Pharmacology of Abused Drugs 1-3 Flashcards
What is the neurobiological vs neuropharmacological model of addiction pathogenesis?
Neurobiological - medication will be effective in managing the neurobiology of addiction
Neuropharmacological - the addictive substance modifies the brain
What is the current predominant theory of addiction today?
Bio-Psycho-Social - multifaceted
What is a substance-induced disorder?
Intoxication / withdrawal / other substance/medication-induced mental disorder
How are substance use disorders classified now?
Based on 11 behavioral criteria, from mild (2+) to severe, with severe being 6+ criteria for SUD.
What are the 11 behavioral criteria for alcohol SUD?
- More excessive use than intended
- Persistent desire to control use
- Lots of time dedicated to finding, taking, and recovering from the drug
- Craving drug
- Failure to meet obligations of life
- Recurrent social / interpersonal problems because of drug
- Activities are given up / reduced for drug
- Use of alcohol where it is hazardous (i.e. DUI)
- Continued use despite knowledge that it is causing problems
- Tolerance
- Withdrawal
What happens to alcohol use as you age?
Less binge-drinking with age, and more “current” use, although these parameters both peak around age 21-25
What are the three biggest predisposing factors for an alcohol use problem as you get older?
- Age at first drink -> younger = much more likely
- Family history of alcoholism
- Male gender
What is the major source of opioids for non-medical use?
Prescription via doctor, or from a friend / relative who got it from a doctor
-> we are the problem
Is the prevalence of substance dependence changing over time?
No, despite our best efforts prevalence has been relatively flat
Who is at highest risk for developing a substance use disorder in general?
Those with co-morbid mental illness
What nucleus in the midbrain projects up into the cortex and is involved in addiction? Where does it project?
Ventral Tegmental Area - dopaminergic afferents
Projects to:
- Nucleus accumbens (reward center) - part of ventromedial striatum
- Ventral striatum (basal ganglia)
- Prefrontal cortex (impacts motivation)
What neurocircuit is the main contributor to reward reinforcement? What is its most important subcircuit?
Mesotelencephalic system
Mesolimbic system is subsystem which is VTA to Nucleus accumbens
Both pathways use dopamine
How do addictive drugs function within these neurobiologic systems?
They act as direct dopamine agonists feeding into the pathway, or indirect agonists (serve to increase the dopamine neurotransmitter in the synapse, i.e. how rivastigmine increases ACh)
How can opioids and benzodiazepines be addictive even if they are CNS depressants?
They can act preferentially on GABA interneurons to decrease the inhibition of VTA dopaminergic neurons to NAcc.
Disinhibition will lead to greater activation of dopamine pathway.
ALL addictive drugs increase dopamine delivery to NAcc.
How does the prefrontal cortex modulate limbic thinking and the rewards center?
Projects glutaminergic input onto the nucleus accumbens -> increased ability to have the mental will to suppress urges / emotional side of rewards.
PFC decision making is very important in control of urges
What are the functions of the anterior insular and cingulate cortexes with respect to emotional control?
Anterior Insular - more sensory in nature, control of visceral information coming in
Anterior cingulate cortex - more motor and limbic in nature - control the unpleasant experience of pain
Both are co-activated in response to various emotional stimuli and may play a role in fear and PTSD
How are other brain areas other than VTA to NAcc thought to play a role in addictive behavior?
Especially hippocampal and amygdalar inputs will modulate our stress response / learning, and change the likelihood of manifesting addictive behavior.
How does increasing dopamine and the various mechanisms of addictive drugs change the brain overtime? How does this explain the inheritance of addiction?
Leads to a change in gene expression which is conserved across all addictive drugs
This is often done via epigenetic mechanisms (changes in DNA acetylation / histones) that can persist overtime long after the stimulus is gone. Some of the propensity for these epigenetic changes may even be heritable -> some people are more prone to addiction.
Do antidepressants simply treat the symptoms of depression?
Actually no, there is some evidence that real meaningful changes of gene transcription can be reversed in various areas of the brain, with treatment
What is the neuroimmunopharmacologic perspective on stress and addiction?
In a high-stress, pro-inflammatory state, immune cells in the CNS actually promote addiction by releasing specific cytokines. Only in stress are these immune cells very active and can modulate limbic dopamine release.
> Reducing immune system can reduce withdrawal in rats
What is the opioid mechanism of immune-system interplay?
Opioids can actually bind the TLR4 receptors of microglia (inflammatory immune cells), and cause the release of cytokines which promote dopamine release (heightened reward).
What are tinctures, AWOL and powdered ethanol?
Tinctures - alcohol is mixed together with a drug in order to dissolve it. I.e. Robitussin
AWOL - Alcohol without liquid - an inhaled vapor
Powdered ethanol (cyclodextrins) - held in crystalline structure and can be eaten
What is the relative potency of ethanol? Where is it absorbed?
Quite low, requires ~13g serving to produce desired psychoactive effects
Absorbed rapidly in small intestines and slowly in the stomach. Does have some pulmonary absorption
What profession is most likely to be associated with alcohol dependence?
Painter’s - inhalation of alcohol in paints (AWOL)
