OPIOID ANALGESICS & ANTAGONISTS

Narcotics ( or opiates) MAINLY OBTAINED FROM OPIUM POPPY. ACT BY BINDING TO SPECIFIC OPIOID RECEPTORS IN THE CNS. MAINLY USED FOR RELIEVING INTENSE PAIN. EUPHORIC PROPERTIES ANTAGONISTS IMPORTANT IN OVERDOSE.

OPIOID RECEPTORS 4 TYPES Mu ( µ ) Kappa ( к ) Delta ( δ ) Sigma ( σ )

Mu ( µ ) Location : supraspinal areas of pain modulation (periaqueductal gray, medial thalamic nuclei, hypothalamus, limbic system) Response : Supraspinal analgesia, euphoria, respiratory depression, sedation, physical dependence, pupil constriction, decreased GI motility. Abuse potential : High

Kappa ( к ) Location: Dorsal horn of spinal gray matter (substantia gelatinosa ); deep layers of cerebral cortex. Response: Spinal analgesia, sedation, depressed flexor reflexes, pupillary constriction. Abuse potential: Low

Delta ( δ ) Location : Substantia nigra, globus pallidus, corpus striatum, other limbic structures. Response: Euphoria, sedation Abuse potential : Low

Sigma ( σ ) Location : Hippocampus. Response : Dysphoria, Hallucinations, cardiovascular stimulation, pupil dilatation. Abuse potential : Low

Other than these responses, Some of them are involved in depression of cough , ↑ nausea, ↑ vomiting, neuroendocrine actions, maintainance of B.P, control of stomach secretions, and also anti-inflammatory effects.

Strong Agonists Morphine Fentanyl Heroin Meperidine Methadone Sufentanil

Moderate Agonists Codeine Propoxyphene

Mixed agonist - antagonist Buprenorphine Pentazocine

Antagonists Naloxone Naltrexone

MORPHINE Main agonist actions on Mu, and also for Kappa and Sigma receptors ACTIONS: - Analgesia – relief of pain without loss of consciousness. - Euphoria - Causes Respiration Depression (This is the most common cause of death in acute opioid overdose)

- Depression of cough reflex MIOSIS – PINPOINT PUPIL. Stimulation of the edinger westphal nucleus of oculomotor nerve which causes parasympathetic stimulation of the eye. Emesis.—stimulates chemoreceptor trigger zone (CTZ) in area postrema - GIT : ↓ motility, relieves diarrhea and dysentery - CVS : high doses cause hypotension and bradycardia

- Cerebral vessels dilate - ↑ CSF pressure ( CI – severe brain injury) - Histamine release causes bronchoconstriction, urticaria, sweating and vasodilation. - Hormonal actions – ( increase in prolactin, GH and ADH)

Morphine is used legally: As an analgesic in hospital settings to relieve Pain in Myocardial Infarction Pain after surgery Pain associated with trauma In the relief of severe chronic pain, e.g. Cancer pain Pain from kidney stones Severe Back pain

As an adjunct to general anesthesia In epidural anesthesia or intrathecal analgesia For palliative care (i.e. to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible) As an antitussive for severe cough In nebulised form, for treatment of dyspnea, although the evidence for efficacy is slim. Evidence is better for other routes .

As an anti-diarrheal in chronic conditions (e. g As an anti-diarrheal in chronic conditions (e.g., for diarrhea associated with AIDS), although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea.

contraindications acute respiratory depression acute pancreatitis (this may be a result of morphine use as well) because morphine may cause spasm of the sphincter of Oddi and worsen the pain renal failure (due to accumulation of the metabolite morphine-6-glucuronide) chemical toxicity (potentially lethal in low tolerance subjects) raised intracranial pressure, including head injury (exacerbation due pCO2 increases from respiratory depression)

SE Sedation Constipation Nausea Vomiting Urinary retention Potential for addiction Resp. depression

Drug interactions: MAO Inhibitors (monoamine oxidase inhibitors ) TCA’s(tricyclic antidepressant) Antipsychotic

MEPERIDINE (Pethidine ) MECH : Binds to Kappa receptors. Actions : Analgesia Resp. depression IV route can cause increase in H.R. Dilates pupil Decreases GI motility ↑ CSF pressure

USES: Any kind of analgesia – preferred for labor analgesia Not used for diarrhea or cough Can replace morphine or heroin in addicts. Route : oral and parental Met : liver Exe : Urine

SE Tremors Muscle twitches Convulsions Dilates pupil Not given with other neuroleptics and MAO inhibitors. Cause hypotension – postoperative.

METHADONE MECH: More on Mu receptors Equal potency to Morphine, but less euphoric and longer duration of action. Actions: Mostly same as morphine. Route : oral Met: Liver Exe: Urine

USES : Analgesia Addicts of heroin and morphine – for withdrawal . SE: Less severe than morphine.

FENTANYL AROUND 100 TIMES MORE POWERFUL ANALGESIC THAN MORPHINE, SO USED during ANESTHESIA Rapid action and short duration of action. Main action is on Mu, and also on kappa sigma receptors.

HEROIN 2-3 times more potent than morphine. More euphoria No therapeutic uses Addiction

PROPOXYPHENE Derivative of Methadone Analgesic for mild to moderate pain Sometimes used in combination with aspirin or acetaminophen - ↑ analgesia Also has antitussive action (used for cough)

SE Nausea, Constipation High doses can cause Resp depression, Convulsion Confusion, Hallucinations Cardiotoxicity, Pul. edema These effects can be antagonized by Naloxone.

CODEINE Good antitussive, Less analgesic than morphine Causes euphoria Sedation Addiction So, many of the newer cough medications do not contain codeine It has been replaced by dextrometharphan

PENTAZOCINE AGONIST ON Kappa AND Partial ANTAGONIST ON Mu & delta. Moderate pain Oral or parental Less euphoric than morphine Not used with morphine.

SE At high doses Increase B.P Hallucinations Night mares Tachycardia Dizziness Resp depression

BUPRENORPHINE AGONIST Mu receptors Parenteral Moderate pain Morphine withdrawal SE: Resp depression Nausea, dizziness

NALOXONE OPIOID ANTAGONIST Rapidly reverse the effects of opioids, which can increase withdrawal symptoms Reverse the coma and resp depression of opioid overdose. IV route – In 30 sec shows significant changes in resp depression and coma. Precipitates the withdrawal symptoms in morphine and heroin abusers.

NALTREXONE SAME AS NALOXONE Longer duration of action than naloxone Oral route Used in opiate dependence maintainance programs.