1. School of Pharmacy, University of Nizwa
Narcotic Analgesics
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-28
April 16, 2012

2. Pain
An unpleasant sensation that can be either acute or chronic and that is a consequence of complex neurochemical processes in both PNS and CNS

3. Mechanism of Pain
Pain is usually triggered by a potentially harmful peripheral stimulus. The perception of such stimuli is termed nociception

4. Analgesics Analgesics: Drugs which relieve the pain
Types of analgesics:
Opioid or narcotic analgesics
Non-narcotic analgesics

5. Site of Action of Analgesics
Site of injury: By interfering with the chemical mediators involved in nociception
Blocking transmission in peripheral nerves: As with local anesthetics
Modifying transmission at the dorsal horn: Explains some of the actions of opioids and antidepressants that inhibit reuptake of 5-HT and noradrenaline
Interfering with the central appreciation of pain: An important mode of action of the opioids

6. Opioid Receptors
High affinity for opioid analgesics, present in neuronal membranes
Found in limbic system, thalamus, hypothalamus, medulla oblongata and the substantia gelatinosa
Types of opioid receptor:
μ (mu)
δ (delta)
κ (kappa)

7. Functions of Opioid Receptors
μ (mu) receptor:
Analgesia
Sedation
Respiratory depression
Decreased GI motility
δ (delta) receptor:
Dysphoria
κ (kappa) receptor:
Dysphoria: unpleasant mood

8. Classification of Opioid Analgesics
Agonists
Fentanyl
Heroin
Meperidine
Methadone
Morphin
Codeine
Mixed Agonist/Antagonist
Pentazocine
Antagonists
Naloxone
Naltrexone

9. Narcotic Drug: Mechanism of Action
Exert their effects by entering the brain and binding to opioid receptors
Pharmacological activity depends on their affinity for the various receptors and whether they are full or partial agonists
Morphine: Mechanism of Actions
Morphine acts as a full agonist on opioid receptors (especially μ, but also δ and κ) in the brain and spinal cord

10. Morphine: Clinical Use
The most important use of morphine is for pain relief
More effective in relieving continuous dull pain than sharp intermittent pain 
Diarrhoea
Anti-tussive: depresses the cough center and has been used in small doses to treat cough

11. Morphine: Pharmacokinetics
Well absorbed orally or by s.c., i.m. or i.v. injection
After intramuscular injection the peak therapeutic effect is achieved in about 1 hour and it lasts for 3-4 hours
Morphine is metabolized largely by glucuronic acid
Metabolism occurs in the liver and gut wall and the oral bioavailability of morhine is 16-64%
Morphine: Adverse Effects
Respiratory depression, vomiting, constipation

12. Heroin (Diamorphine) Heroin is diacetylmorphine
Actions are similar to those of morphine although it is more potent as an analgesic when given by injection
More rapid central effect than morphine, due to rapid penetration of the blood-brain barrier
Use:
Used for the same purposes as morphine
Adverse Effects: 
Same as morphine

13. Codeine It is a natural content of opium
About one-tenth of analgesic potency of morphine
Use:
Used for many years as an analgesic, as a cough suppressant and for symptomatic relief of diarrhea
Adverse effects:
Constipation and nausea

14. Pentazocine
Partial agonist on opioid receptors (especially κ-receptors). It blocks μ receptors also
At high doses, can increase blood pressure and heart rate
Pentazocine induces withdrawl symptoms in patients already on morphine

15. Naloxone
Used to reverse the coma and respiratory depression of opioid overdose
Also, able to reverse the effect of a heroin overdose
Half-life is 60 to 100 minutes
A competitive antagonist at μ, κ and σ receptors, with a 10-fold higher affinity for µ than for κ receptors

16. Withdrawal Reactions Acute Actions Withdrawal Signs Analgesia
Respiratory Depression
Relaxation and sleep
Tranquilization
Decreased blood pressure
Constipation
Pupillary constriction
Drying of secretions
Warm skin
Withdrawal Signs
Pain and irritability
Hyperventilation
Restlessness and insomnia
Fearfulness
Increased blood pressure
Diarrohea
Pupillary dilation
Lacrimation, runny nose
Chilliness