Exam 4 Flashcards

Question

What must be done with Risperdal Consta when initiating treatment? What kind of injection is Perseris and what metabolism interactions does it have?

Answer 1

Risperdal Consta (IM injection) - It MUST be supplemented with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment. Until the 3rd injection, which is week 4. Perseris - LAI of risperidone, abdominal SQ injection; 3A4 substrate, use 120mg dose if 3A4 inducer or may need oral supplementation.

Answer 2

Invega Sustenna - paliperidone (IM) - Initiation: loading dose, then booster, then injection q4 weeks starting 5 weeks after the loading injection. *the initial loading dose and booster dose must be given in the deltoid to improve absorption consistency **if loading strategy was followed, we don't need oral antipsychotic overlap - renally eliminated, so may require dose adjustment in moderate to severe renal impairment Invega Trinza - paliperidone (IM) - Initiation: Can be initated for a pt who has been on a stable monthly IM injection of Invega Sustenna for at least 4 doses; This is a q3mo IM injection *recommended to be given in deltoid, gluteal lowers Cmax - Not recommended in CrCL < 50mL/min Invega Hafyera - paliperidone (IM - gluteal) - Can be initiated after 4 months of Invega Sustenna or one 3 month dose of Invega Trinza *gluteal injection ONLY

Answer 3

Zyprexa Relprevv - Olanzapine injection - PDSS: post-dose delirium sedation syndrome - on REMS program due to similar side effect of olanzapine (high risk of sedation, weight gain, hyperglycemia, hyperlipidemia, metabolic syndrome, anticholinergic effects at high doses)

Answer 4

Abilify Maintena - aripiprazole injection - MUST overlap with oral aripiprazole (or other oral antipsychotic) for at least 14 days after the first injection - Deltoid or gluteal injection - Dosage adjuments: If taking 2D6 inhibitor or 3A4 inhibitor or inducer for more than 14 days as concomitant therapy (lower dose with inhibitors, don't use with inducers)

Answer 5

Aristada - aripiprazole lauroxil (prodrug) - overlap with oral aripiprazole for 3 weeks after the first injection

Answer 6

- Haloperidol, chlorpromazine, fluphenazine are used, but haloperidol is used most commonly - Olanzapine IR IM CANNOT be given at the same time as benzodiazepine IR injection due to boxed warning for respiratory depression!! - Loxapine for inhalation is not commonly used due to REMS

Answer 7

acute dystonia - muscle group reaction that is not life-threatening, but very frightening. Give IM anticholinergic NOW dose (ex. benztropine 2mg, diphenhydramine 50mg) drug-induced parkinson's - oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine) akathisia - feeling of restlessness, increases risk for suicidal thinking/behaviors. Use beta-blocker (propranolol is 1st line), benzodiazepine (usually lorazepam) tardive dyskinesia - VMAT inhibitors

Answer 8

tetrabenazine - not FDA approved for TD, boxed warning for suicidality/depression, causes QTc prolongation valbenazine - FDA approved, causes QTc prolongation, 2D6 and 3A4 substrate deutetrabenazine - FDA approved, causes QTc prolongation, 2D6 substrate

Answer 9

Neuroleptic malignant syndrome - life-threatening medical emergency that is caused by the effects of antipsychotics on dopamine blockade. Symptoms include hyperpyrexia, tachycardia, labile blood pressure, muscle rigidity, significantly elevated CK, myoglobinuria Treatment is supportive, d/c antipsychotics, consider DA agonists Future antipsychotic use is NOT contraindicated (you can even use the same drug, but likely switch to another antipsychotic)

Answer 10

metabolic adverse effects - hyperglycemia, hyperlipidemia, hypertension, etc. Most - clozapine & olanzapine Mid - quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexpiprazole Least - Ziprasidone & Lurasidone & Aripiprazole

Answer 11

personal/family hx - at baseline & yearly weight - baseline and q4 weeks-q3 months waist circumference - baseline & yearly BP - baseline, q3 months & yearly A1c - baseline, q3 months & yearly fasting lipids - baseline, q3 months, q5 years

Answer 12

- Boxed Warning: increased risk of death in elderly pts treated with antipsychotics for dementia w/ related behaviors - Metabolic adverse effects - EPS - Risk of somnolence, postural hypotension, and motor/sensory instability increases fall risk *fall risk assessment should be performed for pts at higher risk of falling

Answer 13

clinical features - when the physiological symptoms (decreased sleep, appeptite changes, fatigue, etc) and psychological symptoms (dysphoric mood, worthlessness, excessive guilt) and cognitive symptoms (decreased concentration, suicidal ideation) get so severe that they interfere with your life biogenic amine hypothesis - due to depletion of NE and 5HT. We've seen that reserpine, which causes depletion of NE and 5HT from vesicles causes depresison. We also know that agents that increase 5HT and NE treat depression. Also mutations in the SERT, NET, and DAT (minor) transporters can affect depression. Additionally, alterations in 5HT1A/2C and α2 receptors neuroendocrine hypothesis - overactivity of HPA and elevated CRF is found in almost all depressed pts and can lead to other negative effects. Antidepressants and ECT reduce CRF levels neurotropic hypothesis - decreased BDNF is related to depression. Decreased volume of the hippocampus is also involved (regulates HPA + memory). Loss of BDNF = less dendritic sprouts for neurological processes

Answer 14

- HPA and steroid abnormalities regulate BDNF levels (more BDNF is good, overactivity of HPA is bad) - During stress, hippocampal glucocorticoid receptors are activated by cortisol, which results in a decrease in BDNF - BDNF is increased with chronic activation of monoamine receptors for over 2 weeks - Chronic activation of monoamine receptors also downregulates HPA axis

Answer 15

MAOIs - Block the breakdown of NE and 5HT by monoamine oxidase (MAO), thus increasing their concentration in the synapse - non-selective MAO inhibitors (irreversible): phenelzine, tranylcypromine - MAO-B selective (reversible): selegiline - MAO-A selective (reversible): moclobemine TCAs - - tertiary amines inhibits NE and 5HT reuptake through NET and SERT (also muscarinic, histamine, and adrenergic antagonists); Ex. imipramine, amitrytyline (both of these have active metabolites), doxepin, clomipramine - secondary amines are more selective for NE than 5HT; Ex. desipramine, nortriptyline, protriptyline, and maprotiline; These cause less side effects SSRIs - Blocks reuptake of 5HT through SERT, which allows serotonin to stay in the synapse for longer - fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram SNRIs - NET & SERT inhibitors - venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran

Answer 16

5-HT2 antagonists - - trazodone is a 5HT2a antgonist and weak SERT inhibitor. Almost always used for sleep, not depression tetracyclic and unicyclic antidepressants - - Maprotiline is a NET inhibitor (4º) - Mirtazapine is an α2 antagonist, 5HT2/T3 antagonist, and H1 antagonist (4º) - Bupropion is a DAT inhibitor, NET/SERT inhibitor (1º) NSRIs - norepinephrine selective reuptake inhibitors; These are very similar to secondary amine TCAs, but have less side effects - reboxetine (can't be used in the US) - atomoxetine (not approved for depression, used for ADHD)

Answer 17

MAOIs - headache, drowsiness, dry mouth, weight gain, orthostatic hypotension, sexual dysfunction *avoid foods with tyramine TCAs - QTc prolongation (extremely dangerous), sedation, anticholinergic, autonomic effects, weight gain - secondary amines have a better side effect profile than the tertiary amines SSRIs - N/V, headache, sexual dysfunction, anxiety, insomnia, tremor (these are all pretty modest), serotonin syndrome risk *avoid abrupt d/c SNRIs 5-HT2 antagonists tetracyclic and unicyclic antidepressants

Answer 18

SSRI + HT1A partial agonists - vilazodone (Viibryd), vorioxetine (Brintellex) - these have reduced sexual side effects vs. pure SSRIs, but as a whole are pretty similar to the SSRIs NMDA antagonists - ketamine at subanesthetic doses, esketamine (intanasal, REMS); These are rapid acting

Answer 19

allopregnanolone levels are increased during pregnancy. It's thought that GABA-A receptors may desensitize during this. Postpartum, allopregnanolone levels return the normal. Brexanolone resensitizes these GABA-A receptors.

Answer 20

Filbanserin - agonist at 5HT1A, antagonist at 5HT2A/C - used for hypoactive sexual desire disorder, but it was developed as an antidepressant - selective at prefrontal cortex *controversial approval

Answer 21

MAOIs - one ring with carbon chain TCAs - 3 ring structure SSRIs - don't look like a 3 ring connected structure. Usually has at least one-two aromatic rings

Answer 22

lithium - very dirt drug. Mechanism is not clearly understood, but involves depletion of PIP2 & its associated signaling. Also modulate GSK2. - SE: anticonvulsants - - valproate increases GABAergic tone, block Na+ channels, block T-type Ca2+ channels, inhibits histone deacetylase (HDAC5) - carbamazepine/oxcarbazepine work on Na+ channels - lamotrigine works on Na+ and Ca+ - topiramate works on Na+ and may enhance GABA atypical antipsychotics - these are dirty drugs (but not as dirty as lithium) - olanzapine, quetiapine, risperidone, ziprasidone, lurasidone, aripiprazole

Answer 23

Risk factors for depression - feelings of guilt, chronic fatigue/headache, sleep disturbances, loss of sexual interest, agitation, anxiety, hopelessness S - sleep (too much or not enough) I - interest (loss of interest in things they used to like) G - guilt (excessive guilt) E - energy (not enough) C - concentration (unable to stay concentrated) A - appetite (over/under) P - psychomotor (move slower, no motivation to keep moving) S - suicide Risk factors for suicide - have a detailed plan, anniversary or loss, widowed/unmarried, substance misuse, increasing age, unemployment, gender (more women when younger, more white men when older), living alone, physical or mental illness, family history, lack of social support, PRIOR ATTEMPTS

Answer 24

1. depressed mood most of the day nearly every day 2. markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day

Answer 25

- beta blockers - hormonal therapy - isotretinoin - CNS depressants - interferon-beta - levetiracetam - atomoxetine - indomethacin

Answer 26

- St. John's wort: CYP450 3A4 inducer, causes photo toxicity - SAMe (S-adenoxyl-L-methionine) These two agents can also increase the risk of serotonin syndrome, leading to severe N/D, dizziness, headache, agitation, tachycardia, hallucinations

Answer 27

Week 1 - better appetite Week 2 - better sleep/energy *in weeks 1/2, anxiety will be increased, so anxiolytics may be needed Week 4 - better mood Week 6 - increased mood (the goal is absence of symptoms) Months 2-3 - efficacy can be properly assessed Months 4-9 - continuous phase (goal is to eliminate residual symptoms/prevent relapse) Months 12-36 - (goal is to prevent the recurrence of depression)

Answer 28

Increased risk of suicidal thinking and behavior *there's actually a protective factor for ages ≥65 years old **medguides are required for all antidepressants

Answer 29

Amphetamines Buspirone Cocaine Dextromethorphan Fentanyl Lithium Linezolid LSD Serotonin agonists (ex. triptans) Serotonergic antidepressants - SSRIs, SNRIs, TCAs, etc. St John's Wort Tramadol

Answer 30

citalopram - high rates of QTc prolongation, which is why it requires dose adjustment in elderly, doses above 40mg are most effective for antidepressant effect escitalopram - has less QTc prolongation than citalopram, but it's still significant fluoxetine - has stimulating effect (insomnia, resting tremor), has the longest half life of SSRIs, Sarafem is used for PMDD paroxetine - Brisdelle is for moderate-severe vasomotor symptoms that are associated with menopause. This is anticholinergic and ALWAYS needs to be tapered *lean away from this one sertraline - preferred for patients with cardiac risk, this is the best tolerated

Answer 31

Fluoxetine - 2D6, 2C19 Fluvoxamine - 1A2, 2D6, 2C19, 3A *pretty much only used for OCD Paroxetine - 2D6 Bupropion - 2D6

Answer 32

F - flu-like symptoms L - lightheadedness U - uneasiness S - sleep disturbances H - headaches

Answer 33

venlafaxine - can increase BP and QTc, it in the preferred agent in combination with tamoxifen, it's most likely for a patient to switch into mania with this one, need at least 150mg/day to get the NE benefit desvenlafaxine - better 5HT/NE balance than venlafaxine, has no CYP interactions duloxetine - can be used for musculoskeletal diagnoses, has high affinity for reuptake sites and has more balanced activity between the two levomilnacipran - has more emphasis on NE than 5HT, which increases tolerability with sexual dysfunction

Answer 34

MOA - dopamine norepinephrine reuptake inhibitor (DNRI) - AEs: weight loss, decreases seizure threshold, insomnia - Pearls: contraindicated in pts with hx of seizures, disordered eating, or recent alcohol/sedative withdrawal. Also has risk of abuse. It's a good alternative if pt is having sexual dysfunction with other antidepressants. Contrave is used for weight management Dosing: - Daily dose limits: 450mg IR/XL, 400mg for SR - Single dose limits: 150mg for IR, 200mg for SR, 450mg for XL

Answer 35

SARI - serotonin antagonist reuptake inhibitors trazodone - has dose-related priapism, mostly used for sleep, requires dosing of 300-600mg for antidepressant effect nefazodone - has black boxed warning for liver failure

Answer 36

mirtazapine - makes you hungry, happy, and sleepy. fors at H1, 5HT, and a stimulating effect at higher doses *one of the favs to adjunct with SSRIs vilazodone - can cause nausea, take with food, less sexual dysfunction voritoxetine - less sexual dysfunction *vilazodone and voritoxetine increase serotonin reuptake, push serotonin into the synaptic gap, should work in treatment-resistant depression due to to dual mechanisms

Answer 37

Tricyclics - Amitriptyline, Imipramine (most weight gain), Doxepin - AEs: anticholinergic effects such as sedation, weight gain, orthostasis, anticholinergic effects, and CARDIAC TOXICITY Dosing taper: - start with 25mg/qHS and increase by 25-50mg every 3-4 days until response - 1g can be considered FATAL (potassium changes and seizure risk) - MUST TAPER over 1-2 weeks

Answer 38

serotonergic -> serotonergic = can directly switch SNRI -> SSRI = must taper the SNRI when we switch to an SSRI because we aren't covering norepinephrine with the new medication fluoxetine -> d/c = has a long half life, so we don't have to taper paroxetine -> d/c = must ALWAYS be tapered due to cholinergic rebound and flu-like symptoms

Answer 39

MOAIs are very last line for depression due to side effects! - phenelzine, tranylcypromine, isocarboxazid, selegiline Need tyramine diet because tyramine is increased with MAOIs, which increases BP. With this diet, you CANT eat: - smoked, aged, pickled meats or fish, sauerkraut, aged cheeses, yeast extracts, etc. Need to have at least 14 day wash out period between serotonergic agents (5 weeks with fluoxetine) Selegiline patch doesn't require the tyramine diet for the 6mg dose, but 9mg and 12mg do require the diet

Answer 40

Esketamine (spravato) is an NMDA receptor antagonist that is used for treatment resistant depression and acute suicidality. - It MUST be used as adjunct (not monotherapy) - It is an active metabolite of ketamine - REMS *this is one of the 3 drugs that reduces suicidality Warnings: dissociation or perceptual changes, sedation, misuse, BP elevations, short-term cognitive impairment, etc.

Answer 41

When there is too much serotonin, it can cause serotonin syndrome, leading to severe nausea, dizziness, headache, diarrhea, agitation, tachycardia, and hallucinations. SSRIs, SNRIs, TCAs are serotonergic MAOIs can contribute to serotonin syndrome

Answer 42

SSRI + SNRI = do not combine due to duplicate MOAs + bupropion = can add if the pt would benefit from the side effects, such as increased motivation, stimulation, or decreased appetite. Don't add if the patient is already not eating or sleeping + mirtazapine = add if the pt would benefit from the side effects, such as increased appetite and sedation. Avoid if the pt is overeating, obese, or sleeping too much + atypical antipsychotics = lurasidone, quetiapine, and brexpiprazole are FDA approved as adjunct to antidepressants

Answer 43

Brexanolone - positive allosteric modulator of GABA-A receptors. - REMS program due to excessive sedation and loss of consciousness - Given as a 60 hour infusion post-partum

Answer 44

DSM-5TR had further SDOH and cultural factors in diagnosis. They dropped the multi-axial assessment and reorganized to reflect disorders across a continuum based on developmental and lifespan considerations. - neurodevelopmental disorders: disorders previously referred to as childhood diagnoses (ex. ADHD, autism, etc.) - schizophrenia: now a spectrum - anxiety: anxiety disorders and obsessive-compulsive, trauma, and stressor related disorders are separate - substance use disorders: have set criteria - neurocognitive disorders: includes dementia, alzheimer's, etc.

Answer 45

PHQ-9: depression and suicidal thinking, patient BDI: attitudes and characteristics of depression, patient MDQ: bipolar I (mania and depression), patient HAM-D, HDRS: depression research, clinician MADRS: depression research, clinician YMRS: symptoms of bipolar disorder and generalized anxiety at baseline and over time, clinician HAM-A: psychic and somatic anxiety, clinician

Answer 46

PANSS: schizophrenia symptoms and antipsychotic efficacy, clinician BPRS: very similar to PANSS, clinician SAS: drug-induced parkinsonian symptoms, clinician BARS: observation of akathisia, clinician AIMS: tardive dyskinesia, clinician ESRS: parkinsonian symptoms, akathisia, dystonia, TD, clinician CGI: overall psychiatric functioning, clinician GAF: overall psychiatric functioning, clinician

Answer 47

Mood - euphoric Activity - impulsive behavior - challenging cognitive - grandiosity

Answer 48

amphetamines antidepressants (MAOIs, TCAs, 5-HT/NE/DA reuptake inhibitors, 5-HT antagonists) caffeine decongestants dopamine agonists hallucinogens (LSD, PCP) steroids (anabolic, ACTH, corticosteroids theophylline thyroid meds *a toxicology screen should be done prior to starting treatment to rule out drug-induced mania

Answer 49

- FDA approved for acute mania and maintenance therapy. It is effective for acute bipolar depression. It has a slower onset (steady state is reached after 3 days, onset of action is 1-2 weeks) - Cannot use in CrCL under 30mL/min - therapeutic goal = 0.6-1 mEq/L, 0.8-1.2 mEq/L for mania - toxic levels > 1.5mEq/L (N/V/D -> death if >2.5) - increase risk of toxicity: dehydration, use of diuretic, excessive use of alcohol, fever (may need dialysis if conc is too high) - increase conc: NSAIDs, ACEi/ARBs, thiazides, caffeine - decrease conc: osmotic diuretics, caffeine - decreases CrCL by 2mL/min per year while on lithium - pregnancy: Ebstein's Anomaly causing heart defects; but it can be used during breastfeeding *lithium is like salt. it follows water

Answer 50

mania - distinct period of abnormally and persistently elevated, expansive, or irritable mood & abnormally and persistently increased activity/energy, lasting as least 1 week and is present for most of the day, every day. Has qualities of grandiosity, euphoria, and impulsivity. hypomania - abnormal mood/energy lasts 4 days. Has qualities of mild euphoria, expansive speech, and a reduced need for sleep. Hypomania does not affect social/work functioning and does NOT cause psychosis or hospitalization

Answer 51

bipolar I - at least 1 episode of mania that significantly impairs social/work functioning, causes psychosis or delusions, or requires hospitalization WITH bouts of intense depression bipolar II - at least one episode of HYPOmania (at least 4 consecutive days) and at least one depressive episode

Answer 52

lithium - FDA approved for acute mania and maintenance therapy. It decreases suicide risk by 8-10x. Can be very toxic >1.5 mEq/L. Can't be used in pregnancy. valproic acid - FDA approved for acute mania and maintenance therapy. Can't be used in pregnancy. Hyperammonemia is a big concern. carbamazepine - 2nd or 3rd line. Don't use in pregnancy. HLA*1502 testing needed. Big CYP450 inducer oxcarbazepine - 2nd or 3rd line. Don't use in pregancy. HLA*1502 testing needed. May be used as adjunct. More hyponatremia than carbamazepine, but less hematologic effects. lamotrigine - one of the best options for bipolar 2. 1st line for DEPRESSIVE symptoms, but not useful for acute or manic treatment. Huge SJS risk!! topiramate - used as adjunctive treatment. Need slow dose titration due to cognitive deficits. Teratogen. atypical antipsychotics - chlorpromazine for acute mania, quetiapine/lurasidone/cariprazine for bipolar depression, aripiprazole/olanzapine for maintenance. *we CAN combine mood stabilizers (provides better response & long-term prevention of relapse **don't use more than one atypical antipsychotic at one time

Answer 53

Valproate is FDA approved for acute mania and maintenance therapy. Most formulations are NOT interchangeable. - therapeutic range: 50-125mcg/mL (levels need to be at least 60 to see efficacy, steady state is reached after 3 days) - drug interactions: lamotrigine, phenytoin (hepatotoxicity and/or hyperammonemia), warfarin (elevated INR) - boxed warnings: hepatoxocity (esp. children <2yo), pancreatitis, pts with mitochondrial disease, teratogenicity (decreases IQ, neural tube defects), pts with migraines - adverse effects: hyperammonemia, weight gain, alopecia, PCOS, pancreatitis, sedation/ataxia *always check for acute changes in mental status and get an ammonia level **can't be used in pregnancy

Answer 54

FDA-approved: lurasidone, quetiapine, cariprazine Depression (not mania) symptoms: lamotrigine Avoid: TCAs and venlafaxine - risk of manic switch - antidepressants may not be very effective for depression in bipolar disorder

Answer 55

Clozapine Lithium Esketamine

Answer 56

Acute mania - quetiapine, + divalproex OR lithium; 2º is switching divalproex and lithium; 3º is carb/oxcarb Acute depression - divalproex, atypicals, lamictal, olanzapine/fluoxetine; 2º switch from these; 3º carb/oxcarb Maintenance - lithium, olanzapine, divalproex

Answer 57

sedative - calms anxiety, decreases excitement and activity, does not produce drowsiness or impair performance anxiolytic - relieves anxiety without sleep or sedation (not all anxiolytics are sedatives) hypnotic - induces sleep, implies restful, refreshing sleep (sleep-inducing) narcotic - sleep producing, but now refers to opioids or illegal drugs

Answer 58

The reticular formation (medulla oblongata, pons, midbrain, etc.) is very complex. It contains dopamine, adrenergic, serotonergic, and cholinergic neurons. It regulates sleep-wake transitions and synchronization of EEG.

Answer 59

Stages of sleep: - Wakefulness - Non-rapid eye movement (NREM) slow-wave sleep: really deep sleep. Has 4 stages. EEG looks very different. - Rapid eye movement (REM) sleep: EEG looks almost as if you are awake Factors that regulate sleep: - Age: sleep decreases w/ age due to changes in activity of reticular formation - Sleep history: rebound of REM sleep - Drug ingestion: acute and withdrawal produce rebound effects - Circadian rhythms: "normal sleep cycle"

Answer 60

Neurotransmitters - Almost all of them regulate sleep - catecholamines - serotonin - GABA (main target for current medications, GABA-A, GABA-B, GAT-1, GABA-T) - etc. Neuromodulators: - Growth hormone - Prolactin - Melatonin - Cortisol - etc.

Answer 61

Benzodiazepines bind to an allosteric site in the α1 and γ2 sites on the GABA receptor. This binding site is called the BZD receptor. Benzos facilitate GABA action by increasing frequency. Z-Hypnotics (zolpidem, zalepon, and eszopiclone) bind to BZ1 receptors on the α1 subunit of GABA. - These are more safe because they only bind to the BZ1 region. - only eszopiclone is approved for long-term use, but we see all of them used in practice. - these are better for sleep than benzos, but need to warn about sleep-driving, sleep-cooking, sleep-sex, etc. *-flumazenil is a BZD antagonist that is used for overdose treatment of the benzos and z-hypnotics

Answer 62

BZDs - increase frequency of channel opening Barbiturates - increase duration of channel opening and have direct effects on GABA-A at high doses alcohol - enhances actions of GABA on GABA-A receptor. Alcohol is very dirty

Answer 63

- benzodiazepines can be metabolized at position 1. This is a source of active metabolites. This can be the difference between some benzos having a long vs short half life *diazepam has a long half-life (oxazepam is an active metabolite of diazepam). This is why it's used for seizures. *clonazepam has an intermediate elimination rate and is used as an anticonvulsant *midazolam is rapidly eliminated, thus it's used as anesthesia

Answer 64

- Benzos are safer than barbiturates because there is a plateau of CNS effects. The most you could do is anesthesia. But these decrease REM and stage 3-4 sleep. - Barbiturates can cause coma and death because there is not this plateau *benzos also can be antagonized by flumazenil, which makes it safer

Answer 65

long - phenobarbital (anticonvulsant) short-intermediate acting - pentabarbital (sedative/hypnotic) *risk for respiratory depression -> death

Answer 66

benzodiazepines (BZDs) - bind to all GABA-A α1-5; these increase the frequency of GABA-A channel opening. These have a medium risk barbiturates (BBTs) - bind to all GABA-A α1-5; these increase the duration of channel opening and also have direct effects on GABA-A at higher doses. These have a high risk Z-Hypnotics - bind to GABA-A BZ1 receptors of α1. these increase the frequency of GABA-A channel opening. These have a low risk

Answer 67

albuterol caffeine (high dose) decongestants (pseudoephedrine, ephedrine) levothryroxine steroids stimulants (ADHD meds)

Answer 68

buspirone - 5HT-1a receptor agonist - Approved for generalized anxiety disorder - Dosing: 30-45mg total/day, so 10-15mg TID (need to titrate up due to side effects) - May take up to 3-4 weeks for initial efficacy. Technically only works long-term.

Answer 69

Due to misuse potential, benzodiazepines are usually not supported. But they have shown to be more effective than serotonergic agents. - Long term use is not recommended - Acute withdrawal of benzos may lead to seizures that can be life-threatening (requires a slow taper over weeks-months) - There is overdose risk and a warning against using benzodiazepines + CNS depressants Side effects: - sedation - paradoxical excitement - swallowing difficulties - impairment of memory and recall - psychomotor impairment

Answer 70

No active metabolite: COAL (less likely to accumulate, so less of a fall risk) - clonazepam - oxazepam - alprazolam - lorazepam Long-acting active metabolite: DCC - diazepam - clorazepate - chlordiazepoxide Eldery - LOT - lorazepam - oxazepam - temazepam

Answer 71

Hydroxyzine - approved for generalized anxiety disorder - Used PRN for anxiety or insomnia instead of a BZD - Side effects: sedation, anticholinergic side effects, QTc prolongation risk (not the biggest issue) - avoid use in elderly due to anticholinergic side effects and fall risk

Answer 72

Propranolol - useful for performance and situational anxiety as PRN. Use low doses - Evaluate for history/current asthma and cardiovascular conditions

Answer 73

- St. John's Wort (watch for 3A4 interactions, since it's an inducer) - Passionflower (avoid in pregnancy) - Valerian (avoid in pregnancy) - Chamomile AVOID Kava

Answer 74

1st line - SSRIs/SNRIs are 1st line for all anxiety disorders - buspirone can also be used 1st line for GAD - BZDs are FDA approved to treat anxiety disorders, but guidelines suggest against them *Consider in pts with bipolar disorder who have anxiety or comorbid neruopathic pain

Answer 75

Generalized Anxiety Disorder - excessive anxiety/worry present for at least 6 months Symptoms: (at least 3 of the following) - restlessness/feeling keyed up or on edge - being easily fatigued - difficulty concentrating or mind "going blank" - irritability - muscle tension - sleep disturbances

Answer 76

1º maintenance treatment - SSRIs (takes 2-4 weeks to work) If pt also has a pain syndrome - SNRIs - can use benzos as a bridge therapy to cover the time until the onset of SSRI/SNRI, but MUST taper if the pt has been taking them long term to avoid withdrawal - buspirone or PRN hydroxyzine may also be useful

Answer 77

Social anxiety disorder - persistent fear about social and/or performance situations in which the patient fears embarrassment or humiliation that is unreasonable - duration of symptoms is at least 6 months 1º SSRIs (SNRI if failure of SSRI) - beta blockers may be useful in non-generalized performance-related SAD

Answer 78

Panic disorder - recurrent, unexpected panic attacks. At least one attack has been followed by one month or more of persistent concern about addition attacks or significant maladaptive change in behavior related to the attacks. 1º SSRIs - venlafaxine (SNRI) is FDA approved - benzos shouldn't be considered first line unless there has been an inadequate response to serotonergic drugs

Answer 79

Obsessive-compulsive disorder - obsessions and compulsions that are excessive/unreasonable 1º SSRIs (can expect 25-50% reduction in symptoms) 2º clomipramine (TCA) if patient has failed a few trials of different SSRIs - antipsychotics are not FDA-approved, but can be used as adjunct with SSRIs/SNRIs (risperidone & aripiprazole)

Answer 80

Posttraumatic stress disorder - exposure to real or threatened death, serious injury, or sexual violence (either victim, witness, discovery, exposure to details of traumatic event). Pt experiences flashbacks, reexperiencing, avoidance, hypervigilance. This causes negative alterations in mood or cognition. 1º SSRIs/SNRIs (these are the only drugs that are FDA approved for PTSD) - prazosin may be helpful for sleep or nightmares at low doses - benzodiazepines are NOT recommended - polytherapy is common - substance use is common - CBT and eye movement desensitization and reprocessing may be helpful *drug therapy may be more effective in civilian trauma (one-time event) vs combat trauma, so non-drug treatments are especially useful

Answer 81

Jitteriness can result from SSRIs/SNRIs when treating anxiety, so initial doses should be lower.

Answer 82

GABA-A: chloride ion channel - BZDs, BBTs, z-hypnotics GABA-B: Gi coupled (inhibitory); located in brain and limbic system - it's a heterodimer with a unique binding site. Need GABA to bind to B1, then B2 will be activated for Gi action. - agonist: baclofen, GHB - antagonist: mostly for research purposes; phaclofen, saclofen, 2-hydroxysaclofen

Answer 83

GHB is a very dirty drug. It hits GABA-B, GABA-A, etc. The mechanisms isn't really known. It can cause CNS depression (dizziness, drowsiness, coma) Concerns: - No antagonist - Date-rape drug - amnesia

Answer 84

Ramelteon - melatonin agonist. It binds to MT1 and MT2. - Treats insomnia characterized by difficulty with sleep onset - No abuse, no withdrawal, no dependency!

Answer 85

Suvorexant - orexin antagonist. Orexin is at the hypothalamus. This signal is promoting wakefulness. In order for people to go to sleep, we want to reduce orexin signaling. Antagonizing this receptor can reduce reward stimulti via receptors that mesolimbic projections between the VTA and nucleus accumbens.

Answer 86

diphenhydramine doxylamine pyrilamine

Answer 87

Norepinephrine - stimulates autonomic nervous system. NE is dysregulated in GAD and other types of anxiety. It projects to the amygdala (fear center). GABAergic system - GABA/glutamate balance is important. glutamate is converted to GABA by glutamic acid decarboxylase. We want more GABA signaling in anxiety. Serotonin - 5HT1A receptors are effective Corticoptropin-releasing factor (CRF) and the HPA axis - hyperregulation is bad.

Answer 88

anxiety amphetamines beta agonists beta blockers bupropion decongestants methylphenidate modafinil mood disorders thyroid meds

Answer 89

Insomnia - difficulties with sleep initiation (latency), sleep maintenance, and/or early morning awakening. - at least 3x per week for at least 3 months 1º is non-pharm treatment (behavioral therapies, sleep hygiene) - Z-hypnotics (zolpidem, eszopiclone, zaleplon) are the most commonly used *initial dose of zolpidem is lower in women (5mg) *z-hypnotics are 3A4 substrates

Answer 90

Ramelteon - - contraindicated with fluvoxamine - side effects: GI upset, next day somnolence, hyperprolactinemia, prolactinoma Tasimelteon - FDA approved for non-24 sleep-wake disorder in adults - same side effects as ramelteon *1A2 substrates

Answer 91

suborexant lemborexant daridorexant These all need the pt to get 7 hours of sleep. These are all contraindicated in narcolepsy due to causing narcolepsy-like side effects.

Answer 92

doxepin - TCA - low doses exert H1 antagonism, causing sedation - anticholinergic side effects trazodone - not FDA approved for insomnia - long-half life, may see daytime hangover - this is very common, but not in guidelines

Answer 93

mirtazapine - not FDA approved for insomnia - clinically used as a sleep agent, especially in pts with depression who have difficulty sleeping - if pt has depression as well as insomnia, use mirtazapine instead of a z-hypnotic quetiapine - low dose quetiapine is not recommended for use in insomnia unless there is a co-morbid psychiatric disorder

Answer 94

diphenhydramine/doxylamine - not recommended to use melatonin/valerian/chamomile - melatonin can be considered in jet lag and in pts with low melatonin levels *melatonin is 1A2 substrate *chamomile can cause allergic reaction in pts with daily or ragweed allergies

Answer 95

Obstructive sleep apnea - patient must have evidence of at least 5 obstructive apneas per hour of sleep confirmed by polysomnography - many patients may have both apnea AND insomnia. Both need to be treated, but apnea should be treated first. - patients can do a home test, but they MUST so polysomnography if they are on chronic opioids, have severe insomnia, cardiorespiratory disease, respiratory muscle weakness due to a neuro-muscular condition, hx of stroke, or sleep-related hypoventilation

Answer 96

- Weight loss, smoking cessation, avoid alcohol and CNS depressants, sleep on side rather than back - excessive daytime sleepiness can be treated with modafinil or armodafinil (but reveiw CPAP adherence and RLS or PLMS) *if patient is obese and is coming in for insomnia, should test for sleep apnea before starting treatment for insomnia

Answer 97

EDS - (excessive daytime sleepiness) occurs in ALL patients, generally more severe in Type I narcolepsy, which is narcolepsy with cataplexy or hypocretin deficiency syndrome Cataplexy - sudden loss of muscle tone triggered by emotion (75% of patients) Hallucinations - 30-60% of patients Sleep paralysis - 25-50% of patients *10-33% of patients have all 4 symptoms

Answer 98

cataplexy - sodium oxybate (GHB) is most effective - Xywav can be used for adults and children >7yo, also for idiopathic hypersomnia in adults EDS - sodium oxybate (GHB) - pitolisant and solriamfetal - recently FDA approved

Answer 99

Pitolisant - FDA approved for EDS - contraindications: severe hepatic impairment - 2D6/3A4 substrate, weak 3A4 inducer (think about oral contraceptives) - avoid use with centrally acting H1 receptor antagonists (OTC antihistamines) solriamfetol - indicated for improvement in wakefulness in adults with EDS due to narcolepsy or OSA - requires dose decrease in renal impairment - warnings: BP & HR increases, so avoid in unstable CV disease and arrhythmias; caution in pts with psychosis or bipolar disorder, decrease dose or d/c if psychiatric symptoms develop; caution with dopminergic drugs

Answer 100

Shift work sleep disorder - modafinil and armodafinil (take 1 hour before work period starts) *DON'T use sleep medications, want to help wakefulness Restless leg syndrome - - 1º dopamine agonists - gabapentin enacarbil (prodrug of gabapentin) is FDA approved, so may be considered 1st line - iron supplementation may be considered

Answer 101

Anorexia - restriction of energy intake leading to a significantly low body weight. Involves an intense fear of gaining weight or becoming fat. - Restricting type: during the last 3 months, pt has NOT engaged in recurrent episodes of binge eating or purging. The weight loss is accomplished primarily through dieting, fasting, and/or excessive exercise - Binge-eating/purging type: during the last 3 months, the individual has engaged in recurrent episodes of binge eating or purging *BMI under 18.5kg/m2 is considered to be on the low end of normal mild = >17 moderate = 16-16.99 severe = 15-15.99 extreme = <15

Answer 102

*lack of energy to perform daily functions, body slows down down to preserve energy - slow HR/BP, cardiac muscle atrophy, hypotension, arrhythmias - decreased bone density, low estrogen, amenorrhea, infertility - fainting, fatigue, decreased metabolic weight, weakness - dry skin, hair loss, hypercarotenemia - severe dehydration - downy layer of hair all over body - cold intolerance - delayed gastric emptying, constipation

Answer 103

Treat - slowly increase calories, correct electrolyte and fluid deficits, cognitive behavioral therapy *bupropion is contraindicated Re-Feeding syndrome!!! Results from a shift from fat metabolism to glucose metabolism - hypokalemia, water retention, severe edema - end result is multiple organ failure!!

Answer 104

mild: 1-3 episodes per week moderate: 4-7 episodes per week severe: 8-13 episodes per week extreme: ≥14 episodes per week *related to episodes, not BMI *not related to recurrent use of inappropriate compensatory behavior

Answer 105

- hypertension - elevated cholesterol - cardiovascular disease - type 2 diabetes - gall bladder disease

Answer 106

Lisdexamfetamine (vyvanse) - approved for moderate or severe binge eating disorder (mod = 4-7 episodes; severe = 8-13 episodes) - CBT + medications provides best outcomes

Answer 107

mild: 1-3 episodes per week moderate: 4-7 episodes per week severe: 8-13 episodes per week extreme: ≥14 episodes per week - recurrent bingeing and purging can affect the entire digestive tract (tooth decay, fastric rupture, electrolyte imbalances, irregular bowel movements, physical sores, etc.) - amenorrhea - orthostatic hypertension - bradycardia - arrhythmias - osteopenia - osteoporosis

Answer 108

- vomiting - laxatives - diuretics - excessive exercise - diabulimia (taking less insulin than they need to promote weight loss) Fluoxetine is FDA approved for bulimia nervosa. CBT + medication provides best benefit.

Exam 4 Flashcards

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