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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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