Opioids

Opioids

1. OPIODS By: Mrs. Kalaivani Sathish M. Pharm Assistant Professor, PIMS - Panipat

2. OPIODS Opiod analgesics are one of the oldest remedies for relief pain. Opium is the dark brown gummy exudate obtained from the poppy capsule ( papaver somniferum ) Opium has been in use since 4000BC.

3. CLASSIFICATION Based on receptor occupation 1.Agonists A.Natural opium alkaloids Morphine ,codeine, B.Synthetic opioids Pethidine,Methadone

4. CLASSIFICATION 2.Andagonists Naloxone,naltrexone Mixed agonist antagonists Pendazocine,nalpurine,butorphanol , Buprenorphine,nalorphine

5. CLASSIFICATION CHEMICALLY THE OPIUM ALKALOIDS CAN BE GROUPED INTO 1.THE PHENANTHRENE GROUP Morphine,codeine,thebaine 2.The benzylisoquinoline group Papaverine,noscapine,narcine

6. CLASSIFICATION Opioids can also be classified depending on their sources as: A.Natural opium alkaloids Morphine , codeine,noscapine B.Semisynthetic derivative Heroin,oxymorphone,pholcodeine c.Synthetic opioids Pethidine,Methadone,loperamidefentanyl

7. MORPHINE Morphine is the most important alkaloid of opium.many new opioids with actions similar to morphine have been synthesized .

8. Mechanism of action Morphine and other opioids produce their effects by acting on specific opioid receptors mu(  ),kappa( k)and delta(  ).these receptors are present in the CNS and other tissues. Stimulation of opioid receptors finally results in a decrease in the intracellular calcium which in turn decrease the release of neurotransmitters.

9. In CNS mu (  ),kappa( k)and delta(  ) receptors Stimulation of opioid receptors (Morphine) Decrease the Intra cellular Calcium Level Decrease the release of Neurotransmitter It decreases the visceral Pain

10. Pharmacological action 1.Analgesia: Morphine is a potent analgesic and relieves pain without loss of consciousness.in higher doses it relieves severe pain as that of biliary colic. 2.Euphoria ,sedation and hypnosis Rapid IV inj of morphine produces a warm flushing of the skin and an immensely pleasurable sensation in the lower abdomen about 45 sec.it also produces drowsiness ,a calming effect,inability to concentrate , indifferance to surroundings.

11. Pharmacological action 3.Respiration Morphine produce respiratory depression. It directly depresses the respiratory center in the brain stem.Death from morphine poisoning is almost always due to respiatory arrest. 4.Cough center It directly depress the cough center and thereby suppress cough.opioids should be used as antitussive only in the dry cough

12. Pharmacological action 5.Nausea and emesis Morphine directly stimulates the CTZ in the medula causing nausea and vomitting.in higher doses it depress the vomitting center and hence there is no vomitting in poisoning . 6.pupil Morphine produces miosis resulting in a characteristic pinpoint pupil in high doses. 7.vagus Morphine stimulates vagal center causing bradycardia .

13. PHARMACOLOGICAL ACTION 8.Heat regulation Opioids shift the equlibirium point of heat regulating center so that body temperature falls slightly. 9.Truncal rigidity Higher dose of fentanyl found to enhance the tone of the large trunk muscles by acting at supraspinal levels. 10.Excitatory effect In high doses opioids produce convulsion

14. PHARMACOLOGICAL ACTION Cardiovascular system In therapeutic dose morphine produces hypotension by; Direct peripheral vasodilatation. Inhibition of baroreceptor reflexes. In higher doses ,it causes depression of vasomotor center and histamine release both contributing to a fall in BP.

15. PHARMACOLOGICAL ACTION GIT Opioids decrease the motility of the gut. Stomach: Gasric motility is decreased resulting in increased gastric empting time.gastric acid secretion is reduced. Intestine : Morphine diminises all secretions,delays digestion of food in the small intestine.

16. PHARMACOLOGICAL ACTION Other Smooth Muscles Biliary tract – Morphine causes spasm of the sphincter of Oddi . Atrophine partially antagonise this . Urinary Bladder and Ureter – Opioids inhibit urinary voiding reflex, as a result of this urinary retention occurs especially in the elderly males with Prostatic hypertrophy. Uterus – No significant effect, may prolong labour in high doses. Bronchi –Morphine causes release of histamine from the mast cells leads to broncho constriction.

17. PHARMACOLOGICAL ACTION Other Smooth Muscles Biliary tract – Morphine causes spasm of the sphincter of Oddi . Atrophine partially antagonise this . Urinary Bladder and Ureter – Opioids inhibit urinary voiding reflex, as a result of this urinary retention occurs especially in the elderly males with Prostatic hypertrophy. Uterus – No significant effect, may prolong labour in high doses. Bronchi –Morphine causes release of histamine from the mast cells leads to broncho constriction.

18. PHARMACOKINETICS Given Orally, absorption of morphine is slow and incomplete. Morphine undergoes first pass metabolism.

19. Absorbed well in Orally Metabolized in Liver Excreted by kidney

20. ADVERSE EFFECTS Nausea, Vomiting Respiratory Depression Dysphoria (State of being Unhappy) Dizziness Hypotension Skin Rashes

21. TOLERANCE Tolerance is defined as the capacity of the body to endure or become less responsive to a substance. Lethal dose of Morphine is 250 mg, addict can tolerate morphine in gm.

22. DEPENDENCE Its ability to produce euphoria, makes it a drug of addiction. Opioids produce both psychological and physical dependence.

23. MANAGEMENT OF ADDICTION Morphine slowly withdrawn over several days and substituted by oral Methadone. Later on methadone is gradually withdrawn. Acute Morphine Poisoning Symptoms includes respiratory depression, with shallow breathing, pinpoint pupils, hypotension, shock, coma and death.

24. Acute Morphine Poisoning Treatment Positive Pressure Respiration Maintenance of BP Gastric lavage with potttasim permanganate to remove unabsorbed drug. Specific antidote is Naloxone 0.4 to 0.8 mg IV repeated every 10 to 15 minutes.

25. OTHER OPIOIDS Heroin It is converted to morphine in the body. It has higher lipid solubility. It gives euphoric effects faster and greater. It is used as analgesics and banned in most countries.

26. OTHER OPIOIDS CODEINE It is Commonly used anti tussives . It is also available with Paracetamol for analgesia.

27. OTHER OPIOIDS DEXTROMETHORPHAN It acts centrally to elevate the threshold for coughing. It is effective as codeine.

28. OTHER OPIOIDS TRAMADOL It is an effective analgesic, it is a weak opioid agonist.

29. OTHER OPIOIDS PETHIDINE It produce corneal anesthesia . It has anticholinergic effects, it cause dry mouth and blurring of vision Dose and Uses – 25 – 100 mg IM. SC. Used as analgesics in visceral pain. Given as pre anesthetc medications Adverse Effects – it is similar to morphine.

30. OTHER OPIOIDS fentanyl It is about 100 times more potent than morphine. It is highly lipid soluble and fast acting. Epidural fentanyl is used for postoperative and obstetric analgesia It can also used in chronic pain . ADVERSE EFFECT Cough muscle rigidity, Nausea & Vomiting Respiratory Depression

31. OTHER OPIOIDS (METHADONE) It is a synthetic opioids and mu receptors agonist. Its action is similar to morphine. It is an effective analgesic and is more effective when administered via oral, rectal, SC, IV and Spinal route. It is effective for certain Cancer Pain, which are not relieved by morphine. It has a long duration of action. Dose – 10 mg oral or IM.

32. OPIOIDS ANTAGONISTS Naloxone It is a pure antagonist, does not produce any significant action. It antagonise the morphine action, especially respiratory depression, sedation and precipitate morphine withdrawal syndrome. Given orally, it undergoes first pass metabolism, hence it is given IV. Dose – 0.4 mg IV. Uses – Drug of choice for Morphine Over Dose. It can also be used for diagnosis of opioid dependence.

33. OPIOIDS ANTAGONISTS Naltrexone It is another pure opioid antagonist. It is more potent than naloxene . Orally Effective Uses – To prevent the relapse of heavy drinking of alcohol.

34. MIXED AGONIST & ANTAGONIST Pentazocine are similar to morphine. 20 mg pentazocine is equal to 10 mg morphine. Sedation and respiratory depression are less marked. Doses – 50 – 100 mg oraL 30 – 50 mg IM Uses – Used as opioid analgesics especially in post operative and chronic pain. Adverse Effect – Sedation, Sweating, Anxiety, Hallucination.

35. MIXED AGONIST & ANTAGONIST Nalorphine is also an agonist – antagonist. At low doses it is a good analgesics, but increase in dose no increase in analgesic effect. It causes dysphoria , respiratory depression. Uses – It may be usesd in acute opioid poisoning and it is used for the diagnosis of opioid addiction.

36. NURSING IMPLICATIONS Respirations should be monitored closely while patients are in opioids . Watch for signs of tolerance in patients while patient is using this drug for a prolong periods. Antidote must be kept readily available for use in case of emergency.