1. Pain Management Opioids
Tasneem Jabr

2. Opioids
The word opioid refers to derivatives of the opium plant or to synthetic drugs that imitate natural narcotics.
Opioid agonists (also called narcotic agonists) include opium derivatives and synthetic drugs with similar properties.
They are used to relieve or decrease pain without causing the person to lose consciousness.
Some opioid agonists may also have
Anti-tussive effects that suppress coughing
Anti-diarrheal actions that can control diarrhea.

3. Tolerance – Physiologic phenomenon resulting in progressive decline in potency of an opioid with continued use. (require escalating doses of opioid to maintain the same analgesic effect)
Tolerance can be conferred from one opioid agonist to others (cross-tolerance)
Dependence – Physiologic state characterized by withdrawal symptoms upon abrupt discontinuation/ reduction of narcotic therapy.
rare in cancer patients
Opioid withdrawal phenomena can be precipitated by the administration of opioid antagonists that do not cross the blood–brain barrier.
Addiction – Psychological & behavioral syndrome manifested by drug seeking behavior, loss of control of drug use, and continued use despite adverse effects.

4. the patient fails to adequately respond
Intravenous (intermittent or continuous )
intraspinal (epidural or intrathecal)
transdermal routes
Intramuscular opioid administration is rarely optimal because of variability in systemic absorption and resultant delay and variation in clinical effect
Oral
the patient fails to adequately respond
patient-controlled analgesia (PCA)
allowing the patient to self-treat for breakthrough pain
If pain increases significantly, or changes markedly in quality
Reevaluate the patient for adequacy of pain diagnosis and for the potential of disease progression
In patients with cancer, adjunctive treatments may be helpful

5. Spinal opioid therapy (epidural and intrathecal)
Indications - for patients obtaining poor relief with other analgesic techniques who experience unacceptable sideeffects.
When compared with intermittent boluses, continuous intraspinal infusion techniques
reduce drug requirements
minimize side effects
Complications
local skin infection or intrathecal pump pocket infection
Meningitis
death or permanent injury related to pump programming, pump refill or drug dilution errors.
epidural hematoma
respiratory depression - secondary to spinal opioid overdose

6. Epidural or intrathecal catheters can be placed percutaneously or implanted to provide long-term effective pain relief.
Epidural catheters can be attached to lightweight external pumps that can be worn by ambulatory patients.
Completely implantable intrathecal catheters with externally programmable pumps can also be used for continuous infusion
The reservoir of the implanted pump is periodically refilled percutaneously.

7. Morphine
Morphine exerts its major effects by interacting with opioid receptors in the CNS and other anatomic structures, such as the GI tract and the urinary bladder.
Agonist to all opioids receptors with high affinity to μ receptor
Duration of action 4-5 hours

8. Morphine Administration Distribution:
Because significant first-pass metabolism of morphine occurs in the liver, intramuscular, subcutaneous, and IV injections produce the most reliable responses.
Absorption of morphine from the GI tract after oral absorption is slow and erratic.
When used orally, morphine is commonly administered in an extended-release form to provide more consistent plasma levels
Distribution:
Morphine rapidly enters all body tissues, Including the fetuses of pregnant women.
It should not be used for analgesia during labor.
Infants born to addicted mothers show physical dependence on opioids and exhibit withdrawal symptoms if opioids are not administered.
Only a small percentage of morphine crosses the blood–brain barrier, because morphine is the least lipophilic of the common opioids

9. Morphine
Morphine metabolisim occurs in the liver and excreted primarily in urine, with small quantities appearing in the bile.
The duration of action of morphine is 4 to 5 hours when administered systemically, but considerably longer when injected epidurally because the low lipophilicity prevents redistribution from the epidural space
Age can influence the response to morphine.
Elderly patients are more sensitive to the analgesic effects of the drug, possibly due to decreases in metabolism, lean body mass, or renal function.
Lower starting doses should be considered for elderly patients.
Hydromorphone is an excellent alternative to morphine, particularly in elderly patients because of fewer side effects, and in patients with impaired kidney function.
Neonates should not receive morphine because of their low conjugating capacity.

10. Morphine - Actions Analgesia
It decreases the release of substance P(which modulates pain perception in the spinal cord)
Morphine also appears to inhibit the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli
Used to treat moderate- severe acute and chronic pain

11. Morphine -Actions Analgesia – in chronic pain
Moderate to severe cancer pain is usually treated with an immediate-release oral morphine preparation (10–30 mg every 1–4 h).
These preparations have an effective half-life of 2 to 4 h.
Once the patient’s daily requirements are determined, the same dose can be given in the form of a sustained-release morphine preparation (which is dosed every 8 to 12 h).
The immediate-release preparation is then used only as needed for breakthrough pain.

12. Morphine -Actions
Respiratory system respiratory depression by reduction of the sensitivity of respiratory center neurons to carbon dioxide. This can occur with ordinary doses of morphine in patients who are opioid-naïve and can be accentuated as the dose is increased until ultimately respiration ceases. Respiratory depression is the most common cause of death in acute opioid overdoses. Tolerance to this effect does develop quickly with repeated dosing, which allows the safe use of morphine for the treatment of pain when the dose is correctly titrated. Depression of cough reflex (antitussive effect)
Euphoria
Miosis:
Results from stimulation of μ and κ receptors
There is little tolerance to the effect (all morphine abusers demonstrate pinpoint pupils)
This is important diagnostically, because many other causes of coma and respiratory depression produce dilation of the pupil.
Labor:
Morphine may prolong the second stage of labor by transiently decreasing the strength, duration, and frequency of uterine contractions.

13. Morphine -Actions Cardiovascular system :
Morphine has no major effects on the blood pressure or heart rate at lower dosages.
With large doses, hypotension and bradycardia may occur.
Because of respiratory depression and carbon dioxide retention, cerebral vessels dilate and increase cerebrospinal fluid pressure.
Therefore, morphine is usually contraindicated in individuals with head trauma or severe brain injury
GI tract:
Emesis
Constipation – Antidiarrheal effect
by decreasing the motility and increasing the tone of the intestinal circular smooth muscle and anal sphincter.
little tolerance developing.
stool softeners or laxatives are often indicated.
Morphine can also increase biliary tract pressure due to contraction of the gallbladder and constriction of the biliary sphincter.
Hormonal actions:
Morphine increases growth hormon release and enhances prolactin secretion.
It increases antidiuretic hormone and leads to urinary retention.
Histamine release:
Morphine releases histamine from mast cells causing urticaria, sweating, and vasodilation.
Because it can cause bronchoconstriction, morphine should be used with caution in patients with asthma.

14. Morphine – Adverse effect
severe respiratory depression can occur and may result in death from acute opioid overdose.
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.

15. Morphine - Tolerance and physical dependence
Repeated use produces tolerance to
the respiratory depressant
Analgesia
Euphoric and sedative effects
Tolerance usually does’nt develop to
the pupil-constricting
constipating effect
Physical and psychological dependence can occur with morphine
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.

16. Pethidine (Meperidine)
Is a lower-potency synthetic opioid structurally unrelated to morphine.
Acts primarily as a κ agonist, with some μ agonist activity
It’s very lipophilic has anticholinergic effects
Meperidine is renally excreted.
It has a short duration of action
It has significant neurotoxic actions that can lead to
Delirium
Hyperreflexia
Myoclonus and seizures
increased incidence of delirium
meperidine should only be used for short-term (≤48 hours) management of pain-acute pain

17. Pethidine (Meperidine)
Meperidine should not be used in
elderly patients
patients with renal insufficiency
patients hepatic insufficiency
preexisting respiratory compromise

18. Fentanyl Uses of Fentanyl
a synthetic opioid chemically related to meperidine
has 100-fold the analgesic potency of morphine and is used for anesthesia.
The drug is highly lipophilic
It has a rapid onset and short duration of action (15 to 30 minutes).
It is usually administered IV, epidurally, or intrathecally.
An oral transmucosal preparation and a transdermal patch are also available.
The drug and inactive metabolites are eliminated through the urine
Uses of Fentanyl
combined with local anesthetics to provide epidural analgesia for labor and postoperative pain.
IV fentanyl is used in anesthesia for its analgesic and sedative effects.
The oral transmucosal preparation is used in the treatment of cancer patients with breakthrough pain who are tolerant to opioids.

19. Fentanyl – Transdermal patches
The transdermal patch creates a reservoir of the drug in the skin. Hence, the onset is delayed at least 12 hours, and the offset is prolonged (48 to 73 hrs)
Rate of absorption is dependent on a number of factors
Body temperature
skin type
amount of body fat
placement of the patch
must be used with caution because death resulting from hypoventilation has been known to occur.
Contraindicatoin
in opioid-naïve patients
in managing acute and postoperative pain

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