OPIOID

ANALGESIC

OPIOIDS (MORPHINE-LIKE) ANALGESICS

AND ANTAGONISTS
Opioids
natural or synthetic; produce morphine-like effects.
They act by binding to specific opioid receptors in the CNS
effects mimic the action of endogenous peptide neurotransmitters
(e.g., leu- and met-enkephalins).
They relieve severe pain - essential in treatment of major diseases,
trauma, and surgery.
Danger of the drug abuse.
Although the opioids have a broad range of effects, their primary use
is to relieve intense pain and the anxiety that accompanies it.
Antagonists they can reverse actions of opioids, important
clinically treatment of overdose.

History of Opioids
Opium is extracted from poppy seeds
(Paper somniforum)
Used for thousands of years to
produce:
Euphoria
Analgesia
Sedation
Relief from diarrhea
Cough suppression

Terminology
opium is a Greek word meaning
juice, or the exudate from the
poppy
opiate is a drug extracted from the
exudate of the poppy
opioid is a natural or synthetic drug
that binds to opioid receptors
producing agonist effects

Mechanism of Action

bind to G-protein-coupled neural receptors (mu,

delta,kappa) to reduce adenylyl cyclase activity,
to reduce prejunctional calcium conductance, which
causes a decrease in neurotransmitter release, and to
enhance postjunctional potassium conductance, which
causes a decrease in cell responsiveness to excitatory
neurotransmitters

Action of endogenous and exogenous opioids at

opioid receptors

Opioid Receptors
-receptors are thought to be responsible for most of the
analgesic effects of opioids, and for some major
unwanted effects (e.g. respiratory depression, euphoria,
sedation and dependence). Most of the analgesic opioids
are -receptor agonists.
-receptors are probably more important in the
periphery, but may also contribute to analgesia.
-receptors contribute to analgesia at the spinal level,
and may elicit sedation and dysphoria, but produce
relatively few unwanted effects, and do not contribute to
dependence. Some analgesics are relatively -selective.

Mu and Kappa Receptor Activation

Response
Analgesia
Respiratory
Depression
Euphoria
Dysphoria
Decrease GI
motility
Physical
Dependence

Mu-1

Mu-2

Kappa

Effects of opioids

Opiods: dose-response
relationship

comparison of the maximum efficacy and addiction/abuse

liability of commonly used narcotic analgesics

Morphine

The opioids are classified in several

ways:

Therapeutic uses morphine

Division (in relation to the activity)

1. Strong agonists (e.g. morphine, meperidine=pethidine,
methadone, fentanyl, sufentanil, alfentanil, remifentanil)
2. Moderate agonists (e.g. propoxyphene, codein, oxycodone)
3. Mixed agonist-antagonists (e.g. pentazocine, buprenorphine,
nalbuphine, butorphanol)
4. Other analgesics ( tramadol)
5. Antagonists (naloxone, naltrexone)

OPIOID ANALGESICS AND ANTAGONISTS

STRONG AGONISTS

Alfentanil
Fentanyl
Heroin
Meperidine
Methadone
Morphine
Remifentanil
Sufentanil
MODERATE/LOW AGONISTS
Codeine
Oxycodone
Propoxyphene
MIXED AGONIST-ANTAGONISTS AND PARTIAL AGONISTS
Buprenorphine
Butorphanol
Nalbuphine
Pentazocine
ANTAGONISTS
Naloxone
Naltrexone
(according to
OTHER ANALGESICS
Lippincotts
Tramadol
Pharmacology, 2006

Morphine
CNS effects
Respiratory depression and
suppression of cough: reducing the
responsiveness of the respiratory
centers in the brain stem to blood
levels of carbon dioxide and inhibiting
directly the respiratory center.

Morphine
CNS effects
Nausea and vomiting: stimulating the
chemoreceptor trigger zone. In most
cases, after therapeutic dose,
subsequent doses of morphine do not
produce vomiting.
Miosis: pinpoint pupils are indicative
of toxic dosage prior to asphyxia. It
can be block with atropine.

Morphine
Cardiovascular effects:
Orthostatic hypotention can occur
due to vasomotor medullary
depression and histamine release.

Gastrointestinal effect:
Reduces gastrointestinal motility,
causing constipation
Decreases biliary and pancreatic
secretions.
Constriction at the spincter of Oddi
causes an increase in biliary pressure.

Morphine
Other systemic effects:
Increases detrusor muscle tone in the
urinary bladder, producing a feeling
of urinary. Vesical sphincter tone is
also increased, making voiding
Inhibits the cellular immunity and
humoral immunity, which is
significant in withdrawal syndrome
and tolerant in chronic administration.

Farmakokinetik Opioid

Adverse effects

Contraindications and
cautions

Interaksi Obat
Obat yang bekerja secara sentral
seperti barbiturat, fenotiazin,
penghambat MAO, antidepresan
trisiklikefek sedatif dan
depresi pernafasan
Fenotiazinefek menurunkan
tek.darah
Amphetamineanalgesia dari
morphin dan mengurangi efek sedasi
dan depresi pernafasan

Keracunan Akut Morfin

Gejala : coma, miosis, eksterm dari
pernafasan (hingga 2-4 tarikan nafas permenit),
sianosis, suhu tubuh rendah, kehilangan tonus
otot rangka.
Tindakan :
Pembebasan jalan nafas dan pemberian O2
memberikan suatu antagonis morfin untuk
menghilangkan kelumpuhan pernafasan
(naloxone sbg antagonis kompetitif)
Shock ditangani, mungkin perlu pemberian Ab
untuk pencegahan pneumonia

Methadone

Fentanyl

Meperidine

Pharmacokinetics:
Meperidine is well absorbed from the
gastrointestinal tract, and is useful
when an orally administered
However, meperidine is most often
administered parenterally
The drug has a duration of action of 2
to 4 hours, which is shorter than that
of morphine

Adverse effects:
Large or repetitive doses of
meperidine can cause anxiety,
tremors, muscle twitches, and rarely,
convulsions due to the accumulation
of a toxic metabolite, normeperidine.

Time to peak effect and duration of action of

several opioids administered intravenously

Codeine

Pethidine

Tramadol
a centrally acting analgesic that
binds to the -opioid receptor
it weakly inhibits reuptake of
norepinephrine and serotonin
It is used to manage moderate to
moderately severe pain
Its respiratory-depressant activity is
less than that of morphine

Adverse effects commonly observed in

individuals treated with opioids

Opiate Withdrawal syndrome

Opioid Antagonists

Opioid Antagonists

Clinical Use of Analgesic

Drugs

Clinical Use of Analgesic

Drugs

Clinical Use of Analgesic

Drugs

ALHAMDULILLAH.