Transcript Opiates - UNM Biology Department Home Page

Opiates and you
By Steven Malins
Morphine and other opiates are
used extensively in our society
As biologists we must decide when
and how to use them
Though useful as painkillers,
opiates have drastic negative
effects
Understanding how opiates work
mitigates risk and enhances
benefits
We must examine the effect and
action of opiates
Doctors use
opiates for a
variety of
reasons
Opiates reduce pain from trauma
• Morphine and derivatives are used to treat
pain such as long bone fractures, and
other injuries with significant pain
• Side effects include nausea, dependence
on the drug, and respiratory depression
• Despite side effects, opiates like morphine
are some of the best painkillers available
to medical professionals.
Opiates can be used to treat
chronic pain
• Along with acute pain from trauma, opiates
are used to treat many disorders with
chronic pain
• Doctors in the US and UK advise the use
of morphine or other opiates for the
treatment of vaso-occlusive crises
associated with sickle cell disease
Solomon, Lawrence (2006). Treatment of pain due to vaso-occlusive
crises (VOC) in adults with sickle cell disease (SCD): Limited
awareness of available guidelines. 48th Annual Meeting of the
American-Society-of-Hematology
Opiates may help treat cancer
• Opiates have a wide range of effects
besides acting as analgesics
• They negatively regulate many cell
processes, in several of the bodies tissues
• Opiates were found to decrease growth of
Hepatocellular carcinoma and cause
apoptosis in these tumor cells
Notas, G et all (2007). The inhibitory effect of opioids on HepG2 cells is
mediated via interaction with somatostatin receptors. European Journal
of Pharmacology 555(1)
Opiates cause
widespread
changes in the
body
Opiates act on G-Protein linked
receptors
• Opiate drugs act on membrane receptors that
are linked with protiens that use GTP
– These proteins are called G protien coupled receptors
(GPCRs)
• It has been shown that these receptors have
multiple active states, not just a single activated
state
– These different states are believed to be caused by
different opiates and may be the key to minimizing
side effects
Pineyro, G, Elodie Archer-Lahlou (2007). Ligand-specific receptor states:
Implications for opiate receptor signalling and regulation. Cellular Signalling 19 (1)
Opiates cause GI problems
including constipation
• Among the other negative side effects of opiates
is their depression of the Gastro Intestinal
system causing constipation
• The enteric nervous system(ENS) is located in
the digestive tract and it manages propulsion
through the intestines
• Opiates act on opioid receptors and ophianin
FQ/nocieptin receptors in the ENS inhibiting GI
functionality.
Bohn, L, Kirsten Raehal (2006). Opioid receptor signaling: relevance for
gastrointestinal therapy. Current opinion in Pharmacology vol 6 (6)
Opiates affect gene expression
in the hippocampus
• Opiate addiction is often long term and
recovering addicts report cravings long
after use is discontinued.
• Studies in rats have shown that at least 20
genes show differential expression after
exposure to morphine
– This data was gathered by a cDNA
comparison of hippocampus’ of the rats
Marie-Claire et al (2007). Sensitization to the conditioned rewarding
effects of morphine modulates gene expression in rat hippocampus.
Neuropharmacology 52(2)
Discontinuing opiate
use is difficult
Opiates affect gene expresion
• Morphine causes gene expression changes in
neuron cells and other cells in the body
• These genes affect cell growth and death, and
cell morphology as well as neuron excitability
• Many of these changes, while relatively quick to
take place once on morphine, take time to
reverse
– Thus the body response with cravings for morphine
long after its use is discontinued
McClung, C.A. (2006). The molecular mechanisms of morphine addiction.
Reviews in the Neurosciences 17 (4)
Withdrawal symptoms are
unpleasant
• Between 8 and 12 hours after taking heroin, or
other opiates, individuals experience:
– Watery eyes, yawning, sweating
– Restlessness, insomnia, bone and joint pain
• Symptoms peak between one and two days after
the last dose
• Though symptoms of withdrawal dissipate after
about 10days, cravings and fatigue continue.
Mattick, R.P., Wayne Hall. (1996) Are detoxification programmes effective?
The Lancet 347 pp97-100
Our brains associate related
experiences with the “high” of
morphine
• Opiates like morphine trigger the “reward”
mechanism of our brain
– In the limbic system
– This is asociated with feelings of euphoria
• It has been shown in mice, which are a model
organism for humans, that locations where
morphine was administered triggered the reward
response even when there was no drug being
administered.
German, P.W. and Howard L. Feilds (2006). Rat Nucleus Accumbens
Neurons Persistently Encode Locations Associated
With Morphine Reward. Journal of Neurophysiology 97
We now have the
tools and
knowledge to
understand
opiate’s affects
Only with continued research
can we learn to use opiates
more effectively
Research must continue on
medicines like morphine
You will be the ones doing such
research
Image credits, in order of use
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J.J. (2005) Mad scientist caricature Retrieved May 04 2007 from
http://commons.wikimedia.org/wiki/Image:Mad_scientist_caricature.png
Theo (1999) The final solution med Retrieved May 04 2007 from
http://commons.wikimedia.org/wiki/Image:The_final_solution_med.jpg
Felix Plasser (2007) 3D structural formula of morphine Retrieved May 04
2007 from http://commons.wikimedia.org/wiki/Image:MorphinPyMOL.png
Public domain, from US Department of Agriculture.
Ignis (2005). Drug ampoule Retrieved May 04 2007 from
http://commons.wikimedia.org/wiki/Image:Drug_ampoule_JPN.jpg
Albrecht Durer (1471-1528). Anatomy and geometrical proportions
Retrieved May 04 2007 from
http://commons.wikimedia.org/wiki/Image:Anatomical_and_geometrical_pro
portions_-_Albrecht_Dürer.png
Pollo Telescopic aerial platform unit Helsinki H16 Retrieved May 04 2007
from http://commons.wikimedia.org/wiki/Image:H16_training.jpg
Microsoft clip art included with PowerPoint
J Rawls (2005) What's behind me Retrieved May 04 2007 from
http://commons.wikimedia.org/wiki/Image:Car_side_mirror_sunset.jpg