1. Alkaloids (Lecture 5) By Ms. Tehseen Quds

2. Learning Objectives At the end of this lecture students will be able to: At the end of this lecture students will be able to: Identify Opium and their alkaloids. Identify Opium and their alkaloids. Know the isolation of latex from Opium capsules. Know the isolation of latex from Opium capsules. Perform extraction of Opium alkaloids. Perform extraction of Opium alkaloids. Explain in detail about Opium alkaloids and their uses. Explain in detail about Opium alkaloids and their uses.

3. Opium Biological Source: Opium or gum opium is the air dried milky exudates obtained by incising the unripe capsules of Papaver somniferum. Annual herb.Annual herb. Term opium is from Greek Opion meaning Poppy juice.Term opium is from Greek Opion meaning Poppy juice.

4. Opium History: In 1806 Serturner isolated the alkaloid morphine from Opium. The opium poppy is grown commercially now in many countries throughout the world. History: In 1806 Serturner isolated the alkaloid morphine from Opium. The opium poppy is grown commercially now in many countries throughout the world. Cultivation and Collection: The cultivation of Opium poppy is controlled internationally by the International Narcotics Control Board of the United Nations. Cultivation and Collection: The cultivation of Opium poppy is controlled internationally by the International Narcotics Control Board of the United Nations.

5. How to obtain Latex from Capsules?

6. Latex Collection from Capsules The capsules are incised with a knife, which is usually 3- bladed and the incision is made around the circumference of the capsule. The latex which flows out at first is white, rapidly coagulates and turns brown to blackish. The capsules are incised with a knife, which is usually 3- bladed and the incision is made around the circumference of the capsule. The latex which flows out at first is white, rapidly coagulates and turns brown to blackish. Each capsules incised 4 or 5 separate times. Each capsules incised 4 or 5 separate times.

7. Latex Collection from Capsules (Continued) The congealed opium is scraped off with an iron scoop or knife before the heat makes it more tightly. The congealed opium is scraped off with an iron scoop or knife before the heat makes it more tightly. When sufficient latex is collected, it is kneaded into bails that are wrapped in poppy leaves and dried in the shade. When sufficient latex is collected, it is kneaded into bails that are wrapped in poppy leaves and dried in the shade.

8. Constituents More than 30 different alkaloids have been obtained. Most important of these are Morphine (4-21%), Codeine (0.8-2.5%), Noscapine formerly narcotine (4-8%), Papaverine (0.5-2.5%), thebaine (0.5- 2%) and narceine etc. More than 30 different alkaloids have been obtained. Most important of these are Morphine (4-21%), Codeine (0.8-2.5%), Noscapine formerly narcotine (4-8%), Papaverine (0.5-2.5%), thebaine (0.5- 2%) and narceine etc. Externally, opium is pale olive brown or olive gray. Externally, opium is pale olive brown or olive gray.

9. Extraction from Opium Powdered Opium Shaken with Calcium chloride solution and filtered Filtrate concentrated+10% NaOH solution Precipitate (Narcotine, Papaverine, Thebaine) Filtrate (Morphine, Codeine, Narceine)

10. Extraction from Opium (Continued) Filtrate extracted With Chloroform 1. Dissolve ppt. in alcohol 2. Acidify with Acetic acid 3. Add 3 volumes of boiling water Precipitate (narcotine) Aqueous Solution (Thebaine) Dissolve in boiling 0.3% oxalic acid sol and cool Aq.sol. Narcotine oxalate Crystals (Papaverine Oxalate) Chloroform Aqueous sol. Morphine, Narceine Acidify then make slightly Alkaline with Ammonia Precipitate (Morphine) Aqueous sol. (Narceine)

11. Opium Uses Pharmaceutic necessity for powdered opium. Pharmaceutic necessity for powdered opium. As an analgesic, a hypnotic, narcotic and antidiarrheal. As an analgesic, a hypnotic, narcotic and antidiarrheal. Checks excessive peristalsis. Checks excessive peristalsis. Dose: 60 mg Dose: 60 mg Prescription products: Dover’s powder and camphorated opium tincture. Prescription products: Dover’s powder and camphorated opium tincture.

12. Opium uses (Continued) Paregoric or Camphorated opium tincture is classed as an antiperistaltic. Paregoric or Camphorated opium tincture is classed as an antiperistaltic. Usual dose is 5-10ml 1-4 times a day. Usual dose is 5-10ml 1-4 times a day.

13. Poppy seeds Poppy seed or Maw seed is the dried seed of Papaver somniferum. Poppy seed or Maw seed is the dried seed of Papaver somniferum. Poppy seeds contain no significant quantity of alkaloids contains 50% fixed oil. Poppy seeds contain no significant quantity of alkaloids contains 50% fixed oil. Seed used as food and salad dressing. Seed used as food and salad dressing.

14. Opium Alkaloids Morphine Morphine and its salts are classed as narcotic analgesic. Morphine and its salts are classed as narcotic analgesic. Strongly hypnotic and narcotic. Strongly hypnotic and narcotic. Induces nausea, vomiting, constipation and habit formation. Induces nausea, vomiting, constipation and habit formation. Dose: Morphine Sulfate parentrally is 10mg 6 times a day. Dose: Morphine Sulfate parentrally is 10mg 6 times a day.

15. Codeine Codeine Most widely used opium alkaloid. It may be either obtained from opium (0.2 to 0.7%). Most widely used opium alkaloid. It may be either obtained from opium (0.2 to 0.7%). Prepared from morphine by methylation. Prepared from morphine by methylation. From thebaine by demethylation. From thebaine by demethylation.

16. Codeine Uses Narcotic analgesic and antitussives. Narcotic analgesic and antitussives. As sedative especially in allaying coughs. As sedative especially in allaying coughs. It is considerably less toxic and involves much less danger of habit formation. It is considerably less toxic and involves much less danger of habit formation. Dose: Dose: Usual doses of codeine phosphate and Codeine sulfate are Usual doses of codeine phosphate and Codeine sulfate are As analgesic: 15-60 mg every 4 hrs. As analgesic: 15-60 mg every 4 hrs. As antitussive:10-20 mg every 4-6 hrs. As antitussive:10-20 mg every 4-6 hrs.

17. Heroine Heroine Diacetyle morphine or heroine is formed by the acetylation of morphine. Diacetyle morphine or heroine is formed by the acetylation of morphine. Danger of habit formation its manufacture in the United States is forbidden by law and its use in medicine has been discontinued. Danger of habit formation its manufacture in the United States is forbidden by law and its use in medicine has been discontinued.

18. Apomorphine HCl Preparation Preparation When Rejected? When Rejected? Used as an emetic and is particularly valuable in cases of poisoning because it may be administered SC. Used as an emetic and is particularly valuable in cases of poisoning because it may be administered SC. Dose: SC is 100µg/Kg of body weight. (Max 6mg) Dose: SC is 100µg/Kg of body weight. (Max 6mg)

19. Papaverine Papaverine Occurs naturally in opium to the extent of about 1%. Occurs naturally in opium to the extent of about 1%. Used as Smooth muscle relaxant and an antitussive in combination with Codeine sulfate. Used as Smooth muscle relaxant and an antitussive in combination with Codeine sulfate. Dose: Orally 150 mg, IM 30 mg. Dose: Orally 150 mg, IM 30 mg. As antitussive 15mg. As antitussive 15mg. Products Pavabid, Pavadyl, Copavin (Comb.) Products Pavabid, Pavadyl, Copavin (Comb.)

20. Hydromorphone HCl Morphine derivative Morphine derivative Use: powerful narcotic analgesic. Use: powerful narcotic analgesic. Dose: 2 mg every 4 hrs Dose: 2 mg every 4 hrs Product: Chief ingredient in Dilaudid cough syrup. Product: Chief ingredient in Dilaudid cough syrup. Side effects Side effects

21. Hydrocodone bitartarate or Dihydrocodeinone bitartarate Hydrocodone bitartarate or Dihydrocodeinone bitartarate Codeine derivative Codeine derivative Use: As an antitussive Use: As an antitussive Dose: 5-10mg, 3 to 4 times a day. Dose: 5-10mg, 3 to 4 times a day. e.g. Dicodid and Codone e.g. Dicodid and Codone

22. Noscapine Commonly called Narcotine and Anarcotine. Commonly called Narcotine and Anarcotine. Antitussive. Antitussive. Dose: 15mg up to 4 times a day. Dose: 15mg up to 4 times a day. Available in syrup and chewable tablets. e.g. Conar and Theo-Nar. Available in syrup and chewable tablets. e.g. Conar and Theo-Nar.

23. Opioid Analgesics What “Opioid” term indicates ? What “Opioid” term indicates ?

24. References Pharmacognosy by Varro E Tyler, 10 th Edition,pp. 195-261 Pharmacognosy by Varro E Tyler, 10 th Edition,pp. 195-261 Trease and Evans, Pharmacognosy, 16 th Edition pp. 353-415. Trease and Evans, Pharmacognosy, 16 th Edition pp. 353-415. Pharmacognosy by CK Kokate, 39 th Edition, Pp.460-530 Pharmacognosy by CK Kokate, 39 th Edition, Pp.460-530 www.google.com www.google.com www.google.com