Neurochemistry – Exam 1

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Different routes of administration can determine how rapidly a drug reaches its target organ and which organs it affects.
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What is the relevance of different routes and properties of drug administration?
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Oral administration
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taken by mouth and typically results in a slow onset of action.
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Parenteral administration
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includes all other routes of drug administration, other than oral:
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Subcutaneous administration
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under the skin.
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Intraperitoneal administration
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into the peritoneal-abdominal cavity.
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Intravenous administration
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into the venous system.
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Intracerebroventricular administration
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into the cerebral ventricular system.
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Intrathecal administration
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into the spinal fluid.
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Intracerebral administration
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into the brain parenchyma.
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Bio-availability of a drug
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refers to how much of a drug reaches its target.
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4 Factors that affect bio-availability.
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1. The absorption of the gut if taken orally. 2. The drug binding to blood plasma, which makes it unavailable to bind to its target. 3. The blood-brain barrier restricts some medications from getting into the CNS for drugs that act on the brain. 4. The ability to penetrate the cellular membrane.
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Why is the relationship between drug concentration and ligand binding hyperbolic in shape?
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The relationship between drug concentration and ligand binding hyperbolic in shape because the ligand binding happens at a faster rate in the beginning and tapers off as the ligand binding approaches Bmax (B sub-max).
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Potency
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the strength of binding between the drug and its target.
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Efficacy
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the maximal biologic effects that the drug exerts by binding to its target.
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Agonist
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a substance that initiates a physiological response when combined with a receptor: can be an agonist, partial agonist, partial inverse agonist, or inverse agonist.
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Antagonist
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a substance that interferes with or inhibits the physiological action of another.
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Synaptic cleft
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space between the axon terminal of the presynaptic neuron and the dendritic spine of the postsynaptic neuron at a nerve synapse across which a neurotransmitter transmits a nerve impulse.
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Synapse
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the minute space between the post-synaptic neuron and the pre-synaptic neuron where neurons communicate with each other with chemicals and/or ions. Can be as small as 20 to 40 nm.
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Dendrite
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Branchlike parts of a neuron that are specialized to receive information and transmits information towards the cell body.
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Axon
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A threadlike extension of a neuron that carries nerve impulses away from the cell body.
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Axon hillock
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the specialized part of the cell body that attaches to the neuron. It is the last site of the soma where membrane potentials are summated and transmitted down the axon.
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Cytoskeleton
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the inner scaffolding of a neuron formed by a system of interconnected protein filaments called microtubules, intermediate filaments, and actin filaments that plays a key role in the structure of neurons and in the transport of various proteins and organelles from the cell body to axonal and dendritic processes.
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Soma
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The cell body of a neuron.
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What four general criteria must be met to consider any particular candidate chemical to be considered a neurotransmitter employed at specific synapses?
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1. Localization – the neurotransmitter and/or its components must be localized to the cell, dendrites, or axon terminal. 2. Release – classically Ca2+ is associated with neurotransmitter release. By altering calcium and then testing intercellular fluid for the suspect candidate, it is possible to identify a possible neurotransmitter candidate. 3. Synaptic mimicry – neurotransmitter candidate can be tested in a lab exogenously. 4. Synaptic Pharmacology – the action evoked by the neurotransmitter is able to be blocked by an antagonist for that receptor.
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Membrane potential
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the internal electrical potential relative to the outside of the cell.
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How is membrane potential established within a neuron (or any cell)?
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The concentration of charged ions inside and outside of the cells establish the membrane potential. Large intracellular proteins contribute a large negative influence on membrane potential. Overall membrane potential is determined by the internal electrical potential relative to the electrical environment outside of the cell.
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What three properties of neurons allow them to utilize membrane potential in cell signaling?
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1. Semi-permeable membrane 2. Ability to change permeability of select ions 3. Ability to restore original potential through ion pumps, ion channels and electrochemical concentration gradient.
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Nernst potential
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relates the equilibrium cell potential to its concentration gradient across a membrane. The Nernst equation is based on no net flow of ions and focuses on one ion individually. Cells have the interaction of many ions.
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Summation
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Summation is the adding of the electrical potentials, temporally and/or spatially, to increase the effect.
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Current (A)
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is the rate at which electrical charge flows past a point in a circuit. Current is the effect; voltage being the cause. Current cannot flow without voltage.
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Voltage (V)
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is the electrical force that would drive a current between two points. Voltage is the cause and current is its effect. Voltage can exist without current.
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Ionotropic receptor
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is a neurotransmitter-gated ion channels.
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Ligand-gated ion channel
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is a neurotransmitter or molecule-gated ion channel.
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Metabotropic receptor
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are receptors that result in a range of biological effects on the cell: ex. G-Protein coupled receptors, tyrosine-kinase receptors.

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