Drugs and Behavior Week 3

Pharmacokinetic vs pharmacodynamic tolerance

  • Whether the drug is physiologically affected in its processing, vs whether the effects can be observed

  • Pharmacokinetic: metabolism 

  • Pharmacodynamic: any other method of compensation other than adjusting metabolism

  • Sensitization: drug becomes more potent/effective w/ repeated adminstration

  • In-class assignment (missed):

    • First-pass metabolism is specific to digestive system administration

    • Sub q is slow absorption

    • Tight junctions regulate the blood-brain barrier

Chapter 4: Nervous System

  • Neuron communicatoin is electrical

    • Charged particles across cell membrane

    • Difference in charge across the cell membrane (-70 mV)

      • If a stimulus starts moving the neuron to a membrane potential of zero, that leads to an action potential

      • Threshold= -55 mV, means there is absolutely going to be an action potential

      • Action potentials happen due to depolarization

  • Between cells: chemical (neurotransmitter)

  • Vesicles approach the membrane until it is enclosed/fused and releases NTs

  • Ionotropic receptor is ligand-gated, has an ion channel

    • Ions flow through the channel rather than neurotransmitters entering the cell (when opened by NTs)

    • Quick change

  • Metabotropic receptor: G protein-mediated receptor (receptor attached to g protein)

    • G protein goes and does something in reponse to activation

    • Slower and more long lasting

    • Chain reactions

  • Autoreceptor: monitors and regulates NT levels in the cleft

    • Same structure as metabotropic

  • Heteroreceptor: responds to chemicals from postsynaptic/other cells (same structure as auto)

  • Neurotransmitter transporter: large protein molecules involved in reuptake embeded in presynaptic cell membrane

    • Takes in excess NTs in the cleft

  • Metabotropic or ionotropic are receptor structure types

  • Post-synaptic potentials: changes in the membrane potential 

    • Excitatory (EPSP): membrane potential becomes more positive (closer to threshold)

    • Inhibitory (IPSP): Membrane potential becomes more negative

  • Temporal summation: occurs when a neuron experiences two or more post synaptic potentials closely in time

    • May add together if they come close enough in time

  • Spatial summation: two or more post synaptic potentials occur in close proximity on a neuron

    • EPSP + EPSP= geater EPSP (Same with IPSP)

    • EPSP + IPSP = cancels out

9/25

  • Communication btwn two neurons is chemical, within neurons is electrical

  • Electron microscopy can see shapes of neuron receptors

    • Can also use software to predict how proteins would fold

  • Neuroanatomy

    • Medulla: superior of the spinal cord, affects functioning of ANS, including breathing

      • Death due to drug overdose often a result of depression of the breathing center

      • Narcan competes w/ opioids and kicks out opiates from the receptors

      • Area postrema: not protected by blood brain barrier (BBB)

        • Monitors blood and induces vomiting when something is there that isn’t supposed to be there (toxins)

    • Pons: holds the locus coeruleus- influences sleep, wakefulness, attention

    • Midbrain: superior and inferior colluli

      • Periacqueductal gray: involved with pain, has receptors for endogenous opioids (endorphins, enkephalins)

      • Ventral Tegmental Area (VTA): contains cell bodies of dopamine-producing neurons

        • Part of reward pathway w/ nucleus accumbens 

          • VTA → NA→prefrontal cortex

  • Neurotransmitters

    • Molecules released by presynaptic cell that are recieved in postsynaptic cell

    • 50 molecules fully meet criteria for NTs, list is growing

      • Acetylcholine (ACh): always released if it is a neuromuscular junction (Neuron talking to muscle fiber), may be N-N

        • Nicotinic receptors: ionotropic, responds to ACh and nicotine

          • Drug identified first, responsive structure named after the drug 

        • Muscarinic receptors: also stimulated by muscarine (poisonous mushrooms), metabotropic

      • Dopamine (DA)

        • Tyrosine (amino acid) → L-DOPA (commonly given to treat Parkinson’s Disease, can cross BBB)→ Dopamine

        • Important in the reward pathway

      • Norepinephrine (NE)

        • Dopamine converts to norepinephrine using an enzyme

        • Key for locus coeruleus (affects alertness/sleep)

      • Serotonin (5-HT)

        • Trypophan (amino acid) → 5-Hydroxytryptophan → 5-HT (5-Hydroxytryptamine/serotonin)

        • Common target for antidepressants (prevents the reuptake of serotonin)

      • Glutamate: major excitatory (starts action potentials) nt in brain

        • Found throughout the brain

      • Gamma-aminobutyric acid (GABA)

        • Made from glutamate

        • Inhibitory (less likely to start aciton potential), widespread

      • Biogenic amines or Monoamines

        • Made from a single amino acid

        • Includes dopamine, norepinephrine, epinephrine, and serotonin

  • Development of the nervous system

    • Neurulation: nervous system cells are separated in embryo (tube for brain and spinal cord)

    • Neural progenitor proliferation: not functioning neurons, can become neurons and divide, but not yet neurons

    • Neural differentiation: takes progenitor and turns it into a specific type of neuron cell

      • Giving neurons jobs

    • Neural migration: cells moving to where they’ll need to be for the nervous system

    • Apoptosis: Cell death, killing off excess neurons

    • Synaptogenesis: forming synapses, life long

    • Myelination: development of myelin

    • Drugs that can cross the BBB can typically cross the placenta

      • Some drugs might negatively affect development (teratogens)

        • Ex: thalidomide, causes differences in development

    • Alternatives, risks with discontinuing medication, risks of harm to fetus, ways to mitigate harm, acceptable impacts, personal values, termination opinions, data on the drug w/ pregnant people 

      • Category A: human studies suggest medicine safe for pregnant individuals and their babies 

        • Ex: levothyroxine

      • B:Fewer studies or mixed findings or low level of risk detected

        • Glocophage for diabetes, Zofran for nausea

      • C: Same as B, slightly less strong evidence or more risk

        • Ex: Zoloft and Prozac

      • D: Evidence of risk, some situations the medicine may help the parent more than it harms the baby

        • Ex: dilantin for epileptic seizures 

      • X: No situations in which the medicine can help parent or baby enough to make the risk of problems worth it 

        • Ex: acutane 

      • Letter system is no longer used, started being used in 1979 

      • Now they use narrative secitons and subsections

        • Pregnancy (includes labor and delivery)

        • Lactation

        • Females and Males of reproductive potential

        • Tells us about timing

        • Next Thursday is the exam (schedule w/ Accom)