Analgesics

Analgesics Analgesics are common pain relievers. Some analgesics also have antipyretic properties as well. They can be used to reduce fever. Some analgesics are also anti- inflammatory drugs. They reduce inflamation as well 2

Classification of Analgesics Aspirin Heroin Codeine Opium Ibuprofen Acetaminophen Mild Analgesics Strong Analgesics 3

Mild Analgesics Mild Analgesics include many over-the-counter pain relievers and fever depressants. Examples of mild analgesics include aspirin, acetaminophen, and ibuprofen. 4

Mechanism of Mild Analgesics The mechanism by which mild analgesics act is still controversial. It is believed that they inhibit the formation of prostaglandins at the site of the injury. Prostaglandins are involved in the transmission of pain signals to the brain 5

Aspirin Aspirin is a derivative of salicyclic acid Salicyclic acid was found in the bark of the willow tree and was used as a pain reliever and as a way to relieve fever symptoms of malaria. Salicyclic Acid Aspirin 6

Aspirin In 1899, Felix Hoffman, a chemist from the Bayer Company, developed a low-cost process to synthesize an ethanoate ester of salicyclic acid, called aspirin In the synthesis of aspirin, the ethanoic acid forms an ester with the alcohol group on the second carbon 7

Aspirin As a mild analgesic, aspirin is believed to inhibit the enzyme, Prostaglandin Synthase which is formed at the site of an injury. This inhibits the production of prostaglandins which produce fever and swelling as well as transmitting pain signals to the brain. 8

Aspirin -- Uses and Benefits Aspirin is able to reduce pain and fevers and dilate blood vessels Aspirin enlarges blood vessels which helps prevent blood clots. This vasodilation of the surface blood vessels also allows an increase of heat released which lowers the temperature of a fever Aspirin is also taken to prevent recurring heart attacks It may also be effective in preventing prostate cancer 9

Side Effects of Aspirin Aspirin can irritate the stomach lining which may lead to ulcers If aspirin is used over long periods of time, it may lead to problems with blood clotting An overdose on aspirin, such as the case with some arthritis sufferers, may lead to dizziness, ringing in the ears, gastrointestinal problems, mental confusion, and bleeding. Some people are allergic to aspirin leading to bronchial asthma In children under 12 Aspirin has been linked to Reye’s syndrome 10

Other Mild Analgesics Acetoaminophen (Paracetamol) –Commonly sold as Tylenol Ibuprofen –Commonly sold under the name Advil 11

Acetoaminophen Acetoaminophen can be easily synthesized from phenol 12 The relative ease with which acetoaminophen can be synthesized makes it a rather common inexpensive analgesic

Acetaminophen Acetaminophen is a pain reducer, such as Tylenol but does not reduce inflammation. When taken at recommended doses, it has negligible side effects. It’s low level side effects make it favorable to arthritis patients and children. Overuse and overdoses can lead to acute liver failure and kidney damage. 13

Ibuprofen Ibuprofen is a more powerful pain reliever than aspirin in high doses, but is inferior as an anti-inflammatory drug. Side effects include gastrointestinal bleeding and irritation Can aggravate kidney problems. 14

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 opiates that are derived from the opium poppy or synthetically produced Basically three types: Natural, semi-synthetic, and synthetic 15

Morphine Naturally occurring in the poppy- Only needs to be isolated Very strong pain reliever but also very addictive (2 nd to Heroin) Usually injected but can be smoked, sniffed or swallowed Commonly used in hospitals Large illegal street culture 16

Codeine Most commonly used strong analgesic Similar to Morphine except for the replacement of a (OH- ) group for (OCH 3 ) group Commonly used with Tylenol as a more mild analgesic 1/6 as strong as Morphine and less addictive 17

Heroin Originally sold as cough suppressant and pain killer. 10 times stronger than Morphine Incredibly addictive (many times, other strong analgesics are needed for withdrawal) 18

Heroin Synthesized from morphine in a esterification reaction with acetyl chloride It is absorbed by the brain very quickly resulting in a potent high. The ester group in heroin makes it less polar and therefore more fat soluble. It is more easily absorbed in brain tissue. Many other problems are associated with heroin addiction including as prostitution and AIDS. 19

Other Synthetic Strong Analgesics Vicodin Is solution of acetaminophen and hydrocodone (the latter being the stronger analgesic) Hydrocodone is addictive and can cause highs. Usually taken orally Stronger than codeine but not as strong than morphine. 20

Synthetic Strong Analgesics (Opioids) 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. 21

Demerol Demerol (Meperidine) Used for moderate to severe pain and to stop muscle spasms. Usually injected or taken orally. 22

Methadone 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. 23

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. Strong analgesics bind to the endorphin receptors in the brain. When these are absorbed by receptors in the brain the body feels analgesia and the pain is reduced. 24

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. 25

Side Effects of Strong Analgesics Short term Dulling of Pain Euphoria Slow Nervous system Slowed heart rate Loss of cough reflex Nausea Overdoses can lead to death Possibility of stroke Overall slowdown of biological systems Long Term Addiction and very strong withdrawal effects Constipation Loss of libido Disruptions in menstruation “Cross-tolerance” Loss of appetite Problems associated with buying street drugs i.e. sharing needles AIDS and prostitution. 26

Local Anesthetics -- Cocaine Cocaine used in 1885 as a local anesthetic. Extracted from the plant Erythoxylum coco ([1R-(exo,exo)]-3-(Benzoyloxy)-8-methyl-8- azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester 27

History of Cocaine Coca leaves have been chew by South American Indians for thousands of years Was banned by Spanish settlers in the 1500s but the ban was repealed when it became apparent that slaves worked harder while on it United States cocaine was used in soft drinks until it was classified as narcotic in 1914 Clinically used as a local anaesthetic for eye operations and in modified synthetic forms for dental treatment (novocaine) and sore throats (benzocaine) 28

Cocaine The leaves of the coca plant contain 0.6% - 1.8% alkaloidal cocaine To extract, cocaine leaves are soaked in kerosine or sulphuric acid HCl is added creating HCl is added creating cocaine hydrochloride, which can be extracted as powdery flakes or rocks 29

Clinical Action Acts as a Acts as a reuptake blocker for the monoamines dopamine, norepinephrine and serotonin. Interacts with serotonin and muscarinic acetylcholine receptors and the sodium channels. Influence on the axonal voltage-gated sodium channels that provides cocaine's local anaesthetic properties. 30

Derivatives of Cocaine Cocaine is too addictive and in appropriate for medicinal use Two derivatives of cocaine are widely used as local anesthetics –Lidocaine –Procaine (Novacaine) 31

Effects of Cocaine Subjective Euphoria Increased sociability Increased energy Hypervigilance Physiological Increased heart rate Increased respiration rate Increased body temperature Increased blood pressure Pupil dilation 32

Lidocaine First modern local anesthetic agent Sodium channel blocker Administered parenterally for ventricular arrhythmias, subcutaneously for minor surgical procedures, and topically to mucosal surfaces prior to invasive procedures 33

Procaine (Novacaine) Principal use in dentistry for temporary numbing of mouth area First synthesized in 1905 and was the first injectable man-made local anesthetic Restricts blood vessels, reducing bleeding 34