1. Patty Ghazvini, PharmD., CGP. Associate Professor of Pharmacy Practice FAMU College of Pharmacy

2.  http://www.youtube.com/watch?v=lOLb2 1bii-A http://www.youtube.com/watch?v=lOLb2 1bii-A

3.  http://www.youtube.com/watch?v=mhla HwnErBI http://www.youtube.com/watch?v=mhla HwnErBI

4.  Chronic brain disease  Compulsive obsession to use a substance despite serious detrimental and sometimes irreversible concsequences  Brain changes cause a dysfunctional ability to render any control over the cravings or urge to use the substance

7.  Nucleus Accumbens (NA) – anterior in the mesolimbic system; mediates the positive reward behaviors  Amygdala (striatum) – mediates the negative or fear-motivated behaviors  Prefrontal cortex (PFC) – involved in decision making by assigning stimuli to direct behavioral response. Nat Neurosci 2006;9(11): 1440 – 1441.

9.  Genetics – Inherited differences among individuals affect their response to drugs (most studies done in alcoholism)  Biochemical – Studies have shown low levels of serotonin is correlated to violent and impulsive behavior  Environmental – School, home, peers, community  Psychiatric Disorders – Depression, conduct disorder, anti-social personality, ADHD, anxiety disorders

10.  Neurophysiologic reinforcement (reward) is the main factor in the development of addiction Achieved through the reward pathway in the mesolimbic area of the brain  Pathway involves the dopaminergic neurons that originate in the ventral tegmental area (VTA) and project into the forebrain, particularly the nucleus accumbens Release of dopamine from these neurons onto the dopamine receptors in the nucleus accumbens produces positive reinforcement.

11.  Stimulant-reward system Directly influence the neurons that connect from the ventral tegmental area (VTA) to the nucleus accumbens and thereafter to the frontal cortex by the use of dopamine  Opioid system The amygdala and locus coeruleus, use peptides that mimic the action of drugs such as heroin and morphine; activates mu-opioid receptors Involves the above areas to indirectly influence the nucleus accumbens in a manner similar to that of stimulants  Alcohol and other sedative-hypnotics GABA receptors are distributed widely and influence the central dopaminergic reward system through mechanisms that include opioid pathways Uses the mediation of mediation of GABA receptors Also affect the ventral tegmental area - nucleus accumbens (VTA-NA) reward system indirectly

12.  Overall drug abuse  According to the 2009 National Survey on Drug Use and Health (NSDUH):  An estimated 21.8 million Americans (8.7 percent of the population) aged 12 or older were current (past month) illicit drug users, meaning they had used an illicit drug during the month prior to the survey interview  Illicit drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used nonmedically  Marijuana was the most commonly used illicit drug; and in 2009, there were 16.7 million past month users  There were 7.0 million (2.8 percent) persons aged 12 or older who used prescription-type psychotherapeutic drugs nonmedically in the past month

13.  College Students There was an increased rate of use of the following among full-time college students aged 18 to 22 from 2008 to 2009:  Current use of marijuana (from 17.9 to 20.2 percent)  Current nonmedical use of psychotherapeutic drugs overall (from 5.2 to 6.3 percent)  OxyContin ® (from 0.2 to 0.6 percent).

16.  Alcohol  Cocaine  Cannabis  Amphetamines  Hallucinogens  Inhalants  Prescription Drugs of Abuse  Non-Prescription Drugs of Abuse

17.  Alcohol Dependence  Alcohol Withdrawal

18.  Oldest drug of abuse, second in incidence of use only to caffeine  WHO – alcohol causes nearly 1.8 million deaths each year, with 76 million people worldwide having diagnosable alcohol use diosrders  In the US, alcohol is responsible for for up to 85,000 deaths annually

19.  Rapidly absorbed from the GI tract  Absorption begins in minutes, presence of food in the stomach, delayed GI motility or co-ingestion of other drugs can delay absorption  Oxidized by alcohol dehydrogenase  More than 90% of absorbed alcohol is oxidized in the liver  Zero-order kinetics – fixed amount is metabolized per unit of time regardless of concentration; 25mg/dL/h

20. Alcohol Use Among Persons Aged 12 or Older

22.  DSM-IV Criteria: A maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by 1 (or more) of the following occurring within a 12-month period:

23.  Alcohol prevents fulfillment of major role obligations  Recurrent use of alcohol in physically hazardous situations  Recurrent alcohol-related legal problems  Continued use of alcohol in the face of social or interpersonal problems  Does not meet criteria for dependency

24.  DSM IV Criteria: Maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by 3 or more of the following, occurring at any time in the same 12- month period:

25.  Tolerance  Withdrawal  Use of more alcohol or use for a longer time than intended  Unsuccessful efforts or desire to cut down or control alcohol use  A great amount of time is spent getting alcohol, using alcohol or recovering from use  Alcohol-associated decrease in social, occupational, or recreational activities  Continued use in the face of persistent or recurrent physical or psychological problems

26.  Disulfuram (Antabuse®) – 125 – 500 mg orally every morning  Naltrexone (Revia®) – 50 mg orally in the mornings; Vivitrol® - 380 mg IM every 4 weeks  Acamprosate (Campral®) – 666 mg orally 3 times a day

28.  Features of AWS: tachycardia, diaphoresis and hypertension – secretion and excretion of epinephrine and norepinephrine are increased

29.  Glutamate – excitatory, affects NMDA receptors  Acute administration of ethanol – suppression of NMDA receptor function; symptoms of intoxication: sedation, amnesia  Chronic alcohol use – upregulation of these receptors – agitation, seizures, delirium tremens

30.  Acute ingestion – inhibitory effects  Chronic alcoholism – increased number of low-affinity GABA-receptor sites; during withdrawal, the affinity is decreased.  AWS – Blunting of GABA inhibition

31.  Clinical Institute of Withdrawal Assessment for Alcohol scale – assess the severity and progression of AWS

32. Carlson, eta al. Alcohol Withdrawal Syndrome. Critical Care Clinics 2012; 28: 1235-1243. 1 8+ hours after cessation or reduction of alcohol intake Mild tremulousness, nervousness, nausea, with or without tachycardia or hypertension 2 Approximately 24 hoursMarked tremors, diaphoresis, hyperactivity, insomnia, might have illusions 3 12 – 48 hoursSimilar to stage 2, plus tonic-clonic seizures; one-third progress to stage 4 4 Usually 3-5 days; may be delayed up to 12 days Delirium tremens, typically with ongoing agitation, confusion, respiratory and cardiovascular abnormalities ONSETSIGNS & SYMPTOMS

33.  Most common form of ethanol withdrawal  Altered mental status; sympathetic overdrive  Medical emergency  Occurs 3-10 days following the last drink  Symptoms: confusion, hallucinations, agitation, tachycardia, fever

34.  Thiamine deficiency – B1  Medical emergency  Symptoms: oculomotor disturbances, altered mental status and ataxia  80% of those who survive Wernicke’s but do not recover in 48-72 hours will progress to Korsakoff’s psychosis: - psychosis, retrograde amnesia, anterograde amnesia, confabulation

35.  Supportive – folic acid, thiamine, MVI  Parenteral Thiamine 100mg (IV or slow IV push) given concurrently with IV fluids containing dextrose – Prophylaxis  Acute treatment: Thiamine 100-200 mg IV x 3 days.  Oral thiamine 50-100 mg/d x 30 days  Thiamine is a co-factor in glucose metabolism; Wernicke can be precipitated by administration of large glucose load

36.  Benzodiazepines – - Chlordiazepoxide (Librium®) - Diazepam (Valium®) - Lorazepam (Ativan®) - Midazolam (Versed®)  Antipsychotics – Haloperidol (Haldol®)  Propofol  Dexmetedomidine  Folic acid, Thiamine, MVI