Post-Mid Mod Flashcards
What are the characteristics of a psychotic patient
-Demonstrating a loss of reality
-Experiencing delusions/hallucinations/thought disorders
What are the differential diagnoses for psychotic patients
-Schizophrenia
-Brief psychotic
-Delusional
-Schizophreniform
-Schizoaffective
-Substance/medication-induced psychosis
-Mood disorders
-Other medical conditions inducing psychosis
Symptoms of hallucinations, delusions, disorganized speech, grossly disorganized/catatonic behavior, negative symptoms (emotional blunting) WITH loss of social/occupational functioning
Schizophrenia
Symptoms of hallucinations, delusions, disorganized speech, disorganized/catatonic behavior, and negative symptoms for at least 1 month and less than 6 months; less socially/occupationally impaired
Schizophreniform Disorder
Symptoms of a major depressive/manic episode concurrently with the core symptoms of schizophrenia; must be present without prominent mood symptoms for at least 2 weeks
Schizoaffective Disorder
Symptoms of persistent but relatively circumscribed delusions for at least one month in the absence of other schizophrenia symptoms; able to function in daily life normally
Delusional Disorder
Symptoms of psychosis, delusions, hallucinations, disorganized speech/behavior that are persistent for at least one day by for less than one month; return to full premorbid functioning
Brief Psychotic Disorder
Symptoms of hallucinations, delusions, gross disorganization that are directly caused by the effects of a medical illness (neurological, endocrine, metabolic, autoimmune, delirium)
Psychotic Disorder due to another medical condition
What is the presentation difference between delirium and schizophrenia
Delirium has fluctuating levels of alertness/orientation; schizophrenia patients are consistent and usually well-oriented
What drugs can induce psychosis
Adrenocorticosteroids
Atropine/Anticholinergics
Ketamine
NMDA receptor antagonists
Symptoms of psychosis, hallucinations, delusions, as a direct result of substance intoxication/withdrawal
Substance/Medication Induced Psychotic Disorder
What illicit substances can cause psychosis
Alcohol
Amphetamines
Cannabis
Cocaine
Hallucinogens
Inhalants
Opioids
Phenylcyclidine
Sedatives
What are the positive symptoms of schizophrenia
Delusions and hallucinations
Fixed ideas based on incorrect perceptions of reality and do not stem from a shared system of cultural beliefs (i.e. internal to the individual)
Delusions
What are Schneider’s first-rank symptoms of schizophrenia (3)
- Thought broadcasting- believe that their thoughts can be perceived by others (no privacy)
- Thought insertion- believe that their thoughts are not their own but of someone else who inserted it into their heads
- Thought withdrawal- believe that thoughts are being removed from their heads (typically paranoid)
What is the most common perceptual symptom of schizophrenia
Auditory hallucinations
Are visual hallucinations more indicative of schizophrenia or delirium
Delirium
What are the negative symptoms of schizophrenia
Affective blunted/flattened expressions (robot-like)
How is the blunted/flattened affect of schizophrenia defined
Loss of volition + development of apathy (but NOT depressed)
What are the disorganized symptoms of schizophrenia
Bizarre/idiosyncratic thought processes
Loosening of associations
Clanging
Word salad (incoherent word patterning)
Disturbed word choices
Neologisms
Thought-blocking
Catatonia/Wavy flexibility
What are the chances of inheritance of schizophrenia
10% in siblings
13% in children (one parent- two parents is 30-40%)
What is a major risk factor for inheriting risk genes for schizophrenia
Advanced paternal age
What is the general mechanism of antipsychotic drugs
Block postsynaptic dopamine receptors > decrease activity in the dopamine pathways of the brain (the opposite of Parkinson’s drugs)
What is the action of dopamine on the tuberoinfundibular tract
Inhibits prolactin secretion from the posterior pituitary gland (responsible for many of the side effects of antipsychotics)
What part tract of the brain are affected by the dopamine signaling in schizophrenia
Mesolimbic (increase in DA) and mesocortical (deficiency in DA) tracts
Mesocortical acts as feedback inhibitor of mesolimbic
What is the state of cortical and mesolimbic activity in Schizophrenia (aka what causes the positive and negative symptoms)
Hypodopaminergic mesocortical activity > negative symptoms
Hyperdopaminergic mesolimbic activity > positive symptoms
What are the initial (prodromal) signs of schizophrenia and when do they typically emerge
Negative symptoms (similar to schizotypal personality disorder) in adolescents
What usually precipitates the long-lasting (residual) symptoms of schizophrenia
Social changes; major life changes; stress
What is usually the pattern of schizophrenia symptoms
A first episode followed by extended period of time in remission, then can be followed by multiple/continuous episodes; variable time tables, but symptoms progressively worsen; will eventually plateau at a variable level
Positive symptoms typically lessen over time, while negatives worsen
What are the common side effects of antipsychotics
Cardiometabolic effects (weight gain, elevated glucose/cholesterol > cardiovascular disease, metabolic syndrome)
most people with schizophrenia die of cardiovascular disease
What is the primary mechanism of second-generation antipsychotic drugs
5-HT2A-receptor (activated by serotonin) inverse agonists > inhibit cortical and limbic dopamine release
What is the primary mechanism of first-generation antipsychotic drugs
Blocks dopamine D2-receptors in the mesolimbic and striatal-frontal system
What diseases are first-generational (typical) antipsychotics used for
Schizophrenia (positive symptoms)
Psychosis
Bipolar Disorder
Delirium
Tourettes
Huntington Disease
OCD
What are the side effect mechanism of low-potency first gen antipsychotics
Anticholinergic
Antihistamine
Anti-A1 adrenergic
Increased prolactin
What are the side effects of high-potency first gen antipsychotics
Pseudoparkinsonsim
Akathisia- treat with B-blockers
Acute Dystonia- treat with benztropine
Neuroleptic malignant syndrome- treat with Bromocriptine/Dantrolene
Tardive dyskinesia- treat with benztropine
Which antipsychotic has a high risk for agranulocytosis
Clozapine
Largely used for refractory schizophrenia
Why might atypical antipsychotics be associated with less side effects
Atypical antipsychotics block the D2 receptor as well, but at a lower affinity (does not interfere with DA needed for voluntary movement)
What antipsychotic has been used to reduce risk of suicide in schizophrenic patients
Clozapine
What antipsychotic is the most commonly prescribed in the US
Aripiprazole
If a patient develops tardive dyskinesia when using a typical antipsychotic, which atypical antipsychotics should they be switched to
Clozapine or Quetiapine
What are the symptoms and causes of Neuroleptic Malignant Syndrome
Typical Antipsychotics > truncal rigidity, hyperpyrexia, and altered mental status
Symptoms of persistent, distinct, depressed mood* or loss of pleasure/interest in normal activities*; can include significant weight loss/gain, insomnia, psychomotor agitation, fatigue, guilty/worthless/pessimistic/angry feelings/ideations, loss of focus, recurrent thoughts of death/suicide; present for at least 2 weeks
Major Depressive Disorder
What emotions are included in the feelings of sadness associated with depression
Hopelessness
Helplessness
Worthlessness
Loss of ability to experience pleasure
Anhedonia
Depressed patients that cannot sense or articulate their sadness, and instead focus on their loss of interest
Alexithymia
What sleep abnormalities are associated with depression
Sleep onset insomnia (trouble falling asleep)
Sleep maintenance insomnia (waking in middle of night)
Terminal insomnia (waking early in the morning)
Also: hypersomnia is common
Decreased REM latency, Increased REM duration
What is the differential for patients presenting with dementia symptoms, withdrawal, apathy, and/or irritability)
Pseudodementia associated with depression
What are the two patterns of depressive symptoms
Diurnal variation: Consistently at one particular time of the day
Mood reactivity: Inconsistent; temporarily relieved by good things
Symptoms of mild depression characterized by low mood, lack of energy/interest, low self-esteem, and irritability; lasts for at least 2 years with little/no remission
Dysthymic/Persistent Depressive Disorder
What are the characteristics of chronic depressive disorders
Last for more than 2 years
Associated with poor response to treatment
Slower rate of improvement
Younger onset
Longer episodes
Greater burden
High rates of comorbidity
High rates of suicidality
Symptoms of mild depression with long-standing personality difficulties, irritable/gloomy/complaining; hardworking, eager to please, cheerful yet fearful of making mistakes
Depressive personality
Symptoms of 1 manic episode with/without 1 depressive episode
Bipolar I Disorder
Symptoms of 1 hypomanic episode with 1 depressive episode
Bipolar II Disorder
Irritability or abnormal euphoria, high energy (grandiose), impaired insight for at least one week; often a decreased need for sleep, increased sexual drive, cognitive hastening/impulsivity
Mania
What can mania be confused for and why
Schizophrenia- loosening of associations, clang associations, and thought-disordered speech
Energetic with heightened cognitive and sensual alertness- creates a slightly euphoric feeling > will develop into unrealistic expectations and questionable judgement > depression and despair
Hypomania
Symptoms of alternating mild depression and hypomanic symptoms of short durations, and continue for several weeks to several months; complaints of chronic depression with fluctuating sleep patterns, agitation, and irritability
Cyclothymic Disorder
Symptoms of depressed mood/anhedonia in women associated with breast tenderness, headaches, bloating (during last week of luteal phase) in a cycle-pattern for 2 consecutive months
Premenstrual Dysphoric Disorder
What is the difference between normal bereavement and major depression symptoms
Bereavement has no pervasive low self-esteem, and symptoms will resolve naturally within 2-3 months (up to 1-2 years); no psychosis
What personality disorders typically are comorbid with depression
Borderline
Histrionic
Narcissistic
What is the major difference between personality disorders and mood disorders
Personality disorders are long-standing and consistent, mood disorders are abrupt and change pre-existing social functioning
What neurotransmitters might be associated with depressive symptoms
Decreased levels of norepinephrine and serotonin
Serotonergic system modulates dopaminergic neurons in VTA
What is the (rate-limiting) metabolic precursor to serotonin
Tryptophan
What structures of the brain are affected by depression
Hippocampus
Amygdala
Pre-frontal cortex
Anterior cingulate/medial orbital frontal cortex
Antidepressants increase BDNF levels- which promote neuronal growth/survival/maturation in these areas
What is the pathogenesis of damage to the brain by depression
Acute stress exposure causes prolonged glutamate release in the prefrontal cortex and hippocampus > neuroexcitotoxicity
What evidence has suggested the connection between prolonged stress and depressive disorders
Elevated serum cortisol, increased adrenal mass, decreased glucocorticoid receptor mRNA expression
Possibly explains why hx of childhood abuse can cause depression in adults
What hormones are decreased in patients with depression
Thyroid hormones
Estrogen
Testosterone
Which mood disorders are especially genetically-linked
Bipolar Disorder!
Depression Disorders
Likely has to do with biological vulnerability + trigger factors
What are the pertinent atypical features of depression
Increased sleep/appetite
Extreme fatigue/leaden limb paralysis
Mood reactivity
What are the pertinent psychotic features of mood disorders (esp. bipolar)
Delusions/Hallucinations that are mood-congruent (themes of guilt, pessimism, deserved punishment)
What are common features of seasonal recurrent depression
Lethargy and fatigue; hypersomnia and overeating
Symptoms of depressive symptoms (no psychotic features) for up to one year post-partum
Major depression with peripartum onset
What does “mixed feature” mood depression describe
Mixtures of mood, thought, and behavioral symptoms that can be simultaneous/out of sync (ex: mania, hypomania, and depressive symptoms happening concurrently and without order)
High risk of suicide
What type of patients is electroconvulsive therapy used for
Depressed patients who are psychotic, extremely suicidal, or medically ill; delusional depression
What is the treatment for life-threatened manic episodes
Electroconvulsive Therapy
What is the mechanism of electroconvulsive therapy
Downregulation of NE receptors
Increase 5-HT receptors
Regulate Ca2+ entry into neurons
What is a common symptom of depression in elderly patients
Pseudodementia- lack of comprehension, memory loss, lack of recognition; transient in nature
What is a major risk in geriatric patients with depression
Increased incidence of cardiovascular and cancer-related deaths (high risk for MI)
What is the cognitive theory of depression
Proposes that the primary defect in depression is not a mood issue, but rather distorted thinking- unrealistic, pessimistic, negative views of oneself, the world, and the future
What is the mechanism of action of Lithium
Inhibits inositol signaling (IP3-DAG pathway) (via depleting intracellular inositol); inhibits glycogen synthase kinase-3
Blocks a-adrenergic and muscarinic transmission (which are increased during a manic episode)
What is the optimal maintenance serum level of Lithium
Between 0.6 and 0.9 mEq/L
What type of drugs reduce renal clearance of lithium
Diuretics (by about 25%)
NSAIDs
Also avoid with typical antipsychotics- will worsen EPS
What are the common side effects of lithium
Tremor (use propranolol and atenolol)
Decreased thyroid function
Polydipsia/Polyuria/Diabetes insipidus
Edema
SA depression
Teratogen
Leukocytosis
Which antiepileptics can be used to treat bipolar disorder
Valproic Acid (often combined with lithium)
Carbamazepine (acute mania/prophylactic therapy)
What drugs are SSRIs
Fluoxetine
Sertraline
Citaprolam
Paroxetine
Fluvoxamine
Escitalopram
Are antidepressants lipophilic or hydrophilic
Lipophilic
What is the general rule of prescribing fluoxetine
It must be discontinued >4 weeks before starting a MAOI
Which SSRIs are CYP2D6 inhibitors
Fluoxetine and Paroxetine
What is the MOA of SSRIs
Inhibit (allosterically) serotonin transporter (SERT), and DO NOT effect histamine/acetylcholine/a adrenoreceptors
What are the notable drug interactions of SSRIs
CYP2D6 Inhibition
Interactions with MAOIs can cause serotonin syndrome
What are the notable side effects of SSRIs
Nausea
GI upset
Diarrhea
Diminished sexual function/interest/arousal
Weight gain (paroxetine)
Teratogen
What drugs are SNRIs
Venlafaxine
Desvenlafaxine
Duloxetine
What are some of the uses of SNRIs
Major Depression
Neuropathy/Fibromyalgia
Generalized anxiety
Stress urinary incontinence
Vasomotor menopause symptoms
What is the MOA of SNRIs
Bind to serotonin (SERT) and norepinephrine (NET) transporters; DO NOT have affinity for other receptors (histamine, a-adrenergic, cholinergic)
What are the side effects of SNRIs
All the SSRI side effects
Increased BP + HR
Insomnia/Anxiety/Agitation
Cardiac toxicity (venlafaxine)
What drugs are TCAs
Desipramine
Imipramine
What is the MOA of tricyclic antidpressants
Inhibit serotonin and norepinephrine reuptake; imipramine is highly anticholinergic; anti-muscarinic; anti-histamine (H1)
What are the pertinent side effects of TCAs
Dry mouth/constipation/urinary retention/blurred vision/confusion
Orthostatic hyotension
Convulsions/Coma/Cardiotoxicity
What drugs are 5-HT2 receptor modulators
Trazodone
Nefazodone
What is the most common use of trazodone
Hypnotic/Sedative
What is the MOA of trazodone/nefazodone
Inhibit the 5-HT2 receptor > antianxiety/antipsychotic/antidepressant effects
What are the side effects of 5-HT2 antagonists
Hepatotoxicity (nefazodone)
Sedation
GI Disturbances
Priapism (trazodone)
Orthostatic hypotension
What drugs are tetracyclics/unicyclics (more of a catch-all for other antidepressants)
Mirtazapine
Amoxapine
Maprotiline
Bupropion
Vilazodone
It says these are not often used… so yeah
What drugs are MAO Inhibitors
Phenelzine
Isocarboxazid
Tranylcypromine
Selegiline
What are the uses for MAO inhibitors
Depression
Anxiety
Panic Disorder
Parkinson’s Disease (selegiline)
What is the MOA of MAOI’s
Inhibit MAO-A and MAO-B > increase monoamine content by inhibiting their metabolism (dopamine, norepinephrine, and serotonin)
What are the common side effects of MAO inhibitors
CNS Stimulation
Hypertensive Crisis
Serotonin Syndrome
What class are the most commonly used antidepressants
SSRIs and SNRIs
What do SERTs reuptake
5-HT
What does sustained NE or 5-HT signaling do to BDNF
Increases expression of BDNF
Which antidepressants have been used to treat anxiety disorders
SSRIs and SNRIs
What antidepressants have been used to treat pain disorders
TCAs
Duloxetine (SNRI)
Milnacipran (SNRI)
What antidepressants have been used to treat premenstrual dysphoric disorder (severe PMS)
Fluoxetine and Sertraline (SSRIs)
What antidepressants have been used to treat eating disorders
Fluoxetine (SSRI)
What antidepressant is used to treat seasonal depression/smoking cessation
Bupropion
What is used to treat TCA overdoses
Sodium bicarbonate
What are the three signs of TCA overdoses
Cardiac toxicity (malignant arrhythmias)
Convulsions
Coma
Which antidepressant can cause seizures
Bupropion
What family history is a risk for SSRIs
Bipolar Disorder (can precipitate manic episodes)
What drug is used in severe cases of serotonin syndrome
Cyproheptadine (antihistamine, anticholinergic, antiserotoninergic)
When is the threshold for when anxiety becomes maladaptive
When it is out of proportion to the threat
Persists after the threat has been resolved
Impairs personal functioning
Symptoms of tachycardia, palpitations, chest pain, difficulty breathing, restlessness, insomnia, headaches, GI issues, paresthesia, dizziness, nausea
Anxiety
Anxiety symptoms that are prolonged and excessive, not focused on a specific source; for at least 6 months
Generalized Anxiety Disorder
What is the treatment for Generalized Anxiety Disorder
First line: SNRIs/SSRIs, CBT
Second line: buspirone
Symptoms of recurrent, debilitating panic attacks w/ or w/o a trigger for at least 1 month
Panic disorder
What is the treatment for acute and long-term management of panic attacks
Acute: short-acting benzodiazepines (alprazolam)
Long-term: SSRIs, SNRIs, CBT, TCAs
What are the symptoms of a panic attack
Palpitations
Shortness of breath
Paresthesias
Depersonalization/Derealization
GI distress
Intense fear of dying
Intense fear of losing control
Dizziness
Diaphoresis
What are the requirements to diagnose panic disorder
Symptoms of recurrent panic attacks + persistent concern/worrying/behavioral change dictated by panic attacks
Symptoms of pronounced anxiety of social situations that involve scrutiny from others (fear of social interaction/performance; for at least 6 months
Social Anxiety Disorder
What is the treatment for Social Anxiety Disorder
CBT; SSRIs/SNRIs
Symptoms of persistent and intense fears of particular situations and objects for more than 6 months
Specific phobias
What is the treatment for specific phobias
CBT (desensitization therapy)
Benzodiazepines
SSRIs
Symptoms of pronounced fear/anxiety of situations that are perceived to be difficult to escape from; lasts for > 6 months in > 2 situations
Agoraphobia
What is the treatment for agoraphobia
CBT
SSRIs
Symptoms of prominent anxiety or panic attacks after using/stopping a substance/medication
Substance/Medication-induced Anxiety Disorder
What substances are typically causative of anxiety disorder
Alcohol
Caffeine
Corticosteroids
Amphetamines
Cannabis
What is the treatment for substance-induced anxiety disorder
Discontinue substance use
CBT
SSRIs/SNRIs
What is the characteristic triad of panic disorder
Acute panic attacks
Anticipatory anxiety
Phobic avoidance
What age group is most likely to experience onset of panic disorder
Between late adolescence and mid-30s
What are the comorbidities of panic disorder
Major Depressive Disorder
Substance Abuse Disorders
What situations/locations are diagnostic for agoraphobia
Lines/Crowds
Public Transport
Open Spaces
Closed Spaces
Being alone outside of home
Describe the course of symptoms of Generalized Anxiety Disorder
Usually constant anxiety across multiple domains, but can be waxing/waning, and exacerbated during times of stress
What is an important differential to consider in symptoms of anxiety
Hyperthyroidism
How long does it take for the symptoms of alcohol withdrawal to appear
24-48 hours
Symptoms of jitteriness, nervousness, mild tremor, and mild increase in HR and BP; also can cause panic attacks
Classic withdrawal
Symptoms of anxiety with mild nervous, tremor, and HR/BP increase along with insomnia
Nocturnal withdrawal syndrome
What is the cause of nocturnal withdrawal syndrome
Wearing off of depressants (usually decrease REM), results in rebound effect of increasing REM
What is the difference in presentation of benzodiazepine and alcohol withdrawal
Benzodiazepine withdrawal is more rapid and more intense- mild tremulousness; anxiety disorder symptoms
Symptoms of tachycardia, elevated BP, mydriasis, restlessness, vomiting/diarrhea, hyperthermia, hyperalgesia and respiratory depression associated with 8-12 hours after withdrawal of what?
Opioid withdrawal
What patient groups are at risk for paradoxical reactions of benzodiazepines and barbiturates (cause anxiety)
Elderly and children
Symptoms of intrusive/recurrent/persistent thoughts/urges that cause marked anxiety, and then lead to repetitive behaviors that alleviate the symptoms
Obsessive-Compulsive Disorder
What is the degree of insight in patients with OCD
Some can have good insight to their situation, but others are more delusional
What is the typical demographic of a patient with OCD
Male adolescent/young adult
Symptoms of intrusive re-experiencing, avoidance, mood disorders, and changes in arousal, depersonalization, distorted cognition/memory associated with direct/indirect exposure to a traumatic experience, particularly one that is harmful
Posttraumatic Stress Disorder
What is the timeline for PTSD
Symptoms usually begin within 3 months of the event (can be years), and symptoms must be present for 6 months
What are the differentiating factors between acute stress disorder and PTSD
Acute Stress Disorder symptoms appear more rapidly post-trauma and are resolved within 1 month
What are the differentials to include for Acute Stress Disorder
Delirium
Substance-induced Anxiety Disorder
Brief Psychotic Disorder
Primary anxiety disorders
Adjustment Disorder
What are the neurotransmitter mechanisms of treatment for anxiety disorders
Increase serotonin availability (SSRIs)
Block noradrenergic signaling (a2 agonists)
Increase GABA signaling (benzodiazepines)
What is the basic goal of therapy-based treatment for anxiety disorders
Extinction of conditioned responses associated with traumatic memories
What cognitive distortions are usually present in patients with anxiety disorders
Catastrophizing
Overestimating
What are the key components of CBT
Psychoeducation
Somatic management
Mindfulness
Identifying distorted ways of thinking
Exposure therapy
Coping skills
Problem solving
What is the difference in usage of sedatives and hypnotics
Sedatives reduce anxiety (minimal CNS depression)
Hypnotics produce drowsiness/sleep (more CNS depression)
Are sedatives/hypnotics usually more lipophilic or hydrophilic?
Lipophilic
Describe the process of clearance of benzodiazepines
CYP450 in the liver oxidize the benzos (phase I) > conjugated to glucuronides (phase II)
What is the product of the oxidization (via CYP450) of chlordiazepoxide, diazepam, prazepam, and chlorazepate; and why is it notable?
Desmethyldiazepam; has a half-life of over 40 hours
Which benzodiazepines have a longer half-life and which ones have a shorter half-life
Longer: Diazepam, prazepam, flurazepam
Shorter: Alprazolam, triazolam, lorazepam, oxazepam
Describe the general rate of hepatic metabolism of barbiturates and which group is the exception to this
Slow; thiobarbiturates (phenobarbital)
Which hepatic enzyme is used to metabolize the hypnotic drugs
CYP3A4
What are the effects of decreased hepatic function on drug elimination
Increases drug half-life (can build up after multiple successive doses)
What is a major difference between the metabolization of benzodiazepines/hypnotics and barbiturates
Barbiturates can increase the rate of hepatic metabolism; benzos/hypnotics do not do this (with continuous use)
Describe the MOA of sedative-hypnotic agents
GABAa receptor agonists > pumps Cl- ions into the neuron > IPSP
How does the difference in binding of sedatives and hypnotics to the target receptor have different results in function
Hypnotics are very selective of the alpha-1 subunit-containing isoform
Benzos/Barbs can bind to multiple isoforms of the receptors
Recall that benzos inc. frequency, and barbs inc. duration of channel opening
Why are barbiturate associated with more CNS depression than benzodiazepines
Barbs are less selective- also depress AMPA receptor functioning
Can be used to induce surgical anesthesia
What is the function of flumazenil
Blocks benzo and Z-hypnotic action (but not barbiturates or ethanol)
Used for benzo overdoses, but must be given repeatedly due to low half-life
What are the effects of benzodiazepines/older sedative-hypnotics on sleep
Decreased sleep latency
Decreased Stage 2 sleep
Decreased REM sleep
Decreased Stage 4 sleep
What are the effects of newer hypnotics on sleep
Decrease sleep latency
Decrease REM sleep
No change on slow-wave sleep
Increases Stage 2 sleep
What side effect is associated with higher doses of zolpidem and zaleplon
Rebound insomnia
Which sedative agents are often used for induction of anesthesia and why
Thiopental and methohexital; very lipid-soluble and rapidly absorbed
What sedative agents are used in adjunct to general anesthesia for persistent post-anesthetic respiratory depression
Diazepam, lorazepam, and midazolam
What are the symptoms of sedative-hypnotic withdrawal
Increased anxiety
Insomnia
CNS excitability
Seizures
What are common adverse effects of sedative-hypnotics
Drowsiness, diminished motor skills
Anterograde amnesia
Confusion
Behavioral inhibition
Respiratory/Cardiovascular depression (high-doses)
Do NOT use with alcohol, opioids, anticonvulsants, anti-histamines, or phenothiazines
Which benzodiazepine is the “most toxic” and at risk for overdoses
Alprazolam
Which benzodiazepine is most often associated with behavioral disinhibition
Triazolam
What is a notable contraindication of barbiturates
Porphyria
What is the timing for the onset of postpartum depression
Within 4 weeks of delivery; does not resolve within 2 weeks post-delivery
What is the mechanism/use of buspirone
Parial 5-HT receptor agonist; used for Generalized Anxiety Disorder (more mild than barbs and benzos)
What is the difference between substance abuse and intoxication
Abuse is a pattern that results in significant impairment/distress
Intoxication is acute or chronic, and has maladaptive behavioral/psychological changes
What is the difference between substance dependence and withdrawal
Withdrawal is a symptom of dependence
What drug is associated with most drug-related ER visits
Cocaine (~40%)
Heroin (~30%)
Meth (~8%)
What method of treating substance abuse disorder has been becoming more popular; describe it
Harm reduction model- promotes less frequent, lower doses, and safer environments for drug use
Transtheoretical model is also in play here
What are some common triggers of drug abuse relapse
Re-exposure to the addictive drug
Stress
Context that recalls prior drug use (classical conditioning)
What is the difficulty with diagnosing substance use disorder in elderly patients
Usual progressive neurological impairment secondary to aging can mask substance use symptoms
Describe the brain system that is targeted by addictive drugs
Mesolimbic dopamine system- ventral tegmental area > nucleus acccumbens/amygdala/hippocampus/prefrontal cortex
What is the basic mechanism of opioids
In the VTA, u-opioids bind to and inhibit GABAergic inhibitory interneurons > disinhibit the dopaminergic neurons
What are some commonly abused opioids
Morphine
Heroin
Codeine
Oxycodone
Meperidine
Symptoms of intense dysphoria, nausea/vomiting, muscle aches, rhinorrhea, mydriasis, respiratory depression, sweating, diarrhea, and fever
Opioid withdrawal
What drug is used to reverse the effects of opioid overdoses
Naloxone
Will cause an acute withdrawal syndrome
What drug is used for relapse maintenance in opioid users
Naltrexone
What are some longer-acting opioids that are substituted for MAT use
Methadone
Buprenorphine
What is the mechanism of exogenous cannabinoids
Inhibit GABA neurons in the VTA > Disinhibits dopaminergic neurons
Symptoms of restlessness, irritability, mild agitation, insomnia, nausea, and cramping (very mild and short-lived)
Cannabinoid withdrawal
What are some uses of therapeutic cannabinoids
Nabilone- Chemo-induced emesis
Nabixmols- MS
Symptoms of euphoria, enhanced sensory perceptions, social elevation, amnesia > sedation and coma
GHB intoxication
What is the mechanism of GHB
Binds to GABAb receptors (weak agonist) > inhibits GABA neurons
Symptoms of psychosis-like manifestations, reality distortion, dizziness, nausea, paresthersias, and blurred vision
Hallucinogen intoxication (LSD, Mescaline, Psilocybin)
Not typically associated with dependence or addiction?
What is the mechanism of hallucinogens
Enhance presynaptic serotonin receptors (5-HT2A) > increase glutmate release in the cortex
What is the addictive mechanism of nicotine
Agonist of nicotinic acetylcholine receptor (on dopaminergic neurons of the VTA)
Symptoms of irritability, insomnia, depression, muscle cramps, and seizures
Benzodiazepine withdrawal
What is the mechanism of ketamine/PCP
Non-competitive antagonism of NMDA receptor
Do not cause addication/dependence
What substances are often abused as inhalants
Nitrites
Ketones
Aliphatic/aromatic hydrocarbons
What is the mechanism of Cocaine
PNS- inhibits voltage Na+ channels > blocking action potentials
CNS- block uptake of DA/NOR/SER via transporters > inc. in NOR causes activation of sympathetic nervous system
Symptoms of hypertension, tachycardia, ventricular arrythmias, loss of appetite, hyperactivity, insomnia, hyperthermia, coma, and death
Cocaine intoxication
What is the treatment for Cocaine overdoses
Benzodiazepines and a-adrenergic antagonists
DO NOT give B-blockers
What is the mechanism of amphetamines
Indirect sympathomimetics that cause release of endogenous amines (reverse the transporters)
Symptoms of increased arousal, reduced sleep, abnormal movements, hyperthermia, hallucinations, and psychotic episodes
Methamphetamine intoxication
What is the mechanism of MDMA-ecstasy
Reverse serotonin transporters > inc. extracellular serotonin
Which addictive drugs are notably irreversibly neurotoxic
Amphetamines
MDMA-Ecstasy
What is the progression of alcohol withdrawal symptoms
Tremors/insomnia/GI distress/diaphoresis/agitation > seizures > visual hallucinations > AMS, autonomic hyperactivity
What is the treatment for alcohol withdrawal
Chlordiazepoxide (benzo)
Diazepam if seizures occur
What drugs are used to treat alcohol use disorder
Disulfiram- inhibits alcohol dehydrogenase
Naltrexone- reduces cravings avoid in liver disease
Acamprosate- reduces cravings
What kind of genetic factors are involved in predisposition to alcohol abuse
Genes affecting personality traits
Genes affecting alcohol metabolism
Why do women generally have high blood-alcohol levels after consuming a drink than men
They have less ADH activity (becomes even greater with chronic consumption)
Women also typically have less water space
What is the danger of using alcohol with acetaminophen
Alcohol induces CYP2E1, which increases acetaminophen metabolism to toxic NAPQI
What is the danger of using alcohol with the barbiturate phenobarbital
Ethanol inhibits P450 metabolism of phenobarbital, which can accumulate in the blood
What are the pharmacological treatments for nicotine addiction
Nicotine replacement
Varenicline (partial agonist w/ high affinity)
Buproprion (inhibits NOR and DA reuptake)
What are the strategies for acute pain management
Relaxation/Immobilization
Analgesics (NSAIDs)
Massage
TENS
What type of pain are narcotics liberally used for
Malignant chronic pain (often associated with cancer)
What is the emphasis of treatment for benign chronic pain
Increased activity (NOT narcotics)
Symptoms high levels of anxiety about health, disproportionate thoughts about seriousness of one’s symptoms, excessive time/energy devoted to these symptoms for more than 6 months; disrupts daily life; commonly experiences psychogenic pain
Somatoform Pain Disorder
Multiple, unexplainable symptoms; patients often undergo excessive unneeded testing, and have catastrophic/magical thinking about their illness; believe that others are blowing them off; high comorbidity with anxiety/depression
Multisomatoform Disorder
Increased fear of pain returning that results in drug-seeking behavior
Pseudoaddiction
What is the most common comorbidities for patients with chronic pain
Major Depressive Disorder
Anxiety disorders
What are some common conditions associated with chronic pain
Postherpetic Neuralgia
Diabetic Peripheral Neuropathy
Parkinson’s Disease
Central Postroke Pain/Spinal Cord Injury
Migraine/Chronic Daily Headache
Fibromyalgia
Phantom Limb Pain
Complex Regional Pain Syndrome
Trigeminal Neuralgia
Lower back pain
What is a common cause of rebound headaches
Overuse of analgesics
Ongoing spontaneous pain in a region of the body that is characterized by burning sensation that is precipitated by a specific noxious trauma or cause of immobilization; hyperalgesia
Complex Regional Pain Syndrome
Widespread musculoskeletal pain in all four limbs/trunk, stiffness and exaggerated tenderness
Fibromyalgia
Episodic, unilateral, orbital headache that is described as excruciating; lasts minutes to hours
Cluster Headaches
What is the function of endogenous opioid pathways
Activation of postsynaptic opioid receptors hyperpolarizes the dorsal horn interneurons to reduce the duration of an EPSP for the pain pathways
What are the endogenous opioid peptides and where are they located
Enkephalin and Dynorphin; located in the interneurons of the dorsal horn
What drugs have been used to treat neuropathic pain
Gabapentin (Ca2+ channel blocker)
Lidocaine (membrane stabilizer)
Baclofen (GABA inhibitor)
Ketamine (NMDA antahonist)
Opioids
What genes have been found to be associated with difference in perception of pain
KCSN1 (K+ channel subunit)
GHC1 (GTP cyclohydrolase)
What is the central tenet of the cognitive behavioral approach to pain
Perceived control over pain (and associated/underlying life aspects)
Coping skills
What is the guidelines for prescribing opioids for acute use
Prescribe lowest effective dose of immediate-release opioids; 3 days should be sufficient, very rarely more than 7 days
What drug is contraindicated for use with opioids
Benzodiazepines
What type of receptors are all three types of opioid receptors
Inhibitory G-protein coupled receptors (inhibit cAMP production)
What is the mechanism of opioid tolerance (i.e. morphine)
A lack of receptor internalization (recycling) > is rather, phosphorylated + down-regulated (degraded)
Which opioids are mild-moderate mu agonists (often combined with acetaminophen to treat moderate pain)
Oxycodone
Hydrocodone
Codeine
What are the risk factors for chronic pain
Older age
Female sex
Anxiety/Depression
Obesity
Heavy Lifting
Nicotine use
Lower socioeconomic background
Veterans
Rural areas
What are some medications used to treat chronic pain
NSAIDs/Acetaminophen
Opioids
Topicals (Capsaicin, Lidocaine)
Anticonvulsants (Gabapentin)
TCAs (Topiramate, Valproate)
Corticosteroids
Muscle relaxants (Cyclobenzaprine)
Sedatives (Benzodiazepines)
Medical Marijuana
What are the indications for co-prescribing naloxone
-Taking >50 morphine milligram equivalents per day
-Existing respiratory conditions
-Taking benzodiazepines
-Have another substance use disorder
What drugs are given in cases of acute-on-chronic pain
Parenteral opioids (acutely)/Epidural anesthesia
NSAIDs
Gabapentinoids
Which opioid receptors do the endogenous opioids- endorphins, enkephalins, and dynorphins bind to
Endorphins- mu
Enkephalins- delta
Dynorphins- kappa
Which opioid receptors are responsible for respiratory depression
mu
Which opioid receptors are responsible for psychotomimetic effects
delta
What is the primary metabolism route of opioids
Hepatic CYP450 (CYP2D6 enzyme)
What are the two synaptic effects of opioids
- Close presyn voltage Ca2+ channels (inhibits neurotransmitter release)
- Opens postsyn K+ channels (hyperpolarizes neurons)
What are the two sites of opioid activity to produce an analgesic effect
Ascending pathway (peripheral nociceptive terminals)
Descending pathway (activates inhibitory neurons)
What are the CNS effects of opioids
Analgesia
Sedation
Respiratory depression**
Cough suppression
Miosis**
Truncal rigidity
Nausea/vomiting
Hyperthermia
Sleep disturbances
What is a major peripheral effect of opioids
Constipation
Which opioid is generally safer to use during child labor
Meperidine
Which opioid is commonly used to treat cough
Codeine
What are the major symptoms of opioid withdrawal
Rhinorrhea
Yawning
Hyperventilation/hyperthermia
Mydriasis
Anxiety/Hostility
What is the general onset of morphine/heroin withdrawal timeline
Starts 6-10 hours after last dose, and peaks 36-48 hours after last dose
Describe the formulations of the following opioid-NSAID combinations: Percocet, Percodan, Vicodin/Lortab, Vicoprofen
Percocet: oxycodone + acetaminophen
Percodan: oxycodone + aspirin
Vicodin/Lortab: hydrocodone + acetaminophen
Vicoprofen: hydrocodone + ibuprofen
P=Oxycodone, V=hydrocodone
alpha-2 agonist used to treat opioid use disorder
Clonidine
What is the recommended course for a pregnant patient with opioid detoxification
Not recommended (can precipitate dangerous withdrawal in child) > treat with methadone/buprenorphine
Centrally acting muscle relaxants
Spasmolytics/Antispasmodics
What is the MOA of baclofen
GABAb agonist > Inhibits action potentials (pre and post-synaptically)
What are the side effects of high-dose baclofen
Somnolence
Respiratory depression
Coma
What drugs can be used to treat spasticity
Baclofen
Benzodiazepines
Tizanidine
Gabapentin
Riluzole
Succinylcholine
What is the MOA of tizanidine
a2-adrenergic agonist > decreases cAMP and increases K+ conductance
What is the major use for riluzole
Amyotrophic Lateral Sclerosis
What is the MOA of riluzole
Blocks glutamate neurotransmission > reduces cytotoxicity to upper motor neurons
What is the MOA of succinylcholine
Create a high concentration of ACTH in the synaptic cleft
What are some side effects of succinylcholine
Muscle soreness
Hyperkalemia
Bradycardia
Malignant hyperthermia
What drug should be used in cases of suspected malignant hyperthermia
Dantrolene
Which spasmolytic is typically used for relief of acute muscle spasm caused by local tissue trauma/muscle strains
Cyclobenzaprine
What is the difference in the mechanism of depolarizing vs non-depolarizing neuromuscular blocking agents
Depolarizing: Inc. ATCH in synapse
Non-Depolarizing: Block ATCH binding
What is the treatment for Neuroleptic Malignant Syndrome
Remove offending agent (usually typical antipsychotic)
Bromocriptine (DA agonist)
Dantrolene
What are the symptoms of serotonin syndrome
AMS
Autonomic dysfunction
Neuromuscular excitation
GI dysfunction
Hyperrflexia
Myoclonus
Hyperthermia
Muscular rigidity (last two are less severe than in NMS)
What drugs can precipitate hyperthermia
Typical antipsychotics
Antidepressants
Cocaine, meth, ecstasy, PCP
Succinylcholine
What are two labs used to indicate malignant hyperthermia
Elevated serum creatine kinase
Myoglobinuria
What drugs are used to treat acute muscle spasm pain (cramps)
NSAIDs/Acetaminophen
Physical symptoms and related fears that are disproportionate to object medical findings; not intentionally produced; disruptive to daily functioning
Somatic Symptom Disorder
Patients intentionally stimulate/produce symptoms of illnesses in themselves/others for the purpose of appearing ill/impaired/injured
Factitious Disorder
Intentionally producing/mimicking symptoms that is motivated by external rewards
Malingering Disorder
What are the three subtypes of somatic symptom disorders
Somatic
Dissociative
Obsessive/Cognitive
What are key psychosocial criteria for somatic symptom disorders
Symptoms must be disruptive to daily functioning
Patients must have excessive thoughts/feelings/behaviors related to the somatic symptoms
How long should symptoms of Somatic Symptom Disorder persist
More than 6 months
Neurological symptoms affecting their voluntary motor/sensory function that cannot be fully explained physiologically
Conversion Disorder
Pseudocyesis
Symptoms and signs of pregnancy, despite there being no actual pregnancy
Preoccupation for >6 months with the fear or belief that they have or might acquire a serious disease, to the point that it interferes with daily functioning
Illness Anxiety Disorder
What disorders do most hypochondriacs fit into
Somatic symptom disorder (75%)
Illness anxiety disorder (25%)
Preoccupation with a perceived defect in physical appearance that is markedly out of proportion to objective findings
Body Dysmorphic Disorder
Multiple hospitalization with repeated invasive testing and surgical procedures due to factitious disorder
Munchausen’s Syndrome
Note that factitious disorder by proxy, imposed on a minor, is a form of child abuse (*)
*
What about the course of Conversion Disorder is different than the other somatic disorders
Course is short, with full resolution
What are the comorbidities for somatic disorders
Depression
Anxiety
Suicidality
Medication abuse
Borderline, narcissistic, OC, and histrionic personality disorders
What is the first option in the differential for somatic symptoms
An unrecognized illness or coexistence with known illness
What is a major difference between the presentation of factitious disorder and schizophrenia
Factitious disorder does not have psychosis
What is a major precipitator of Illness Anxiety Disorder
Experience with a medical condition (in self or in loved one) > creates fear/anxiety, as well as dependence on the physician to diagnose
What is the first step in treating somatic disorders
Careful medical and parallel psychosocial history (screen for depression, bipolar, schizophrenia, neurocognitive disorders, and personality disorders)
What is a helpful strategy for managing care for a patient with somatic symptom disorder
Limit contact with other physicians- maintain strong ties to patient to avoid overprescribing; empathy and involvement
What medications have been shown to be effective in treatment somatic symptom disorder
SNRIs
TCAs
Gabapentinoids
Ketamine
What is the treatment for Illness Anxiety Disorder
SSRIs
CBT
What is the treatment for Body Dysmorphic Disorder
SSRIs
CBT
What is the treatment for Factitious Disorder
We don’t really have one
Avoid unnecessary/dangerous procedures
What is the difference between primary and secondary headaches
Primary- not caused by underlying conditions
Secondary- precipitated by another underlying condition
What are the different types of primary headaches
Migraine headaches
Tension headaches
Cluster headaches
Symptoms of headache and increased ICP often in adolescent, obese females
Pseudotumor cerebri
Symptoms of headaches in elderly patients with an enlarged/sensitive temporal artery
Temporal arteritis/Giant cell arteritis
What are some physiological mechanisms of secondary headaches
Compression of adjacent brain tissue
Raising intracranial pressure
Shift nervous system structures from one compartment to another (herniation)
Can present with seizures, vasogenic edema, and hydrocephalus
What is the mechanism of acute headache medicaitons
5-HT receptor agonists
Symptoms of bilateral, band-like pain across the forehead; not associated with nausea or vomiting, not usually associated with photophobia; more commonly in females
Tension-type headache
How long do tension headaches usually last
Constant, usually 4-6 hrs (>30 minutes)
Symptoms of unilateral, pulsating pain on the forehead/periorbital area; associated with nausea, photophobia; more commonly in females
Migraine headaches
How long do migraine headaches usually last
4-72 hours (the longest of the primary headaches)
Symptoms of unilateral, excruciating periorbital pain along with lacrimation, rhinorrhea, conjunctival injection, and Horner Syndrome; more commonly in males
Cluster headaches
How long do cluster headaches typically last
Repetitive over 15min-3hrs
What is the MOA and use of sumatriptan
Use: acute moderate/severe migraine headaches; cluster headaches; NOT prophylaxis
MOA: 5-HT agonist
What are the side effects of sumatriptan
Bitter taste; paresethesia; asthenia; dizziness/fatigue/nausea
Rarely- MI, angina, cardiac arrythmia, stroke
What are the contraindications of sumatriptan
-Any kind of arterial disease (vasoconstrictive)
-Any other triptan/ergot use
-MAOI/SSRI/SNRI/TCA use (serotonin syndrome)
What is the MOA and use of Ergotamine
Use: acute moderate/severe migraine headaches, especially if triptan don’t work
MOA: Nonspecific serotonin agonist
What are the side effects of ergotamine
Nausea/vomiting
Rare- vascular occlusion
What are the contraindications of ergots
-Using other ergots/triptans
-Uncontrolled hypertension/arterial disease
-Beta blockers; dopamine; nicotine; CYP3A4 inhibitors
What is the MOA and use of timolol and propronalol
Use: Migraine headache prophylaxis
MOA: Beta blockers
What are the side effects of timolol/propranolol
Fatigue
Orthostatic hypotension
What are the contraindications for timolol/propranolol
Heart failure
Asthma
Depression
Which antiepileptic is used for migraine headache prophylaxis
Valproate
What antidepressants are used for migraine prophylaxis
Amitriptyline (TCA)
Nortriptyline (TCA)
Duloxetine (SNRI)
Venlafaxine (SNRI)
What are the monoclonal antibodies used for severe/frequent migraine prophylaxis and what is the MOA
Erenumab, Fremanexumab, Galcanezumab
MOA: anti-CGRP receptor (proinflammatory mediator)
What is the specific use of botox in treatment of headaches
Used for chronic migraine prophylaxis (>15 per month)
NOT effective for preventing episodic migraines
What is the acute and prophylactic treatment for tension-type headaches
Acute: NSAIDs, acetaminophen
Prophylactic: Amytriptyline
What is the acute and prophylactic treatment for migraine headaches
Acute: NSAIDs, sumatriptan, ergotamine, antiemetics
Prophylactic: B-blockers, amitryptiline, topiramate, valproate, botox, monoclonal antibodies
What is the acute and prophylactic treatment for cluster headaches
Acute: sumatriptan, 100% O2
Prophylactic: verapamil
What is the MOA and function of aspirin
COX-1 inhibitor > blocks TXA2, PGA2 synthesis
Anti-pyretic, anti-inflammatory, and analgesic
What is the MOA and function of acetaminophen
Reversible COX inhibitor > blocks PGA2 synthesis
Anti-pyretic, analgesic (NOT an anti-inflammatory)
What is the MOA and function of NSAIDs
Reversible COX inhibitor > blocks PGA2 synthesis
What is often used to treat migraines during pregnancy
Acetaminophen (NSAIDs until end of 2nd trimester)
What are some signs of drug abuse among physicians
Physical/Social/Emotional changes
Diet changes
Anxiety/Depression
Defensiveness/Disruptive behavior
Unusual drug orders
Domestic distress
Inaccessibility and social withdrawal
What are some factors that are associated with higher levels of alcohol dependence in medical students
Burnout
Depression
Lower quality of life
Also: younger and single (and in hella debt lol)
