- A marked antitussive activity → used in
cough mixtures
-  20% of the analgesic potency of
morphine → used as oral analgesic for mild
types of pain (headache, backache, etc.)
- Little or no euphoria & rarely addictive
2. DEXTROPROPOXYPHENE
- Well absorbed orally (peak plasma levels
occurring in 1 hour)
- Similar to CODEINE but has a longer
duration of action & free from dependence
liability
- Often used in combination with aspirin or
acetaminophen for a greater ANALGESIA
than that obtained with either drug alone
ANTAGONISTS

1. NALOXONE
- Naloxone is used to reverse the resp.
depression & coma of opioid overdose.
- It rapidly displaces all receptor-bound
opioids → reversal of heroin overdose
effect
- Within 30 seconds of its i.v. injection, the
resp. depression & coma; characteristics of
high doses of heroin, are reversed → the
patient is revived and alert
2. NALTREXONE
- Actions similar naloxone
- A long t1/2 → a longer duration of action
than naloxone; a single oral dose blocks the
effect of injected heroin for up to 48 hours
- Available in oral form only
- It is used in opiate-dependence
maintenance programs and chronic
alcoholism.
3. NALMEFENE
- Intermediate duration (4-6 hr)
- Orally active
- No hepatotoxicity

NURSING CONSIDERATIONS

➢ The role of the nurse involves careful monitoring

of the client’s condition and providing education
as it relates to the prescribed drug regimen.
➢ When providing care for clients who are taking
opioids, perform an initial assessment