Morphine and fentanyl are potent opioid analgesics that act on mu-opioid receptors in the central nervous system. Morphine is a naturally occurring substance extracted from poppy plants, while fentanyl is a synthetic opioid. Both drugs are used medicinally to treat moderate to severe pain. Common side effects include respiratory depression, nausea, constipation, and euphoria. Withdrawal from long-term opioid use can cause pain, irritability, and dysphoria.

1. MORPHINE & FENTANYL
DR NIDA FATIMA
JAWAHARLAL NEHRU MEDICAL
COLLEGE ALIGARH

2. Opioid Receptors
• Mu, Delta, Kappa
• All pure agonists act at Mu receptor
• Opioid receptors act on
–CNS: cortex, thalamus, periaquaductal
gray, spinal cord & Peripheral neurons
–Inflammed tissue & Immune cells
–Respiratory and GI tract

3. MORPHINE
• Morphine - white, crystalline powder.
• µ-opioid receptor agonist.

4. • Synonyms:
• Morphine: Astramorph®, Duramorph®,
Infumorph®, Kadian®,Morphine Sulfate®,
MSIR®, MS-Contin®, Oramorph SR®,
Roxanol®

5. • Source: Morphine is a naturally occurring
substance extracted from the seedpod of the
poppy plant, Papavar somniferum.
• Morphine concentration in opium can range
from 4-21%.

6. HISTORY
About 1806, a german youth,
Frederich Serturner isolated the primary
active ingredient in opium.
He tested the new drug on his friends at 10
times the modern recommended dose!
-Active agent was 10x more potent than
opium -He named it morphium after
morphius, the god of dreams!!!

7. DRUG- MORPHINE
• Drug Class: Narcotic analgesic (schedule II)
• prescription forms:
• Injectable (0.5-25 mg/mL strength);
• oral solutions (2-20 mg/mL);
• immediate and controlled release tablets
and capsules (15-200 mg); and
• suppositories (5-30 mg).

8. Pharmacokinetics
• Orally -absorbed very slowly,
• Extensive first pass metabolism - 20%- 40% of
bio-availability.
• Duration of action – ( 3 – 6 hours)
• Distribution is wide ;concentration in liver,
spleen and kidney is greater than plasma.
• Morphine freely crosses placenta.
• Plasma half life 3hours (1-5 hrs).
• 30% is plasma protein bound

9. Metabolism
• The primary site metabolism is liver, where
it undergoes rapid glucuronidation.
• However, extrahepatic metabolism up to
30% of its total clearance.
• Morphine-6-glucuronide (m6g), as potent
as morphine. M6G has a half-life of
approximately 1-2 hours.

10. USES
• Morphine is used medicinally –
• Relief of moderate to severe pain in both
acute and chronic management.
• pre-operative sedation and to facilitate the
induction of anesthesia.
• For long-term treatment of terminally ill,
pain ridden patients

11. Route of Administration
• Oral (capsule, syrups, tablets )
• Intravenous
• Intramuscular
• Subcutaneous
• Epidural Administration
• Intrathecal administration.

12. Dosage
• Oral: Short-acting oral dose-severe, chronic
pain in Adults: 10 to 30 mg 4 hrly.
• I.M/S.C : 5 to 20 mg (usually 10 mg), 4 hrly
• I.V : initial dose 4 mg to 10 mg slowly over
4-5 min 4hrly. Daily dose range 12-120mg.
• Pediatric: I.V-0.025–0.1 mg/kg.
S.C- 0.1-0.2mg/kg

13. Epidural Adult Dosage
• 5 mg in lumbar region -pain relief up to 24 hrs
• Incremental doses 1-2 mg.
• Max 10 mg/24 hr
• For continuous infusion an initial dose of
2 to 4 mg/24 hours is recommended
• INTRATHECAL DOSAGE IS USUALLY
1/10 THAT OF EPIDURAL DOSAGE.

14. Intra-thecal Adult Dosage
• A single injection of 0.2 to 1 mg pain relief
for up to 24 hours.
• A constant intravenous infusion of naloxone
hydrochloride, 0.6 mg/hr, for 24 hours after
intrathecal injection may be used to reduce
the incidence of potential side effects.

15. Side effects
• Miosis
• Orthostatic hypotension
• Respiratory depression
• Pain suppression/ Pruritus
• Histamine release/hormonal release
• Increased intracranial tension.
• Nausea
• Euphoria
• Sedation

16. Contraindications
• respiratory depression,
• hypersensitivity,
• paralytic ileus, and delayed gastric emptying,
• Obstructive airway disease,
• acute hepatic disease,
• MAO Inhibitor administration,
• pregnancy, lactation and in children.

17. Interactions
• Morphine will not be effective in people
taking naltrexone.
• It can increase the sedative effect of alcohol,
• Increase the risk of respiratory depression
when used with MAO inhibitors and
cimetidine.
• It antagonises the effects of diuretics.

18. FENTANYL
• a potent, synthetic
opioid analgesic with a
rapid onset and short
duration of action.
• a strong agonist at the
μ-opioid receptors.

19. HISTORY
• Fentanyl first synthesized by Paul Janssen in
1960 by assaying analogues of the structurally
related drug pethidine for opioid activity.
• Historically, used to treat breakthrough pain
and is commonly used in pre-procedures as a
pain reliever as well as an anesthetic in
combination with a benzodiazepine.

20. • In the mid-1990s, fentanyl was first
introduced for widespread palliative use
with the clinical introduction of the
Duragesic patch, Actiq lollipop and Fentora
buccal through, sublingual spray

21. Fentanyl
Onset: 1-2 minutes IV/IO
8 minutes IM
Peak: 3-5 minutes IV route
Less predictable IM route
Duration: 30-60 minutes IV
1-2 hours IM
Duration of respiratory depressant effect of
fentanyl may be longer than the analgesic effect

22. Metabolism
• Hepatic, primarily by CYP3A4
• Metabolized to 3-glucuronide metabolites
–No analgesic properties
–CSF doses often exceed doses of parent
compound (rats)
–Cause neuroexcitation
• 6-glucuronide has analgesic properties

23. Medical uses
• Fentanyl has a therapeutic index of 270.
• Intravenous fentanyl is often used for
anesthesia(often used along with a hypnotic
agent like propofol) and analgesia.
• along with local anesthetic for neuraxial
administration (epidural or intrathecal or
spinal).

24. • In combination with benzodiazepine, like
midazolam, - procedural sedation for
endoscopy, cardiac catheterization, oral
surgery, etc.
• Management of chronic pain including
cancer pain.
• In children intranasal fentanyl is useful for
the treatment of moderate and severe pain.

25. Fentanyl patch
• Takes 12 hours for onset of analgesia
• Need adequate subcutaneous tissue for
absorption
• Work by slowly releasing fentanyl through
the skin into the bloodstream over 48 to 72
hours.
• Takes 24 hours to reach maximum effect
• Suitable for stable pain only

26. Patches
• Durogesic/duragesic/matrifen
• Dosage is based on the size of the patch.
• Dosage change after six days on patch
• Change patch every 72 hours
• Transdermal absorption rate is constant at
a constant skin temperature

27. Lozenges
• Fentanyl lozenges (Actiq) are a solid
formulation of fentanyl citrate as lollipop that
dissolves slowly in the mouth for transmucosal
absorption.
• Effective in treating breakthrough cancer pain
• It is most effective within 15 minutes.

28. • Rate of absorption depends on:
1. Body temperature,
2. skin type,
3. amount of body fat, and
4. placement of the patch
Under normal circumstances, the patch will
reach its full effect within 12 to 24 hours

29. • About 25% of the drug is absorbed through
the oral mucosa, resulting in a fast onset of
action, and the rest is swallowed and
absorbed in the small intestine, acting more
slowly.
• extensive first-pass metabolism, leading
to an oral bioavailability of about 33%
and 50% when used correctly (25% via
the mouth mucosa and 25% via the gut).

30. Adverse effects
• Most common side-effects (> 10% of patients).
• CVS: Bradycardia, edema
• CNS: depression, confusion, dizziness,
drowsiness, fatigue, headache, sedation
• Endocrine & metabolic: Dehydration
• Gastrointestinal: Constipation, nausea,
vomiting, xerostomia

31. • Local: Application-site reaction erythema
• Neuromuscular & skeletal: Chest wall
rigidity (high dose I.V.), muscle rigidity,
weakness
• Ocular: Miosis
• Respiratory: Dyspnea, respiratory depression
• Miscellaneous: Diaphoresis

32. • less frequent (3 to 10% of patients)
• abdominal pain, headache, fatigue,
• anorexia and weight loss, dizziness,
• nervousness, hallucinations, anxiety,
• depression, flu-like symptoms,
• dyspepsia (indigestion),
• dyspnea (shortness of breath), apnea,
hypoventilation,
• urinary retention

33. • Fentanyl -associated with aphasia
• fentanyl tends to induce less nausea, as well
as less histamine mediated itching, in
relation to morphine.
• Fentanyl - prolonged respiratory depression
than other opioid analgesics.

34. Dosage
Surgery:
• Premedication: I.M., slow I.V.: 50-100
mcg/dose (1-2mcg/kg) 30-60 minutes prior
to surgery
• Adjunct to regional anesthesia: Slow I.V.:
25-100 mcg/dose (0.5-2mcg/kg) over 1-2
minutes.

35. Adjunct to general anesthesia: Slow I.V.:
• Low dose: 0.5-2 mcg/kg/dose depending on
the indication.
• Moderate dose: Initial: 2-20 mcg/kg/dose;
Maintenance (bolus or infusion): 1-2
mcg/kg/hour.
• High dose: 20-50 mcg/kg/dose.

36. Pain management
• Adults:
• I.V.Bolus:1-2 mcg/kg or 25-100µg/dose;
infusion @ 1-2 µg/kg/hour or 25-200 µg/hr .
• Severe: I.M, I.V.: 50-100 µg/dose every 1-2
hours as needed.

37. Patient-controlled analgesia (PCA)
• Usual concentration: 10 mcg/mL
• Demand dose: Usual: 20 mcg; range: 10-50
mcg
• Lockout interval: 5-8 minutes
• Usual basal rate: ≤50 mcg/hour

38. • Critically-ill patients:
• Slow I.V.: 25-35 mcg or 0.35-0.5 mcg/kg
every 30-60 minutes as needed
• Continuous infusion: 50-700 mcg/hour
(based on ~70 kg patient) or 0.7-10
mcg/kg/hour

39. Intrathecal fentanyl
• Must be preservative-free.
• Single dose: 5-25 mcg/dose- relief up to 6 hours.
• Continuous infusion: Not recommended
• For chronic cancer pain, infusion of very small
doses may be practical (American Pain Society,
2008).

40. Epidural fentanyl
• Must be preservative-free.
• Single dose: 25-100 µg/dose-relief up to 8 hrs
• Continuous infusion: 25-100 mcg/hour

41. • Pain relief (IV) 1–2 mcg/kg
• Pain relief (Intranasal) 2 mcg/kg
• Premedication 10–15 mcg/kg
(Actiq PO)
• Anesthetic adjunct (IV) 1–5 mcg/kg
• Maintenance infusion2–4 mcg/kg/h
• Main anesthetic (IV) 50–100 mcg/kg
Pediatric Dosage

42. Opioid withdrawal

43. Acute action
• Analgesia
• Respiratory Depression
• Euphoria
• Relaxation and sleep
• Tranquilization
• Decreased blood pressure
• Constipation
• Pupillary constriction
• Hypothermia
• Drying of secretions
• Reduced sex drive
• Flushed and warm skin
Withdrawal signs
• Pain and irritability
• Hyperventilation
• Dysphoria and depression
• Restlessness and insomnia
• Fearfulness and hostility
• Increased blood pressure
• Diarrhea
• Pupillary dilation
• Hyperthermia
• Lacrimation, runny nose
• Spontaneous ejaculation
• Chilliness & “gooseflesh”

44. Opioid Tolerant
"Opioid-tolerant" patients-who are taking at least:
• Oral morphine 60 mg/day, or
• Transdermal fentanyl 25 mcg/hour, or
• Oral oxycodone 30 mg/day, or
• Oral hydromorphone 8 mg/day, or
• Oral oxymorphone 25 mg/day, or
• Equianalgesic dose of any opioid for at least 1 wk

45. Opioid Induced Neurotoxicity
–Neuroexcitability - agitation, confusion,
myoclonus, hallucinations and seizures
• Predisposing Factors:
–High opioid doses & Prolonged opioid use
–Recent rapid dose escalation
–Dehydration & Renal failure & Advanced age
–Other psychoactive drugs

46. Management of OIN
• Rehydration
• Treat concurrent causes of delirium e.g.
UTI, pneumonia
• Reduce dose if pain controlled
• Switch to a different opioid