sensory event of both pns and cns emotional component cognitive component
TRANSCRIPT
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sensory event of both PNS and CNS emotional component cognitive component
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acute pain
chronic pain
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pain can be modulated, enhanced or diminished by both central and peripheral mechanisms◦ peripheral aspect – non steroidal
antiinflammatory drugs◦ central aspects – opioid analgesics
Roxicet, Tylox (acetaminophen and oxycodone)
Percocet – (oxycodone with paracetamol)
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opium extracted from opium poppy◦ used for thousands of years to produce euphoria,
analgesia, sleep and relief from diarrhea and cough
ancient times – primarily for constipating effects
Homer, Hippocrates, et◦ sleep producing effects
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Early 1800’s – morphine isolated from opium as its active ingredient◦ treating severe pain
1856- invention of the hypodermic syringe◦ Civil War – “soldiers disease”
1910 – concern about dangers of opioids and dependence
1914- Harrison Narcotic Act◦ use of most opioids strictly controlled
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1970 – ◦ established current schedules of drugs
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opium – juice or sap from the poppy opiate – drug extracted from the sap
morphine codeine
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opioid – any exogenous drug (natural, semisynthetic or synthetic) that binds to an opiate receptor and produces agonist or morphine-like effects
endorphin – endogenous substance that exhibits pharmacological properties like morphine
3 familes of endogenous opioid peptides
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enkephalins
dynorphins
beta endorphins
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opioids occur in nature in 2 places
the juice of the poppy
in our bodies……
all other opioids are either prepared from morphine (semisynthetic opioids like heroin) or synthesized from other precursors (synthetic opioids such as fentanyl)
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analgesic potency of the agonist correlates with affinity of agonist for opioid receptor
at least 3 types of opioid receptors◦ mu-◦ kappa◦ delta
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some areas have all 3 types of opioid receptors◦ (spinal cord)
some have predominantly one type of receptor
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brain, sc, and periphery morphine – mu agonist
◦ exerts effects in thalamus and striatum◦ brain stem (affects respiration)◦ spinal cord (analgesic effects)
PAG, brain stem, nucleus accumbens,
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may modulate mu receptors
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minor analgesic effects; pinpoint pupils modest analgesia no addiction potential dysphoria
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pure agonists – mu agonists
◦ produces analgesia, reward, respiratory depression
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morphine codeine heroin meperidine (Demerol) methadone (Dolophine) oxymorphone (Numorphan) hydromorphone (Dilaudid) fentanyl (Sublimaze) oxycodone
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produces agonist effects at one receptor and antagonist at another
clinically useful mixed drugs – kappa agonist and weak mu antagonist
useful for moderate pain
not good if someone is dependent on opiates
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binds to opioid receptors but has low intrinsic activity (low efficacy)
can produce analgesia – but ceiling lower than pure agonist
buprenorphine (Suboxone) binds to all 3 receptors
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block opiate receptors naloxone, naltrexone depot injections of naltrexone
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pure agonist more potent and represents about 10% of
crude sap codeine much less potent
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usually administered via injection although rectal or oral is possible
intranasal system under development absorption from GI slow and incomplete
compared to other routes morphine crosses bbb fairly slowly (more
H20 soluble than lipid soluble)◦ heroin, fentanyl – cross bbb much more quickly
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liver metabolizes morphine; one metabolite is actually 10 – 20X more potent than morphine for analgesia
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analgesia euphoria respiratory depression cough suppression pupillary constriction nausea and vomiting GI symptoms endocrine symptoms immune system effects histamine release
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codeine – ◦ one of the most commonly prescribed opioid◦ usually combined with aspirin or acetaminophen
for relief of mild to moderate pain
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heroin◦ (diacetylmorphine)◦ 3X more potent than morphine◦ produced by a slight modification of morphine
structure◦ increased lipid solubility◦ metabolized to monoacetylmorphine and
morphine◦ legally available in Great Britain
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(Percodan, OxyContin)- semisynthetic opioid percodan short-acting; oxycontin – long-
acting current abuse high;
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hydromorphone (Dilaudid), oxymorphone (Numorphan)
both structurally related to morphine as effective but 6 – 10X more potent
meperidine (Demerol)◦ structurally different from morphine – different
side effect profile
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rate at which tolerance develops can vary widely; pattern of use plays a role
cross-tolerance physical dependence can develop
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many of the effects observed are opposite of opiate
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Opiate withdrawal: ◦ Acute symptoms: restlessness, lacrimation, runny nose,
yawning, perspiration, goose flesh ("cold turkey"), restless sleep and dilated pupils during the first 24 hours (onset usually 8 to 12 hours after a reduction in dose or cessation of use)
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◦ 5 – 7 days into withdrawal; symptoms can become more severe
can be characterized by twitching and spasms of muscles; kicking movements (“kicking the habit”), severe aches in the back, abdomen, and legs; abdominal and muscle cramps; hot and cold flashes; insomnia; nausea, vomiting, and diarrhea; sneezing; fever
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Jittery, high pitched cry, hyperactive reflexes, restlessness, GI upset, etc.
heroin withdrawal occurs within 48-72 hours in 50-80% of infants
Methadone withdrawal may be delayed up to 6 days after birth
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1935 - first federal "narcotics farm" (U.S. Public Health Prison Hospital) opens in Lexington, Kentucky
Role of cues
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substitution therapy
What are the advantages of substitution therapy?
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methadone – ◦ synthetic mu agonist◦ 2 primary legitimate users
substitution for opiate dependent heroin users long acting analgesic for chronic pain syndromes
Physicians who are not in licensed methadone programs cannot prescribe methadone for opioid dependence
methadone clinics locations diversion
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Oral administration – reaches peak levels in ~ 2 hrs;
Half life – the amount of time necessary for ½ of the drug to be metabolized in the body; for methadone – very variable but for most people ~ 24-25 hours◦ When used for treating addiction – 1/day◦ For pain management – more likely 3 – 4
times/day
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levo-alpha acetylmethadol approved in mid 1993 for clinical
management of opioid dependence longer ½ life not currently available because of possible
serious cardiac complications
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Subutex – advantages – longer ½ life
Suboxone- buprenorphine/naloxone
advantages of buprenorphine
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naloxone (Narcan)◦ treating overdose
what happens in opiate dependent individuals?◦ must be given by injection- short ½ life
naltrexone (Trexan, ReVia)◦ longer duration of action and can be taken orally
◦ downside to naltexone
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How was it discovered---
1982 – San FranciscoDesigner Drug that was supposed to mimic heroin
Seven heroin addicts at ERAll showed signs of severeParkinsons like Disease
Found that the drug had beencontaminated with a toxin called MPTP
First human cohort of MPTP-induced parkinsonism
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Vanguard◦ “The Oxycontin Express”
◦ Can be found on Hulu
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June 2010
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July 1, 2001, nationwide law in Portugal decriminalized all drugs, including cocaine and heroin◦ drugs were "decriminalized," not "legalized.”◦ drug possession for personal use and drug usage
itself are still legally prohibited FINES BUT NOT JAIL
◦ trafficking still a criminal offense
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