Pharm Section 5 Flashcards
psychiatric disorders or mental illness may involve either a ______ or ______ in one or more chemical mediators
excess or deficiency
schizophrenia is associated with an excessive amount of….?
dopamine
depression is associated with a deficient amount of….?
serotonin
psychiatric symptoms can be caused by what?
drug effects underlying illness psychopathology psychosocial factors withdrawal from drugs
when diagnosing mental illness, what should you be sure to rule out?
drug-induced psychiatric symptoms
DSM
Diagnostic and Statistical Manual of Mental Disorders. Standard criteria for diagnosing mental disorders.
DSM IV vs V?
Critics say that DSM V includes too much diagnostic inflation.
normal grief > major depressive disorder
forgetfulness > neuro-cognitive disorder
temper tantrum > disruptive mood dys-regulation disorder
overeating > binge eating
PMDD > mental illness
Psychiatric illness in A Beautiful Mind (and treatments)
Schizophrenia
Treatments: clorpromazine (Thorazine), then risperidone (Risperdal)
schizophrenia
characterized by delusions, hallucinations, disorganized speech/behaviors, social/occupational dysfunction, grossly abnormal psychomotor behaviors, negative symptoms. Must have at least two symptoms for 6 mo with 1 mo. active symptoms.
schizophrenia epidemiology
affects ~1% population in all cultures. affects men and women equally. Onset later in women. 10% lifetime suicide risk with schizophrenia.
antipsychotic drug group
aka neuroleptics or psychotropics
used to treat schizophrenia
first antipsychotics
phenothiazines, 1950s in Paris
dopamine
neurotransmitter associated with feelings of pleasure and well-being. Associated with “addicting” agents.
MOA for typical antipsychotics
block postsynaptic dopamine receptors and increase dopamine turnover by blocking the D2 somato-dendritic auto-receptor. Decreases dopamine neurotransmission.
Typical antipsychotics and side effects
D2 blockade responsible for extrapyramidal symptoms (EPS) of typical antipsychotics, plus antiemetic and hiccup relief. EPS include: akasthesia, parkinsonian symptoms, dystonia, and tardive dyskinesia. Other side effects include: sexual dysfunction, orthostatic hypotension, anticholinergic effects, poikilothermia, hyperprolactinemia, tranquilization, cardiac toxicity, and neuroleptic malignant syndrome.
MOA for atypical antipsychotics
mixed neuro-receptor agonists with low-affinity dopamine D2 blockade and high-affinity serotonin 5HT blockade
Side effects of atypical antipsychotics
Much less likely to cause EPS, but cause serious metabolic side effects (weight gain, T2 diabetes, hypercholesterolemia, and metabolic syndrome)
blocking dopamine D2 receptor causes what effects?
EPS, increased prolactin levels, antiemetic effects, and decreases intractable hiccups
blocking the serotonin 5HT2 receptor causes what effects?
mitigates some EPS
anxiety
insomnia
blocking the H1 receptor causes what effects?
drowsiness
increased appetite
weight gain
blocking the alpha-1 adrenergic receptors causes what effects?
orthostatic hypotension
dizziness
reflex tachycardia
blocking the muscarinic/cholinergic receptors causes what effects?
dry mouth, constipations, blurred vision, urinary retention
akasthesia
EPS characterized by motor restlessness, agitation, and aggression
Parkinsonism symptoms
EPS characterized by slow movement, apathy, masked face, social withdrawal, flattened affect, “pill-rolling” movement
Dystonia
EPS characterized by acute muscle spasms like oculo-genic crisis (eyes roll back in head), etc.
what can sometimes treat coulee-genic crises?
Artane, Cogentin, or Benadryl
Tardive Dyskinesia (TD)
EPS characterized by persistent and involuntary hyperkinetic abnormal movements, such as spasms of tongue, face, lips, neck, trunk, and limbs. Dopamine probably plays role. Associated with long-term antipsychotic use. More likely with typical antipsychotics than atypical antipsychotics.
poikilothermia
temperature regulation abnormalities
hyperprolactinemia
overproduction of prolactin that leads to amenorrhea, gynecomastia, and galactorrhea.
neuroleptic malignant syndrome (NMS)
rare, rapidly developing, occasionally lethal reaction caused by acute reduction in dopamine activity resulting from drug-induced dopamine blockade. S/s include: rigidity, hyperthermia, tachycardia, hypertension, diaphoresis, incontinence, and confusion.
treatment for NMS?
skeletal muscle blocker dantrolene (Dantrium)
dopamine agonist bromocriptine (Parlodel)
black box warning for antipsychotics
cause increased risk of death with off-label use for behavioral problems in older people with dementia
atypical antipsychotics are generally approved for schizophrenia and…?
bipolar disorder/disease
chlorpromazine (Thorazine)
typical antipsychotic (phenothiazine) than also has many other uses (nausea, hiccups)
thioridazine (Mellaril)
typical antipsychotic (phenothiazine) rarely used due to black box warning for OTc prolongation resulting in torsades de points arrhythmias and sudden death.
trifluperazine (Stelazine)
typical antipsychotic (phenothiazine) with high potency and the most EPS.
fluphenazine decanoate (Prolixin)
typical antipsychotic (phenothiazine) that’s a long-acting form for injections. Lasts 3-4 weeks and helps assure compliance.
thiothizene (Navane)
typical antipsychotic (non-phenothiazine)
loxapine (Loxitane)
typical antipsychotic (non-phenothiazine)
halperidol (Haldol)
typical antipsychotic (butyrophenone). has a long acting form (halloo dacanoate) to ensure compliance. Still used a lot in jails, but has a lot of EPS.
Clozapine (Clozaril, Fazaclo)
the first atypical antipsychotic. Most effective antipsychotic agent, but only used for refractory patients because of risk of neutropenia, agranulocytosis, seizures, and myocarditis. Causes little to no EPS. Distributed through monitored program. REMS registry.
Olanzapine (Zyprexa)
atypical antipsychotic. oral tablet or long-acting injection. chemically similar to clozapine but without agranulocytosis. Major weight gain (30% gained more than 20lbs in 3 mo). Carries FDA DRESS warning and requires continuous monitoring for reaction for at least 3 hours after injection.
Risperidone (Risperdal)
atypical antipsychotic comes in oral tablets or long acting injections. Causes more EPS than other atypicals. Approved for kids and adolescents with autism. Drug in A Beautiful Mind.
Quetiapine (Seroquel)
atypical antipsychotic with dibenzothiazepine ring (clozapine and olanzapine). Abused for sedative and anti-anxiety effects (esp. among inmates/substance abusers). Called “quell” or “baby heroin.” Not controlled substance.
Ziprasidone (Geodon)
atypical antipsychotic that prolongs QTc at higher doses. FDA DRESS warning…reaction may start with rash all over.
Aripiprazole (Abilify)
atypical antipsychotic with slightly different MOA: dopamine system stabilizer (partial D2 agonist–adjusts dopamine instead of totally blocking it). FDA warning for impulse control (gambling, shopping, eating, sex). Fewer side effects compared to other atypicals
Paliperidone (Invega)
atypical antipsychotic that is the active metabolite of risperidone (Risperdal). 24-hour extended release form.
Iloperidone (Fanapt)
atypical antipsychotic that is reportedly better tolerated than some others but may prolong QTc interval like Geodon.
Asenapine (Saphris)
atypical antipsychotic that comes as sublingual tablet. Is inactive if swallowed (important for “cheekers”) and carries FDA warning for severe allergic reactions, including anaphylaxis and angio-edema.
Lurasidone (Latuda)
atypical antipsychotic marketed with less metabolic effect and 1x/day dosing. 10th atypical.
Brexipiprazole (Rexulti)
atypical antipsychotic approved for tx of adult schizophrenia and as an add on for adult major depressive disorder. Med Letter says no reason to use this over aripiprazole (Abilify) which has longer history and proven efficacy/safety and costs less.
Cariprazine (Vraylar)
atypical antipsychotic approved for schizophrenia and bipolar disorder. Carries boxed warning for inc. risk of death in tx elderly with dementia-related psychosis. Adverse effects: tremor, slurred speech, involuntary muscle movements.
FDA class labeling change for atypical antipsychotics?
patients should be monitored at least every 6 mo for diabetes, obesity, and hypercholesterolemia.
What should be included when initiating long-term antipsychotic therapy for the first time?
Make sure to include an Rx for daily orals because the long-acting injectables take a while to generate a therapeutic effect. E.g.: Kingsport woman who killed mom after switching.
Atypical antipsychotics in children?
Risperidone/ Risperdal is good first choice, Olanzapine/Zyprexa is worst. Concern about metabolic effects: monitor weight, BP, BGC, and lipids every 6 mo. Some may gain 10-20lbs in 3 mo. and they inc. risk for T2 diabetes by 3-fold even for short therapy.
Psychotropic drugs are most commonly prescribed for children to treat what condition?
ADHD
atypical antipsychotics and depression?
some are approved for resistant depression. especially useful if have depression and psychotic symptoms, but can be used for patients with just depression and no psychotic symptoms.
what are some CMS recommendations for reducing the # of elderly in nursing homes on antipsychotics?
evaluate all PRN antipsychotics
evaluate any antipsychotics used for 3+ mo
evaluate all antipsychotic Rxs for new pts
evaluate all rxs initiated on nights/weekends
evaluate “off-label” use
discontinue when possible.
What were the results of the CMS initiatives to reduce antipsychotic use in nursing homes?
use of these meds fell by 9.1% TN went from 4th in Rxs to 48th…huge reduction in antipsychotic use in nursing homes. Improves quality of life and health care costs. TN lowered #s through training sessions for providers.
what percentage of patients with depression respond to 1st line pharmacotherapy?
Fewer than 50%
2009 SAMHSA report on TN and MDD?
Tennessee had highest rate of people with a major depressive disorder in the last year
what percentage of women ages 50-64 are on antidepressants?
25%
DSM-V criteria for diagnosing depression?
must experience 5 out of following 9 symptoms: depressed mood, loss of interest, weight change, sleep disturbance, psychomotor agitation or retardation, fatigue, feelings of worthlessness/guilt, loss of concentration, suicidal ideation
chronic depression diagnosis in DSM IV vs V?
DSM IV: dysthymia
DSM V: persistent depressive disorder
Onset of action for antidepressants?
May see side effects in a number of hours, but don’t actually start to get the therapeutic effect for around 2 weeks. May take 6+ weeks to achieve maximum benefit from antidepressants.
neurotransmitters involved in the pharmacology of depression include?
Norepinephrine
Dopamine
Serotonin primary
First line recommendations for treating major depression in adults?
SSRI
SNRI
bupropion (Wellbutrin)
mirtazapine (Remeron)
First line recommendations for treating depression in adults?
sertraline (Zoloft)
escitalopram (Lexapro)
First line recommendations for treating depression in kids/adolescents/young adults?
fluoxetine (Prozac)
Most clinicians start with what when treating depression? What if that doesn’t work?
SSRI. If doesn’t work, switch to another SSRI or try antidepressant from another class. Then start trying combinations like SSRI and bupropion (Wellbutrin) or adding augments like an antipsychotic.
TCAs
tricyclic anti-depressants that probably interfere with repute of norepinephrine at the neuronal membrane. Not used much anymore because to anticholinergic effects, cardio-toxicity, and suicide.
side effects of TCAs
anticholinergic (dry mouth, constipation, etc)
cardio-toxic (dysrhythmias)
weight gain
dosing considerations for TCAs?
dose at bedtime to decrease awareness of side effects and because get sedation
amitriptyline (Elavil)
first TCA
imipramine (Tofranil)
TCA. also used for enuresis (urinary incontinence)
nortriptyline (Pamelor)
TCA
desipramine (Norpramin)
TCA
clomipramine (Anafranil)
TCA. also used for OCD.
doxepin (Sinequan, Adapin)
TCA. more sedative effects than others, so used to tx anxiety or insomnia.
SSRIs
Selective serotonin re-uptake inhibitors that block the reabsorption of serotonin, increasing available levels in the brain.
Why do SSRIs have less sedative and cardiovascular effects than TCA drugs?
they bind significantly less to histamine, acetylcholine, and norepinephrine receptors.
Why are SSRIs first-line agents for treating depression?
proven efficacy favorable side effect profile long-term tolerance 1x/day dosing wide therapeutic index
What are some side effects of SSRIs?
nausea, headache, nervousness, insomnia, fatigue, weight change (usually loss), sexual dysfunction, GI and cranial bleeds (dec. platelet aggregation), hypo-natremia, withdrawal (discontinuation syndrome), Serotonin syndrome, osteoporosis, increased fracture risk, pregnancy issues/birth effects, “bizarre” behavior and murder, and cardiac issues (prolonged QT interval)
Boxed warning for all antidepressants?
should not be used in anyone under the age of 25, even though many are approved for kids.
What is the dangerous period during initiation of SSRI treatment?
first week or two considered the “dangerous period” when people may have violent tendencies towards others or self
SSRIs and safety in pregnancy?
some concern for autism, absolute risk very small. some concern for birth defects, absolute risk very small.
SSRIs and osteoporosis?
SSRIs inhibit serotonin transport protein…also found in bone. Inc risk for fractures.
What is serotonin syndrome? how is it treated?
a life-threatening condition caused by excessive levels of serotonin in the brain. S/s: altered mental status, fever, tachycardia, HTN, agitation, tremor, myoclonus, hyper-reflexia, ataxia, incoordination, diaphoresis, shivering, and GI symptoms. Usually occurs because of drug interactions. Treat with benzodiazepines or anti-serotonergic agent cyproheptadine (Periactin).
What should SSRIs and SNRIs not be used with?
MAOIs or drugs with MAOI activity (like St. John’s Wart). Can cause serotonin syndrome
How do SSRIs impact sexual function? What drugs can help with this side effect?
serotonin is involved in inhibitory sexual activity and dopamine/norepinephrine are involved in excitatory activity. when increase serotonin, more sexual inhibition than excitement. Decreases libido/sex drive/ ability to perform sexually. Type 5PDE inhibitors (Viagra, Cialis) and Bupropion (Wellbutrin) may help with this side effect.
fluoxetine (Prozac)
SSRI with long half life. Requires longer wash out period before switching to MAOI. Approved in children >8 years for major depression and >7 years for OCD.
fluoxetine and olanzapine (Symbyax)
combination of SSRI antidepressant and antipsychotic used to treat bi-polar disease and treatment-resistant depression (TRD)
Sarafem
fluoxetine approved for PMDD
Prozac Weekly
once-weekly administration for stable patients
sertraline (Zoloft)
SSRI
paroxetine (Paxil)
SSRI that’s worst choice for pregnancy (category D)–causes heart defects.
paroxetine mesylate (Brisdelle)
SSRI? contains lesser amount of paroxetine than antidepressant formulation. First non-hormonal drug approved to treat hot flashes
citalopram (Celexa)
SSRI with warning to limit dose to avoid changes in electrical activity @ heart and serotonin syndrome. Don’t exceed 40mg/day in general and don’t exceed 20mg/day in women on estrogen BC or over 60 years.
Escitalopram (Lexapro)
SSRI L-enantiomer of citalopram (Celexa). Approved for depression in pediatric patients >12 years. Reasonable 1st-line choice for general depression in adults.
All SSRIs are averrable as…?
generics
SNRIs
serotonin/norepinephrine re-uptake inhibitors that block the re-uptake of serotonin and norepinephrine, so called “dual action” antidepressants. More likely to increase BP than SSRIs because they act on norepinephrine.
SNRI and withdrawal?
Patients can experience intense withdrawal symptoms after missing only one dose of an SNRI.
Venlafaxine (Effexor)
SNRI that may be more effective than SSRI, not enough evidence to tell.
Desvenlafaxine (Pristiq)
SNRI. Metabolite of venlafaxine. Hoped it would be longer acting than 1x/day formulation but no evidence of such. May be less effective for depression. Warn patients about ghost tablet in stool.
Duloxetine (Cymbalta)
SNRI approved for MDD, diabetic peripheral neuropathy pain, chronic pain, and fibromyalgia management. Not actually approved for general depression, but still used for it.
Levomilnacipran (Fetzima)
SNRI approved for MDD. Active isomer of Milnacipran (Savella).
Milnacipran (Savella)
SNRI approved for fibromyalgia management, but not for psychiatric use.
Vortioxetine (Brintellix, now Trintellix)
aytpical antidepressant often listed as an SSRI. A serotonin modulator and stimulator (inhibits re-uptake and is a partial serotonin agonist). May cause more nausea than some other antidepressants.
Hetero-cyclic antidepressants
Aka multiple-receptor agents. Antidepressant agents that affect one or more of serotonin, norepinephrine, acetylcholine, and dopamine neurotransmitters
trazodone (Desyrel, Oleptro)
heterocyclic antidepressant that works like an SSRI with alpha-adrenergic and histamine blocking action. Used in the treatment of MDD, generalized anxiety, and insomnia. Anxiolytic effect. Widely used off-label as a hypnotic (many call it their “sleeping pill”). Most likely drug to cause priapism in males.
bupropion (Wellbutrin)
heterocyclic antidepressant that inhibits the re-uptake of dopamine and epinephrine. Greater potential for seizures than other antidepressants. Less adverse sexual side effects > may improve sexual function. May cause weight loss. May be abused or diverted for cocaine-like high.
bupropion (Zyban)
bupropion formulation used for smoking cessation
Mirtazapine (Remeron)
heterocyclic antidepressant, not chemically related to any other class of antidepressants. MOA: increases central nor-adrenergic and seroton-ergic activity. Useful for patients with coexisting depression and anxiety. Faster one, less sexual dysfunction than SSRIs.
Vilazodone (Viibryd)
heterocyclic antidepressant that not many people use. First approved SSRI and serotonin 5HT receptor partial agonist. Prescribers Letter says doesn’t work any better than fluoxetine or citalopram and has more GI side effects.
MAOIs
monoamine oxidase inhibitors. there are two types (A and B).
MAOI interactions
interacts with tyramine in foods (beer, wine, cheese) to cause HTN crisis.
interacts with all other antidepressants
interacts with many drugs like sympathomimetics
Phenelzine (Nardil)
MAOI Type A agent (only used 4-5th line or in psych hospitals). Cause HTN.
Tranylcypromine (Parnate)
MAOI Type A agent (only used 4-5th line or in psych hospitals). Cause HTN.