1. Phytochemistry II Professor Suleiman Olimat

2. Isoquinoline Alklaoids

3. Tetrahydroisoquinoline

4. Ipecacuahna alkaloids Ipecacuahna alkaloids: Rhizome of Cephalis ipecacuhana Rubiaceae Emetine and Cephaline alkaloids

5. Chemistry R= CH3: Emetine R= H: Cepheline

6. Ipecac Syrup -Ipecac is used in the emergency treatment of certain kinds of poisoning. It is used to cause vomiting of the poison. -Only the syrup form of ipecac should be used. - Ipecac Fluidextract or Ipecac Tincture should not be used. These dosage forms are too strong and may cause serious side effects or death. -Only ipecac syrup contains the proper strength of ipecac for treating poisonings. Ordinarily, this medicine should not be used if strychnine, corrosives such as alkalies and strong acids, or petroleum distillates such as kerosene, gasoline, coal oil, fuel oil, paint thinner, or cleaning fluid have been swallowed. It may cause seizures, additional injury to the throat, or pneumonia.

7. Dosing For treatment of poisoning: Adults and teenagers—The usual dose is 15 to 30 milliliters (mL) (1 to 2 tablespoonfuls), followed immediately by one full glass (240 mL) of water. The dose may be repeated one time after twenty to thirty minutes if vomiting does not occur. Children 1 to 12 years of age—The usual dose is 15 mL (1 tablespoonful). One-half to one full glass (120 to 240 mL) of water should be taken right before or right after the dose. The dose may be repeated one time after twenty to thirty minutes if vomiting does not occur. Children 6 months to 1 year of age—The usual dose is 5 to 10 mL (1 to 2 teaspoonfuls). One-half to one full glass (120 to 240 mL) of water should be taken right before or right after the dose. The dose may be repeated one time after twenty to thirty minutes if vomiting does not occur. Children up to 6 months of age—Ipecac must be given only under the direction of your doctor.

8. Ipecac misuse Some people who have bulimia nervosa or anorexia nervosa use ipecac regularly to make themselves vomit. If used too often, ipecac can cause:Ipecac Abusebulimia nervosa. Ipecac abuse can result in severe medical complications and even death. Diarrhea.Diarrhea Drowsiness. Coughing or choking. Low blood pressureLow blood pressure and a rapid heartbeat. Chest and stomach pain.stomach pain Breathing problems. If this product is abused or if too much of it is absorbed into the body, it can cause serious heart problems, such as cardiomyopathy, atrial fibrillation, or myocarditis, all of which can lead to death.heartcardiomyopathyatrial fibrillationmyocarditis

9. Goldenseal Goldenseal: Root and rhizomes Hydrastis canadensis Ranunculaceae

10. Benefits and uses Goldenseal has both internal and external applications. It is taken orally to alleviate colds and fevers, stop recurrent ear infections, and stimulate the immune system. Its ability to counter microbes and parasites makes it useful in conditions such as vaginitis and urinary tract infections, and digestive ailments such as infectious diarrhea. Can be used topically for its anti-inflammatory and antiseptic actions, which make it useful to clean wounds, reduce hemorrhoids, soothe canker sores, and alleviate skin infections (including ringworm and athlete’s foot). It can also help treat eye infections such as conjunctivitis and blepharitis.

11. Active Constituents Goldenseals benefits can be attributed to its alkaloids, especially hydrastine and berberine. The latter is also responsible for its characteristic golden color. The alkaloids are strongly astringent and help reduce inflammation of the mucous membranes. Hydrastine has also been reported to lower blood pressure and stimulate peristalsis (bowel elimination) Berbine and its sulfate, berberine sulfate have been demonstrated to have anticancer activity in vitro and also have been shown to have antibacterial, anti-fungal and immunostimulatory activity, as well. Berberine has shown marked effects on acute diarrhea and its antibacterial qualities interfere with the ability of microorganisms to adhere to the walls of host cells.

12. Chemistry Hydrastine

13. Curare Common Names: Curare Genus: Chondrodendron Species: tomentosum Parts Used: Leaf, Root Curare grows as a large liana, or vine, found in the canopy of the South American rainforest.

15. Curare arrow poison The active ingredient in "curaré", D-tubocurarine, is used in medicine. Curare acts as a neuromuscular blocking agent to produce paralysis in muscles. It first affects the muscles of the toes, ears, and eyes, then those of the neck, arms and legs, and finally, those involved in breathing. In fatal doses, death is caused by respiratory paralysis. Curare must get into the blood system for it to work. It doesn't hurt to eat something killed by a poisoned curare arrow, for instance.

16. Bamboo

17. Tubocurarine

18. Bisbenzylisoquinoline d-tubocurarine.is a bisbenzylisoquinoline alkaloid. The alkaloid works by blocking the signals in the brain which tell the muscles to move - thereby rendering the whole body immobile to the point of becoming virtually paralyzed. It's not a toxin - and the effects generally wear off in about 90 minutes. In 1942 curare and d- tubocurarine were introduced into clinical anesthesia, starting the modern era of surgery. Today it is still sold as a prescription drug which is used as a general anesthetic and muscle relaxant in various types of surgeries (during which breathing can be controlled with machines)

19. Structures of d-tubocurarine analogs. The distance between the 2 Nitrogen atoms is 14 Å

20. Opium alkaloids Opium contains a complex mixture of almost twenty- five alkaloids. The principle alkaloid in the mixture, and the one responsible for analgesic activity, is morphine,named after the Roman god of sleep—Morpheus. Morphine is still one of the most effective painkillers available to medicine. It is especially good for treating dull, constant pain rather than sharp, periodic pain. It acts in the brain and appears to work by elevating the pain threshold, thus decreasing the brain's awareness of pain

21. Papaver somniferum opium, opium poppy originated in western Mediterranean & Near East dried latex from immature fruit capsules traditionally used as an analgesic, inebriant, hypnotic, and treatment for diarrhea

22. History 3000 BC – first records of use; 2500 BC – Sumerian “joy plant” Romans/Greeks – familiar with opium Europe – 1525, rediscovery of solution of opium in alcohol = laudanum (Paracelsus) Chinese – first introduced in 7th century AD by Arab traders Banned by government British trade policies  forced Chinese to trade for opium 1803 – morphine purified  able to deliver it in defined doses Potent painkiller, but problem – addictive

23. narcotics The term "narcotic" is believed to have been coined by the Greek physician Galen to refer to agents that numb or deaden, causing loss of feeling or paralysis. It is based on the Greek word (ναρκωσις =narcosis), the term used by Hippocrates for the process of numbing or the numbed state.Galen Hippocrates Narcotics refer to opium, opium derivatives, and their semi-synthetic or fully synthetic substitutes. Typical classes of narcotics include morphine, opium, and heroine.

24. Papaver Alkaloids- Opiates Fig. 11.6, p. 279

25. Papaver somniferum opium contains 20 alkaloids, including: morphine (  heroin) codeine papaverine thebaine noscapine

26. Papaver somniferum Therapeutic uses: morphine = analgesic, morphine named after the Roman god of sleep—Morpheus. codeine = analgesic, antitussive noscapine (narcotine) = antitussive Papaverine: smooth muscle relaxant Mechanism of analgesis: stimulation of opiate receptors inhibits the release of substance P, the neurotransmitter responsible for inflammatory responses and pain

27. Natural Morphine

29. Narcotics and addiction It is the neurological effects of narcotic drugs that make them addictive. Narcotics bind to painkilling sites throughout the brain, known as opioid-u receptors, or the "reward pathway. " This leads to slower uptake of neurotransmitters such as dopamine between neurons. Immediate effects include cessation of pain, drowsiness, and a feeling of well-being associated with pain reduction. Addiction occurs when the brain stops producing its own natural painkilling chemicals, called endorphins, and depends on the narcotics instead.neurologicalneurons

30. What is addiction? (Latin) addictus---attached to something, positive. Today alcoholism called a “brain disease”or bad habit or sin. Leading assumption of the text: Addiction is the key, not the substance or behavior Addiction defined by researchers as “a bad habit,” “a brain disease,” “helplessness,” “a problem of motivation”

31. Nicotine Causes Addiction

32. Dependence With repeated use of narcotics, tolerance and dependence develop. The development of tolerance is characterized by a shortened duration and a decreased intensity of analgesia, euphoria and sedation, which creates the need to administer progressively larger doses to attain the desired effect. Tolerance does not develop uniformly for all actions of these drugs, giving rise to a number of toxic effects. Although the lethal dose is increased significantly in tolerant users, there is always a dose at which death can occur from respiratory depression. Physical dependence refers to an alteration of normal body functions that necessitates the continued presence of a drug in order to prevent the withdrawal or abstinence syndrome.dependencewithdrawal

33. Withdrawal Symptoms The withdrawal symptoms experienced from opioid addiction are usually first felt shortly before the time of the next scheduled dose. Early symptoms include watery eyes, runny nose, yawning and sweating. Restlessness, irritability, loss of appetite, tremors and severe sneezing appear as the syndrome progresses. Severe depression and vomiting are not uncommon. The heart rate and blood pressure are elevated. Chills alternating with flushing and excessive sweating are also characteristic symptoms.

34. Psychological Dependence The psychological dependence that is associated with narcotic addiction is complex and protracted. Long after the physical need for the drug has passed, the addict may continue to think and talk about the use of drugs. There is a high probability that relapse will occur after narcotic withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered.think

35. Papaverine Papaverine Hydrochloride, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.

36. CLINICAL PHARMACOLOGY The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Papaverine Hydrochloride apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.

37. INDICATIONS AND USAGE Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such asvascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal Given as Papaverine HCl Injection

38. Apomprphine HCl Apomorphine hydrochloride is synthesized by heating stoichiometric amounts of morphine and concentrated hydrochloric acid at 140ºCstoichiometricmorphinehydrochloric acid

39. Therapeutic indications Apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The ''apo''- prefix relates to it be an aporphine derivative.Historically, apomorphine has been tried for a variety of uses including psychiatric treatment of homosexuality in the early 20th century, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Parkinson's disease. opioid receptoraporphinetreatment of homosexualityerectile dysfunctionParkinson's disease The treatment of disabling motor fluctuations (“on-off” phenomena) in patients with Parkinson's disease which persist despite individually titrated treatment with levodopa (with a peripheral decarboxylase inhibitor) and/or other dopamine agonists.

40. Posology and method of administration Apomorphine hydrochloride is for subcutaneous use by intermittent bolus injection. Apomorphine hydrochloride may also be administered as a continuous subcutaneous infusion by minipump and/or syringe driver. Apomorphine hydrochloride may be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection or Water for Injections. Apomorphine must not be used via the intravenous route.