Lecture 4 Flashcards
How much is heritability responsible for the populations variability in developing an addiction?
Heritability is responsible for 40-60% of the population’s variability in developing an addiction
What can genetic factors do in relation to genetic predisposition and vulnerability?
There are genetic factors that:
- Influence the susceptibility of developing some type of an addiction
- Are more specific (sets of genes) for one substance or type of addiction
- Polymorphisms (gene variants) are associated with many differences in humans
True or False: Over 100 gene variants that lead to variant proteins that are associated with vulnerability to addiction
TRUE
What are examples of gene variants that are associated with vulnerability to addiction?
- One study concluded that genetic influences were decreased in adolescent twins that smoked when the parental monitoring increased
- There is a greater risk of addiction associated with the variant of a gene responsible for the number of D2 receptors; however, family and community factors insulate against the development of an addiction
- Childhood adversity, stressful life events and lower levels of education seem to have a stronger effect that protective alcohol-etabolizing, and dopaminergic transporter genes
What was the substance use risk profile (SURPS) developed for?
It was developed to identify four personality dimensions associated with risk for substance abuse:
- Hopelessness/introversion
- Anxiety sensitivity
- Impulsivity
- Sensation seeking
How does temperament affect environment?
- Difficult childhood temperament is likely to elicit negative reactions from others including teachers, parents, and peers
- Over time, these interactions may result in disengagement from school, a lack of closeness from family members, social rejection from healthy peers, and increased affiliation with deviant peers
What is the gene-environment correlation: evocative?
An individual indirectly shapes his/her environment because of genetic predisposition
- They evoke behaviors from others that increase risk
- A child with behavioral problems may evoke poor parenting interactions, leading to promoting the risk for psychopathology, including addiction
What are the four patterns of attachment?
Secure
Insecure-anxious avoidant
Insecure-anxious resistant
Disorganized, disoriented
Are insecure attachments implicated in childhood disorders?
YES
True or False: The strongest and most reliable indicator of substance abuse is a consistent early patter of antisocial behavior
TRUE
- There are robust and enduring connections observed over time between childhood antisocial behavior and the subsequent development of substance abuse, evident in both epidemiological studies and high-risk samples
How do prenatal stress and anxiety affect children?
- Externalizing problems and conduct disorder in children have been shown to be associated with prenatal stress, independent of postnatal maternal or genetic factors
- Prenatal anxiety were prospectively associated with child externalizing difficulties and verbal IQ
- Anxiety and substance use disorders are correlated
What are passive gene-environment correlation? Example?
Child passively inherit the genes AND are exposed to the environment their parent/s provide
Example:
- Pass down the genetic vulnerability. parents with SUD have deficits in parenting, which is associated with psychological disorders in children SUD. Exposed to SUD in the home, associated with problem parenting can all lead to an increased risk for SUD
What are active gene-environment correlation? Example?
Child selects environments based on genetically influenced trait. Niche picking
Example:
- Children with a genetic propensity to engage in sensation-seeking behaviors are more likely to affiliate with peers who use illicit drugs, increasing their risk for SUD
What are the parts of the diathesis stress model?
Diathesis:
- A predisposition or vulnerability (Ex: temperament)
- Constitutional traits
- Genetically inherited characteristics
+
Stress:
- Environmental stresses, including exposure to drugs
- Exposure ‘stresses’ the individuals predisposition
=
Development of the disorder (SUD):
- The stringer the diathesis, the less stress or exposure necessary to produce the disorder
What are examples of the diathesis stress model?
- Exposure to low levels of stress will increase the likelihood of the development of a disorder for someone with a high vulnerability to a disorder (genetically predisposed and difficult temperament)
OR
- Exposure to a lot of stress would be needed if the person had a vulnerability for a disorder
What does the diathesis stress model attempt to account for?
This model attempts to account for variability in the onset, and occurrence of SUD’s and mental health disorders by the dynamic interaction between the diathesis and stress processes
How does ACEs relate to AUD?
- Stressful or traumatic events, including abuse and neglect
- Early use of alcohol
- Higher risk of mental and substance use as an adult
- Strong correlation with addictive prescription drug use as an adult
-Lifetime illicit drug use, drug dependency and self-reported addiction
What is the percentage of people who had experienced 4 or more ACEs compared to those who experienced no in relation to alcoholism, drug abuse, depression, and suicide attempts
Subjects in a study who had experienced four or more categories of adverse childhood exposure, compared to those who had experienced none, had approximately 8 times more instances of alcoholism, drug abuse, depression, and suicide
attempts.
- While 2/3rds of Americans teenagers score a 1 or 2; the incarcerated teenagers score a 7 or 8 approximately 95% of the time.
What are opiates and opioids?
Opiates are chemical compounds that are extracted or refined from natural plant matter (opium poppy sap and fibers)
- Morphine
- Codeine
Opioids are chemical compounds that not derived from natural plant matter. They are synthesized in the lab
What are semisynthetic vs synthetic opioids?
Semisynthetic (chemically Modified Opiates)
- Heroin
- Hydrocodone
- Oxycodone
Synthetic (Man-made)
- Fetanyl-approx. 100x stronger than morphine.
- Methadone
- Demerol
What schedule drug are opioids?
They are a schedule II drug
What is drug scheduling?
Drug Enforcement Administration (DEA) Drug Schedules
- Drugs substances, and certain chemicals used to make drugs are classified into 5 distinct categories or schedules depending upon the drug’s acceptable medical use and the drug’s abuse or dependency potential
What is Schedule I of the drug scheduling categories?
Schedule I - no currently accepted medical use and a high potential for abuse
- Heroin
- LSD
- Cannabis
What is Schedule II of the drug scheduling categories?
Schedule II - high potential for abuse, dangerous and may lead to severe psychological or physical dependence
- Hydocodone
- Cocaine
- Methamphetamine
- Oxycodone (oxycontin)
- Fentanyl
- Adderall
What is Schedule III of the drug scheduling categories?
Schedule III - moderate to low potential for physical and psychological dependence
- Tylenol with codeine
- Ketamine
What is Schedule IV of the drug scheduling categories?
Schedule IV - low potential for abuse and low risk of dependence
- Xanax
- Soma
- Valium
- Ativan
What is Schedule V of the drug scheduling categories?
Schedule V - lower potential for abuse than schedule IV and contains limited quantities of certain narcotics
- Cough medication with less than 200 milligrams of codeine
What is the loss of control portion of Opioid Use Disorder (OUD)?
- Opioids are often taken in larger amounts or over a longer period than was intended
- There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
- A great deal of time is spent in activities necessary to obtain the opiod, use the opiod, or recover from its effects
- Craving, or a strong desire or urge to use opioids
What is the risky use portion of Opioid Use Disorder (OUD)?
- Recurrent opioid use in situations in which it is physically hazardous
- Continued opioid use despite knowledge of having persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance
What is the Social/Vocational Problem portion of Opioid Use Disorder (OUD)?
- Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home
- Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids
- Important social, occupational, or recreational activities are given up or reduced because of opioid use
What is the Pharmacological/Physical Symptoms portion of Opioid Use Disorder (OUD)?
- Exhibits tolerance
- Exhibits withdrawal
What is the nonfatal opioid overdoses in Urban ED?
- The total number of nonfatal opioid overdose visits increased from 102 to 227
- In contrast the total number of common heart related diagnoses decreased from 41 to 31
- The total emergency department visits decreased from 35,565 to 26,061 in March through June 2020
What happened during the covid-19 pandemic for the OUD?
- Rates of overdose and relapse for OUD significantly rise
- Non-fatal overdoses cause including brain hypoxia, decreased cognitive performance, clinical depression, and increased suicidal ideation
- Those who experience a non-fatal overdose are at greater risk of experiencing a subsequent overdose
Is OUD a new problem?
Iatrogenic addiction to opioids: induced in a patient by the treatment
- Between 1870 and 1880 American’s use of opiates almost tripled
Drivers: No regulation
- Physicians disregarding the issues
- They were readily accessible - allowing the population to be overexposed to morphine
- Doctors were advertising morphine injections
In what year did James F.A. Adams publish about toxicity and addiction?
In 1889
What was the first epidemic? What happened?
During this morphine epidemic Bayer corporation developed and marketed a “safer alternative to morphine”
Heroin:
- Morphine derivative
- Lower risk of overdose compared to morphine
Used to treat morphine addiction???
- Cough medicine
- They cited preclinical studies in mice
- It made its way to the streets for illicit/nonmedical use
- Crushing and snorting heroin tablets
What was the second epidemic? What happened?
In response: Harrison Narcotic Control Act in 1914 acknowledged the dangers
- You had to purchase a tax bill to register and get star opioids
- A way to keep track
- Many people who were cut off abruptly suffered a great deal
- Considered ‘malingerers. Even if they had cancer
Second wave after WWII
- Affecting inner-city minorities
- Underground market -> manufactured heroin
- Because it has been cut with fillers for profit, the effect wasn’t as potent unless injected
- By the 1970s its at epidemic proportions
What was the call to use narcotics again for pain (1980s)?
- Reported .03% addiction rate in this ‘paper’
- Paragraph in a letter to the editor
- Doctors were using this data
- This was their evidence base
- “Addiction rare in patients treated with narcotics”
How were doctors trained to be humane with hospice and pain patients? How was is separated between mild, moderate, or severe pain?
- WHO -> 1986. Treatment ladder
- Aggressive and humane treatment
- Methodology used worldwide to train physicians
- Mild pain: non-opioid analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs or acetaminophen with or without adjuvants
- Moderate pain: weak opioids (hydrocodone, codeine, tramadol) with or without non-opioid analgesics and with ot without adjuvants
Severe and persistent pain: Potent opioids (morphine, methadone, fentanyl, oxycodone, hydromorphone, oxymorphone) with or without non-opioid analgesics
What is the humane treatment for pain?
- “Opioid maintenance therapy can be safe and human”
- “Tragedy of Needless Pain” published in 1990
- “Therapeutic use of opiates rarely results in addiction”
- Call for physicians to use opioids
- Lack of evidence
What is the third epidemic? What happended?
First wave of opioid crisis as we know it
1991-present
- More overdose deaths than any other time in history
Drivers:
- As prescriptions for opioids increased, rates of addiction increased
- CDC reported it is caused by the medical community over-prescribing opioids
- This was a result of aggressive and unethical marketing by Perdue Pharma for OxyContin in 1996
- Physicians knew the issues with opioids; however, PF reframed OxyContin as safe because of its time release
-Thousands of educational programs funded by pharmaceutical company - Claiming low addiction rate
- Framed it as “compassionate care” for pain patients
Reps got major financial incentives
- Medical boards at hospitals and in the community began supporting this message
- “ If you are an enlightened, compassionate physician, you’ll prescribe opiates”
This was a result of aggressive and unethical marketing by Perude Pharma for OxyContin in 1996
What is the timeline for the opioid crisis?
1995 “Pain is the 5th vital sign”
- Patient satisfaction and hospital quality/ratings is measured by patient pain
- Directly related to funding and physician retention
- 1-10 pain scale
OxyContin prescriptions in 1997 -> 670,000
2002-> 6.2 million
- Almost 90% of patients on opioids did not have cancer pain
True or False: Doctors encourage to write prescriptions without fear of disciplinary action.
TRUE.
1998 - Federation of State Medical Boards of the United States, Inc. “Physicians should not fear disciplinarily action for prescribing opioids in the usual course of professional practice”
2000 - The Joint Commission Doctors are mandated to assess and treat pain, or hospitals may lose federal funding
What happened to the opioid prescriptions in US?
- In 2011, 219 million prescriptions were dispensed
- This suggests that almost every adult in the US would have enough pills to treat themselves for one month
- 2017 declared a national PH emergency
- 2.1 million people in the US were dx with OUD
- 6 fold increase in OD deaths since 1999
What was the national overdose deaths involving any opioid in 2021?
80,411
