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Thursday Feb 22

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Rare; thiamine now routinely administered during detox. Initial symptoms ... Permanent effects less likely to develop when thiamine administered. VIII. Withdrawal ... – PowerPoint PPT presentation

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Title: Thursday Feb 22


1
Thursday - Feb 22 Alcohol (cont)
2
  • VII. Chronic Effects
  • BRAIN
  • With repeated use, cellular tolerance occurs
    changes at sites of action (highpoints only)
  • 1. GABAA receptor system become less sensitive to
    alcohol via reduced number of receptors (fewer
    produced when action is constantly amplified by
    alcohol)
  • 2. Since alcohol has been inhibiting the NMDA
    receptor, system adapts by building more to
    provide Glutamate binding sites (more to find
    what little Glutamate seems to be present)
  • (In absence of alcohol, GABA does not produce
    enough inhibition and the excess Glutamate
    receptors cause increased excitation)
  • 3. Threshold for release or action of Dopamine
    in reward pathway changes (no alcohol, not enough
    reward, craving)

3
  • B. Repeated use at high levels damages the brain.
  • depresses synthesis of protein important to
    neuronal function and repair
  • brain shrinkage occurs (death of neurons and
    glia)
  • increases ventricular size (fluid fills in the
    space)
  • reduces myelin content
  • Particularly vulnerable brain areas hippocampus,
    cerebellum, prefrontal cortex
  • increased risk for Wernicke-Korsakoff Syndrome
    (will discuss later)

4
BODY C. Cardiovascular effects increased risk
for heart disease D. Alcoholic Fatty Liver
chronic fatty liver condition interferes with
general metabolism increases risk for
nutritional deficiencies and disease E. Cirrhosis
inflammation of liver 7th most common cause of
death in U.S. 75 of deaths caused by alcoholism
are due to cirrhosis F. Increased risk for cancer
5
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6
  • VIII. Withdrawal
  • Changes with chronic use produce symptoms of
    withdrawal when alcohol is not available
  • extent of withdrawal symptoms varies with the
    pattern of alcohol use
  • Chronic, daily repetitive, high use worst
    symptoms
  • Binge drinkers, those who drink lesser amounts,
    and those who drink heavily for lesser period
    milder symptoms

7
  • General Symptoms of withdrawal (opposites of
    action)
  • agitation
  • tremor
  • seizures
  • insomnia
  • discomfort and craving
  • Not enough inhibition inhibitory systems dont
    work excitatory systems go unchecked
  • Not enough reward reward systems not adequately
    activated (dopamine opiates)

8
  • VIII. Withdrawal
  • Mild disturbed sleep nausea, weakness,
    anxiety, mild tremors occurring in lt 24 hours
    after alcohol was consumed (overlaps with
    hangover symptoms)
  • Severe symptoms
  • Tremulous syndrome
  • Seizures can be life-threatening
  • Delirium tremens - delirious, agitated, anxious

9
  • VIII. Withdrawal
  • C. Timecourse for unassisted pattern of
    withdrawal
  • For repeated use/withdrawal, withdrawal gets
    worse each time.
  • 3-24 hours
  • Tremors
  • nausea, anxiety, sweating
  • Sleep disturbances nightmares REM rebound
  • Hallucination (alcoholic hallucinosis paranoid
    persecutory)
  • Postural hypotension
  • seizures

10
  • VIII. Withdrawal
  • C. Timecourse
  • By 3rd day
  • Hyperthermia
  • Continued hallucination delirium
  • Cardiovascular collapse possible
  • Death may occur
  • If one survives, most recovery in 5-7 days
    (unassisted)
  • Months later
  • Abnormal EEG

11
  • VIII. Withdrawal
  • C. Timecourse
  • D. Possible permanent disorder Korsakoffs
    Psychosis Alcohol Amnestic Disorder
  • Caused by long-term heavy drinking (5-15 years)
    accompanied by thiamine deficiency (vitamin B1)
  • Rare thiamine now routinely administered during
    detox
  • Initial symptoms
  • Behavioral Symptoms - confusion, anterograde
    memory deficits some memory retrieval problems
  • Visual problems - blurred vision, nystagmus gaze
    palsy
  • Peripheral neuropathy ataxia muscle weakness
  • Permanent effects less likely to develop when
    thiamine administered

12
  • VIII. Withdrawal
  • D. Possible permanent disorder Korsakoffs
    Psychosis Alcohol Amnestic Disorder
  • LongTerm Effects
  • Memory deficits
  • Hippocampal abnormalities
  • Most affected require custodial care

13
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat withdrawal
  • Drugs used to promote avoidance
  • Drugs used to reduce craving
  • Drugs used to treat comorbid conditions and
    reduce dependence on alcohol

14
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat acute withdrawal
  • Benzodiazepines help facilitate actions of GABA
    in absence of alcohol continuing to potentiate
    GABA action
  • Chlordiazepoxide (Librium)
  • Diazepam (Valium)

15
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat withdrawal
  • Drugs used to promote avoidance
  • Alcohol sensitizing drugs make you sick if you
    drink
  • Antabuse (disulfiram) block aldehyde
    dehydrogenase and cause acetaldehyde (toxic
    metabolite) to build up
  • Calcium carbimide (Canada Temposil) similar
    action
  • Acetaldehyde syndrome flushing, throbbing
    headache, nausea, vomiting
  • Can help but not much better than placebo
    agents.

16
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat withdrawal
  • Drugs used to promote avoidance
  • Drugs used to reduce craving
  • 1. opioid antagonists
  • Naltrexone (ReVia, Trexan, Nalorex, Phaltrexia)
    Reduces reinforcement value of alcohol by
    preventing opioids from producing it, and
    preventing opioids from increasing release of
    dopamine
  • Not much better than placebo
  • Nalmefene (Revex) similar and works a little
    better

17
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat withdrawal
  • Drugs used to promote avoidance
  • Drugs used to reduce craving
  • 1. opioid antagonists
  • 2. Dopaminergic agonists elevate dopamine and
    provide some reward
  • Bupropion (Wellbutrin Odranol) antidepressant
    effects
  • 3. Acamprosate GABAA agonist and antagonist at
    NMDA receptors

18
  • IX. Drugs for the Treatment of Alcohol-Related
    Problems
  • Drugs used to treat withdrawal
  • Drugs used to promote avoidance
  • Drugs used to reduce craving
  • Drugs used to treat comorbid conditions and
    reduce dependence on alcohol
  • Serotonergic drugs used to treat depression and
    anxiety
  • SSRIs selective serotonin reuptake inhibitors
    (Prozac Zoloft Paxil)
  • Serotonergic agonist - buspirone (BuSpar)
  • Ondansetron (Zofran) efficacy not yet
    documented marketed as antiemetic for radiation
    and chemotherapy patients Touted for anxiety,
    bulemia, Schizophrenia.

19
  • X. Alcohol and Prenatal Development
  • Readily crosses the placental membrane
  • Developing embryo/fetus lacks detoxifying enzymes
  • Alcohol interferes with normal developmental
    processes (reduces folic acid levels alters
    Vitamin A actions)
  • Effects occur over a continuum from death,
    malformation, growth retardation, behavioral
    dysfunction
  • Most research has focused on the severe end of
    the spectrum Fetal Alcohol Syndrome
  • Fetal Alcohol Effects lesser effects than full
    syndrome may be physically normal but have
    learning or behavioral problems

20
  • Variables Governing Susceptibility
  • Gestational Age at Exposure
  • Genotype
  • Amount consumed
  • drinking frequency
  • Among chronic alcoholics, 30-50 of infants have
    FAS.

21
  • Diagnosis of Fetal Alcohol Syndrome
  • Minimal criteria
  • Abnormalities in three areas
  • Prenatal and/or postnatal growth retardation
  • Central nervous system involvement
  • Characteristic facial dysmorphology

22
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24
CNS Dysfunction Infants feeding problems
sleep problems irritable difficult to soothe
abnormal muscle tone Permanent reduced
intelligence behavioral abnormalities (reduced
inhibitory control social difficulties
increased activity) Alcohol is the 1 preventable
cause of mental retardation. May have anatomical
malformations heart and brain
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