opiates

Question 1

THE OPIATES
Definitional Issues

Answer 1

▪ Naturally occurring, derived, and synthetic
compunds with analagesic properites**

▪ Often referred to as “narcotic analgesics” narcotic= drowsiness inducing, analgesic = pain treatment

now: pain agents that have potential to be dependant upon***

problems: saying theyre narcotics links them with coke and meth
- better to say analgesic alone than narcotic analgesic

Question 2

Naturally Occuring

▪ Morphine, codeine, and thebaine found in opium

▪ Opium is the sap from seedpods of opium poppy

• scratches are made on the seedpod –> results in white substance ooze from seedpod –> turns reddish brown with air (dries and hardens) –> then scraped off as a syruppy substance (this is opium)

Opium is
▪ Morphine – 10%
▪ Codeine - .75 to 2.5 %
▪ Thebaine - <1%

Question 3

Opiate Derivatives/Semi-Synthetics

▪ Heroin (semi synthetic)
- adding acetyl group –> becomes more potent and lipid soluble than morphine (3x more potent than morphine)

▪ Other examples

• Hydromorphone –> derived from morphine
• Oxycodone –> derived from thebaine
• Oxymorphone –> derived from morphine or codeine
• Hydrocodone –> derived from codeine or thebaine

Question 4

THE OPIATES
Synthetic

▪ Meperdine –> common pain killer (less potent than morphine)

▪ Methadone –> treats chronic pain , is used to treat dependency programming (less potent than morphine in treating pain) less potent iin euphoric effects than morphine)

▪ Other examples
▪ Fentanyl –> 60s marketed as sublimase as an IV anaesthetic
70/80s tablets to treat chronic pain associated with cancer
- same time, marketed as a patch
- became a concern on the streets (dismodification of patches)

2005–> outbreaks of deaths with fent use
- reason was fent is 30-50 times more potent than heroine

LAMM
- used to treat opiate depedancy

laurie has a cross tolerance with opiates and alc

Question 5

Opiate Antagonists

▪ Useful in treating overdoses

▪ Naloxone (brand name or trade name: narcan)

▪ Nalorphine

• reverse depressed breathing in minutes
• fx don’t last as long and don’t produce euphoria like other opiates

Question 6

Uses
▪ Medical uses include

Answer 6

▪ primary use Treatment of pain (acute pain, after surgery, chronic pain)

▪ Treatment of diarrhea
- oldest use to treat diarrhea
- reduces peristalsis and increase tension (may lead to constipation)

▪ Treatment of cough
- effective opiate = codeine

Question 7

Uses and History
Medical use dates back hundreds of years
▪ opium Documented in Egyptian medical scrolls dating
back to 1550 BC
- prevent excessive crying of children
▪ In second century AD, Claudius Galen (roman gladiator) recommended it for practically everything
- resists poison, vanomous bites, cures chronic headaches, vertigo, deafness (over prescibing drug exaple)

Question 8

Uses and History
Medical use dates back hundreds of years
▪ Documented in Egyptian medical scrolls dating
back to 1550 BC
▪ In second century AD, Galen recommended it for
practically everything
▪ In 1520, medicinal drink called laudanum
introduced –> 46% alcohol and 1 gram of opium
- Miss windlows soothing syrup
- pennys worth of peace

18th century: women took it for menstrual pain
- took it for 2 things
- for tooth aches - DeQuincy T loved it (Englihs opium eater )

Question 9

Uses and History
Recreational use dates back hundreds of years
(at least!)
▪ 2nd Century AD: Galen noted that opium cakes
and candy sold everywhere on the street
▪ 18th Century: Opium Dens Appear in China, and
elsewhere (e.g, North America, Asia, France) With
Chinese “Invention” of Opium Smoking (heating and inhaling)
- provided with drug and paraphernalia to use the drug
- lined up or separated

Question 10

History
Up until early to mid 1800s, opium use was
widely socially accepted and not perceived
as a social or medical problem
– despite large number of individuals being
addicted (wasnt a controlled substance **) - laudinum was particularity acceptable
- wasn’t seen as a social medical problem until 1860/70s
- 2500000 people in US were addicted

▪ Mid to late 1800s saw some governmental
efforts in US and Britain to regulate use and selling of drug
- some people saw this as government intervention –> saw this as racist to chinese people

• Due to concern about negative consequences
  of chronic opium use or anti-Chinese
  prejudice?

Question 11

History
▪ San Franciso Newspaper Quote
“…many women and young girls, as wellas
young men of respectable family, were being
induced to visit the dens, where they were
ruined morally and otherwise”

Answer 11

• not the use of alcohol just opium

Question 12

History
▪ Canada: Opium Act, 1908: prohibited the “importation, manufacture, and sale of opium for other than medicinal purposes” –> targeted the dealers of the drug

▪ Canada: Opium and Narcotic Act, 1911:
prohibited the “improper use of Opium and other drugs” t target the users as well

Question 13

MOA
▪ Opiates will be administered

Answer 13

▪ Orally –> tablet (historically = opium cake)

▪ Parenterally
▪ Via inhalation
▪ Transdermally –> patches to treat chronic pain (slow release)

Question 14

Distribution
▪ High concentrations in lungs, liver, spleen

▪ Readily passes thru placental barrier –> infants will exhbit withdrawal symptoms if mom used it

▪ In brain, concentrated in limbic system, basal
ganglia, nucleus acumbens, ventral tegmental
areas, periaqueductal gray area (pain area), brain
stem (rephei nuclei)

Question 15

Metabolization
▪ Codeine and much of heroin inactive until
metabolized –> into morphine , codeine is morphne + other metabs

▪ Metabolization is rapid
- 4-6 hours 1/2 life

▪ Exception is some of the synthetic compounds (e.g.,
methadone, LAAM)
- these are longer 1/2 lives
- methadone 24 hours
- LAMM longer than 24 hours

• makes them important in treating pain

Question 16

Pharmacological Actions
▪ Mimic endorphins (pain reducing hormones)

▪ Agonist action at six types of receptors: mu, kappa,
delta most understood
- act on sigma encephalon and lambda as well

fex: Decrease rate of neuronal firing via two
mechanisms:
–> Inhibiting Ca influx (AP decrease, not allowing NT to reach the synapse)

–> Enhance flow of K –> hyperpolarizing the neuron**

from 2 above: decreases NT released (NE, Do, ACh)

▪ Increase firing in some neurons by preventing
inhibition of those neurons (inhibition prevented by
depressing/inhibiting “inhibitory “synapses)
- causes the release of dopamine (look at TB for this)

Question 17

CNS Effects
▪ Analgesic Effects (2)
–> 1. block incoming info from other receptors , depress their action–> not reaching higher brain centers
–> 2. increase activity from PAG centre –> causes release of Sero in Raphe nuclei –> synapse with interneurons of SC –> release of enkephalons and dynorphins –> these bind to opiate receptors (located on interneuron) by reducing release of substance P –> reducing pain signals going up to CNS

release of enkephalon at SC –> mu delta (SC) and kappa receptors –> enkephalons bind at interneuron levels

serotonin and enkepahlons both reduces substance P

▪ Depress respiratory center (mu receptor)
▪ Suppress cough center (in Brain stem)
▪ Depress vomiting center (first effect of demerol is nausea and vomiting cuz its a synthetic opiate) –> tolerance can develop to this

▪ Drowsiness
▪ Decrease levels of sex hormones –> results in reduces sex drive in m/f and stop menzies in women
- prostitutes used this in 18th century which caused them to be addicted
causes atrophy in sexual characteristics in men

SO opiates reduces fertility

Question 18

Effects on Eyes
▪ Constriction of pupil
▪ Mechanism unknown
- tell tale sign of opiate use is pinpoint pupils

Question 19

Gastrointestinal Effects

▪ Diminish Peristalsis in Intestine (slows down movement)
▪ Increase muscle tone in Intestine
▪ Above two effects lead to constipation (by decrease of movement of intestine -> causing dehydration of material in there–> creating constipation)

Question 20

Psychological Effects
(1) Euphoria –> especially IV use
(2) Dysphoria –> some people will have dysphoric reactions to it –> can become hostile to it (get delusions)
–> lauries mom had delusions

(3) Decreased Concentration –> secondary to drowsiness induced

(4) Dulling of Emotional Pain –> mediated through receptors in limbic system and frontal lobe
- can also dull physical pain (in frontal lobe) –> not experiencing pain
- feedforward with substance P

Question 21

Tolerance
▪ Develops to:

Answer 21

▪ Respiratory depression
▪ Analgesic
▪ Sedation
▪ Euphoria

May develop to:
▪ Pupil constriction

Does NOT develop to:
▪ Constipation –> given drug on top to treat constipation

Develops rapidly in8-10 days of daily use
- consumption increases 10 fold for same effects to be realized
- doeses taken by regular user could be high enough to kill a first time user
- intermittent use –> develops littel tolerance
- weekend user would take a year to have tolerance

▪ Three types:
- pharmacokinetic tol –> incre enzymes
- pharm dyn –> decrease in senstivity of opiate receptros and chanegs in recep density
- cross toelrance –> opiates and alcohol

physical dependance

Question 22

Physical Dependence

Answer 22

Characteristic withdrawal
- start with craving of drug 4-6 hours after durg was used
- 8-12 hours causes these symptoms::: below
▪ Restlessness and agitation
▪ Yawning appears
▪ Fever and chills (hugging themsleves)
▪ Deep sleep (yen sleep for many many hours)
–> sleep will cause profuse sweating
–> upon wakening cramps, v/d and twtiching of limbs

withd = wicked case of the flu

can have mild physiological symp for 6 months
- increase BP and HR (check TB)****

Symptoms intensify to a peak (36 to 72 hours); over in 5 to 10 days
▪ Withdrawal not typically life-threatening

Question 23

Psychological Dependence

Answer 23

both primary and secondary dependance*
is much More difficult to treat than physical dependence*
–> cuz of other durgs and food

▪ Some success seen with Methadone and other synthetic opiates (e.g.,LAAM, buprenorphine (these people do not experience euphoria with these drugs**)!!!) to treat opiate dependancy (secondary **) not to go with withdrawal

Question 24

Methadone Treatment

Answer 24

Factors contributing to potential
effectiveness include:
▪ Oral admin (juice) –> takes away potential reinforcing effects seen in different settings (from iV seen with that movie)

▪ Long acting effect –> 1/2 life is long –> facilitates conpliance with the regime

▪ Antagonistic action to opiates –> removes pleasure effects as heroine ***

▪ Are advantages to terminate use