Download Opiates lecture opiatesONLY

Turn in Problem set 4 Friday
UNIT FIVE
Review: What is a monoamine?
1. A metabolic enzyme
2. A molecule with a CH3
group on it
3. A molecule with an NH2
group on it
4. Any neurotransmitter
5. None of the above
Always: What Information Will be
Covered for EVERY Drug:
What is drug?
Why is it used?
How is it administered?
How much is used?
Metabolism?
Affects on the cell?
Addiction?
Benefits?
Harms?
Individual experience may vary
Which depressants will be covered?
• Analgesics
– Opiates
– OTC pain killers
• Ethanol
• Cannabis
What do we experience on
depressants?
Increasing dosage
disinhibition
tranquilizing
hypnotic
Increasing depression of the central nervous system
Disclaimer – babies should not do drugs 
• Analgesics
– Opiates
– OTC pain killers
• Ethanol
• Cannabis
Why do we take opiates? Activity 2
Pain
Substance P
Prostaglandin
Pain stimulus picked up by
peripheral nervous system
Pain signal amplified by
central nervous system
Opiate (and Opioid) forms
http://www.jimemery.com/flowers/poppyduo.jpg
Interrelated opiate forms
Codeine is converted to
morphine in brain, but
some people CAN’T
morphine
OH
OH
Heroin – more lipid
soluble, so crosses BBB
quickly. BUT must be
chemically converted to
morphine to work.
codeine
OH
CH3
CH3-COO
heroin
CH3-COO
How are opiates administered? Activity 3
Unknown artist
Wikimedia
commons
How much opiate is used?
Oxycodone dose:
5-15 mg
(200? mg lethal)
Morphine dose:
4-10 mg
(200-2000 mg
lethal)
Heroin dose: 5-200 mg
(200-? mg lethal)
Activity 4
Opiate
Morphine
Heroin
Opiate metabolism?
Half life
male
Metabolic
enzyme
Fat
solubility
CYP2D6
Moderately
lipid
soluble
10 minutes 10 minutes CYP2D6
Highly lipid
soluble
2 hours
Oxycodone 4 hours
Half life
female
3 hours
5 hours
CYP2D6
Water
soluble
Examine the previous graph on opiate
metabolism. Which is unexpected?
1. That all opiates are
metabolized by CYP2D6
2. That fat-soluble heroin has
the shortest half life
3. That there is a different
half life for male vs. female
4. That there is a different
metabolic enzyme for male
vs. female
Activity 5
Why do we react to opiates?
endorphin
OH
Endorphin = internally produced morphine
Internally made = endogenous
OH
Many endorphins. Dynorphin – 200 x more potent than
morphine!
Receptor
locations
Mu
Spinal cord,
thalamus, NA,
brain stem
affects
Control
respiration
ABUSE
Analgesia
NA, VTA, spinal
cord
Causes
DYSphoria, not
EUphoria
Spinal cord,
Emotional state
regulation,
limited analgesia
Kappa
Limbic pathway
Delta
Opiate receptors,
types and
locations
Opiate receptor
AGONISTS
How do opiates reduce substance P?
By inhibiting action potentials
• Recall – resting potential
More positive, and more
Na OUTSIDE
More negative, and more
K INSIDE
Audesirk Figure 33.E1
• Opiate receptors are ligand-gated potassium channels
How do opiates reduce substance P?
By blocking exocytosis
Opiate is the ligand
that opens K+
channels. This will
cause K+ to do what?
1.
2.
3.
4.
5.
Flow down concentration gradient
into a cell (making it more positive)
Flow against concentration gradient
into a cell (making it more positive)
Flow down concentration gradient out
of a cell (making cell more negative)
Flow against concentration gradient
out of a cell (making cell more
negative)
Stay where it is
Graphic – Conn McQuinn
How do opiates inhibit neurons?
Normal action potential
threshold
Threshold hard to reach
Opiate
binds
Making a neuron even more negative =
hyperpolarize
Threshold is what part of this graph?
1.
2.
3.
4.
A
B
C
D
Opiate
Addiction?
Activity 6
• Reward
• Tolerance
More enzyme, less receptors
• Dependence?
Less endorphin, less receptors
PAIN is a very difficult withdrawal
symptom to ignore!
How do opiates cause euphoria?
Dopamine release is regulated (inhibited)
Opiate block exocytosis of regulator, allowing
dopamine release (two negative make a positive)
Activity 8
What are the side effects of
opiates?
HARD to quit!
http://www.healingdaily.com/
NOT life-threatening to quit, unless you start to use your old dose
again after being off a while.
How are opiate addiction and OD treated?
antagonist
OH
0
OH
OH
naloxone
Weak agonist
methadone
Which of the following does NOT
contribute to opiate addiction?
1. Kappa opiate
receptors
2. Mu opiate receptors
3. CYP2D6
4. Endorphins
Individual experience may vary…
Hyperpolarization Football
• Push the offense farther away from first down
line, make it harder to progress the ball up the
field.
• Hyperpolarization pushes the cell’s charge
farther away from threshold, harder to achieve
action potential