The document discusses several opioid agonists and antagonists including fentanyl, sufentanil, alfentanil, morphine, nalbuphine. It describes their classification, uses, mechanisms of action, presentations, routes of administration, doses, effects, and other key details. Fentanyl, sufentanil, and alfentanil are synthetic opioid analgesics used for analgesia. Morphine is an opioid analgesic that acts on mu and kappa receptors. Nalbuphine is an agonist at kappa receptors and antagonist at mu receptors, producing analgesia without respiratory depression.

1. Opioid
Agonists And Antagonists
Mr. Harshad Khade
MSc. Medical Technology (OTA)
Symbiosis International University, Pune.

2. Classification
Natural opium alkaloids:
• Morphine, Codeine
Semi-synthetic opiates:
• Diacetylmorphine (Heroin), Pholcodeine, Ethylmorphine
Synthetic opioids:
• Fentanyl, Pethidine (Meperidine), Methadone ,Tramadol

3. Fentanyl Sufentanil Alfentanil Morphine

4. Fentanyl
Class
• Synthetic opioid analgesic (intermediate-acting).
Uses
1.To provide the analgesic component in general anaesthesia
2. In combination with a major tranquillizer to produce neuroleptanalgesia
3.To provide analgesia during labour when regional anaesthesia is not in use
4. As an agent used for patient-controlled analgesia
5. In premedication and
6. For palliative care.
Mechanism of action
• Acts at the mu-and kappa opioid receptors.

5. Presentation
• As a clear, colourless solution for injection containing 50 micrograms/ml
fentanyl citrate;
• As transdermal patches which deliver 12/25/50/75/100 micrograms/hour
over a 72-hour period;
• As sublingual tablets containing 100/200/400/600/800 micrograms;
• As lozenges containing 200/400/600/800/1200/1600 micrograms;
• As fentanyl hydrochloride in an iontophoretic transdermal system.
• The pka of fentanyl is 8.4, is 9% unionized at a ph of 7.4, has a molecular
weight of 286, and is highly lipid-soluble, having an octanol:
• Water partition coefficient of 717
Main actions
• Analgesia and respiratory depression

6. Mode of action
• Fentanyl is a highly selective mu-agonist (or MOP agonist);
• the MOP receptor appears to be specifically involved in the mediation of
analgesia.
• Opioids appear to exert their effects by interacting with presynaptic Gi-
protein receptors, leading to hyperpolarization of the cell membrane by
increasing K+ conductance.
• Inhibition of adenylate cyclase, leading to reduced production of cAMP,
and closure of voltage-sensitive calcium channels also occur.
• The decrease in membrane excitability that results may decrease both
pre- and post-synaptic responses.

7. Routes of administration/doses
• The adult dose for premedication by the intramuscular route is 50–100
micrograms.
• For the induction or supplementation of general anaesthesia, an
intravenous dose of 1– 100 micrograms/kg may be used.
• The drug may be administered by intravenous infusion.
• Fentanyl may also be administered via the epidural route—a dose of 50–
100 micrograms is usually employed—or via the spinal route at doses of
5–25 micrograms.
• The drug acts rapidly in 2 – 5 minutes due to its high lipid solubility when
administered intravenously;
• a small dose has a duration of action of 30–60 minutes, whereas high (>50
micrograms/ kg) doses may be effective for 4–6 hours.

8. Cont.-
• Following application of a transdermal patch, serum fentanyl
concentrations only increase gradually, with equilibrium occurring
at between 12 and 24 hours.
• Transdermal fentanyl patches should be replaced every 72 hours,
whilst iontophoretic transdermal system devices should be
replaced or stopped after 24 hours.
• Administration of fentanyl reduces the amount of hypnotic/volatile
agent required to maintain anaesthesia.

9. Dose
• General anesthesia: 1-20 ug/kg IV according to physical status,
other agents used, duration and nature of surgery.
Onset
• IV 4-6 minutes
Duration
• IV 30-45 minutes
Elimination
• Hepatic

10. Effects
• CNS
• Potent analgesic effects; some sedative effect.
• Rarely causes blurred vision, seizures.
• All of the depressant effects of fentanyl are potentiated by concurrent use
of sedatives, volatile anesthetics and nitrous oxide.
• CVS
• Hypotension, bradycardia.
• The synthetic opioids are not direct myocardial depressants but they do
reduce sympathetic drive which may result in decreased cardiac output in
patients who are relying on ssympathetic tone to support their circulation
such as those in hypovolemic or cardiogenic shock

11. • Respiratory
• Respiratory depression which at the extreme leads to apnea.
• GI
• Nausea, vomiting, biliary tract spasm, constipation.
• Misc
• Muscle rigidity

12. Sufentanil
Class
• Synthetic opioid analgesic (intermediate-acting), adjunct to
anesthesia. Mechanism of action acts at the mu-and kappa opioid
receptors.
Uses
1. The induction and maintenance of general anaesthesia.
2. Used in Post-operative analgesia
Main actions
• Analgesia and respiratory depression.

13. Presentation
• As a clear solution containing 50 micrograms/ml of sufentanil citrate.
• The drug is not commercially available in the India.
Mode of action
• Sufentanil is a highly selective mu-agonist;
• the MOP receptor appears to be specifically involved in the mediation of
analgesia.
• Part of the analgesic effect of the drug may be attributable to stimulation
of 5HT release.
• Opioids appear to exert their effects by increasing intracellular calcium
concentration which, in turn, increases potassium conductance and
hyperpolarization of excitable cell membranes.
• The decrease in membrane excitability that results may decrease both
pre- and post-synaptic responses.

14. Routes of administration/doses
• The intravenous dose is 0.5– 50 micrograms/kg, and the adult dose via the
epidural route is 10–100 micrograms (the optimal post-operative dose being 30–
50 micrograms).
• When administered intravenously, the drug acts in 1–6 minutes, and the duration
of effect is 0.5–8 hours, dependent on the other components of the anaesthetic
Dose
• General anesthesia: 0.3-1 ug/kg IV, Depending on patient condition, Other
agents used, Nature and duration of surgery.
• Infusion dose: 0..3-1 ug/kg/hour
Onset 1-2 minutes
Duration 20-40 minutes
Elimination Hepatic

15. Effects
• CNS
• Potent analgesic properties and some sedative effect.
• All of the depressant effects of sufentanil are potentiated by concurrent use
of sedatives, volatile anesthetics and nitrous oxide.
• CVS
• Bradycardia, hypotension.
• The synthetic opioids are not direct myocardial depressants but they do
reduce sympathetic drive which may result in decreased cardiac output in
patients who are relying on sympathetic tone to support their circulation,
such as those in hypovolemic or cardiogenic shock.
• Respiratory Respiratory depression, which at the extreme leads to apnea.
• GI Nausea, vomiting, biliary tract spasm, constipation.
• Misc. Muscle rigidity

16. Alfentanil
Class
• Synthetic opioid analgesic (short-acting); adjunct to anesthesia.
Uses
• 1. to provide the analgesic component in general anaesthesia
• 2. in sedation regimens for intensive care, and
• 3. to obtund the cardiovascular responses to laryngoscopy
Main actions
• Analgesia and respiratory depression

17. Presentation
• As a clear, colourless solution for injection containing 0.5/5 mg/ml of
alfentanil hydrochloride.
• The pka of alfentanil is 6.5; alfentanil is 89% unionized at a ph of 7.4 and
has a relatively low lipid solubility.
• Despite the low lipid solubility of the drug (octanol:water partition
coefficient of 128.1), it has a faster onset of action, compared to fentanyl
which has a much higher lipid solubility due to its low pka and
consequently large amount of unionized drug available to cross lipid
membranes

18. Mode of action
• Alfentanil is a highly selective mu-opioid (MOP) agonist; the MOP
receptor appears to be specifically involved in the mediation of analgesia.
• Opioids appear to exert their effects by interacting with pre-synaptic GI
protein receptors, leading to a hyperpolarization of the cell membrane by
increasing potassium conductance.
• Inhibition of adenylate cyclase, leading to a reduced production of cAMP
and closure of voltagesensitive calcium channels, also occurs.
• The decrease in membrane excitability that results may decrease both
pre- and post-synaptic responses.

19. Routes of administration/doses
• Alfentanil is administered intravenously in boluses of 5–50
micrograms/kg.
• The drug may be administered by intravenous infusion at a rate of 0.5–1
micrograms/kg/min.
• Alfentanil acts rapidly, with the peak effect occurring within 90 seconds of
intravenous administration, and the duration of effect is 5–10 min.
• Administration of alfentanil reduces the amount of hypnotic/volatile
agents required to maintain anaesthesia
Dose 5-50 ug/kg IV, according to physical status, other agents used, nature
and duration of surgery.
Onset 1-2 minutes Duration 20 minutes
Elimination Hepatic

20. Effects
• CNS Analgesia, sedation.
• All of the depressant effects of alfentanil are potentiated by concurrent use of
sedatives, volatile anesthetics and nitrous oxide.
• CVS Bradycardia, hypotension.
• The synthetic opioids are not direct myocardial depressants but they do
reduce sympathetic drive, which may result in decreased cardiac output in
patients who are relying on sympathetic tone to support their circulation, such
as those in hypovolemic or cardiogenic shock.
• Respiratory Potent respiratory depression which at the extreme, leads to apnea.
• GI Nausea, vomiting, biliary tract spasm.
• Misc. Muscle rigidity, pruritis

21. Morphine Sulfate
Class
• Opioid analgesic (long acting)
Uses :
1. for premedication
2. as an analgesic in the management of moderate to severe pain
3. in the treatment of left ventricular failure
4. to provide analgesia during terminal care, and
5. in combination with kaolin in the symptomatic treatment of diarrhoea.
Main actions
• Analgesia and respiratory depression.

22. Mode of action
• Morphine is an agonist at mu- and kappa-opioid receptors.
• Opioids appear to exert their effects by increasing intracellular calcium
concentration which, in turn, increases potassium conductance and
hyperpolarization of excitable cell membranes.
• The decrease in membrane excitability that results may decrease both
pre- and post-synaptic responses.
Presentation
• As 5/10/30/60/100/200 mg tablets,
• as a syrup containing 2/10/20 mg/ml,
• as 15/30 mg suppositories, and
• as a clear, colorless solution for injection containing 10/15/30 mg/ml of
morphine sulfate;
• preservative-free morphine must be used for epidural/spinal use.

23. Routes of administration/doses:
• The initial adult oral dose is 5– 20 mg 4-hourly, increased as required.
• The dose by the rectal route is 15– 30 mg 4-hourly.
• The corresponding intramuscular or subcutaneous dose is 0.1–0.2 mg/kg,
and the intravenous dose is 0.05–0.1 mg/kg 3- to 4-hourly.
• Morphine may also be administered intrathecally; an adult dose of 0.2–1
mg has been recommended.
• The drug has a peak analgesic effect 30–60 minutes after intramuscular
injection and has a duration of effect of 3–4 hours.
Dose: Adults: 2.5-15 mg IV/IM/SC,
Children: 0.05-0.2 mg/kg IV/IM/SC
Onset: IV 5-10 minutes, IM 15-30 minutes
Duration: 2-5 hrs IV/IM/SC
Elimination: Hepatic

24. Effects
• CNS
• Reliable analgesic effects; sedation. May cause blurred vision, syncope,
euphoria, dysphoria.
• All of the depressant effects of morphine are potentiated by concurrent
use of sedatives, volatile anesthetics, nitrous oxide and alcohol.
• Morphine’s depressant effects are also potentiated by antihistamines,
phenothiazines, butyrophenones, MAOIs and TCAs.
• CVS
• May cause hypotension, hypertension, bradycardia, arrhythmias.

25. • Respiratory
• Respiratory depression which at the extreme leads to apnea. May cause
bronchospasm or laryngospasm.
• GI
• Nausea, vomiting, constipation, biliary tract spasm.
• Misc.
• Releases histamine.
• May cause pruritis, urticaria, muscle rigidity, urinary retention

26. Nalbuphine
Uses
• 1. for premedication and
• 2. as an analgesic in the treatment of moderate to severe pain.
Chemical
• A semi-synthetic phenanthrene derivative.
Main action Analgesia.
Presentation
• As a clear, colourless solution for injection containing 10 mg/ml of
nalbuphine hydrochloride

27. Mode of action
• Nalbuphine is an agonist at kappa-opioid receptors and an antagonist at
MOP receptors;
• it thus produces analgesia (a kappa effect), whilst antagonizing both the
respiratory depressant effects and the potential for dependency that are
associated with the mu-receptor.
Routes of administration/doses
• The drug may be administered intravenously, intramuscularly, or
subcutaneously in an adult dose of 10–20 mg.
• Nalbuphine acts within 2–3 minutes when administered intravenously and
within 15 minutes when administered intramuscularly.
• The duration of action is 3–6 hours.

28. Effects
• CVS
• Nalbuphine has little significant effect on the heart rate, mean arterial
pressure, systemic or pulmonary vascular resistance, or cardiac output.
• RS
• The drug has a respiratory depressant effect equal to that of morphine but
demonstrates a ceiling effect at a dose of 0.5 mg/kg.
• It will antagonize the respiratory depressant effects of co-administered
pure mu-agonists, whilst adding to the analgesic effect of the latter.
• CNS
• Nalbuphine has an analgesic potency equivalent to that of morphine. It
has no euphoriant effects.

29. “
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