AnalgesicsAnalgesics

AnalgesicsAnalgesics

Analgesics are common pain relievers.Analgesics are common pain relievers.

Some analgesics also have Some analgesics also have antipyreticantipyretic properties as well. They can be used to properties as well. They can be used to reduce fever.reduce fever.

Some analgesics are also Some analgesics are also anti-anti-inflammatoryinflammatory drugsdrugs. . They reduce They reduce inflamation as wellinflamation as well

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Classification of AnalgesicsClassification of Analgesics

Aspirin Heroin

Codeine

OpiumIbuprofen

Acetaminophen

MildAnalgesics

StrongAnalgesics

Analgesics

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Mild AnalgesicsMild Analgesics

Mild Analgesics include Mild Analgesics include many over-the-counter pain many over-the-counter pain relievers and fever relievers and fever depressants.depressants.

Examples of mild Examples of mild analgesics include aspirin, analgesics include aspirin, acetaminophen, and acetaminophen, and ibuprofen.ibuprofen.

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Mechanism of Mild AnalgesicsMechanism of Mild Analgesics

The mechanism by which The mechanism by which mild analgesics act is still mild analgesics act is still controversial. controversial.

It is believed that they inhibit It is believed that they inhibit the formation of the formation of prostaglandins at the site of prostaglandins at the site of the injury.the injury.

Prostaglandins are involved Prostaglandins are involved in the transmission of pain in the transmission of pain signals to the brainsignals to the brain

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AspirinAspirin

AspirinAspirin is a derivative is a derivative of salicyclic acidof salicyclic acidSalicyclic acidSalicyclic acid was was found in the bark of found in the bark of the willow tree and the willow tree and was used as a pain was used as a pain reliever and as a way reliever and as a way to relieve fever to relieve fever symptoms of malaria.symptoms of malaria.

Salicyclic AcidAspirin

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AspirinAspirin

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

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

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Aspirin -- Uses and BenefitsAspirin -- Uses and BenefitsAspirin is able to reduce pain and fevers Aspirin is able to reduce pain and fevers and dilate blood vesselsand dilate blood vesselsAspirin enlarges blood vessels which Aspirin enlarges blood vessels which helps prevent blood clots. helps prevent blood clots. This vasodilation of the surface blood This vasodilation of the surface blood vessels also allows an increase of heat vessels also allows an increase of heat released which lowers the temperature of released which lowers the temperature of a fevera feverAspirin is also taken to prevent Aspirin is also taken to prevent recurring heart attacksrecurring heart attacksIt may also be effective in It may also be effective in preventing prostate cancerpreventing prostate cancer

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Side Effects of AspirinSide Effects of AspirinAspirin can Aspirin can irritate the stomachirritate the stomach lining which lining which may lead to ulcersmay lead to ulcers

If aspirin is used over long periods of time, it If aspirin is used over long periods of time, it may lead to may lead to problems with blood clottingproblems with blood clotting

An An overdose on aspirinoverdose on aspirin, such as the case with , such as the case with some arthritis sufferers, may lead to some arthritis sufferers, may lead to dizziness, dizziness, ringing in the ears, gastrointestinal problems, ringing in the ears, gastrointestinal problems, mental confusion, and bleeding.mental confusion, and bleeding.

Some people are Some people are allergic to aspirinallergic to aspirin leading to leading to bronchial asthmabronchial asthma

In children under 12 Aspirin has been linked to In children under 12 Aspirin has been linked to Reye’s syndromeReye’s syndrome 10

Other Mild AnalgesicsOther Mild Analgesics

Acetoaminophen (Paracetamol)Acetoaminophen (Paracetamol)

– Commonly sold as TylenolCommonly sold as Tylenol

IbuprofenIbuprofen

– Commonly sold under the name AdvilCommonly sold under the name Advil

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AcetoaminophenAcetoaminophenAcetoaminophen can be easily synthesized from phenolAcetoaminophen can be easily synthesized from phenol

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The relative ease with which acetoaminophen can be synthesized The relative ease with which acetoaminophen can be synthesized makes it a rather common inexpensive analgesicmakes it a rather common inexpensive analgesic

AcetaminophenAcetaminophenAcetaminophen is a pain Acetaminophen is a pain reducer, such as Tylenol but reducer, such as Tylenol but does not reduce inflammation.does not reduce inflammation.

When taken at recommended When taken at recommended doses, it has negligible side doses, it has negligible side effects.effects.

It’s low level side effects make It’s low level side effects make it favorable to arthritis patients it favorable to arthritis patients and children.and children.

Overuse and overdoses can Overuse and overdoses can lead to acute liver failure and lead to acute liver failure and kidney damage.kidney damage.

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

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Strong AnalgesicsStrong Analgesics

Only available by prescriptionOnly available by prescriptionUsed to relieve Used to relieve severesevere pain associated with pain associated with injuries, heart attacks, or chronic diseases injuries, heart attacks, or chronic diseases such as cancer.such as cancer.Most strong analgesics are opiates that are Most strong analgesics are opiates that are derived from the opium poppy or derived from the opium poppy or synthetically producedsynthetically producedBasically three types: Natural, Basically three types: Natural, semi- semi-synthetic, and syntheticsynthetic, and synthetic

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MorphineMorphineNaturally occurring Naturally occurring in the poppy- Only in the poppy- Only needs to be isolatedneeds to be isolatedVery strong pain Very strong pain reliever but also reliever but also very addictive (2very addictive (2ndnd to to Heroin)Heroin)Usually injected but Usually injected but can be smoked, can be smoked, sniffed or swallowedsniffed or swallowedCommonly used in Commonly used in hospitalshospitalsLarge illegal street Large illegal street cultureculture

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Codeine Codeine Most commonly used Most commonly used strong analgesicstrong analgesicSimilar to Morphine Similar to Morphine except for the except for the replacement of a replacement of a (OH-) group for (OH-) group for (OCH(OCH33) group) groupCommonly used with Commonly used with Tylenol as a more mild Tylenol as a more mild analgesicanalgesic1/6 as strong as 1/6 as strong as Morphine and less Morphine and less addictiveaddictive

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

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HeroinHeroinSynthesized from Synthesized from morphine in a morphine in a esterification reaction esterification reaction with acetyl chloridewith acetyl chloride

It is absorbed by the It is absorbed by the brain very quickly brain very quickly resulting in a potent high.resulting in a potent high.

The ester group in heroin The ester group in heroin makes it less polar and makes it less polar and therefore more fat therefore more fat soluble. It is more easily soluble. It is more easily absorbed in brain tissue.absorbed in brain tissue.

Many other problems are Many other problems are associated with heroin associated with heroin addiction including as addiction including as prostitution and AIDS.prostitution and AIDS.

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Other Synthetic Strong Other Synthetic Strong AnalgesicsAnalgesics

VicodinVicodinIs solution of Is solution of acetaminophen and acetaminophen and hydrocodone (the latter hydrocodone (the latter being the stronger being the stronger analgesic)analgesic)Hydrocodone is addictive Hydrocodone is addictive and can cause highs.and can cause highs.Usually taken orallyUsually taken orallyStronger than codeine Stronger than codeine but not as strong than but not as strong than morphine.morphine.

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Synthetic Strong Analgesics Synthetic Strong Analgesics (Opioids)(Opioids)

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

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DemerolDemerol

Demerol (Meperidine)Demerol (Meperidine)

Used for moderate to Used for moderate to severe pain and to severe pain and to stop muscle spasms.stop muscle spasms.

Usually injected or Usually injected or taken orally.taken orally.

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

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Mechanism of Strong Mechanism of Strong AnalgesicsAnalgesics

The human body contains “natural The human body contains “natural opiates” in the brain called endorphinsopiates” in the brain called endorphinsThese are produced in the body during These are produced in the body during extreme conditions such as “running extreme conditions such as “running high” and extreme injuries.high” and extreme injuries.Strong analgesics bind to the Strong analgesics bind to the endorphin receptors in the brain.endorphin receptors in the brain.When these are absorbed by receptors When these are absorbed by receptors in the brain the body feels analgesia in the brain the body feels analgesia and the pain is reduced.and the pain is reduced.

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Mechanism of Strong Analgesics Mechanism of Strong Analgesics cont.cont.

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

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Side Effects of Strong Side Effects of Strong AnalgesicsAnalgesics

Short termShort termDulling of PainDulling of PainEuphoriaEuphoriaSlow Nervous system Slow Nervous system Slowed heart rateSlowed heart rateLoss of cough reflexLoss of cough reflexNauseaNauseaOverdoses can lead Overdoses can lead to deathto deathPossibility of strokePossibility of strokeOverall slowdown of Overall slowdown of biological systemsbiological systems

Long TermLong TermAddiction and very strong Addiction and very strong withdrawal effectswithdrawal effectsConstipationConstipationLoss of libidoLoss of libidoDisruptions in menstruationDisruptions in menstruation““Cross-tolerance”Cross-tolerance”Loss of appetiteLoss of appetiteProblems associated with Problems associated with buying street drugs i.e. buying street drugs i.e. sharing needles AIDS and sharing needles AIDS and prostitution.prostitution.

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Local Anesthetics -- Local Anesthetics -- CocaineCocaine

Cocaine used in Cocaine used in 1885 as a local 1885 as a local anesthetic.anesthetic.Extracted from the Extracted from the plant plant Erythoxylum Erythoxylum cocococo

([1R-(exo,exo)]-3-(Benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester

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History of CocaineHistory of CocaineCoca leaves have been chew by South American Coca leaves have been chew by South American Indians for thousands of yearsIndians for thousands of years

Was banned by Spanish settlers in the 1500s but Was banned by Spanish settlers in the 1500s but the ban was repealed when it became apparent the ban was repealed when it became apparent that slaves worked harder while on itthat slaves worked harder while on itUnited 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)

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CocaineCocaine

The leaves of the coca plant The leaves of the coca plant contain 0.6% - 1.8% contain 0.6% - 1.8% alkaloidal cocainealkaloidal cocaine

To extract, cocaine leaves To extract, cocaine leaves are soaked in kerosine or are soaked in kerosine or sulphuric acidsulphuric acid

HCl is added creating HCl is added creating cocaine hydrochloride, which can be extracted as powdery flakes or rocks

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Clinical ActionClinical ActionActs 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.

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Derivatives of CocaineDerivatives of Cocaine

Cocaine is too addictive and in Cocaine is too addictive and in appropriate for medicinal useappropriate for medicinal use

Two derivatives of cocaine are widely Two derivatives of cocaine are widely used as local anestheticsused as local anesthetics

– LidocaineLidocaine– Procaine (Novacaine)Procaine (Novacaine)

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Effects of CocaineEffects of CocaineSubjectiveSubjective

Euphoria

Increased sociability

Increased energy

Hypervigilance

Physiological

Increased heart rate Increased respiration rate Increased body temperature Increased blood pressure Pupil dilation

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LidocaineLidocaine

First modern local anesthetic agent

Sodium channel blockerSodium channel blockerAdministered parenterally for ventricular arrhythmias, subcutaneously for minor surgical procedures, and topically to mucosal surfaces prior to invasive procedures

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Procaine (Novacaine)Procaine (Novacaine)

Principal use in dentistry for temporary Principal use in dentistry for temporary numbing of mouth areanumbing of mouth areaFirst synthesized in 1905 and was the first injectable man-made local anesthetic

Restricts blood vessels, reducing bleeding

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