Opioid Analgesics &

Antagonists
Nur Hesti Kusumasari, dr

Opioid Analgesics
Classification :
Spectrum of Clinical Uses :
Analgesics
Antitussive
Antidiarrheal drugs

Strength of Analgesia :
Strong analgesia
Moderate analgesia
Weak Analgesia

Ratio of Agonists to Antagonist Effects :

Agonists (receptor activator)full or partial

Antagonists (receptor blocker)
Mixed agonist-antagonists (capable of activating one
opioid receptor subtype & blocking another subtype)

Pharmacokinetics
Most drugs are well absorbed orally
& can be given parenterally
Opioid drugs are widely distributed
to body tissues
They cross the placental barrier &
exert effects on the fetus
The opioid are metabolized by
hepatic enzymes

Mechanism of action
Interaction with specific opioid receptors in the
CNS & peripheral tissues
Three major opioid receptors are , ,
& receptor : contributed to analgesia,
respiratory depression, physical dependence
receptor : contributed to spinal analgesia &
sedative effects of opioid drugs
Opioid receptors are thought to be activated by
endogenous peptides under physiologic
conditions.
these peptides are enkephalins, dynorphin,
beta-endorphin
Ionic mechanisms

The Effects
Acute Effects
Analgesia :

Strong agonists (morphine, methadone, meperidone,

fentanyl, levorphanol, heroin)
Mild to moderate agonists (codeine, hydrocodone,
oxycodone)
Weak agonists (propoxyphene)

Sedation & euphoria :

These effects occur at doses below maximum

analgesia doses
At higher doses, the drugs may cause mental
clouding, stuporous, or comatose state

Respiratory depression :

Decreased response to carbondioxide challenge

Antitussive actions :

Suppression of the cough

The Effects
Nausea & vomitus

Caused by activation of the chemoreceptor trigger

zone & are increased by ambulation

Gastrointestinal effects :

Constipation (decreased intestinal peristalsis, which

is probably mediated by effects on opioid receptors in
the en teric nervous system

Smooth muscle :

Contraction of biliary tract muscle

Increased uretral & bladder sphincter tone
Reduction in uterine tone

Miosis :

Pupillary coonstriction, is a characteristics effects of

all opioid except meperidine

The Effects
Chronic Effects
Tolerance

Involve receptor uncoupling

Physical dependence

Is an anticipated physiologic responese

to chronic therapy with drugs in this
group, particularly the strong agonists
Abstinence syndrome (rinorrhea,
lacrimation, chills, gooseflesh, muscle
aches, diarrhea, yawning, anxiety, &
hostility

Clinical Uses
Analgesia

To treatment of moderate to severe pain

Cough suppression

Include codein & dextromethorphan (orally)

Treatment of diarrhea

Include diphenoxylate & loperamide (selective antidiarrheal

opioids)

Management of acute pulmonary edema

Morphine (parenterally) is useful in acute pulmonary edema

because its hemodynamics action & its calming effects to
relief of the pulmonary symptoms

Anesthesia

Are used as preoperative medications & intraoperaive

adjuntive agents

Opioid dependence

Methadone is used in the management of opioid withdrawal

states & in maintenance programs for addicts

Toxicity
Overdose
Coma with marked respiratory deppression
& hypotension
Treatment : naloxone, ventilatory support

Drug interactions
Interaction with ethanol, sedative hypnotic,
anesthetic, antipsychotics drugs, tricyclic
antidepressants, & antihistamine (additive
CNS deppression)

Mixed agonist-antagonists
& Partial Agonist drugs
Mixed agonist-antagonists drugs :
Prototype : butorphanol, nalbuphine,
pentazocine
Are agonists with weak
antagonists activity
Partial Agonists drugs :
Prototype : buprenorphine
Is a partial agonists at receptor

Mixed agonist-antagonists
& Partial Agonist drugs
Effects :
Sedation at analgesic doses
Dizzines, sweating, nausea, anxiety,
hallucinations, nightmares
Less intense respiratory deppression
than with pure agonists
Less tolerance
Less physical dependence

Opioid Antagonists
Prototype : naloxone (duration
of action 1-2h), naltrexone (2448h)
Clinical uses : management of
acute opioid overdose
Given intravenously