Analgesics

L. Scheffler

Analgesics
Analgesics are common pain relievers. Many analgesics also have antipyretic properties as well. They can be used to reduce fever Some analgesics are also antiinflammatory drugs as well

Classification of Analgesics
Analgesics
Mild Analgesics

Analgesics

Strong

Aspirin

Ibuprofen

Opium

Heroin
Codeine

Acetaminophen

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

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
Aspirin

Salicyclic Acid

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

Aspirin
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.

Aspirin
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 prostrate cancer

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 Reyes syndrome

Other Mild Analgesics

Acetaminophen (Paracetamol) Commonly sold as Tylenol Ibuprofen Commonly sold under the name Advil

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

Ibuprofen
Ibuprofen is a more powerful pain reliever than aspirin in high doses, but is inferior for anti-inflammation Side effects include gastrointestinal bleeding and irritation Can aggravate kidney problems

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 three types: Natural, semi-synthetic, and synthetic

Morphine
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

Codeine
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

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

Heroin
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.

Other Synthetic Strong Analgesics

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

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.

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

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.

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.

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.

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.

Local Anesthetics -- Cocaine

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

History of Cocaine
Coca leaves have been chewed by South American Indians for thousands of years. There were used to induce feelings of euphoria 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)

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

Clinical Action
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

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

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

Procaine (Novacaine)

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

Lidocaine
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