Turn in Problem set 4 Friday UNIT FIVE

Review: What is a monoamine? 1.A metabolic enzyme 2.A molecule with a CH 3 group on it 3.A molecule with an NH 2 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 depression of the central nervous system disinhibitiontranquilizinghypnotic Disclaimer – babies should not do drugs Increasing dosage

Analgesics – Opiates – OTC pain killers Ethanol Cannabis

Pain Pain stimulus picked up by peripheral nervous system Substance P Prostaglandin Pain signal amplified by central nervous system Why do we take opiates? Activity 2

Opiate (and Opioid) forms

Interrelated opiate forms OH morphine CH 3 OH codeine CH 3 -COO heroin Heroin – more lipid soluble, so crosses BBB quickly. BUT must be chemically converted to morphine to work. Codeine is converted to morphine in brain, but some people CAN’T

How are opiates administered? Activity 3 Unknown artist Wikimedia commons

How much opiate is used? Morphine dose: 4-10 mg ( mg lethal) Heroin dose: mg (200-? mg lethal) Oxycodone dose: 5-15 mg (200? mg lethal)

Activity 4 Opiate metabolism? Opiate Half life male Half life female Metabolic enzyme Fat solubility Morphine2 hours3 hoursCYP2D6 Moderately lipid soluble Heroin10 minutes CYP2D6 Highly lipid soluble Oxycodone4 hours5 hoursCYP2D6 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? OH endorphin Endorphin = internally produced morphine Internally made = endogenous Many endorphins. Dynorphin – 200 x more potent than morphine!

Opiate receptors, types and locations Mu Kappa Delta Receptor locations affects Spinal cord, thalamus, NA, brain stem Control respiration ABUSE Analgesia NA, VTA, spinal cord Causes DYSphoria, not EUphoria Spinal cord, Limbic pathway Emotional state regulation, limited analgesia Opiate receptor AGONISTS

How do opiates reduce substance P? By inhibiting action potentials More negative, and more K INSIDE More positive, and more Na OUTSIDE Audesirk Figure 33.E1 Opiate receptors are ligand-gated potassium channels Recall – resting potential

How do opiates reduce substance P? By blocking exocytosis

Opiate is the ligand that opens K+ channels. This will cause K+ to do what? Graphic – Conn McQuinn 1.Flow down concentration gradient into a cell (making it more positive) 2.Flow against concentration gradient into a cell (making it more positive) 3.Flow down concentration gradient out of a cell (making cell more negative) 4.Flow against concentration gradient out of a cell (making cell more negative) 5.Stay where it is

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.A 2.B 3.C 4.D

Activity 6 Opiate Addiction? Reward Tolerance Dependence? More enzyme, less receptors 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! 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? OH methadone OH 0 naloxone antagonist Weak agonist

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