what are opioid analgesics? history morphine mechanism of opioids side

8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side

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What are opioid analgesics?HistoryMorphineMechanism of opioidsSide effectsAdverse reactions

Addiction, overdose and withdrawalsymptoms

OpiophobiaOpioids of abuseHeroinFentanyl

Future of opioids



Analgesics, or pain killers, that bind to opioid receptors whichare found principally in the:

CNS

Gastrointestinal tract

There are a number of broad classes of opioids: Natural opiates

Alkaloids contained in the resin of the opium poppy includingmorphine, codeine and thebaine

Semi-synthetic Opiates

Created from the natural opioids such as hydromorphone,

oxycodone and diacetylmorphine (heroin) Fully synthetic opioids

Fentanyl, methadone and tramadol

Endogenous opioid peptides

Proudced naturally in the body, such as endorphins,enkephalins, dynorphins and endomorphins



Opioids have been the mainstay of pain treatment for thousand of years, and they remain so today The search for a safe, orally active, and non-addictive analgesicbased on the opiate structure is one of the oldest fields inmedicinal chemistry The opiates are perhaps the oldest drugs known to humanity The first undisputed reference to opium is found in thewritings of Theophrastus in the third century B.C. The use of opium was recorded in China over 2000 yearsago, and was known in Mesopotamia before that

Its use in medicine is quoted in a twelfth-century prescription:

Take opium ,mandragora, and henbane in equal parts and mix with water. When you want to saw or cut a man, dip a rag inthis and put it to his nostrils. He will sleep so deep that youmay do what you wish.



Opium contains a complex mixture of 20 alkaloids,principle one being morphine› Responsible for analgesic activity

Because of morphine’s poor oral bioavailability, itwas little used in medicine until the hypodermicsyringe was invented in 1853

Morphine was used during the American Civil Warand the Franco-Prussian war.› Due to poor understanding about:

Safe dose levelsEffects of long-term useAnd increased risks of addiction, tolerance and

respiratory depression

› Many casualties were either killed by overdoses orbecame addicted to the drug



3-D Structure of Morphine

http://www.3dchem.com/3dmolecule.asp?ID=186

http://www.3dchem.com/3dmolecule.asp?ID=186



In general, opioids actupon mu-, delta-, andkappa-receptors on CNSneurons producing:

Analgesia via

decreasedneuronaltransmitterrelease anddecreasednociceptiveimpulsepropagation

Appears to work byelevating the painthreshold, thusdecreasing thebrain’s awareness of pain

Receptor type

Location Effects

μ Brain,spinalcord

Analgesia, respiratorydepression, euphoria,addiction, ALL painmessages blocked

κ Brain,spinalcord

Analgesia, sedation, allnon-thermal painmessages blocked

δ Brain Analgesia, antidepression,dependence



Dangerous side effects are those of tolerance and dependence, allied withthe effects morphine can have onbreathing

› Most common cause of death from morphineoverdose is suffocation

›

These side effects in one drug are particularlydangerous and lead to severe withdrawalsymptoms when the drug is no longer taken



AnorexiaWeight lossPupil dilationChills

ExcessivesweatingAbdominalcrampsMuscle spasmsHyperirritability

Lacrimation TremorIncreased heartrateIncreased bloodpressure



A study was done in W. Virginia to evaluate personsdying of unintentional pharmaceutical overdose, thetypes of drugs involved and role of drug abuse in thedeaths

Opioid analgesics were taken by 93.2% (275/295) of all people who died of pharmaceutical overdoses in W.Virginia in 2006

Only 44.4% (122/275) of those people had ever beenprescribed these drugs

The majority of overdose deaths in West Virginia in2006 were associated with nonmedical use anddiversion of pharmaceuticals, primarily opioidanalgesics



The fear of prescribing opioidpain medications is known as"opiophobia”

Goodman and Gillman’sPharmacological Basis of Therapeutics insists thatalthough physical dependence

and tolerance may develop,this should not in any wayprevent physicians fromfulfilling their primaryobligation to ease the patient’sdiscomfort

No patient should ever wish for death because of a physician’sreluctance to use adequateamounts of effective opioids

Physical dependence is notequivalent to addiction



First synthesized in1874 by an Englishchemist but onlybecame popular more

than 20 years later From 1898 through

1910, under thename heroin,diacetylmorphine was

marketed as a non-addictive morphinesubstitute and coughsuppressant



A heroin overdose is usually treated with an opioidantagonist, such as naloxone (Narcan) which has high affinityfor opioid receptors but does not activate them

Many fatalities reported as overdoses are probably causedby interactions with other depressant drugs like alcohol orbenzodiazepines

It has been speculated that an unknown portion of heroinrelated deaths are the result of an overdose or allergicreaction to quinine, which may sometimes be used as acutting agent

A final factor contributing to overdoses is placeconditioning. Heroin use is a highly ritualized behavior



Morphine Fentanyl



1959-Fentanyl first synthesized by Paul Janssen under Janssen Pharmaceutica

1960s-Introduced as intravenousanesthetic (Sublimaze) 1990’s-same company produced

Duragesic patch

Next came Actiq, flavored lollipop of fentanyl citrate

Present-Effervescent tab for buccalabsorption and buccal spray device



The pharmaceutical industry has developed several analogues of

fentanyl:

Alfentanil (Alfenta), an ultra-short acting (5-10 minutes)

analgesic Sufentanil (trade name Sufenta), a potent analgesic (5 to 10

times more potent than fentanyl) for use in heart surgery

Remifentanil (trade name Ultiva), currently the shortest actingopioid, has the benefit of rapid offset, even after prolongedinfusions

Carfentanil (Wildnil) is an analogue of fentanyl with an analgesicpotency 10,000 times that of morphine and is used in veterinarypractice to immobilize certain large animals such as elephants



Fentanyl is normally sold on the black market in the form of transdermal fentanyl patches such as Duragesic, diverted fromlegitimate medical suppliesthe patches may be cut up and eaten, or the gel from insidethe patch smoked

Another dosage form of fentanyl that has appeared on the streets

is fentanyl lollipops Actiq, which are sold under the street name of "percopop” They are sold for anywhere from $15-$40 per unit

Some heroin dealers mix fentanyl powder with larger amounts of heroin in order to increase potency or compensate for low-quality

heroin, and to increase the volume of their productAs of December 2006, a mix of fentanyl and either cocaine orheroin have caused an outbreak in overdose deaths in theUnited States The mixture of fentanyl and heroin is known as "magic" or"the bomb", among other names, on the street



Generic Name Brand Name

buprenorphine Buprenex

butorphanol Stadol

codeine Tylenol with codeine

fentanyl Duragesic

hydrocodone Vicodin

hydromorphone Dilaudid

methadone Dolophine

morphine Astramorph

oxycodone OxyContin

porpoxyphene Darvon

what are opioid analgesics? history morphine mechanism of opioids side

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