Analgesics

1. Analgesics

2. 1. Discuss the three different ways in which drugs can be administered by injection. State three other ways in which drugs can be administered. 2. The therapeutic window gives information on the amount of a drug that can be safely administered to give the desired effect without causing adverse harm. It is effectively the safety range of the drug and is related to the therapeutic index. Therapeutic index = LD50 / ED50 Explain what is meant by Effective Dose 50 and Lethal Dose 50 and discuss the problems associated with determining the LD50. 3. Discuss the term ‘side effects’ in relation to the two drugs aspirin and morphine. 4. Explain why morphine is usually administered as a salt (morphine sulfate or morphine hydrochloride) rather than in its pure form.

3. 5. The image below shows a child victim of thalidomide. Discuss why the ‘thalidomide story’ was more of a scandal than simply a tragedy.

4. 1. Drugs can be injected under the skin (subcutaneous), into the muscle (intramuscular) and directly into a vein (intravenous). Injecting directly into a vein produces the quickest reaction that affects the whole body. Subcutaneous injections are used for topical effects such as for local anaesthetics. Three other ways in which drugs can be injected are by mouth (orally), by inhalation and through the anus (rectally). Drugs can also be applied topically on the surface of the skin.

5. 2. The ED50 is the dosage of the drug required to bring about a noticeable effect in fifty percent of the population. The LD50 is the dosage required to bring about the death of 50% of the animal population to whom the drug has been administered. Determining the LD50 causes the ethical problem that animals must be killed in the interests of scientific research. There is also the problem that different animals react to drugs in different ways so there is no easy way to extrapolate the finding to human beings.

6. 3. Side effects are the unwanted effects of a drug. They may be mild or severe and possibly even life-threatening and can vary from person to person. If aspirin is taken as an analgesic (pain killer) then common side effects include bleeding of the stomach and also thinning of the blood. However this second ‘side effect’ of aspirin can alter the reason why aspirin is taken and become the main effect when aspirin is prescribed for people at risk of heart problems or a stroke to lower the risk of blood clotting. Similarly one of the side effects of morphine, which is a strong pain killer, is constipation and sometimes morphine is prescribed for someone suffering from diarrhoea. Other unwanted side-effects of morphine can include headaches, nausea and dizziness as well as the possibility of addiction.

7. 4. Morphine acts directly on the central nervous system. Morphine itself is only sparingly soluble in water. Because they are far more polar, ionic salts of morphine are considerable more soluble in water so enable the morphine to be carried around the body more effectively.

8. 5. Thalidomide was introduced as a sedative in the 1950s. It was found to be an effective anti-emetic and was given to pregnant women to prevent morning sickness. At that time no real research had been done on the possibility of drugs crossing the placental barrier to the foetus. The drug was produced by a German company called Grünenthal and by the Distillers Company in the UK. Although their own research showed some problems they did not initially withdraw the drug even when there were reports that babies were being born with severely deformed limbs. This was because they were making large profits from its sales. The drug was eventually withdrawn in the early 1960s after more than 10,000 babies had been born with the deformities. In 1968 a successful court case led to the Distillers Company paying out a large sum of money in compensation. Since the thalidomide affair there has been a much stricter policy of regulating and licensing new drugs.

9. What is pain? An unpleasant sensory and emotional experience associated with actual or potential tissue damage.

10. What are pain receptors and their functions. Pain receptors in our bodies are nerves that transmit pain. These are free nerve endings located in various body tissues that respond to thermal, mechanical and chemical stimuli. When stimulated, these pain receptors generate an impulse. The pain results of various impulses arriving at the spinal cord and the brain. When tissues become injured, they release chemicals called prostaglandins and leukotrienes that make the pain receptors more sensitive and thus causing pain.

11. Definition of analgesics and categories Analgesics are drugs that relieve pain. These are: Mild analgesics: used for relief of mild pain. (aspirin, acetaminophen) Strong analgesics: used for relief of very severe pain.(morphine, heroin, codeine) Local anesthetics: used as pain killers in localized areas.(lidocaine, procaine) General anesthetics

12. Mild analgesics They work by blocking the enzyme-controlled synthesis of prostaglandins. The main effects prostaglandins are: The constriction of blood vessels, which helps increase the body temperature. Direct effect on the body’s heat regulating centre, hypothalamus, which produces fever. Increase of the permeability of capillaries which allows water to pass to the tissue and cause pain and swelling.

13. Natural painkillers They are produced naturally in the body. Endorphins and enkephalins are the natural opiates found in the part of the brain and the spinal cord that transmit pain impulses. They are able to bind to neuro-receptors in the brain and produce relief from pain. The temporary loss of pain immediately after an injury is associated with the production of these chemicals.

14. Salicylic acid-Aspirin Salicylic acid was widely used as a fever reducer However, it is relatively strong acid so it was unpleasant to take orally and it damaged the membranes lining the mouth, esophagus and stomach. Sodium salicylate (its salt) was used but it was also highly irritating to the stomach. Its ester called Acetyl Salicylic Acid (ASA) named aspirin retains the beneficial properties of salicylic acid but is less irritating to the stomach. ASA is relatively tasteless so it can be taken orally.

16. Uses of derivatives of salicylic acid As mild analgesic for minor aches and pains. As an antipyretic. As an anti-inflammatory agent when there is swelling from injuries. As an anti-clotting agent in the prevention of abnormal blood clotting and as an anti clotting agent after heart surgery.

17. Disadvantages of Aspirin Aspirin can cause stomach upset and internal bleeding due to its acidic nature. There is a risk of developing severe gastrointestinal bleeding following use of alcohol. 0,5% are allergic to aspirin leading to skin rashes, respiratory difficulty and even shock Aspirin is one of the most frequent causes of accidental poisoning in infants. The taking of aspirin by children under twelve has been linked to Reye’s disease (a fatal liver and brain disorder with the symptoms of vomiting, lethargy, irritability and confusion.)

18. Aspirin substitutes (Acetaminophen) Acetaminophen is the metabolic byproduct of phenacetin and is active ingredient of many over-the-counter drugs (OTC) It is like aspirin as it is an anti-pyretic. It is an analgesic to reduce mild pain. It does not upset the stomach or cause bleeding. It is not an effective anti inflammatory drug. It is a safe drug when it is used in the correct dose BUT can rarely cause side effect such as blood disorders and kidney damage. In great dose (>20 tablets) can cause serious liver damage, brain damage, coma and even death.

19. Phenacetin

20. Aspirin substitutes(Ibuprofen) Ibuprofen has many of the same effects as aspirin but seems to cause fewer stomach problems. It is an anti-inflammatory drug. It is effective in low doses and has a wide margin of safety. In great dose has similar side effects as ASA.

22. Strong Analgesics • Only Available by prescription • Used to relieve severe pain associated with injuries, heart attacks, or chronic diseases such as cancer • Most strong analgesics are derived from the opium poppy or synthetically produced • Basically two types: Natural • and synthetic

23. Strong analgesics They temporarily bind to the opiate receptor sites in the brain preventing the transition of pain impulses -The opium alkaloids: Opiate: it is a natural or synthetic drug that exerts actions on the body similar to those induced by morphine. Narcotic: is a term generally used for drugs that have both a narcotic and analgesic action.

24. morphine, heroin and codeine Morphine is the principal alkaloid and makes up about 10% by mass of raw opium. Codeine makes up about 0.5% by mass of raw opium. Heroin is usually synthesized from morphine and thus is a semi-synthetic drug and it is obtained by relatively simple structural modification of morphine or codeine.

25. Naturally occurring in the poppy- Only needs to be isolated Very strong pain reliever but also very addictive (2nd to Heroin) Usually injected but can be smoked, sniffed or swallowed Commonly used in hospitals Large illegal street culture Morphine

26. Most commonly used strong analgesic Similar to Morphine except for the replacement of a (OH-) group for (OCH3) group Commonly used with Tylenol as a more mild analgesic 1/6 as strong as Morphine and less addictive Codeine

27. Originally sold as cough suppressant and pain killer10 times stronger than Morphine Incredibly addictive (many times, other strong analgesics are needed for withdrawal) Heroin

28. Synthesized from morphine in a esterification reaction with acetyl chloride It is absorbed by the brain very quickly resulting in a potent high Many other problems are associated with heroin addiction including as prostitution and AIDS. Heroin

30. Opium plant Morphine

31. Advantages and disadvantages of opiates. Pharmacological effects: Opiates exert major effects on: The central nervous system. The eye The gastrointestinal tract (the digestive system) The prime medical uses of opiates are: As strong analgesic in the relief of severe pain caused by injury and chronic disease. In the treatment of diarrhea by producing a constipating effect. To relieve coughing by suppressing the “cough centre” situated in the brain system.

32. Advantages and disadvantages of opiates. Physiological effects of opiates: Opiate produce: Analgesia Drowsiness Mood changes Medical clouding Some individuals experience: Anxiety Fear Lethargy Sedation Lack of concern Inability to concentrate

33. Mechanism of Strong Analgesics • The human body contains “natural opiates” in the brain called endorphins • These are produced in the body during extreme conditions such as “running high” and extreme injuries. • When these are absorbed by receptors in the brain the body feels analgesia and the pain is reduced.

34. Mechanism of Strong Analgesics cont. • Opiates derived from the poppy act in the same way as endorphins but are not natural to the human body. • The “high” is produced because of the absorption of opiates is quicker than endorphins • Drugs such as naloxone act to fill the receptors in the brain but are not analgesics and thus are used to prevent overdoses on analgesics. • Endorphins are not used as analgesics because the cannot be stored and are unstable.

35. Tolerance Tolerance appears due to the induction of drug metabolizing enzymes in the liver and also to the adaptation of neurons in the brain to the presence of the drug. The users that became tolerant to one opiate will also exhibit a tolerance to all other opiates.

36. Dependence Physical dependence is the state in which people do not function properly without a drug. Symptoms: Restlessness Sweating Fever Chills Vomiting Increase rate of respiration Cramping Diarrhea Unbearable aches

37. Dependence Depends on: The dose Frequency of drug administration The duration of the drug dependence The opiate used

38. The opiates (in general) They are extremely potent and valuable drugs for the treatment of pain They have the capacity of inducing a state of euphoria and relief from physiological pain The opiates induce profound tolerance and physiological dependence They are important both medically and sociologically as the user is difficult to treat and must frequently resort to crime to support the habit and reach a source of supply.

39. Summary of the effects of opiates Short term effects Sedation and stupor Euphoria Reduced tension, worry and fear Reduced coughing reflex Occasional death from overdose Long term effects Loss of appetite Sterility Withdrawal illness, loss of job, crime Diversion of energy and money Risk of dangerous infections due to shared needles.

40. Vicodin Is solution of acetaminophen and hydrocodone (the latter being the stronger) Hydrocodone is addictive and can cause highs. Usually taken orally Stronger than codeine but not as strong than Morphine Other Synthetic Strong Analgesics

41. The active area of morphine has been identified and can be synthesized. This has produced many synthetic analgesics and has allowed scientists to eliminate some of the harmful side effects of more natural analgesics. Synthetic Strong Analgesics (Opioids)

42. Demerol (Meperidine) Used for moderate to severe pain and to stop muscle spasms. Usually injected or taken orally. Demerol

43. Compared to most strong analgesics it is weaker. Has been synthesized to not have euphoric properties and mild withdrawal effects but is still addictive. Used as an analgesic but most commonly to help in the withdrawal for Heroin addicts. Methadone