Addiction is an old enemy of mankind. Here in this presentation, it is discussed how substances having abuse potential causes temporary and permanent changes to neuronal circuits in our brain.
Addiction is an old enemy of mankind. Here in this presentation, it is discussed how substances having abuse potential causes temporary and permanent changes to neuronal circuits in our brain.
Pharmacotherapy of Drug Abuse or Addiction (Intoxication and Withdrawal Syndr...Sawsan Aboul-Fotouh
. Addiction Circle (Abuse, Dependence, Addiction)
2. Pathophysiology of Addiction and Reward or pleasure pathway
3. Mechanism of addictive Drugs on Reward System
4. Signs and Symptoms of intoxication and Withdrawal of different Drugs
5. Table List of most common Addictive drugs classified according to action
6. treatment of intoxication
7. Treatment of Withdrawal Syndrome
Pharmacotherapy of Drug Abuse or Addiction (Intoxication and Withdrawal Syndr...Sawsan Aboul-Fotouh
. Addiction Circle (Abuse, Dependence, Addiction)
2. Pathophysiology of Addiction and Reward or pleasure pathway
3. Mechanism of addictive Drugs on Reward System
4. Signs and Symptoms of intoxication and Withdrawal of different Drugs
5. Table List of most common Addictive drugs classified according to action
6. treatment of intoxication
7. Treatment of Withdrawal Syndrome
A literature review of research on profound giftedness (including my research), as well as a list of resources for parents, educators, and other interested individuals who want to dive deeper.
Deep vs diverse architectures for classification problemsColleen Farrelly
Deep learning study, comparing deep learning methods with wide learning methods; applications include simulation data and real industry problems. Pre-print of paper found here: https://arxiv.org/ftp/arxiv/papers/1708/1708.06347.pdf
Follow-up to a literature review on the profoundly gifted. Creates composite sketches of adolescents with different ability levels and areas of strength.
Generative AI for Social Good at Open Data Science East 2024Colleen Farrelly
A brief overview of generative AI technologies and their use for social good initiatives, including cultural training, medical image generation, drug design, and public health.
PyData Global 2023 talk overviewing case studies in network science, including stock market crash prediction, food price pattern mining, and stopping the spread of epidemics.
Overview of mathematical and machine learning models related to climate risk modeling, climate change simulations, and change point detection. Includes a hands-on session with geometry-based systems analysis of food prices related to climate change and geopolitical factors.
WiDS Workshop on natural language processing and generative AI. Details common methods that tie into coding examples. Ends with ethics discussion regarding these technologies and potential for misuse.
Link to talk YouTube: https://www.youtube.com/watch?v=byGzKm0H1-8&list=PLHAk3jHXWpxI7fHw8m5PhrpSRpR3NIjQo&index=3
ODSC-East 2023 presentation covering topics related to my book, The Shape of Data, including how geometry plays a role in text/image embeddings, network science problems, survey data analytics, image analytics, and epidemic wrangling.
This talk overviews my background as a female data scientist, introduces many types of generative AI, discusses potential use cases, highlights the need for representation in generative AI, and showcases a few tools that currently exist.
Emerging Technologies for Public Health in Remote Locations.pptxColleen Farrelly
The tools possible to leverage for public health interventions has changed significantly in the past decades. Tools from geometry, natural language processing, and generative AI allow for a quick design and implementation of interventions, even in very rural parts of the world. Case studies involve HIV, Ebola, and COVID interventions.
WoComToQC workshop lecture on Forman-Ricci curvature for applications in industry (social networks, disaster logistics, spatial data, and spatiotemporal goods pricing data).
PyData Global talk covering tools from geometry/topology and their uses in public health, public policy, and social good initiatives. Examples include food price prediction, COVID policies, public health interventions, and fair AI.
Data Science Dojo Talk on comparing time series using persistent homology. Short overview of time series data. A bit of topology. Code available. Example includes stock exchange data.
Statistical and topological algorithm piece of an Applied Machine Learning Days Morocco talk. Covers ARIMA models, SSA models, GEE models, and persistent homology. Applications include pricing data, stock data, development data, and healthcare data. Datasets and full presentation can be found on GitHub: https://github.com/gabayae/Time-Series-Applications_AMLD2022
An introduction to quantum machine learning.pptxColleen Farrelly
Very basic introduction to quantum computing given at Indaba Malawi 2022. Overviews some basic hardware in classical and quantum computing, as well as a few quantum machine learning algorithms in use today. Resources for self-study provided.
Indaba Malawi workshop on basic approaches to time series data, including ARIMA models and SSA models. Example in R includes an agricultural example from historical Malawi data with Rssa package and base ARIMA models.
NLP: Challenges and Opportunities in Underserved AreasColleen Farrelly
This talk highlights the challenges and opportunities that exist in linguistically underserved areas. It highlights NLP initiatives in Sub-Saharan Africa, as well as financial opportunities in technology if areas neglected linguistically can produce tools in their local languages. Ethics, ownership, and other concerns are highlighted to guide development initiatives.
Geometry, Data, and One Path Into Data Science.pptxColleen Farrelly
Women in Data Science (Alexandria, Egypt) keynote address. Topics cover my journey into data science/machine learning, an overview of data science as a profession, and some case studies on topology/geometry in analytics. Example case studies include insurance, natural language processing, social network analysis, and psychometrics.
WiDS Alexandria, Egypt workshop in topological data analysis (Python and R code available on request), covering persistent homology, the Mapper algorithm, and discrete Ricci curvature. Examples include text data and social network data.
First part of a workshop looking at industry case studies in natural language processing for From Theory to Practice Workshop (AIMS, Kigali, March 2022).
SAS Global 2021 Introduction to Natural Language Processing Colleen Farrelly
Overview of text data, processing of text data, integration of text data with structured databases, and uses of text data in analytics across a variety of fields. Here's the talk link: https://www.youtube.com/watch?v=wS0X1bSsuUU
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
2. Overview of
Neurotransmission
Key Concepts:
Action Potentials
Life-cycle of the
Neurotransmitter
Synapses and Receptor
Types
G-Proteins and
Regulation of Ion
Channels
3. Electric current through cell
membrane resulting in
intracellular action at a
synapse
Absolute threshold
All or none behavior
Excitatory (EPSPs)
increases electrical
potential
Inhibitory (IPSPs)
decreases electrical
potential
Saltatory conduction, as
Schwann cells wrap cell
membranes
Current hits presynaptic
terminal and opens voltage-
gated Ca++ channels
Leads to neurotransmitter
release
Action Potentials
4. Neurotransmitter Lifecycle
Location of synthesis
Soma (peptides)
Presynaptic
terminals (small-
molecule
transmitters)
Storage until release
signal (electrical
current)
Released with Ca++
increase through
exocytosis
Involves many
intracellular
proteins
Re-uptake after
release
Degradation after
release
5. Synapses and Receptor Types
Receptor types:
Ligand-gated
(ionotropic)
G-protein-coupled
(metabotropic)
A subunit activates
effector enzyme
2nd
messenger
effects ion channel
Additionally,
intracellular
receptors
Marijuana’s effects
on amanamide
receptors
Can effect gene
expression
Enzyme coupled
(tyrosine
hydroxylase)
6. Downstream Effects
Neurotransmitters interacting
with these receptors can:
Elicit short- or long-term
modulatory processes
Impact learning and memory
Impact an important process
called synaptogenesis
Create connections
between neurons in memory
structures reiterated by the
same stimuli
Involved in triggers for
relapse
Ingrained in memory with
connections and pathways
New pathways that form
are difficult to destroy
quickly.
7. G-Proteins and Secondary
Receptors
Cascades and amplification of signal
G-proteins activated by ligand binding (neurotransmitter)
Activates effector protein (such as adenylyl cyclase)
Creates many other effectors (such as cAMP)
Which then release the catalytic subunit on a kinase (such as PKA)
Kinase phosphorylates many second effectors
Many targets of which regulate channels
Other targets of which impact gene regulation (epigenetic changes)
8. The Limbic System
Structures
Ventral Tegmental Area
Nucleus Accumbens
Lateral Nuclei of Hypothalamus
Reticular Activating System
(regulation and affective stimuli),
Cingular Gyrus (top of brainstem
affecting emotions, too)
Main Neurotransmitters
Dopamine
Associated with pleasure
100,000 molecules per neuron in a
dopaminergic system
Dopamine in cocaine abuse
Main transmitter involved
Agonist amantadine decreases
craving
GABA
Inhibition
Mediates reinforcement in
hippocampus and amygdala when
paired with stress
Reinforcement
Initially build to
associate behavior with
feeding and sex
Controls emotional
memory, as well as other
behavioral responses
Highjacked by drugs of
abuse
Much like a biological
simulation of Pavlov’s
conditioning
9. Affects of Neurotransmitters
Gene Regulation
G-proteins effect CREB genes, which modulate cAMP
production via adenylyl cyclase
cAMP systems implicated in many systemic affects of addiction
Additionally, amphetamines and cocaine induce c-fos gene
Also acts on CREB gene regulation
Creates regulation loop involving CREB, cAMP, and transmitters
Channel Regulation
Long-term synaptic depression
Makes it more difficult to activate the neuron’s electrical
potential
Long term depression and glutamate
Hits NMDA receptor
Then acts on PLC, which clips PIP2 to IP3 and DAG
DAG, with the addition of Ca++ from intracellular store release
and from Ca++ channels opening, acts on PKC
IP3 acts on endoplasmic reticulum stores of Ca++, which then
binds to calmodulin, which activates CaM-KII
PKC and CaM-KII act on channel effectors that produce long-term
depression
10. Types of Neurotransmitters
Acetylcholine
Acts on the
parasympathetic
system
Anti-excitatory
Substances affecting
acetylcholine
receptors
Nicotine
nAChR ionotropic
receptors
Increases
parasympathetic
activity
Faster response,
effect from the
neuron
Excitatory effect
(EPSPs)
11. Types of Neurotransmitters
Catecholamines
Synthesized from amino
acid tyrosine
Dopamine from dopa
conversion via tyrosine
hydroxylase
Metabolized into
norepinephrine and then
into epinephrine
Pathway modulated by
mAChR receptors via PKA
interactions with CaM-KII
Degraded by COMT and
MAO enzymes
Functions
Reward pathways
Mimicked by many drugs of
abuse (cocaine,
amphetamines)
12. Drugs and Catecholamines
Norepinephrine
Circuits acted upon by
amphetamine and cocaine
Modulates learning and
memory circuits, including
emotionally-charged memories
Dopamine acts especially in the
VTA-NA systems
Translates motive states into
overt motor responses
Powerful reinforcement
mechanism
Cocaine and amphetamine as
main drugs of abuse impacting
dopamine
13. Specific Drug Mechanisms
Dopamine re-uptake transporters inhibited (blocked)
by both amphetamines and cocaine
Cocaine
Works on monamine up-take system (inhibits)
Increases mood
MAO inhibitors reverse depression similarly, accounting
for the high of cocaine
Amphetamines
Stimulates more release of dopamine
NE transporter effected similarly
Except that amphetamine works from within the cell on
this receptor (“cell-permeant” drug, as opposed to
cocaine as “cell-impermeant”)
Alcohol
Effects specifically:
VTA
Substantia nigra (“shakes” with withdrawal)
14. Types of Neurotransmitters
Amino Acids
Glutamate
Main excitatory neurotransmitter
Glutamate synthesized from glial glycine release
Converted back to glycine with uptake into glial
cells after transmission
Also can be turned into GABA (inhibitory analogue)
Works through metabotropic receptors
Substances effecting glutamate
Suspected general role in addiction
Possible antagonist of NMDA receptors in
hippocampus when reacts with GABA
Causes long-term potentiation
15. Types of Neurotransmitters
Y-aminobutryric Acid (GABA)
Structure
Ionotropic binding sites
Synthesized from recycled
glutamate via glutamate
decarboxylase
Function
Main inhibitory transmitter
(hyperpolarizing impact through
Cl- influx)
Effects every brain system
(connected with epilepsy)
Connection to glutamate
(depolarizing effect)
Substances effecting GABA regulation
Gamma subunit implicated in
alcohol’s effects on GABA
systems (benzodiazepines and
barbiturates, as well)
These act on GABA-alpha
ionotropic receptors
Produces various inhibitory
responses in body
16. Types of Neurotransmitters
Serotonin
Structure
Indolamine
Function
Regulate sleep-wake
patterns
Mood regulation
Role in Psychiatric
Disorders
Imbalances lead to many
psychiatric mood
disorders.
Bipolar I and II
Depression
Psychodelics and serotonin
responsible for psychedelic
effects
17. Types of Neurotransmitters
Neuropeptides
Function
Endogenous opioid peptides
Role in pain regulation
Long-term depression
in mechanosensory
pathways
Role in reward systems
Substances effecting opioid
receptors
Mainly opiates
Examples include heroin,
morphine, oxycodone, and
fentanyl
Work on mu-1 receptors in
the nucleus accumbens,
triggering dopamine
pathways
18. Neuropeptides In-Depth
Neuropeptide chains effecting pain regulation, especially
(enkephlins and dynorphins)
Periaquiductal gray of midbrain
Controls pain with dynorphins for long-term depression of pain
pathways
Also affect reward systems by the pleasure response
Works on VTA-NA system, especially with mu receptors
Morphine, heroin act as agonists
Heroin changed to morphine in brain
Heroin has 2 additional acetyl groups on the 3 and 7 carbons,
as well as an additional methoxy group)
Act on G-protein receptors (mu and delta)
Increases PK+ and PCa++
In turn inhibits adenylyl cyclase and cAMP
Tolerance develops rapidly
Rregular use over a few months, can tolerate 40-50 times dose L50
Mu and delta receptors reduce consumption of alcohol and opioids
when blocked (effects of Naltrexone
Naloxone is a pure antagonist used in overdoses to block opiate
binding
19. Neurobiological Mechanisms Agonists
Opiates acting directly on opioid receptors
Antagonists
Block drug from binding (use of naloxone in heroin overdoses)
Re-uptake blockers
Amphetamines blocking dopamine re-uptake
Sensitivization/desensitivization and neuronal adaptation
Role in tolerance/reverse tolerance
Cells adapt by increasing/decreasing receptor density at synapse
Dendrites growing or shrinking in response
Remove substance responsible for changes and cells have to re-adjust
to less/more neurotransmitters (law of opposites and withdrawal
symptoms)
20. Neurobiological Model of
Addiction Causes
Genetic predisposition
MZ/DZ twin studies and family studies
Trauma plus genetics implicated in veteran
studies and survivors of child abuse
Genes implicated in addiction
Channel abnormalities
NMDA glutamate receptor
Metabolic abnormalities
Alcohol dehydrogenase
21. Causes of Addiction in the
Neurobiological Model
The Substrate Itself
Actions on Neurotransmission
Channels and Metabolism
TIQs
Local and Global Effects of
Neurotransmission Disturbance
Pathways and Neuronal Adaptation
Stimulants and Re-uptake
22. Diagnosis
DSM-IV Criterion
Substance abuse vs.
substance dependence
(withdrawal)
Metabolite tests
Vital functions
Chemical assessment
Other medical problems
closely associated with
addiction
Cirrhosis
HIV/hepatitis/others related
to injecting practices
Brain damage and nutritional
deficiencies
Comorbid psychiatric
disorders
23. Detoxification as a First Step
in Treatment
Detoxification
Drugs administered
Overdose
Naloxone and opiate
overdoses
Rehabilitation detoxification
Benzodiazepines and
alcohol withdrawal
Treatment options after
detoxification
Psycho-behavioral treatment
Cognitive-behavioral
therapy
12-step groups
Pharmacological treatment
24. Maintenance
Methadone Programs
Long-term treatment
Aversion therapy
Disulfiram and Alcoholism
Treatment of co-morbid disorders
Antidepressants
Antipsychotics
Anti-Craving Drugs
Naltrexone
Alcoholism, narcotic addiction
Bupropion
Anti-smoking drug
Relapse risk for comorbid cocaine addiction)
Pharmacological Treatment
of Addiction
25. Merits of the
Neurobiological Approach
Understanding the risks and mechanisms
behind behavior
Withdrawal avoidance
Importance of abstaining from potentially
addicting drugs
Allows for treatment under Health Care Plans
Developing drugs to reverse overdoses
Shifts the blame
Not completely the addict’s fault
Less guilt over the addiction
More likely to seek treatment
26. Problems of the
Neurobiological Approach
Not everyone with a biological
predisposition becomes addicted to
drugs.
The phenomena of relapsing
Physiology returns to normal at most a 1-2
years after cessation.
Emotional memory should also return to
normal after cessation.
Shifts emphasis from responsibility to
determinism
Allows for an excuse to relapse or to not
seek treatment.
27. Sources
Crabbe, John C., Jr., Harris, R.
Adron, The Genetic Basis of
Alcohol and Drug Actions. Plenum
Press, New York, New York: 1991
Feldman, Robert S., Meyer,
Jerrald S., Quenzer, Linda F.
Principles of
Neuropsychopharmacology.
Sinauer Associates, Inc.,
Sunderland, MA: 1997
http://www.biopsychiatry.com/in
dex.html
http://www.psychologytoday.com
/articles/pto-19980201-
000010.html
http://www.drugdevelopment-
technology.com/projects/bifepru
nox/bifeprunox3.html
Niewink, RJM, Jaspers, RMA, et
al. Drugs of Abuse and Addiction:
Neurobehavioral Toxicology. CRC
Press, Boca Raton, FL: 1999
Perrine, Daniel M. The Chemistry
of Mind-Altering Drugs. American
Chemical Society, Washington
D.C.: 1996
Purves, Dale, Augustine, George
J., et al. Neuroscience. Sinauer
Associates, Inc., Sunderland, MA:
2004
Thompson, Richard F. The Brain.
W. H. Freeman and Company,
New York, New York: 1995
Zernig, Gerald, Saria, Alois, et al.
Handbook of Alcoholism. CRC
Press, Boca Raton, FL: 2000
Editor's Notes
Neuropeptide chains effecting pain regulation, especially (enkephlins and dynorphins)
--periaquiductal gray of midbrain controls pain with dynorphins for long-term depression of pain pathways
-- also affect reward systems by the pleasure response
--works on VTA-NA system, especially with mu receptors
Morphine, heroin act as agonists
--in fact, heroin changed to morphine in brain
--heroin has 2 additional acetyl groups on the 3 and 7 carbons, as well as an additional methoxy group)
Act on G-protein receptors (mu and delta)
--increases PK+ and PCa++
--in turn inhibits adenylyl cyclase and cAMP
Tolerance develops rapidly
--regular use over a few months, can tolerate 40-50 times dose L50
Mu and delta receptors reduce consumption of alcohol and opioids when blocked (effects of Naltrexone)
Naloxone is a pure antagonist used in OD
Need to Cross Blood-Brain Barrier
--lipid or aqueous soluble properties
Agonist/Antagonist display
Re-uptake and Cocaine Addiction
--dopamine and norepinephrin mechanisms
--cocaine blocks re-uptake of these NTs
--more NE and DA hit receptors, eliciting a pleasure response (ADAPTS)
--dysphoria when cocaine withheld
Sensitivization in stimulants
--reverse tolerance found in stimulants
--augmented response that increases with increased dosage
--hence, the mimicking of schizophrenia with extremely high cocaine and amphetamine consumption
Desensitivization in Depressants
--Tolerance consequence of:
--decrease in effective concentration of the agonist
--reduction in number of receptors
--change in response elicited because of the activation of a homeostatic mechanism
--pharmacodynamic tolerance also appears in depressants
--which is a general cellular tolerance to the substances
Re-uptake and Cocaine Addiction
--dopamine and norepinephrin mechanisms
--cocaine blocks re-uptake of these NTs
--more NE and DA hit receptors, eliciting a pleasure response (ADAPTS)
--dysphoria when cocaine withheld
Heroin addiction
acts on dynorpin/endorphin metabotropic receptors.
--activates Gi protein, inhibiting adenylyl cyclase, which decreases cAMP concentration.
--decrease of cAMP and downstream effectors counteracted by increasing adenylyl cyclase concentration.
--balance regained in time (TOLERANCE)
--remove heroin, adenylyl cyclase freed—WITHDRAWAL SYMPTOMS appear
--can eventually return to normal
Withdrawal effects opposite of drug effects and operates on the same time-frame.
--Example: heroin slows stomach contractions, is fast acting.
--Withdrawal has stomach contractions, is fast-acting.
Predisposition
--2.5 times higher chance of alcoholism in Children of Alcoholics than other children
Channel Abnormalities
--second messengers (G-proteins) affected by receptor differences, such as in NMDA receptors and the D4 receptors
--can also interfere with IPSP and EPSP interference in membrane potentials as a consequence
Metabolic Enzyme Differences
-- rate-limiting steps differ
--ex. Alcohol Dehydrogenase gene ADH and ALDH (aldehyde hydrogenase)
--active ALDH gene increases likelihood of alcoholism
--ALDH2-1 as opposed to ALDH2-2
--ADH2 &ADH3 have near loci on chromosomes 11 and 4
--in addition, differences in MAO concentrations in platelet counts
--plus differences in B-endorphin response with alcohol consumption
How Drugs Effect Synapses
--increase/decrease synthesis of NTs
--increase/decrease transport of NTs
--modify storage vesicles
--modify release of NTs
--increase/decrease rate of degradation of NTs
--block re-uptake
--mimic NT (agonist)
--block receptor (antagonist)
--affect up-/down-regulation of receptors
TIQs—
--dopamine + acetaldehyde (from alcohol breakdown)
--possible opioid-like response
DSM-IV Criteria
--tolerance or withdrawal necessary with dependence (physical, rather than only psychological)
Physical tests for Alcoholism
--malnutrition
--red blood cell counts
--liver enzyme analysis (glutamate dehydrogenase, AST/ALT levels)
--carbohydrate-deficient transferrin (CDT) levels
OD
--naloxone acts as antagonist on opioid receptors, reverses effects of heroin/morphine…
AWS Signs
--tremor, hyperhidrosis, tachycardia, insomnia, anxiety, clouding of consciousness, seizure (opposite of intoxication)
--detoxification with benzodiazepines
--usually with diazepam (valium)
Methadone
--less psychological effects than heroin
--longer duration to stave withdrawal
--lots of controversy
Aversion Therapy
--Alcohol metabolism
-- disulfiram blocks aldehyde dehydrogenase (build of acetaldehyde, which causes unpleasant feelings—flushing, vomiting)
--Ro 15-45B blocks behavorial and neurochemical effects of alcohol
Co-Morbid disorders can exacerbate substance use (self-medication)
Anti-Craving Drugs
--Naltrexone in craving prevention in alcoholism (modification of NTs and receptors)
--works on opioid system as well, GABAa system, Glutamate system
--Amantadine for glutamate and dopamine modification in cocaine addicts
--Ibogaine trials in Israel and Netherlands as an anti-craving drug
--unfortunately Schedule I substance in USA
--danger of Bupropion