Upload
runtech67
View
221
Download
0
Embed Size (px)
Citation preview
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 1/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 2/28
What are opioid analgesics?HistoryMorphineMechanism of opioidsSide effectsAdverse reactions
Addiction, overdose and withdrawalsymptoms
OpiophobiaOpioids of abuseHeroinFentanyl
Future of opioids
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 3/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 4/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 5/28
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.
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 6/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 7/28
3-D Structure of Morphine
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 8/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 9/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 10/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 11/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 12/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 13/28
AnorexiaWeight lossPupil dilationChills
ExcessivesweatingAbdominalcrampsMuscle spasmsHyperirritability
Lacrimation TremorIncreased heartrateIncreased bloodpressure
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 14/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 15/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 16/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 17/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 18/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 19/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 20/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 21/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 22/28
Morphine Fentanyl
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 23/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 24/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 25/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 26/28
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 27/28
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
8/14/2019 What Are Opioid Analgesics? History Morphine Mechanism of Opioids Side
http://slidepdf.com/reader/full/what-are-opioid-analgesics-history-morphine-mechanism-of-opioids 28/28