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what happens in the brain in a patient with alzheimer's disease (mid 60s+)?
abnormal deposits of protein form amyloid plaques and tau tangles
what happens in the brain in a patient with frontotemporal dementia (45-64)?
abnormal amounts/forms of tau and TDP-43 proteins accumulate inside neurons in frontal and temporal lobes
what happens in the brain in a patient with lewy body dementia (50+)?
abnormal deposits of alpha-synuclein protein ("lewy bodies") affect the brain's chemical messengers
what happens in the brain in a patient with vascular dementia (>65)?
conditions (e.g. blood clots) disrupts blood flow in the brain
symptoms of mild alzheimer's dementia
wandering, getting lost, repeating questions
symptoms of moderate alzheimer's dementia
problems recognizing friends/family, impulsive behavior
symptoms of severe alzheimer's dementia
cannot communicate
type of dementia:
difficulty planning and organizing
emotional flatness or excessive emotions
shaky hands
problems with balance and walking
difficulty making or understanding speech
frontotemporal dementia
type of dementia:
inability to concentrate, pay attention, stay alert
disorganized ideas
muscle rigidity
loss of coordination
reduce facial expression
insomnia
excessive daytime sleepiness
visual hallucinations
lewy body dementia
vascular dementia symptoms
forgetting current/past events, misplacing items, trouble following instructions, hallucinations / delusions, poor judgement
typical antipsychotic drugs
chlorpromazine (thorazine), haloperidol
atypical antipsychotic drugs (2, 2.5, 3)
2: clozapine, risperidone, olanzapine, quetiapine 2.5: aripiprazole (abilify) 3: ziprasidone (geodon), lurasidone (latuda), cariprazine, lumateperone, pimavanserin
regimen for haloperidol (haldol, typical antipsychotic)
start 2 mg, increase by 2 mg every other day
which typical antipsychotic is low potency and has antihistamine and anticholinergic effects? => lower rates of EPS, higher weight gain and sedation
chlorpromazine (thorazine)
regimen for risperidone (risperdal, atypical antipsychotic)
start 1-2 mg, target 2-6 mg (ADR: prolactin elevation)
regimen for olanzapine (zyprexa, atypical antipsychotic)
start 5-10 mg, goal 10-20 mg (smoking increases clearance, female decreases clearance)
which atypical antipsychotic clearance is increased by smoking and decreased by female gender?
olanzaprine (zyprexa)
what is quetiapine (seroquel) used for?
EVERYTHING...schizophrenia (600 mg daily), bipolar (300-600 mg daily), acute mania, depression
side effects of quetiapine (seroquel, atypical antipsychotic)
EKG changes (qtc), metabolism- weight gain, sedation, agitation, insomnia
what is aripiprazole (abilify, atypical antipsychotic) used for?
MDD (goal 5-15 mg), psychosis (goal 10-30 mg)
transitioning from / to aripiprazole (abilify, atypical antipsychotic) rules
from: stop abilify completely and start other antipsychotic at middle dose
to: start abilify at middle dose (10 mg) and taper other antipsychotic x2 weeks
side effects of aripiprazole (abilify, atypical antipsychotic)
lowers QTc, moderate motor SEs (akathisia), weight gain (less than other antipsychotics)
ADR of antipsychotic/antidepressant drugs: a state of agitation, distress, and restlessness, pacing (tx: BB)
akathasia
which atypical antipsychotic causes the most amount of weight gain and dyslipidemia (high TG, high LDL, low HDL)?
clozapine (12 lb in 10 weeks) (next: olanzapine)
which atypical antipsychotic has the highest risk of seizure?
clozapine (atypical antipsychotic)
general indication for typical and atypical antipsychotics
schizophrenia
what is haloperidol (haldol, typical antipsychotic) used for?
psychotic disorders, tourette's, children with behavioral / hyperactive issues (second line)
what is clozapine (atypical antipsychotic) used for?
treatment-resistant schizophrenia, reduction in suicidal behavior in schizophrenia or schizoaffective
dystonia is muscle spasm (twisting movements esp of the face and neck). what is the tx?
benztropine 2 mg BID x 7 days, benadryl
how do typical antipsychotics work?
block dopamine 2 receptors broadly (anti-dopamine)
advantages of high potency first gen antipsychotics (haloperidol)?
disadvantages: high risk EPS, high risk tardive dyskinesia
injectable formulations (include IV), depot form, inexpensive
advantages of low potency first gen antipsychotics (chlorpromazine)?
disadvantages: high risk QTC prolongation, high risk tardive dyskinesia
highly sedating injectable forms (include IV), inexpensive
how do atypical antipsychotics work?
block 5HT2A receptors (serotonin-dopamine antagonists) aka block receptors --> increase dopamine release in striatum (less EPS) and decrease prolactin release
what must you order before starting clozapine (clozaril, atypical antipsychotic)?
WBC, ANC (neutropenia), lipid panel, EKG
which atypical antipsychotic must be avoided with benzodiazepines (poss respiratory depression) and drugs that cause granulocytopenia (eg carbamazepine)?
clozapine (clozaril, atypical antipsychotic)
side effects of clozapine (clozaril, atypical antipsychotic)
sedation, weight gain, sialorrhea, other (less common/rare): seizure, resp depression, myocarditis, neuroleptic malignant syndrome, PE
MOA benzodiazepines
increase GABA
why can benzos lead to all these things: sedation, muscle relaxation, cognitive / psychomotor impair, tolerance, dependence, anxiety reduction, anterograde amnesia?
GABA receptors widely distributed and benzos broadly inhibit brain function
which class of drugs has been shown to increase risk of hip fracture by 50% in the elderly?
benzos
drug interactions with benzos
carbamazepine (decrease metabolism), methadone (over-sedation), clozapine (increase risk cardiopulm depression), opiates (increase risk resp depression)
withdrawal symptoms of benzos
stiffness, weakness, flu-like, visual disturbances, seizure, tachy, HTN, anxiety/insomnia, nightmares, hallucination, depression
what drug class is eszopicione and zolpidem?
non-benzo receptor agonists
what must you order at baseline when starting lithium? can start lithium concurrently unless reason to suspect abnormal labs/EKG
weight, TSH, BMP (Na, Cr, Ca), urine albumin:Cr ratio (proteinuria), EKG (only if cardiac hx or >40 y/o)
regimen for lithium
start 300 mg qhs, titrate by 300 mg Q4 nights to 900 mg, then check level
ADRs of lithium
renal insufficiency (daily is better than BID), tubular effects (nephrogenic diabetes insipidus), nausea, tremor (tx: propranolol), hypothyroidism (tx: levothyroxine), hyperparathyroidism, weight gain, low lethal dose (tx: dialysis)
what if pt on lithium develops nephrogenic diabetes insipidus?
lower dose or start amiloride
toxic level of lithium
symptoms: anorexia, N/D, nystagmus, muscle weakness, drowsy, ataxia, tremor, jerks, sinus brady, heart block
>1.5
toxic level of lithium: >1.5.
what is the tx?
hydration, gastric lavage, cardiac monitor, dialysis (if >6 mEq/L, coma, convulsions, resp failure)
antipsychotic drugs commonly cause weight gain, esp clozapine and olanzapine. what drugs can you consider to help with weight gain in these pts?
metformin, topiramate, liraglutide (victoza), melatonin, zonisamide, reboxetine
how often do you screen for dyslipidemia when starting a patient on olanzapine and clozapine?
baseline, 3 mo after initiation, then yearly
name the SNRI drugs
venlafaxine (effexor), nefazodone (serzone), duloxetine (cymbalta), desvenlafaxine, levomilnacipran
indications for venlafaxine (effexor, SNRI)
depression, GAD, social anxiety disorder, panic disorder
which SNRI is a rare antidepressant that increases REM sleep rather than suppresses it? other drugs included: mirtazapine (atypical antidepressant)
nefazodone (serzone, SNRI)
BBW of nefazodone (serzone, SNRI)
liver injury
what must you check at baseline when prescribing nefazodone (serzone, SNRI)?
LFTs (baseline, Q3-6 months during first year then 6 mo after... avoid in active liver dz or LFTs 3xNL)
which SNRI is indicated for: MDD, GAD acute / maintenance, chronic MSK pain, diabetic peripheral neuropathic pain, fibromyalgia?
duloxetine (cymbalta, SNRI)
side effects of duloxetine (cymbalta, SNRI)
fatigue, constipation, weight gain, HTN
which SNRI has evidence in vasomotor symptoms in perimenopausal women?
desvenlafaxine (pristiq, SNRI)
active metabolite of venlfaxine
desvenlafaxine (pristiq, SNRI)
which drug had been seen to have lower rates of elevated BP: venlafaxine or desvenlafaxine?
desvenlafaxine (pristiq, SNRI)
which SNRI is it a must to avoid alcohol due to alcohol causing accelerated drug release?
levomilnacipran (fetzima, SNRI)
which SNRIs are appropriate for ADHD with prominent depression and/or anxiety? second-line after stimulants
duloxetine (cymbalta), venlafaxine (effexor)
SSRIs vs SNRIs:
upper/lower GI bleeds
tolerability in regard to AEs
overdose risk
risk of hypomania/maina
GI bleeds: MC in SSRIs
AEs: less tolerable in SNRIs
overdose: MC in SNRIs
mania: MC in SNRIs
explain perimenopause in regards to vasomotor symptoms
irreg estrogen --> dysregu neurotransmitter systems in hypothalamic thermoreg center--> neurotransmitter def--> trigger VNS and depression
explain postmenopause in regards to vasomotor symptoms
low estrogen--> low expression of brain glucose transporters--> CNS glucose transport drops--> hypothalamus detects this drop and triggers noradrenergic alarm--> vasomotor response
which SNRI is most sedating?
duloxetine (cymbalta, SNRI)
ADRs SNRIs
sedation, insomnia, headaches, hyperhidrosis, weight gain
name the SSRIs
fluoxetine, sertraline, citalopram, escitalopram, paroxetine, fluvoxamine, vilazodone, vortioxetine
how do SSRIs work?
block serotonin reuptake pump--> increases seotonin in somatodendritic area of serotonin neuron--> somatodendritic 5HT1a autoreceptors down-regulate--> less inhibit of serotonin impulse flow, more 5HT released from axon
general indications for SSRIs
depression, OCD, panic disorder, bullimia, PMDD
structure to disease
depression
OCD
panic
bullimia
depression: prefrontal cortex (decreased vol)
OCD: basal ganglia (hyperactivity)
panic: hippocampus
bullimia: hypothalamus
benefits SSRIs vs TCAs / MAOIs
fewer anticholinergic side effects, less cardiac toxicity, low risk overdose, no diet restriction, fewer med interactions
most sedating SSRIs
paroxetine, fluvoxamine
which SSRI has the worst withdrawal, causing akathisia, dystonia, restlessness, GI symptoms, dizzy, brain zaps?
paroxetine (paxil, SSRI)
why do SSRIs cause bleeding risk?
SSRIs inhibit the uptake of serotonin into platelets (serotonin limit bleeding when released from platelets in response to vascular injury)
symptoms of serotonin syndrome (HARMED)
hyperthermia, autonomic instability, rigidity, myoclonus, encephalopathy, diaphoresis
medications that increase the risk of serotonin syndrome + SSRI
St. John's wort, fentanyl, tramadol, methadone, flexeril, meperidine, ziprasidone
medications that DO NOT increase the risk of serotonin syndrome + SSRI
triptans, dextromethorphan
which SSRI increases levels of most NSAIDs, warfarin, xanax, valium, clozapine (seizures), haloperidol, imipramine, amitriptyline, fluoxetine?
fluvoxamine (luvox, SSRI)
which SSRI is it not safe to drink alcohol?
vortioxetine (viibryd, SSRI)
general indications for tricyclic antidepressants (TCAs)
MDD, enuresis, antipruritic, neuropathic pain/HA, GI (IBS)
tetracyclic amine: amoxapine (asendin)
tertiary amines: ?
secondary amines: nortriptyline (pamelor), desipramine (norpramin), protryptyline (vivactil)
amitriptyline (elavil, IBS), clomipramine (anafranil, OCD), doxepin (adapin, sinequan), imipramine (tofranil, enuresis)
ADRs of TCAs (fewer in secondary amines)
anti-muscarinic anticholinergic (blurry vision, dry mouth, constipation, urinary retention, heat intolerance, tachy, cognitive impair), anti-histamine (weight gain, drowsy), alpha 1 adrenergic antagonist (dizzy, decreased BP, ortho hypotension, drowsy)
name affective disorders (aka mood disorders)
depression, dysthymia, mania, hypomania
depression key points (SIG E CAPS)
suicide, interests, guilt, energy, concentration, appetite, psychomotor change, sleep
mania key points (DIG FAST)
distractibility, indiscretion, grandiosity, flight of ideas, activity increase, sleep deficit, talkativeness
GAD key points (WATCHERS)
worry, anxiety, tension in muscles, concentration difficulty, hyperarousal, energy loss, restlessness, sleep
PTSD key points (TRAUMA)
traumatic event, re-experience, avoidance, unable to function, month or more, arousal increased
name personality disorders
paranoid, schizotypal, borderline, antisocial, schizoid
substance dependence key points (ADDICTeD)
activities are given up, dependence (tolerance), dependence (withdrawal), intrapersonal consequences, can't cut down, time-consuming, duration
substance abuse key points (WILD)
work/school/home obligations, interpersonal consequences, legal problems, dangerous use
alcohol abuse key points (CAGE)
cut down, annoyed, guilty, eye-opener
extrapyramidal symptoms (EPS) are side effects of antipsychotic medications. name the 3 main symptoms
dystonia, pseudoparkinsonism, akathisia
normal QTC
350-460
questions to ask during visit (SMASH DAT)
sleep, mood, appetite, SI, HI, delusions, hallucinations, tolerating meds
increased risk for suicide (SAD PERSONS)
sex (M), age (45-64), depression, previous attempt, ethanol use, rational thinking loss, social support lacking, organized plan, no spouse, sickness
which atypical antipsychotic is known to modulate dopamine? good use in catatonia pts
aripiprazole (abilify)
which SSRIs are typically recommended in kids?
fluoxetine (prozac), escitalopram (lexapro)
BBW for citalopram (celexa, SSRI)
QTc prolongation
MOA of MAOIs
monoamine oxidase breaks down neurotransmitters (serotonin, norepi, dopamine)--> inhibt MAOs--> more serotonin, norepi, dopamine available