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Introduction to psychopharmacology



Unit I


Unit II


Unit III


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  Unit I

Salvatore Cullari  
PO Box 595  
Hershey, PA 17033  

Cullari@lvc.edu  




A BASIC INTRODUCTION TO PSYCHOPHARMACOLOGY

A BASIC INTRODUCTION TO PSYCHOPHARMACOLOGY

(Copyright 2005, Salvatore Cullari)

 

NOTE: The material in this course is made up of numerous sources including many of those listed in the bibliography and internet sites (which are listed at the very end), my own experience and numerous psychopharmacology courses I have taken over the years. However, as all of you know, this field is changing so rapidly that it is often difficult or impossible to keep up with new developments. In this vein, if you have any new thoughts, suggestions, reading materials or internet sites, please send them to me.

 

This information is presented without charge. However, please do not copy, market or duplicate any of this material in any manner without my written permission.

 

Unit I: The “Basic” Basics

 

Neuroscience Glossary

 

absolute refractory period

The time when another action potential cannot be set off no matter how much current you inject.

 

accommodation

Decrease in spike firing rate with time.

 

acetylcholine

A neurotransmitter that connects nerves to muscles. Also active at other synapses in CNS/ANS.

Chemical structure.

 

action potential

A spike in membrane voltage caused by opening and closing of Na and K channels. This is the

signal that is conducted down the axon to transmit information to other neurons.

 

active (excitable) membrane

Membranes that have voltage-sensitive channels

 

afferent

An axon, neuron or tract that brings information in towards the central nervous system

 

after-hyperpolarization

Hyperpolarization after an action potential

 

agonist

A drug that will activate a particular receptor and opposite of antagonist

 

amino acid

The building blocks of peptides and proteins. Some amino acids also serve as neurotransmitters

 

ampa receptor

A kind of glutamate receptor that mediates excitatory (depolarizing) signals. The channel

conducts both Na+ and K+.

 

amygdala

A nucleus involved in emotional and sexual behavior. Part of the limbic system

 

anatomy

The study of structures in biology. Contrasted with physiology.

 

antagonist

A drug that will block a particular receptor, opposite of agonist

 

aphasia

Loss of language skills following brain damage.

 

area mt

One of many areas for higher cortical processing of vision. This one mediates the visual

perception of motion.

 

artificial neural network (ANN)

Networks of simple units that do complex things due to their connectivity. The computer

science/engineering approach to computational neuroscience.

 

association cortex

An area of cortex that does not receive primary sensory (or give off primary motor) information;

some of these areas are thought to be involved in integrating or associating different types of

information

 

associative long term potentiation

Increased strength in a weakly stimulated synapse with strong activation in a nearby synapse.

This has been shown to occur in some areas of hippocampus

 

astrocytes

Glial cells that are involved in nutritive support for neurons and in maintaining concentrations in

the extracellular space.

 

attention

A neural mechanism that permits brain function to be focused on a particular sensory stream.

 

autonomic nervous system (ANS)

A section of the nervous system innervating organs.

 

axon

The axon is classically regarded as the output side of the neuron. In vertebrates, axons may be

myelinated. Conduction of signals down the axons is due to action potentials which are

self-regenerative signals that propagate by saltatory conduction. A myelinated axon is shown at

the bottom of this picture.

 

axon collateral

A branch of an axon.

 

axon hillock

The initial part of the axon. This may be where action potentials start in some neurons.

 

axon terminal

The end of an axon. There is usually a synapse here.

 

basal ganglia

A large nuclear complex rostral (anterior) to the thalamus. Involved in motor activity, planning,

initiative.

 

binding problem

The brain somehow has to bind together information about a single object that is processed in

different places. For example a visual image is taken apart so that motion, color, shape and other

aspects can be separately analyzed, yet somehow one has a unitary percept of what's being seen.

 

blind spot

The area in which one cannot see because light rays fall on the optic disk. The optic disk has no

photoreceptors. Somehow this blindness is ignored by the brain, an act of completion

 

blood-brain barrier

A barrier that keeps bad stuff floating around in the blood from getting into the brain.

 

bouton en passant

(= synaptic bouton) A synapse that is not at an axon terminal but is just a swelling as the axon

passes by a dendrite.

 

brain

The part of the CNS within the skull

 

brainstem

The part of the CNS between the thalamus and the spinal cord

 

cable equation

An equation that describes how voltage attenuates along an electrical cable. Originally proposed

by Lord Kelvin to describe the reduction of telegraph signals from Europe to North America, it is

also used to describe attenuation of membrane voltage down a passive neural membrane such as

a passive dendrite.

 

cascade

A chemical amplification process where the product of one enzyme (or a second messenger)

augments the rate of another enzyme which creates a large amount of another messenger

controlling yet another enzyme. A few such steps can turn a relatively small chemical signal into

a large number of signaling molecules.

 

CAT scan

Computerized axial imaging. An imaging method that recreates 2 dimensional cross sections

using transforms of x-ray conductance through tissue. Also called CT scan.

 

cauda equina

The big "horses tail" of nerves at the base of the spinal cord.

 

caudal

The tail side of the body. In the brain this is toward the back (posterior) and in the spinal cord it's

towards the bottom (inferior).

 

cell assembly

Hebb hypothesized that cell assemblies (groups of simultaneously active neurons) could

represent perceived or remembered objects.

 

cell body

Synonym for soma

 

central nervous system (CNS)

The brain (including retina and brainstem) and spinal cord

 

cerebellum

A complex movement control center at the caudal end of the brain overlying the brainstem.

 

cerebral cortex

Grey matter at the surface of the brain

 

cerebrospinal fluid (CSF)

The fluid that bathes the CNS and lies inside the ventricles

 

chemical synapse

A synapse where information is conveyed by the diffusion of a neurotransmitter across the

synaptic cleft to bind to and activate receptors on the other side

 

chunking

The ability of the brain to organize complex multi-part information into a single remembered

object. An example is seen in remembering a telephone number -- it is hard to remember as a

collection of digits but chunking into a set of 3 followed by a set of 4 makes it easier

 

co-transmitters

Different neurotransmitters released at a single synapse.

 

completion

The ability of the nervous system to ignore inconsistencies or gaps in incoming information to

construct a complete story. Neglect syndromes may be in part caused by excessive completion.

 

conduction velocity

The speed of spike (action potential) conduction along an axon

 

consolidation

Putative process whereby memories are moved from temporary storage in hippocampus to more

permanent storage in cerebral cortex

 

contralateral

The other side. Most of the brain innervates contralateral structures. Opposite of ipsilateral.

 

contralateral neglect syndrome

A very odd syndrome often seen after strokes affecting the non-dominant hemisphere. The

patient may deny that the contralateral side of his body belongs to him or her.

 

convergence

Multiple inputs coming into one neuron

 

coronal plane

The vertical plane that runs from left to right (or lateral to medial) and up to down (ventral to

dorsal). An example would be the coronal plane running from ear to ear

 

corpus callosum

The large white matter that connects the two hemispheres

 

corticospinal tract

(aka pyramidal tract) A tract of that starts in motor cortex and goes down to the spinal cord.

Responsible for some aspects of fine motor control.

 

critical period

A limited period of time when a particular aspect of brain development is sensitive to a change in

the external environment

 

current

Movement of charge. In a wire this represents a wave of electrons moving but in living tissue

current is carried by ions. current I is measured in Amperes (amps).

 

current clamp

Holding a steady current in a neuron and watching how the voltage responds.

 

cytoarchitectonic map

A map of the cerebral cortex that distinguishes areas according to anatomical differences such as

the prominence of a particular cortical layer.

 

cytoplasm

The contiguous fluid inside a cell that lies outside the organelles.

 

Dale's principle

the hypothesis that a single neuron has only one transmitter that is given off at all its synapses.

Although this has turned out to be wrong in part (see co-transmitters), it seems to still hold true

that major neurotransmitters such as glutamate and GABA are not coexpressed by a single

neuron.

 

delta waves

slow waves (< 4 Hz) of the EEG seen in deep sleep

 

dendrite

Cellular extensions from the soma. They are generally fatter and shorter than axons and are never

myelinated. Dendrites were classically thought to be electrically passive but it now appears that

many are active. Dendrites are classically regarded as the input side of the cell. Again this is not

always the case. Note the apical dendrites at the top of the picture and the basal dendrites to the

side.

 

dendritic spine

A spiny excrescence off the side of a dendrite. Often the site of an excitatory synapse. Has

specialized internal structures presumed related to its signal carrying function.

 

dendritic tree

The full set of dendrites that belong to a neuron.

 

depolarization

Change in membrane potential positive from the resting membrane potential. This is usually

associated with excitation of the cell.

 

diffusion

The tendency of particles at a high concentration to move to places where they are not so

concentrated.

 

disinhibition

Removal or reduction of inhibitory action in a neural circuit.

 

divergence

Multiple outputs coming from one neuron

 

dominant hemisphere

The cerebral hemisphere that controls language. This is the left hemisphere in most people.

 

dorsal

The back side of the body. For the CNS this would be posterior in the spinal cord and superior

(up) in the brain.

 

driving force

The potential felt by ions of a particular type. This depends on the difference between the current

membrane potential and the Nernst potential corresponding to the concentration difference across

the membrane.

 

efferent

An axon, neuron or tract that takes information out away from the CNS.

 

electrical self-stimulation

A mechanism for allowing an animal to deliver small electric currents to activate a particular spot

in its own brain.

 

electrical synapse

A gap junction connection between cells that allows direct current flow that can thereby pass

electrical signals from one cell to another.

 

electrochemical equilibrium

A balance between diffusive force in one direction and a membrane potential gradient in the other

direction. The membrane potential where this occurs is the Nernst potential.

 

electroencephalogram (EEG)

A recording of electrical signals from the brain made on the skin of the head.

 

endorphin

A peptide neurotransmitter that is active at the same location where opium or morphine acts.

 

enteric nervous system

The nervous system that runs the gut. It can function on its own even after being completely

disconnected from other parts of the nervous system.

 

epilepsy

A brain disorder where repeated seizures occur.

 

equilibrium potential

The Nernst potential that produces electrochemical equilibrium for a particular ion.

 

excitatory postsynaptic potential (EPSP)

Depolarization of the postsynaptic membrane potential due to synaptic action. Nominally

excitatory.

 

exocytosis

Release of material from a cell due to fusion of a vesicle with the cell membrane. This is how

neurotransmitters are released into the synaptic cleft.

 

extracellular

The outside of cells.

 

facilitation

The ability of incoming excitatory signals to produce a transient increased excitability. Generally

shorter in duration as compared to potentiation.

 

fovea

The central part of the retina that has the most acute vision

 

frequency coding

The notion that increases in spike frequency are an important part of the code of the nervous

system. Also called rate coding.

 

frontal lobe

The most anterior lobe of the brain. Thought to play a role in initiative and planning.

 

functional magnetic resonance imaging (fMRI)

A technique for imaging physiological activity using magnets and radio waves

 

gaba

The major inhibitory neurotransmitter in the CNS

 

ganglion (plural, ganglia)

A collections of neurons lying outside the CNS

 

gap junction

An ion channel that connects two cells together.

 

gating

The ability of channels to be opened or closed either by membrane potential (voltage-gated) or by

the arrival of a neurotransmitter or other chemical (ligand-gated)

 

glial cell

The most common type of neuron in the nervous system. These cells play roles in support,

hormone release, and balancing extracellular concentrations. Two important types are astrocytes

and oligodendroglia.

 

glutamate

An amino acid that is the major excitatory neurotransmitter in the central nervous system.

 

grandmother cell theory

The theory that the brain codes involves specific neurons that stand for specific things in the

world -- ie a neuron that lights up when grandma is seen, heard, smelled or touched

 

grey matter

Brain volumes made up of cell bodies such as cerebral cortex, basal ganglia and thalamus. Looks

grey when you cut open a brain.

 

gyrus (Plural: gyri)

The cerebral hemispheres are folded; gyri are the ridges.

 

habituation

A nonassociative learning form leading to decreased behavioral responses to repeated stimulation

 

Hebb synapse

A synapse that that increases in strength when both the presynaptic and postsynaptic neurons are

active at the same time.

 

hippocampus

A cortical area in the temporal lobe. This area is involved in declarative memory (memory for

events).

 

Hodgkin-Huxley equation

A set of equations that describe the evolution of the action potential by taking account of changes

in conductance of voltage-sensitive sodium and potassium channels.

 

horizontal plane

The horizontal plane is horizontal with the person in the anatomical position. it runs rostral

(front) to caudal (back); medial to lateral (also left to right).

 

Huntington's disease

An inherited movement disorder characterized by dance-like movements.

 

hyperpolarize

Change in membrane potential negative from the resting membrane potential. This is usually

associated with inhibition of the cell.

 

in vitro

Study of biological tissue that has been taken out of the organism. (means "in glass")

 

in vivo

Study of biological tissue in the intact organism. (means "in life")

 

inactivation

Closing of an ion channel with time.

 

inhibitory postsynaptic potential (IPSP)

Neurotransmitter-induced postsynaptic potential making the postsynaptic neuron less likely to

fire action potentials

 

innervate

For a neuron to connect up synaptically with something

 

integration

Combination of incoming signals in a neuron or neuronal unit.

 

interneuron

A neuron with axons that only project locally. In the cortex many of these appear to be

inhibitory.

 

intracellular

The inside of a cell.

 

invertebrate

An animal without a spine. Can be divided into squishies (clam, octopus, leech) and crunchies

(insect, limulus, lobster).

 

ion

A charged atom. The most important ions in the nervous system are Na+,K+,Cl-,Ca++. The

superscript tells you what type of charge it is and whether it is monovalent (one +) or divalent

(two +s).

 

ion channel

An protein that lies in the cell membrane (integral membrane protein) that has a hole that allows

ions to pass from one side of the membrane to the other. Most of these ion channels are selective,

only allowing passive of certain ions and not letting others through. Picture: Diagrams

 

ipsilateral

On the same side of the midline or body, opposite of contralateral.

 

lateral

Towards the side. For example, the ears are lateral to the brain.

 

lateral geniculate nucleus (LGN)

An area of the thalamus that relays information from the retina.

 

learning

Storage of new information in a biological or artificial system.

 

length constant

Space constant

 

ligand-gated channels

An ion channel which opens and closes depending on the arrival of some chemical -- usually

either a neurotransmitter or second messenger

 

limbic system

A set of interconnected brain structures that may be involved in emotion (see Papez circuit).

 

limulus

The horseshoe crab, an animal whose visual mechanisms have been heavily studied. Picture

 

lipid bilayer

The architecture of membranes in living things. Can be understood by thinking of a soap bubble.

Soaps are amphoteric: one end is fatty and the other end is ionic. This allows them to clean: one

end sticks to grease (hydrophobic = hates water) and the other end sticks to water (hydrophilic =

loves water). In a soap bubble all the hydrophilic ends stick out and the hydrophobic ends point

inward and interact to form a membrane. A lipid bilayer is like 2 soap bubbles one inside the

other with the inner one's hydrophilic heads sticking in to the cytoplasm.

 

long term potentiation (LTP)

A persistent strengthening of synaptic strength that may be the neural analogue of the Hebb

synapse. NMDA receptors are involved in this process.

 

long-term depression (LTD)

A persistent weakening of synaptic strength.

 

magnetic resonance imaging (MRI)

A technique for imaging the anatomy of the brain using magnets and radio waves.

 

map

An area in the nervous system where some aspect of the sensory world is represented. This may

be topographic as in vision or touch or may represent some other aspect of the stimulus as in a

tonotopic (frequency-oriented) map for hearing. Maps are not always continuous, they may be

patchy or scattered.

 

medial

Towards the middle. For example, the nose is medial to the cheeks.

 

membrane capacitance

The ability of the membrane to store charge by keeping positive and negative charge separated on

opposite sides of the membrane. Diagram

 

membrane conductance

The inverse of membrane resistance. The ease with which a particular ion can move across the

membrane. Conductance, g is measured in Siemens S. (See Ohm's law)

 

membrane potential

The voltage drop across a membrane. Specifically, the difference in force that a charge would

feel at opposite sides of the membrane. This term is synonomous with membrane voltage or

membrane polarization. One speaks of membrane voltage or potential being changed in a

depolarizing (more positive) or hyperpolarizing (more negative) direction. (see resting membrane

potential)

 

membrane resistance

Measurement of the difficulty that a charge has moving from one side of the membrane to the

other. Resistance R is measured in Ohms. Resistance is related to current and voltage by R=V/I,

Ohm's law. Resistance = 1 / conductance

 

memory

Storage of information.

 

microelectrode

A small glass tube tapered toward the tip that can be inserted into neurons to allow intracellular

recording. Slightly bigger microelectrodes may be made of different materials and used in

extracellular recording. Picture

 

micron

10-6 meters. A neuron soma may be 5-30 microns in diameter.

 

milliseconds

10-3 seconds. A typical action potential duration is 1-2 ms.

 

millivolt

10-3 volts. A typical neuron resting membrane potential is about -75 mV.

 

motor cortex

Cortical areas that control movement

 

myelin

The insulation that is wrapped around axons by oligodendroglia which permits faster conduction

velocity by saltatory conduction.

 

neglect syndrome

Contralateral neglect syndrome

 

Nernst equation

An equation for calculating the equilibrium potential of a particular ion

 

Nernst potential

The equilibrium potential for a particular ion. This is the potential that balances out the chemical

diffusive gradient to produce electrochemical equilibrium.

 

nerve

A bundle of axons in the peripheral nervous system. Nerves run to muscles and from sensory

organs in the periphery.

 

neuron

The principal information carrying element of the nervous system. These can differ widely in

shape and connectivity. Most neurons have a soma, dendrites and an axon. Two important

neuron types are pyramidal cells and inhibitory interneurons. Generic neuron picture

 

neuron doctrine

The concept put forth by Cajal that suggested that neurons are separate cells. This was contested

by Golgi's reticular hypothesis that suggested that the nervous system was just one big

continuous network.

 

neuronal membrane

The lipid bilayer that separates the outside from the inside of a neuron.

 

neuropeptides

Peptides (short sequences of amino acids) that serve as neurotransmitters

 

neuropharmacology

Study of how drugs alter neural function

 

neuropil

Areas where numerous dendrites and axons come together making connections.

 

neurotransmitter

A chemical released across a chemical synapse to communicate from one neuron to another.

 

NMDA receptor

A type of glutamate receptor that provides a more prolonged time course of excitation than does

AMPA and appears to be responsible for triggering long term potentiation.

 

node of Ranvier

A gap in the myelin sheath where action potentials can be generated. The jumping of the action

potential from one node to the next is saltatory conduction

 

non-dominant hemisphere

The cerebral hemisphere that doesn't control language. This is the right hemisphere in most

people. It is thought to play a role in spatial tasks.

 

nucleus

A collection of cell bodies in the central nervous system. Also, an organelle that is responsible

for reproduction in a cell.

 

occipital lobe

The rearmost cortex where the primary visual area lies.

 

Ohm's law

V=IR (voltage equals current times resistance); since g=1/R can also write I=gV

 

olfaction

the sense of smell

 

oligodendrocytes

These cells directly provide the myelin sheath wrapping that provides insulation for axons.

 

optic chiasm

The crossing point for the optic nerves (which are not really nerves) coming from the retina.

 

organelle

The cell has an anatomy too. Organelles are the organs of the cell and include stuff for making

energy, for reproducing and for making proteins.

 

orientation column

An area of visual cortex with neurons that respond primarily to line segments seen on the retina

that have a particular angle with the horizontal

 

Papez circuit

A set of interconnections within the limbic system that were proposed (by Papez) to form the

emotion system.

 

parallel processing

The idea that calculation in the brain involves many paths working in parallel simultaneously

(opposite of serial processing)

 

parietal lobe

The large middle region between occipital and frontal lobes. Houses language in the dominant

hemisphere and spatial functions in the non-dominant hemisphere. Has many areas of association

cortex.

 

Parkinson's disease

A movement disorder featuring tremor, rigidity, reduced movement (except for the tremor) and

tendency to fall. Associated with loss of dopaminergic neurons in the substantia nigra.

 

passive membrane

Membranes that lack voltage-sensitive channels. Voltage in such membranes is governed by the

cable equation

 

perikaryon

Synonym for soma

 

peripheral nervous system (PNS)

The nervous system that lies outside of the brain and spine.

 

phasic

A transient response to a continuing stimulus, opposite of tonic.

 

physiology

The study of functional interactions in biology. Contrasted with anatomy.

 

plasticity

Changes in neural connectivity

 

positron emission tomography (PET)

A technique for imaging physiological activity using radioactive substances. Picture.

 

posterior

Backwards, depending on the position in the CNS corresponds to either caudal or dorsal.

 

postsynaptic

The part of a synapse on the receiving side

 

postsynaptic potential (PSP)

Change in voltage in the postsynaptic membrane caused by activation at that synapse.

 

presynaptic

The part of a synapse on the transmitting side

 

primary sensory cortex

An area of cortex that receives sensory information directly from the thalamus or other

non-cortical area

 

primary visual cortex

The primary sensory area for vision

 

primate

Monkeys, apes and people

 

proprioception

sensation of movement in muscles and joints

 

prosopagnosia

a neurological condition where specific faces can't be recognized

 

proximal

Closer to the center of the body, opposite of distal

 

pyramidal cell

A characteristic neuron of the cortex that has a cell body shaped like a pyramid which gives off a

large apical dendrite.

 

pyramidal tract

Corticospinal tract

 

rate coding

Frequency coding

 

"realistic" neural network

Networks of neurons simulated to be relatively close to the real thing. The quotes around realistic

are necessary because the complexity of neurons makes it impossible to accurately simulate them

at this time. A neurophysiological approach to neural networks.

 

receptive field

The receptive field of a neuron are the union of all those locations where stimulation will activate

that neuron. For touch this could be an area of skin while for vision this would be the area

(visual field) that this neuron "sees"

 

receptor

A site on a cell membrane where a chemical can bind. Most receptors are highly selective, they

will only bind a particular type of chemical and not others. Receptors are the site where the

neurotransmitter binds on the postsynaptic membrane.

 

recurrent collaterals

Axon collaterals that come back and synapse either on the same neuron or on the same type of

neuron that they come from

 

reflex

A stereotyped closed stimulus-response loop

 

relative refractory period

A period during which a repeated neuron stimulation must be increased in order to generate

another action potential

 

resting membrane potential

The membrane potential that a neuron will remain at in the absence of stimulation of activity. It is

determined by a complex function that takes into account relative permeabilities of different ions

and their respective Nernst potentials. Usually somewhere near -75 mV.

 

reticular activating system

An area of brainstem that causes arousal or wakening when stimulated. Damage to this area can

cause coma.

 

rostral

The head side of the body. In the brain this is toward the front (anterior) and in the spinal cord

it's towards the top (superior). Opposite of caudal.

 

sagittal plane

The vertical plane that runs from front to back and up to down. Mid-sagittal would be the plane

that runs through the middle of the nose.

 

saltatory conduction

The jumping of an action potential from one node of Ranvier to the next in a myelinated axon.

 

second messenger

An intracellular chemical that transmits a message between one place and another. In many cases

a neurotransmitter activates a receptor that then secondarily relays the information to open an ion

channel or activate another series of chemicals.

 

sensory channel

A psychophysics term for a neural pathway for a particular sense or aspect of a sense.

 

soma

The cell body of a neuron. This is where most of the metabolic activity of the neuron is centered.

It has the organelles for producing energy and creating proteins. In the classical view, signals

generally pass through the soma on the way from the dendrite (input) to the axon (output). The

soma is in the middle of this picture

 

space constant (lambda)

The distance along a passive dendrite for a fixed voltage to decline by 1/e (~37%)

 

spatial summation

Adding up of synaptic potentials arriving at different places on one cell

 

spike

An action potential

 

spike frequency

The frequency at which spikes occur. Usually between 5-100 Hz in most cell types.

 

spike-initiation zone

A specialized area with particularly high concentrations of voltage-gated ion channels that is the

first to generate an action potential.

 

spinal cord

The part of the central nervous system that lies in the spine

 

spontaneous activity

The "resting" firing of a neuron when not being stimulated.

 

stimulus

A maneuver that can activate a sensory receptor.

 

sulcus (pl. sulci)

The cortex is a folded 2-dimensional sheet. The infoldings are sulci.

 

summation

The nonlinear adding together of multiple synaptic inputs.

 

synapse

Synapses are the connections between neurons. Some are electric but in vertebrates most are

chemical, involving the diffusion of a chemical messenger from one side (presynaptic) to the

other (postsynaptic) across the synaptic cleft.

 

synaptic cleft

The region separating the presynaptic and postsynaptic membranes at chemical synapse

 

synaptic transmission

The sending of information across the synapse, usually by means of release and reception of a

neurotransmitter

 

synaptic vesicle

Organelles found in the presynaptic cell that store and release neurotransmitter

 

temporal lobe

A lobe of the brain lying mostly inferior (ventral) and pointing forward (rostral-ward) from

below the major fissure. The auditory area and hippocampus (memory area) are in the temporal

lobe.

 

temporal summation

Adding together of postsynaptic potentials arriving one after another at a synapse

 

terminal

The end of an axon

 

terminal arbor

A bunch of axon branches at the end of an axon

 

tetrodotoxin (TTX)

A poison that comes from the puffer fish and blocks voltage-sensitive sodium channels.

Allegedly used in the voodoo religion for creating zombies.

 

thalamus

A large collection of nuclei that forms the major entry point for most sensory systems to the

brain. It is also involved in sleep.

 

threshold

An activation level that causes a neuron or neural analog to pass from a quiescent to an excited

state. In the case of a neuron this would be the voltage where an action potential would be

generated.

 

time constant (tau)

The amount of time it takes a fixed voltage to die off by 1/e (~37%)

 

tonic

A sustained response to a continuing stimulus, opposite of phasic

 

tract

A bundle of axons that run together in the CNS

 

ventral

The belly side of the body. For the CNS this would be anterior in the spinal cord and inferior

(down) in the brain.

 

ventricles

Large cavities in the brain containing fluid

 

vesicle

An organelle that can store a chemical, keeping it from floating loose around the cytoplasm. See

synaptic vesicle

 

voltage

A measure of the force that a charge experiences due to an electric field. Symbol: V, units: volts,

(also called potential)

 

voltage clamp

Holding a steady voltage in a neuron and watching how the current responds.

 

voltage-gated channel

Synonym for Voltage-sensitive channel

 

voltage-sensitive channel

An ion channel that opens or closes in response to changes in membrane potential.

 

white matter

Brain volumes made up of axons going from one place to another. Looks white when you cut

open a brain.

 

 

Common Medical Abbreviations

 

                  ABBREVIATION MEANING

 

ABG Arterial blood gas

ABO A system of classifying blood groups

a.c. Before meals

ACE Angiotensin converting enzyme

ACTH Adrenocorticotropic hormone, corticotropin

ADH Antidiuretic hormone

ADL Activities of daily living

ad lib As desired

Afib Atrial fibrillation

AFL Atrial flutter

AFP Alpha-fetoprotein

AIDS Acquired immunodeficiency syndrome

ALT Alanine aminotransferase (formerly SGPT)

AST Aspartate aminotransferase (formerly SGOT)

ANA Antinuclear antibody

AP Anteroposterior

A&P Anterior and posterior

AQ Water

ARDS Adult respiratory distress syndrome

ASHD Atherosclerotic heart disease

ASO Antistreptolysin-O

AV Arteriovenous, atrioventricular

bact Bacteriology

b.i.d. Twice a day

BLS Basic life support

BMR Basal metabolic rate

BP Blood pressure

BPH Benign prostatic hypertrophy

bpm Beats per minute

BSA Body surface area

BUN Blood urea nitrogen

BX, Bx Biopsy

C Celsius, centigrade, complement

c* With

Ca Calcium

CA, Ca, ca Cancer, carcinoma

CAB Coronary artery bypass

CAD Coronary artery disease

caps Capsules

CAV Cytoxan, adrimycin, and vincristine

CBC Complete blood count

CC, C.C. Chief complaint

cc Cubic centimeter

CCU Coronary care unit

CEA Carcinoembryonic antigen

cg Centigram

CHF Congestive heart failure

CK Creatine kinase

Cl Chloride, chlorine

CLL Chronic lymphocytic leukemia

cm Centimeter

CNS Central nervous system

CO Carbon monoxide, cardiac output

CO2 Carbon dioxide

COMP Compound

COPD Chronic obstructive pulmonary disease

CPK Creatine phosphokinase

CPR Cardiopulmonary resuscitation, C-reactive protein

C&S Culture and sensitivity

CSF Cerebrospinal fluid

CT Computed tomography

CTS Carpal tunnel syndrome

cu Cubic

CVA Cerebrovascular accident

D&C Dilatation and curettage

DIC Disseminated intravascular coagulation

DIFF, diff Differential blood count

dl Decliter (100 ml)

DM Diabetes mellitus

DNA Deoxyribonucleic acid

DO Doctor of osteopathy

DP Dorsalis pedis

DPT Diphtheria, pertussis, and tetanus (toxoids/vaccine)

DSA Digital subtraction angiography

D/W Dextrose in water

DX, Dx, dx Diagnosis

ECF Extracellular fluid

ECG Electrocardiogram

ED Emergency department

EEG Electroencephalogram

EMG Electromyogram

ENT Ear, nose, and throat

ERA Estroadiol receptor assay

ESR Erythrocyte sedimentation rate

exc Excision

F Fahrenheit

FBS Fasting blood sugar

FDA Food and Drug Administration

FSH Follicle-stimulating hormone

ft Foot, feet, (measure)

FUO Fever of undetermined origin

g, gm Gram

gastroc Gastrocnemius

GFR Glomerular filtration rate

GI Gastrointestinal

GP General practitioner

G6PD Glucose-6-phosphate dehydrogenase

gr Grain

gt, gtt Drop, drops

GTT Glucose tolerance test

GU Genitourinary

GYN, gyn Gynecology

Hb Hemoglobin

HCG Human chorionic gonadotropin

HCI Hydrochloric acid, hydrochloride

HCO3 Bicarbonate

HCT Hematocrit

HDL High-density lipoprotein

HDN Hemolytic disease of the newborn

Hg Mercury

Hgb Hemoglobin

HGH Human growth hormone

HI Hemagglutination inhibition

HLA Human leukocyte antigen

HR Heart rate

Hr Hour

h.s. At bedtime, hour of sleep

Hx History

Hz Hertz (cycles per second)

IABP Intra-aortic balloon pump

ICF Intracellular fluid

ICS Intercostal space

ICU Intensive care unit

IgA Immunoglobulin A

IgD Immunoglobulin

IgE Immunoglobulin

IgG Immunoglobulin

IgM Immunoglobulin

IHSS idiopathic hypertrophic subaortic stenosis

I.M. Intramuscular

inf Inferior

inj Inject

I&O Intake and output

IPPB Intermittent positive-pressure breathing

IU International unit

IUD Intrauterine device

I.V. Intravenous

IVP Intravenous pyelogram

IVU Intravenous urography

JRA Juvenile rheumatoid arthritis

K Potassium

kcal Kilocalorie (food calorie)

kg kilogram

17-KGS 17-ketogenic steriods

17-KS 17-ketosteroids

KO Keep open

KUB Kidneys, ureters, and bladder

l Liter

LAD Left anterior descending (coronary artery)

lat lateral

lb Pound

LBBB Left bundle branch block

LDH Lactate dyhdrogenase

LDL Low-density lopoprotein

LE Lupus erythematosus

LH Luteinizing hormone

lt left

LUQ Left upper quadrant

LV Left ventricle

M Molar

m Meter, minim

MCH Mean corpuscular hemoglobin

MCHC Meancorpuscular hemoglobin concentration

MCV Mean corpuscular volume

MD Medical doctor, muscular dystrophy

mm Millimicron (nanometer)

mEq Millequivalent

Mg Magnesium

mg Milligram

m g Microgram

MI Myocardial infarction

ml Milliliter

m Micron

m l Microliter

mm Millimeter

mM Millimole

m m Micrometer, micron

m mol Micromole

mo Month

mol wt Molecular weight

mOsm Milliosmole

m Osm Micro-osmole

MRI Magnetic resonance imaging

MS Multiple sclerosis, morphine sulfate

MSH Melanocyte-stimulating hormone

MUGA Multigated acquisition (scanning)

N Nitrogen, normal (strength of solution)

Na Sodium

NaCl Sodium chloride

ng Nanogram (millimmicron)

NGT Nasogastric tube

NPO Nothing by mouth

Ob-GYN Obstetrics and gynecology

17-OHCS 17-hydroxcorticosteroids

OTC Over the counter (a drug that can be obtained without a prescription)

oz Ounce

P Phosphorus, pressure, pulse

PaCO2 Partial pressure of carbon dioxide in arterial blood

PaO2 Partial pressure of oxygen in arterial blood

Pap Papanicolaou smear

p.c. After meals

PCO2 Partial pressure of carbon dioxide

PO2 Partial pressure of oxygen

peds Pediatrics

Perrla Puplis equal, round, react to light and accommodation

pg Picogram (micromicrogram)

pH Hydrogen ion concentration

PID Pelvic inflammatory disease

PKU Phenylketonuria

PMS Premenstrual syndrome

P.O. By mouth

PPD Purified protein derivative (of tuberculin)

ppm Parts per million

p.r.n. As needed, whenever necessary

Pro time Prothrombin time

psi Pounds persquare inch

PT Physical therapy

PTCA percutaneous transluminal coronary angioplasty

PTH Parathyroid horomone

PVC Premature ventricular contraction

q Every

q.d. Every day

q.h. Every hour

q2h Every 2 hours

q4h Every 4 hours

q.i.d. Four times a day

R Respirations, roentgen

RA Rheumatoid arthritis

RAIU Radioactive iodine uptake

RBBB Right bundle branch block

RBS Red blood cell

RCA Right coronary artery

RF Rheumatic fever, rheumatoid factor

Rh Rhesus blood factor

Rh neg. (Rh-) Rhesus factor negative

Rh pos. (Rh+) Rhesus factor positive

RLQ Right lower quadrant

RN Registered nurse

RNA Ribonucleic acid

R/O Rule out

ROM Range of motion (of joint)

RUQ Right uper quadrant

Rx Prescription

s* Without

SaO2 Systemic arterial oxygen saturation (%)

SBE Subacute bacterial endocarditis

S.C., SQ, subq Subcutaneous

sec Second

sed rate Sedimentation rate

SGOT Serum glutamic-oxalacetic transaminase (see AST)

SGPT Serum glutamic-pyruvic transaminase (see ALT)

SI Internation System of Units

SIADH Syndrome of inappropriate antidiuretic hormone

SIDS Sudden infant death syndrome

SLE Systemic lupus erythmatosus

SOB Short of breath

spec Specimin

sp gr Specific gravity

S&S Signs and symptoms

ss* One-half

stat Immediately

STD Sexually transmitted disease

sx Symptoms

T Temperature; thoracic, to be followed by number designating specific thoracic vertebra

T&A Tonsillectomy and adenoidectomy

Tabs Tablets

TB Tuberculosis

T&C Type and crossmatch

temp. Temperature

TIA Transient ischemic attach

TIBS Total iorn-binding capacity

t.i.d. Three times a day

TMJ Temporomandibular joint

TPA Tissue plasminogen activator

TPN Total parenteral nutrition

TPR Temperature, pulse, respirations

TSH Thyroid-stimulating hormone

tsp Teaspoon

UA Urinalysis

ung Ointment

URI Upper respiratory infection

USPHS United States Public Health Service

VDRL Veneral Disease Research Laboratory (test for syphilis)

Vfib Ventricular fibrillation

VS Vital signs

VSD Ventricular septal defect

VT Ventricular septal defect

VT Ventricular tachycardia

UTI Urinary tract infection

WBC White blood cell

WHO World Health Organization

 

*abbreviations should have a line above

 

 

Common  Abbreviations In Psychopharmacology

 

a.c. before meals

ADD attention deficit disorder

ADHD attention deficit hyperactivity disorder

BZ benzodiazepine

bid twice a day

c capsule

CNS central nervous system

d day(s)

DNRI dopamine norepinephrine reuptake inhibitor

Dx diagnosis

EPS extrapyramidal side effects

ER extended release

FDA Food and Drug Administration

GABA gamma-aminobutyric acid

GAD generalized anxiety disorder

h hour(s)

hs at sleep/at night

HCA heterocyclic antidepressant

i one unit or pill (ii = two, iii = three)

IM intramuscular

I injectable

L liquid

mEq/L milliequivalents per liter

ml milliliter

NE norepinephrine

ng nanogram

MAOI monoamine oxidase inhibitor

mg milligram(s)

NMS neuroleptic malignant syndrome

OCD obsessive-compulsive disorder

OTC over the counter

p.c. after meals

PO by mouth

prn as needed

q every (or with)

qd once a day; daily

qod every other day

qid four times a day

s without

5-HT serotonin

SR sustained release

SSRI selective serotonin reuptake inhibitor

SNRI serotonin norepinephrine reuptake inhibitor

STAT Immediately (right away)

SUPP suppository

T tablet

TCA tricyclic andi-depressant

TD tardive dyskinesia

tid three times a day

Tx treatment

T 1/2 half-life

tpk time to peak concentration

WBC white blood count

XR extended release

 

 

 

New Drug Development

 

Stages:

 

         I. Preclinical Research

 

         II. Application

 

         III. Clinical Trials

 

         IV. Phase IV evaluations

 

I. Preclinical Research

 

Drug synthesis or extraction

 

Establish efficacy and toxicity

 

biochemical effects

physiological effects

genetic effects

behavioral effects

 

Toxicity-use animals, bacteria

Teratogenicity and mutagenicity

 

Use non-human species or human tissue

 

Institutional Review Board (IRB) oversight

 

II. Application to Food and Drug Administration (FDA)

 

Preclinical data are submitted

Apply to perform clinical studies for investigational new drug (IND)

(or new use for previously approved drugs)

 

Upon approval, clinical studies begin

 

III. Clinical Trials

 

Three phases

Each phase addresses different question

All trials must be reviewed and approved by IRB

At least yearly reports must be sent to both FDA and IRB

 

Phase I Trials

 

new drug is given to a small group (20-100)

 

healthy volunteers (usually male, almost never children)

 

Sometimes patient volunteers are used (especially for rare or difficult to treat disorders)

 

Questions for phase I: safety (most important); safe dose range; identify side effects

 

Phase II Trials

 

Drug is given to larger group of persons (100-500)

 

Subjects include persons with the disease or condition

 

Questions for phase II:

 

Efficacy and dose response relationship

 

What type of patients is drug appropriate for (age, sex, condition)

 

Frequency of dose for optimal benefit

 

Further evaluation of safety

 

New indications for previously approved drugs

 

Phase III Trials

 

Drug is given to large group of persons (1,000 to 5,000)

 

Subjects usually limited to patient population indicated for the drug

 

Questions for Phase III

 

Confirm efficacy

 

Monitor side effects

 

Compare to other common treatments

 

Determine safe dosage

 

Efficacy for sub-groups of patient population

 

Upon completion and approval of Phase III, submit new drug application (NDA) to FDA

 

If drug is approved, Phase IV begins

 

IV. Phase IV evaluations

 

Data is collected after drug is marketed

 

New adverse reactions are identified (as we have seen recently, it may take years for some to appear)

 

Full description of adverse effects

 

Identify risk factors

 

New patient characteristics may be identified

 

Further studies of most effective dosage

 

Optimal duration of treatment

 

Drug interactions

 

Comparison to other drug treatment

 

 

Study Design During Clinical Trials

 

May be problems with random selection and assignment

 

         Does sample represent larger population?

 

         Are control and treatment groups identical?

 

         Referring physician as middleman becoming less common

 

 

Placebo

 

         Chemically inert substance

 

         Used as a comparison to compare true drug effect (pharmacological) from non-specific

 

         May not be practical or ethical - e.g., patients with AIDS

 

         Sham injection - Equivalent of placebo in animal studies

 

 

Open label vs double blind

 

         Open Label

 

         Subject and evaluator both know identity of drug

 

         Advantages:  Relatively inexpensive; easy to recruit subjects; simple design

 

         Disadvantages: Demand characteristics and observer bias

 

 

Appropriate dosage forms for placebos

 

         Best to use capsules

 

         Encapsulation is most likely to hide differences between drug and placebo

 

         Taste and size is the same

 

         Can easily be blinded with blister packs

 

 

Cross-over design

 

         AB/BA design or some variant

 

         Subject gets one treatment then switched to second drug and/or placebo after washout period

 

         Advantages of Cross-Over Design

 

                  Large sample size not required - therefore easier to recruit for study

 

                  Reduced within-subject variability

 

                  Good for Phase I trials

 

         Disadvantages of Cross-Over Design

 

                  Risk of carryover effect - Must ensure that washout is long enough

 

                  Requires a stable condition

 

                  Not generally useful with neurodegenerative and many psychiatric conditions

 

                  As disease or condition progresses may negate therapeutic effect or tolerance may develop

 

 

Double Blind Studies

 

         Neither subject nor evaluator knows identity of drug

 

         Employs placebo or another similar drug

 

         Sometimes employs similarly acting known drug, e.g., TCA when determining effect of SSRI

 

         Advantages of Double-Blind design

 

                  Negates demand characteristics and experimenter bias

 

         Disadvantages of Double-Blind Studies

 

                  More expensive and harder to design

 

                  More prone to error in dispensing

 

                  More difficult to recruit subjects (e.g., subjects may not want to risk possibility of getting only placebo)

 

                  Subjects may still determine identity of drug (e.g., taste side effects, lack of beneficial effects)

 

 

Determination of Efficacy of Clinical Trials in Psychopharmacology: Problems & Issues

 

         Rating scales

 

                  e.g., Ham-D; Brief Psychiatric Rating Scale, -

                  Cognitive measures (memory recall, etc.)

 

                  Potential problems with psychometrics of scales and training of raters

 

Determination of Safety of Clinical Trials in Psychopharmacology

 

         Interviews and rating scales

                  e.g., AIMS, DOTES

 

         Physical examination

 

         Laboratory measures and other diagnostic procedures

 

                   e.g., liver function tests, EKG

 

Efficacy vs Clinical Significance

 

         Differences on rating scales may mean little in terms of actual real life functioning level

 

                  e.g., a few points on MMSE with the use of a cognitive enhancer may be statistically significant,  but produce very little change in day-to-day behaviors

 

Subject Compliance

 

         This is an issue for both treatment and clinical trials

 

         Adverse reactions and/or lack of perceived efficacy may be contributory

 

         Self-selected subjects (e.g., via internet) may be more motivated than physician referred

 

Issues related to Informed Consent and Duty to Inform

 

         Is the patient competent and free to consent?

 

                  Special populations – severely mentally ill, demented, children

 

                  Need to explain in a language subject understands the potential adverse reactions and risks (what, how, when, how severe, how often?)

 

Duration of Studies

 

                  Usually too short (6-8 weeks) to determine effect and toxicity of drug over the long term - e.g., Relapse            with antidepressants, serotonin “poop-out;” Tardive dyskinesia (TD), etc.

 

Termination

 

         When is the end point of study reached?

 

                  When toxicity ensues??

 

                  Must be explained to patient when she/he consents

 

Problems with Large Scale Clinical Studies

 

         Very expensive to mount

         May require underwriting from other sources (government; other or larger pharmaceutical companies)

         Requires considerable expertise in design

 

         Record keeping and confidentiality required - Especially problematic when sharing data across the internet -     requires secure codes

 

         Becoming increasingly international in scope

                  Requires knowledge of regulations in other countries

 

Funding For Clinical Trials and Marketing

 

         Requires enormous sums

         Biotech and other start-up companies or academia do not have resources

 

Orphan Drugs

 

         Drugs with presumed market of < 20,000

 

Summary of Drug Development

 

         >$800 million required to develop one drug (drug companies spent more than 33 billion dollars, approximately 18% of their sales, for R & D in 2003).

 

         Only one of 5000 to 10,000 conceptualized drugs are actually marketed

 

         Only 30 % of marketed drugs recoup costs of R & D

 

         Time from initial development to patent approval long (>14 years)

 

         Competition with generic companies

                  Only 12 year between patent approval  and generic approval; often not enough time to recoup development and marketing costs

        

         75% of experimental drugs fail during clinical trials

 

         Intellectual property not respected in many countries (e.g., China and Viagra)

 

 

 

Current Categories for Drug Use in Pregnancy

Category :  Description

 

A: Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

 

B: Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women.

or

Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.

 

C: Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women.

or

No animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.

 

D: Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.

 

X: Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.

 

 

Controlled Drug Schedules

 

A controlled (scheduled) drug is one whose use and distribution is tightly controlled because of its abuse potential or risk. Controlled drugs are rated in the order of their abuse risk and placed in Schedules by the Federal Drug Enforcement Administration (DEA). The drugs with the highest abuse potential are placed in Schedule I, and those with the lowest abuse potential are in Schedule V. These schedules are commonly shown as C-I, C-II, C-III, C-IV, and C-V. Some examples of drugs in these Schedules are as follows:

 

Schedule I — drugs with a high abuse risk. These drugs have NO safe, accepted medical use in the United States. Some examples are heroin, marijuana, LSD, PCP, and crack cocaine.

 

Schedule II — drugs with a high abuse risk, but also have safe and accepted medical uses in the United States. These drugs can cause severe psychological or physical dependence. Schedule II drugs include certain narcotic, stimulant, and depressant drugs. Some examples are morphine, cocaine, oxycodone (Percodan®).

 

Schedule III, IV, or V — drugs with an abuse risk less than Schedule II. These drugs also have safe and accepted medical uses in the United States. Schedule III, IV, or V drugs include those containing smaller amounts of certain narcotic and non-narcotic drugs, anti-anxiety drugs, tranquilizers, sedatives, stimulants, and non-narcotic analgesics.

 

Some examples are acetaminophen with codeine (Tylenol® No.3), paregoric, hydrocodone with acetaminophen (Vicodin®), diazepam (Valium®), alprazolam (Xanax®), propoxyphene (Darvon®), and pentazocine (Talwin®), methylphenidate (Ritalin®), and dextroamphetamine (Dexedrine®).

 

 

Drug Schedules 

(1) Schedule I.

(A) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has no currently accepted medical use in treatment in the United States.

(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

 

(2) Schedule II.

(A) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.

(C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

 

(3) Schedule III.

(A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

 

(4) Schedule IV.

 (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III.

 (B) The drug or other substance has a currently accepted medical use in treatment in the United States.

 (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

 

(5) Schedule V. -

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

 










Salvatore Cullari
Psychological Services


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