CF-501: Biological Perspectives

Exam Two Study Guide

Week Five

 Take Home Points

o Acute pain is from tissue damage and carried by pain nerves. Chronic pain is at least 3 months in
duration and can be related to either cancerous or non-cancerous causes
o 25% of US population had moderate to severe pain
o Nociceptive pain is carried by special pain nerves to spinal cord, thalamus, limbic and cortical area of
the brain
o Important to assess for SUDs and MH issues as part of pain evaluation
o SNRIs, TCAs, and gabapentin can be used for chronic nerve (neuropathic) pain
o Opioids are very useful for acute pain, but often less useful for chronic, non-cancerous pain
 Can actually increase pain perception
 Leads to physical dependence
 Can result in addiction
 Can result in overdose
o Methadone is particularly risky for overdoses
o Primary reward pathway: VTA, Nucleus Accumbens, Prefrontal cortex
o Physiological Dependence to opioids involves: Thalamus and Brainstem
 Know the definitions of nociceptive and neuropathic pain.
o Nociceptive pain
 Pain from stimulation of nociceptos (the nerves that transmit pain signals)
 Pain from touch
o Neuropathic pain
 Pain that results from a lesion, damage or dysfunction in the sensory system
 Pain from nerve
 Understand what hyperalgesia means.
o Opioid induced hyperalgesia—
 increased sensitivity to pain due to
chronic opioid use
 paradoxical increase in pain sensitization
while on opioid therapy
 higher starting dose—increased
hyperalgesia
 tapering opioids—decreases hyperalgesia
o Increased sensitivity to pain, which may be caused
by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus, stimuli which
would not normally cause pain
 Know the different parts of the brain that are involved in the physiologic
dependence of opioids vs. addiction.
o Addiction
 VTA, Nucleus, Accumbens, Prefrontal cortex
o Physiological Dependence
 Thalamus, brainstem
 Know what medications can be used to treat neuropathic pain.
o Tricyclic antidepressants
 Amitriptyline,
 Nortriptyline
o Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
 Duloxetine
 Milnacipran
o Anticonvulsants
 Gabapentin
 Carbamazepine
 Pregabalin
 Understand that opioids are helpful for brief, acute pain and chronic pain related to cancer.
 Understand that the use of opioids for chornic, non-malignant (non-cancer) pain has the risk of physiologic
dependence, addiction, and hyperalgesia.
Week Six

 Know the neurotransmitters involved in anxiety disorders.

o Anxiety
 State of excessive arousal
 Activation of flight or fight mechanism
 Neurotic syndrome
 Common baseline state for many pathologic processes
o Neurotransmitters
 Increased levels of noradrenaline
 Decreased levels of GABA and serotonin
 Dopamine dysfunction in PTSD
 Know that all the drugs of abuse can cause substance-induced anxiety
o Anxiety symptoms are time related to acute intoxication or withdrawal from a mood-altering substance
o Can mimic any of the major depressive disorders
o Cause considerable distress and significantly complicates the treatment of addiction
o Drugs that cause anxiety
 Stimulants
 Amphetamines diet pills, caffeine
 Cannabinoids
 Both in acute intoxication and withdrawal
 Withdrawal from sedative hypnotics and alcohol
 Withdrawal from opioids
 Asthma medications
 Do NOT spend time memorizing all the DSM 5 criteria for anxiety or psychotic disorders
o Panic disorder
 Panic attacks
 Unexpected
 Expected
 Limited symptom attacks
 Agoraphobia
o Anxiety about being in places or situations from which escape might be difficult
o In which help may not be available in the event of panic symptoms
o The situations are avoided or are endured with marked distress or with anxiety
about having a panic attack
o Disturbance is not due to the direct effects of a substance or general medical
condition
 Patients with panic disorder are 18x more likely to make suicide attempts
 Etiology
 Abnormal noradrenergic activity (too much sympathetic function)
 Increased locus of coeruleus activity (flight or fight)
 Serotonergic dysfunction (modulates all other systems in the brain)
 Gaba-ergic dysfunction (too little inhibitory neurons, decreased frontal lobe activity)
o Less of the receptors in the brain v) Suffocation alarm (is it life threatening?)
 Catastrophic interpretation
 Specific Phobia
  Marked and persistent fear that is excessive and unreasonable, cued by the presence or
anticipation of a specific object or situation
o Arachnophobia
 Etiology
o Learning theory
 Exposure
 Stimulus generalization
o Functional imaging studies
 With anxiety there is increased blood flow in the lateral orbital cortex,
anterior insular cortex and cerebellum
 With treatment these abnormalities diminish, and you can see
increased blood flow in the posterior orbital cortex
 Social Anxiety Disorder
 Marked or persistent fear of one or more social or performance situations involving
exposure to unfamiliar people or scrutiny by others, fears of humiliation or
embarrassment
 In co-occurring this is increased with SUD
 Use substances as a social lubricant (Alcohol)
 Etiology
o Noradrenergic dysfunction
o Serotoninergeneric dysfunction
o Gaba-ergic dysfunction
o Learning theory
 Obsessive-Compulsive Disorder
 No longer considered an anxiety disorder
 Egocentonic
o Suicidal ideation
 Egodysonic
o I don’t want to kill myself, but its in my head, intrusive thoughts
 Obsessions
o Recurrent and persistent thoughts, images
 Compulsions
o Repetitive behaviors or mental acts
o Anxiety is secondary symptom
 Etiology
o Serotonergic dysfunction
o Dopaminergic dysfunction
o Cerebral cortical hyperfrontatlity
o Mid brain frontal cortex connection dysfunction
 Disconnect between caudate nucleus and frontal cortex
o Streptococcal infection sequalae
 PTSD
 Exposure to traumatic event
o Etiology
 Disruption of attachment
 ACEs and traumatic event
  Much more likely to be diagnosed with PTSD
o Serotonergic dysfunction
o Dopaminergic dysfunction
o Noradrenergic dysfunction
o Gaba-nergic dysfunction
o CRF dysfunction
 Generalized Anxiety Disorder
 Excessive anxiety and worry occurring more days than not for at least 6 months about a
number of events or activities
 Symptoms impair daily functioning
 Understand that benzodiazepines can be very helpful for acute anxiety, but do have abuse potential
o Benzodiazepines
 Rapidly effective
 Highly efficacious
 Globally effective
 Should be used for short term treatment of anxiety, less than 6 months
 Dependence and tolerance can develop
 Abuse potential
 Withdrawal potential
 Know the mechanism of action of the benzodiazepines
o Enhance the opening of the chloride ion channel
o Enhance the effect of the neurotransmitter gamma-
aminobutyric acid (GABA) at the GABA receptor,
resulting in sedative, hypnotic (sleep-inducing),
anxiolytic (anti-anxiety), anticonvulsant, and muscle
relaxant properties
o Half life of Benzio
 Xanax
 8 to 16 hours
 Librium
 More than 24 hours
 Valium
 More than 24 hours
 Know what other medications can be used for anxiety (SSRI, SNRI, TCA, MAO-I)
o SSRI (Selective Serotonin Reuptake Inhibitor)
 Helps to regulate
 Prozac
 Zoloft
 Advantages
 Medication of choice for depression and anxiety
 Broad wide scale use
 Fewer side effects
 Established efficacy for anxiety
 Safer in overdose
 Generally compatible with other medications
 Disadvantages
  Initial side-effects/intolerability
 Persistent sexual dysfunction
 Often under dosed in anxiety
 Some significant
 SNRI (Serotonin-norepinephrine reuptake inhibitors)
 Effexor
 Cymbalta
 Pristiq
 Fetzima
o Inhibit serotonin and norepinephrine reuptake site, possible dopamine with
high does venlafaxine (effexor)
o Possibly less sexual dysfunction, but may elevate blood pressure
o Wide dose range and effective for anxiety and depression
 TCAs (Tricyclic antidepressants)
 Tofranil
 Elavil
 Norpramin
 Pamelor
 Now reserved to treat-refractory anxiety disorders
 MAO-Is
 Nardil
 Pamate
 Eldepryl
o i. Mostly used for treatment-refractory panic disorder and social phobia
 Know the mechanism of action of Buspar (buspirone)
o Buspirone- Buspar
 FDA approved for GAD
 Can also be used to augment an SSRI for OCD or
depression
 Works as a Serotonin partial agonist
 If there are elevated levels of serotonin,
buspirone will act as a weak antagonist, if
there are decreased levels of serotonin,
buspirone will act as a weak agonist
 The 5HT receptor slows down neuronal
activity and will decrease serotonin release
 Know the difference between the Positive and Negative symptoms of schizophrenia
o Positive symptoms
 Hallucinations, delusions, agitation, behaviors
o Negative symptoms
 Anhedonia (decreased feelings of pleasure) apathy, (loss of interest), blunted affect, poverty of
thought, emptiness, amotivational
o Cognitive symptoms
  Neurocognitive deficits in working memory, attention and in executive functioning, such as the
ability to organize and abstract, also difficulty understanding interpersonal causes and social
relationships
o Mood symptoms
 Patients often seem cheerful or sad I na way that is difficult to understand, they often are
depressed
o Schizophrenia- etiology
 Genetic: based upon family and twin studies
 Environmental: toxins, viral, inter-uterine
 Developmental: abnormal synaptic pruning, neurodegenerative disorder, smaller hippocampus
 Neurochemical
 Dopaminergic theory
 Glutaminergic theory
 Serotoninergic theory
 Clear that this illness is multifactorial and no one theory explains all forms of schizophrenia (or
psychosis in general)
 Also know what neurotransmitters and what regions of the brain are responsible for the Positive and
Negative symptoms
o Dopamine
 Too much dopamine in mid limbic = more positive symptoms
 Too little dopamine in frontal cortex = more negative symptoms
 There are also striatal dopamine pathways and blockade of this system cause the movement
side effects
o Glutamate and Serotonin
 Decreased glutamate (excitatory neurotransmitter) activity can lead to symptoms of psychosis
 Serotonin modulates most other neurotransmitters
 Activating serotonin2 receptors can increase dopamine release
 Newer antipsychotics will block the serotonin2 receptor resulting in increased DA
activity in the mesocortical and striatal systems
 Again, do NOT memorize all the DSM 5 criteria for the psychotic disorders
 Be able to describe the mechanism of action for the older (typical) antipsychotics and whether they help
positive or negative symptoms
o The first-generation antipsychotics
 Typical neuroleptics
 Most were very potent DA d2 receptor antagonists
 Lead to the DA hypothesis: only effect the positive symptoms
 Often have significant side effects
 Extrapyramidal (tremors, slurred speech), akathisia (movement disorder, restlessness),
anticholinergic, antiadrenergic, tardive dyskinesia (stiff jerky movements to face or
body), acute cardiac death
 Chlorpromazine
o First used for postoperative patients, calm agitated patients
 Be able to describe the mechanism of action for the (atypical) antipsychotics and whether they help positive
or negative symptoms – and how they differ from the older medications
o DA antagonism results is decreased DA in mesolimbic pathway and reduced positive symptoms
o Serotonin antagonism results in increased DA in mesocortical pathway and reduced negative symptoms
  Clozapine
 First medication of atypicals
 Had both DA d2 receptor antagonism, but also had Serotonin receptor antagonism
 Treated both the positive and negative symptoms
 Reduced risk of EPS and tardive dyskinesia
o Side effects
 Lowers seizure threshold
 Can cause hepatitis and lead to agranulocytosis, (decreased white blood
cells)
 Causes significant weight gain, sedation, hypersalivation, dizziness
 Know the mechanism of action for Abilify (aripiprazole)
o DA receptor partial agonist, reduces positive symptoms, partial agonist binds to DA partially activates it,
decreases DA in mesolimbic pathway
o Little weight gain, but significant risk of akathisia
o Can help with bipolar disorder, anxiety, depression
 Understand whether or not the compliance with antipsychotics is good or bad
o Compliance is terrible, anywhere from 70-100% of patients with schizophrenia stop their medication
 Know that the antipsychotics can cause movement side-effects, weight gain, and heart disease
o

 Understand that schizophrenia is treatable, but that residual symptoms and impairment often persist after
treatment
o Patients do not return to their premorbid level of functioning even with medications
o Psychoeducation is critical with patient
Week Seven

 Take Home Points

o Depression and SUD’s often co-occur
o Depression is a common consequence of use/withdrawal from mood-alternativing substances
o Antidepressidents are effective and new medications are safer than older medications
 TCA and MAOIs are more toxic and MAOIs need special diet
o Most antidepressants affect the neurotransmitters serotonin, norepinephrine, and dopamine
o There is often a slight delay between the start of medications and the therapeutic effect
 Not as long a delay than was previously thought
 Side-effects usually appear earlier and then resolve
o SSRIs/SNRIs are the most commonly used antidepressants
 Know what neurotransmitter the SSRIs directly affect
o Wellbutrin has less sexual side-effects and can help ADHD
o Look carefully for Bipolar symptoms when someone has an early onset depression or depression that
responds poorly to antidepressants (also ask about family history)
o Bipolar disorder and SUDs often co-occur
o Etiology of Bipolar Disorder is multifactorial, but clearly has strong genetic and physiologic contributions
o Lithium has anti-suicidal properties and is “Gold Standard” for Bipolar I Mechanism of action completed.
o Anticonvulsants (seizure meds) are commonly used for Bipolar Disorder Mechanism of action not clear.
o Atypical antipsychotics are also very helpful in Bipolar Disorder. Patients need to watch their diet and
weight.
o Look carefully for Bipolar symptoms when someone has an early onset depression or depression that
responds poorly to antidepressants (also ask about family history)
o Bipolar Disorder and SUDs co-occur
o Etiology of Bipolar Disorder is multifactorial, but clearly had strong genetic and physiologic contributions
o Lithium has anti-suicidal properties and is “Gold Standard” for Bipolar I. Mechanism of action
complicated.
o Anticonvulsants (seizure meds) are commonly used for Bipolar Disorder. Mechanism of action not clear.
o Atypical antipsychotics are also very helpful in Bipolar Disorder. Patients need to watch their diet and
weight.
 Do NOT memorize the DSM 5 criteria for Bipolar and Depressive Disorders
 Understand that the Bipolar and Depressive disorders are highly genetic, but we still do not fully understand
the biological etiology for these disorders
o Bipolar disorders
 Originally referred to as Manic Depressive Disorder
 Not major depressive disorder
 Know that Bipolar I disorder used to be called Manic Depression
 Characterized by cyclical patterns of mood and behavior
 Strong genetic and physiological etiologies, but not well understood
 Understand that the Bipolar and Depressive disorders are highly genetic, but we still do
not fully understand the biological etiology for these disorders
 Bipolar and SUDs often Co-occur
 Diagnosis and the conceptualization of bipolar has been expanded over the decades
 Use of substances can mimic bipolar through chronic use creates a pattern like bipolar,
bidirectional
  Diagnosing now there is bipolar spectrum, and these are individuals who responded well
to treatment and drugs
 To male diagnosis for bipolar patient must be abstinent for at least 1 year
o Bipolar: Depression
 Must be presence of at least one episode of mania or hypomania along with recurrent episodes
of depression
 Symptoms
 Early age of onset
 Recurrent episodes, depression with agitation, irritability, and peripartum depression
 Depression is much more common than mania/hypomania
 Often responds quickly to antidepressant, but effect is either brief or manic/hypomanic
symptoms appear
o Bipolar: Mania
 Distinct period of persistently elevated, expansive, or irritable mood, and increased energy level
lasting at least one week (or any duration of hospitalized)
 Hypomania
 Symptoms are less severe than mania
 Lasts at least for four days
 Does not necessitate hospitalization
 Know that Bipolar I disorder used to be called Manic Depression
 Understand that the Bipolar disorders are treatable, but often need multiple medications and often have
residual symptoms
o Lithium with an anticonvulsant or atypical antipsychotic
o Anticonbulsant with atypical antipsychotic, or two antipsychotic
 Know that anti-seizure (anticonvulsant) medications and atypical antipsychotics are often used
for bipolar disorder
 Recognize that the use of antidepressants is controversial for bipolar depression, but they are NOT used for
bipolar mania/hypomania
o Do very little for bipolar depression
o At worst they increase cycling
 TCAs and Effexor may have higher rates of cycling
 SSRIs and Wellbutrin have lower rates of cycling
 Only Lithium shows anti-suicidal effects
o Difference between bipolar I and bipolar II
 Bipolar I
 presence of at least 1 manic episode and recurrent episodes of major depressive
 Bipolar II
 presence of at least one hypomanic episode, never manic, with recurrent episodes of
major depression
 Bipolar Etiology
 Genetic: based upon family and twin studies
 Environmental: toxins, seasonal
 Developmental: neuroanatomical and functional abnormalities, neurogenerative
disorder, white matter abnormalities, kindling theory(Epilepsy)
 Neurochemical
o Monoamine Theory
 o Ion Channel theory
o Second messenger system dysregulation
o Cell membrane abnormalities
 Clearly etiology is multifactorial, there are various theoretical etiologies that patients
might ask about
 Understand that there is high co-occurrence rates between bipolar disorder and substance use disorders
 Know that lithium is the GOLD-Standard for treating Bipolar I disorder. Know that lithium has anti-suicidal
properties, has a narrow therapeutic window, and does require monitoring blood levels to prevent toxicity
o Lithium
 Naturally occurring element, salt
 Effective for acute mania and bipolar maintenance therapy, can also help with depression
 Has anti-suicidal effect
 Needs blood monitoring for lithium level, the therapeutic dose and toxic dose are very close to
one another, narrow therapeutic window, also can negatively affect liver and kidney function
 Can cause nausea, diarrhea, tremor, hypothyroidism, renal failure, weight gain, increase in thirst
and urination
 Know that anti-seizure (anticonvulsant) medications and atypical antipsychotics are often used for bipolar
disorder
 Understand that the mechanisms of action for lithium, anticonvulsants, and antipsychotics for Bipolar
disorders are complicated and not fully understood
 Know that all of the drugs of abuse can cause substance-induced mood disorders
 Know that the atypical (newer) antipsychotics can be helpful for mania/hypomania, depression, agitation,
psychosis, and anxiety
 Know that gabapentin (Neurontin) is NOT a medication for Bipolar disorder, but can be used for anxiety and
neuropathic pain
o Widely misrepresented as a mood stabilizer
o No significant benefit as a mood stabilizer
o May help patients with co-occurring pain and anxiety
 Understand the Monoamine Hypothesis for Depression and know the neurotransmitters involved
o Depression is caused by dysregulation of one or more of the monoamines (Norepinephrine NE),
serotonin, and dopamine (DA)
o Evidence is based on the fact that antidepressants typically increase or modulate these
neurotransmitters
 SSRIs, Serozone, Trazadone- serotonin
 SNRIs, TCA, Remeron-serotonin and NE
 MAOIs all three monoamines, inhibits the enzymes which breakdown and metabolize all of the
monoamines
 Bupropion- DA and NE
o NE dysregulation i) Impaired attention, decreased working memory, slowed cognition, depressed mood,
motor slowing, fatigue, pain
o Serotonin dysregulation
 Depressed mood, anxiety, obsessions/compulsions, appetite changes, reduced libido, sleep
changes, agitation, abdominal symptoms
o DA dysregulation
 Depressed mood, decreased energy, decreased motivation/drive, poor concentration, motor
slowing, apathy
 Recognize that medications and therapy in combination is better than either one alone
o With combination of medication and psychotherapy, treatment response rates can reach 80%,
symptoms get better, there is also a gender bias in favor of women because of who actually seeks
treatment
o What we call depression is actually a very heterogenous group of illness with come common clinical
features but different etiologies
o Depressive disorders are probably more accurately described as syndromal illnesses rather than discrete
disease entities
o Major depressive disorder
 Symptoms last more than two weeks
 Symptoms can remit after 9 to 12 months, depression runs its course
 Do know that ECT (electroconvulsant shock therapy) is still used and is still the most rapid antidepressant,
anti-manic, and anti-suicidal treatment available
 Know the mechanisms of action, neurotransmitters targeted, and major side-effects for:
o SSRI
 Most widely prescribed antidepressant
 Inhibit the reuptake pump for SR
 Fewer side effects
 Sexual side effects, insomnia, hypersomnia, increase/decrease in appetite, nausea,
constipation/diarrhea, headache, akathisia, mania, anxiety, suicidality(+/-)
 Increase synaptic SR
 Down regulation of the SR receptors in response to the increased SR
 This down regulation is thought to contribute to some of the therapeutic effects, and
the decrease in side effects after a few weeks
 Fluoxetine (Prozac), Sertraline (Zoloft)
o SNRI
 Inhibit SR and NE reuptake side, possibly DA with high dose venlafaxine
 Less sexual dysfunction
 May elevate blood pressure
 Wide dose range
 Effective for anxiety and depression
 Trazadone
o Antagonizes serotonin 2 receptors, alpha 1, and antihistamine 1
o Inhibits SR reuptake sites
o Most often used for insomnia
 Mirtazepine
o Antagonizes serotonin 2 and 3receptors, alpha 2, and antihistamine 1
o Does not inhibit SR/NE reuptake sites
o Helpful for depression/anxiety, helps treat insomnia
o TCA
 First antidepressant, clinically observed to be effective
 Thought to work by inhibiting the reuptake pump for SR and or NE
 Also has significant anticholinergic (constipation, dry mouth, blurred vision), antihistaminergic(
weight gain and sedation), and alpha 1 adrenergic (dizziness and low blood pressure) blockade.
 Results in many of the side effects
 Can be fatal in overdose due to cardia arrythmias
o MAO-I
 First antidepressant, clinically observed to be effective
 Inhibit the enzyme, monoamine oxidase, which breaks down/metabolizes catecholamines, NE,
DA, and SR
 Can be very effective for severe depression and anxiety
 Increase side effects and most require patients to maintain a tyramine free diet and to avoid
many decongestants and other antidepressants
 The risk is due to having a hypertensive crisis and stroke
 Ex. phenelzine, Tranylcypromine
o Wellbutrin (bupropion) – important to note that has less sexual side-effects than the other
 Norepinephrine and dopamine Reuptake Inhibitor
 This is the only medication of its class
 Inhibition of both NR and DA uptake sites
 Effective for anergic/motivational depressive states
 Poor for most anxiety disorders, can cause panic
 Off-label use for ADHD
 Side effects: headache, tremor, anxiety, restlessness, insomnia, blurred vision
 No/rare sexual side effects, can reduce the sexual side effects from SSRIs
 Therapeutic Effect
 Believed to be directly attributed to the down regulation, the increase in monoamines
happens immediately, therapeutic effect can take weeks because of the down
regulation of receptor sites
Week Eight

 Take Home Points

o Stimulant use and misuse is widespread in the US and worldwide
o Many of the acute effects of stimulants are related to the activation of the sympathetic nervous system
o Stimulants increase both dopamine and norepinephrine
 Tolerance develops rapidly resulting in escalating doses
 Tolerance to the clinical efficacy of ADHD does not commonly occur
o Cocaine blocks reuptake of dopamine and norepinephrine amphetamines force the release, block
reuptake, and inhibit metabolism of the neurotransmitters
o Stimulant withdrawal does not typically require medications or hospitalization (unless psychotic or
agitated)
o Stimulant-induced psychosis is typically acute and brief, but can persist for months
o Khat plant has stimulant properties (cathinone). Bath Salts are synthesized from cathinone.
o Ephedra (Ma Huany) and caffeine have widespread use worldwide
o There are three main symptom domains of ADHD
o The prefrontal cortex functioning is important in maintaining focus and attention
o Both dopamine and norepinephrine are important neurotransmitters in ADHD
o ADHD is highly heritable and most common behavioral disorder of childhood
o ADHD often persists into adulthood, not just a childhood diagnosis
o There is no gold-standard checklists for making the diagnosis
o Increased risk of substance use disorders in ADHD
o Know the difference between stimulants and non-stimulants
o Non-stimulants and extended release stimulants are safer in patients with SUDs
o Misuse and diversion of stimulants is a real issue and there are ways to reduce the risk
 Know the different types of stimulants around the world
o Legal stimulants in the US
 83 million use Tobacco
 166 million drink Coffee
 56 gallons of soda per person
o Worldwide stimulants
 1.3 billion smoke cigarettes
 Betel Nut, Khat, Coca leaf
 Understand that stimulant use is a problem throughout the world, but has been a particular problem in the
US
o Cocaine
 Grown on the slopes in South America
 Columbian cartels grown apprx 2/3rds of the worlds supply
 North America consumes 40-50% of the world’s cocaine
 14,556 overdoes in the US in 2017 (40% increase from 2016)
o Amphetamine
 Discovered in Germany
 Used for inhalers for asthma
 Meth discovered in Japan
 Tend to have stronger effect than other stimulants
 Know well the acute effects of stimulants
 o Boost energy, increase heart rate, increase blood pressure, increase respiration, reduce appetite,
improve concentration, improve alertness, increase activity
o Effects the sympathetic nervous system
 Know the long-term side-effects/consequences of stimulant use disorders
o Weight loss: fools brain as if hunger is satisfied
o Cardiovascular
 Constricts blood vessels, decreasing flow to tissues and organs
 Increases heart rate and can cause arrythmias
 Increase blood pressure
 Weakness blood vessels which can cause strokes
 Can cause heart attacks
o Positive Side effects (think psychosis) too much DA in mesolimbic area
 Irritability
 Paranoia, psychosis
 Aggression and violence
 insomnia
o Dental Erosion
 Oral dehydration, acidic drugs, malnutrition, poor hygiene, meth leeches calcium
o Stimulant induced psychosis
 Most likely caused by elevated DA
 Hallucinations and delusions primarily paranoia
 Typically acute and brief but can persist for months
 Could last longer, Persistent Paranoia: related to something that happened in the past
 Know the symptoms of stimulant withdrawal and that stimulant withdrawal does not typically require
hospitalization or medications (unless there is psychosis)
o Tolerance can develop quickly to stimulants
o Tolerance is not seen with the clinical effects when used for ADHD
o Excessive release of NR and epinephrine is secondary to stimulant use depletes these neurotransmitters,
thus energy, euphoria, and confidence are undermined by the crash (physical and psychological)
o Anhedonia, Anergia, Depression, Loss of motivation, Anxiety, Vivid dreams
o Hypersomnia/insomnia, Increased appetite, Psychomotor agitation, craving
o Withdrawal is uncomfortable and at times requires psychiatric hospitalization due to residual psychosis,
depression, agitation, is typically mild to moderate and does not require medications or hospitalizations
 Also understand the mechanism of action of the stimulants – neurotransmitters involved and what parts of
the nervous system is activated
 Know the differences in mechanisms of action between cocaine, amphetamine/methamphetamine, and
methylphenidate (Ritalin)
o Cocaine
 Increase DA and NE by blocking re-uptake transporters
 NE, DA (Lesser extent SR)
 Only uses the DA that is releasing
o Amphetamine
 Rush lasts longer than cocaine because drug pushes DA out
 Directly stimulates DA and NE release and blocks the reuptake transporters
 Force the release of neurotransmitters, NE, Epinephrine, and DA from vesicles in nerve
terminals
  Block reuptake transporters
 Block metabolic enzymes, allowing for the longer
high than cocaine
 NE and DA
o Methamphetamine
 Available as desoxyn
 Inhalation form-ICE
 Manufactured from ephedrine/pseudoephedrine
 Meth labs were limited by state law,
then federal laws, most labs in Mexico
 10,721 overdose deaths in the US in
2017 (42% increase from 2016)
 Understand the risk of stimulant-induced psychosis and what causes the psychosis
o Most likely caused by elevated dopamine
o Hallucinations and delusions, primarily paranoia
o Typically acute and brief, but can persist for months
 Know the pharmacologic effects of cocaine and the amphetamines
o Cocaine
 Half life 30-90 minutes
 Detectable in urine up to 36 hours
 Effects of NE, DA, SR
 Blocks reuptake and primarily increase DA (and NE)
 Depletion of DA results in depressive feelings, “Crash”
 Brain effects
 Oral: 15 to 20 min
 Snorting: 3-5 Minutes
 IV: 15-30 seconds
 Smoking: 5-8 seconds
 Recognize that Khat, Ephedra, and Betel Nut are all naturally occurring stimulants and that most synthetic
stimulants are derived from Khat
o Khat
 Cathinone: primary stimulant in the plant
 Effect is stronger than coffee
 Oxidizes when exposed to air, wrapped plant in banana leaves
o Methcathinone: bath salts
 Synthetic version of cathinone
 More intense high than khat
o Betel Nuts
 Seeds of betel palm
 Used 12000 years ago
 Active ingredient is arecoline
 Effect similar to nicotine or strong coffee
o Ephedra and caffeine have widespread use worldwide.
 Know the three major symptom domains for ADHD
o Excessive motor activity
o Impulsivity
 o Inattention
 Understand that attention is both the ability to maintain conscious focus AND the ability to inhibit other
irrelevant information
o Inclusionary
 Selective information content that is in the stream of consciousness at any given time. The
ability to maintain that content in the consciousness is the capacity to concentrate attention
o Exclusionary
 Capacity to inhibit or suppress any input (sensory, emotional, language) that is not relevant
 Understand the importance of the prefrontal cortex in maintaining focus and attention
o The executive functioning of the prefrontal cortex include, attention, decision making, working memory,
anticipatory activity, inhibitory control, planning, temporal integration and monitoring
o Neurons found in the frontal cortex also anticipate rewards and are located in areas of the brain
(Orbitofrontal) that are associated with dopaminergic circuitry and is probably part of the cortex
associated with encoding reward
 Know the major neurotransmitters involved in attention
o Dopamine and Norepinephrine
 Know the epidemiology of ADHD and the natural course of symptoms over the lifespan
o The most common behavioral disorder of childhood
o 8-12% of all children
o Boys > Girls (3:1)
o Over 30-50% continue in adulthood, 2-5% of adults
o ADHD like symptoms are common phenotype variant of human behavior
o Most characteristics develop between the ages of 3 and 6 but there is later onset
o Most people develop full symptomatology before age 12
o Symptoms change with the nature of the situation—people do better on a 1:1 basis
o The disorder is chronic and symptoms persist into adolescence (50-80%) and 10-65% may persist into
adulthood, therefore 15-50% may outgrow the disorder
 Know that ADHD is one of the most common behavioral disorders of childhood and is highly genetic
o Characterized by a pattern of behavior, present in MULTIPLE settings, school, home. that result in
performance issues in social, educational, or work settings
 Criteria= overdiagnosis, has to be seen in many different situations and environments
 Neurobiological disorder beings in childhood
 This is why collateral information is important
 Adult onset ADHD is actually referring to ADHD that was diagnosed in adulthood, but symptoms
were present in childhood
 ADD is a colloquial term, most likely refers to ADHA-inattentive type
 High amounts of heritability, one of the highest among psychiatric disorders 80% likelihood
 Recognize that there are rating scales to measure symptom severity, but there is NO gold standard diagnostic
test for ADHD
o Neuropsychological testing or psychometric testing as indicated but does not usually determine
diagnosis
 Recognize that there are non-pharmacologic treatments for ADHD, such as Cognitive Behavioral Therapy (CBT)
o Education about the disorder and comorbidity
o Treat comorbid conditions (anxiety, depression)
o Lifestyle changes
 o CBT: in adults may be effective, it is important to differentiate point with children where it does not add
much beyond the medication effect
o Specific interventions to enhance reading skills
o Exercise
 Know the difference between non-stimulant medications and stimulant medications for ADHD
o Medications are more cost effective, highly effective, excellent safety record, can be prescribed over a
period of years across school and non-school settings to improve outcomes
o Stimulants and atomoxetine have a large evidence base
o Stimulants
 On-set of efficacy- within minutes
 Abuse risk- highest risk for immediate release preparations
 Side effect profile- generally well tolerated
 Site of action- primarily DA and NE, some SR
 DEA- Schedule II
 Mechanism of action review (
o Block DA and NE transporter force the release of DA and NE
 Sustained/extended release preparations
 Concerta: osmotic oral release oral delivery system, pump out an even amount of
methylphenidate
 Vyvanse
o Pro-drug strategy
o Non-stimulants
 On-set of efficacy- days to weeks
 Abuse risk- low
 Side effect profile- depends on the medication
 Site of action- primarily DA and NE, SR, adrenergic receptors
 DEA- none of scheduled
 Norepinephrine reuptake inhibitors: Starttera
 TCAs
 SNRIs
 Dopamine/Norepinephrine reuptake inhibitor: Wellbutrin
 Sympatholyic
 Understand that the stimulants and atomoxetine (Strattera) are FDA-approved for ADHD. The
antidepressants are NOT FDA-approved, but some have been found to be helpful for ADHD
 Know how to assess for stimulant medication misuse and ways to reduce the risk of abuse
o Stimulant diversion and abuse is a clear problem
o Relevant questions about history and diagnosis of ADHD as well as treatment history
o Previous problems with accelerated dosing and running out of meds early
o Taking the medication for reasons other than the primary indication
o Attempting to extract, inject, smoke, or snort meds
o Obtaining the medication from an illegal source
o Using stimulants in the presence of addiction
 Reduce risk of abuse
 Establish rapport and minimize judgment
 Discuss non pharmacological approaches
 Suggested using non addicting medications
 Discussion of the basis that may be present due to past use of stimulant
 Regular follow up
 Refills in office