Psychopharmacology Flashcards
What are the HAM side effects of the TCAs and low-potency antipsychotics?
antiHistamine (sedation, weight gain)
antiAdrenergic (hypotension)
antiMuscarinic (dry mouth, constipation, blurred vision, urinary retention)
What is the diagnosis: confusion, flushing, diaphoresis, tremor, myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal failure….in a patient with lots of psych meds…..
serotonin syndrome
classically occurs when an SSRI is taken with an MAOI
What can happen when you take MAOIs plus foods with tyramine (red wine, cheese, etc) or an MAOI with another sympathomimetic?
hypertensive crisis (caused by a buildup of stored catecholamines)
What are 3 examples of extrapyramidal side effects seen with the high-potency traditional antipsychotics?
parkinsonism, akathisia, or dystonia
What is the typical time of onset for the extrapyramidal side effects?
usually within days of starting (or increasing) the med
What is the drug of choice to treat the extrapyramidal symptoms produced by neuroleptics?
benzotropine
What other movement disorder can occur with antipsychotic medications, but usually with onset after years of being on the drug?
tardive dyskinesia
What’s the diagnosis: fever, tachycardia, hypertension, tremor, elevated creatine phosphokinase, and lead pipe rigidity in a patient on antipsychotics?
neuroleptic malignant syndrome - can be caused by all antipsychotics after a short or long period of time
What is the mortality rate for NMS?
20%
Are the SSRIs and SNRIs cyp450 inhibitors or inducers? So what does this do to warfarin?
inhibitors
increases the levels of warfarin, so requires close monitoring when initiating
True or false: all antidepressants have similar response rates in treating major depression, but differ in safety and side effect profiles
true
What percentage of patients with major depression will respond to an antidepressant?
about 70%
How long should a trial of an antidepressant last?
at least 1 month for effect
Most antidepressants have a withdrawal phenomenon characterized by what symptoms?
dizziness, headache, nausea, insomnia and malaise
True or false: if a patient tries an SSRI and it doesn’t work, you shouldn’t try any more SSRIs
false - although they are structurally very similar, patients often respond differently to different SSRIs
Why are the SSRIs the most commonly prescribed antidepressants?
they work just as well as anything else and have several distinct advantages:
- low incidence of side effects, most of which improve with time
- no food restrictions
- much safer in overdose than the TCAs and MAOIs
What are the 5 main SSRIs?
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro)
Which SSRI has the longest half-life and thus doesn’t need a taper to stop?
fluoxetine
Which SSRI has the highest risk for GI disturbance?
sertraline
Which SRI has the greatest risk for drug-drug interactions because it’s highly protein bound?
paroxetine
What else makes paroxetine a less than ideal choice?
it has more anticholinergic effects than the others
also with the shortest half-life, so you get a withdrawal phenomena if not taken at the same time every day
Which SSRI is currently only approved for those with OCD (but is used off label quite regularly)?
Fluvoxamine (Luvox) - the new one
Which SSRi has the fewest drug-drug interactions and fewer sexual side effects?
Citalopram
If someone on an SSRI gets a cold and then comes into the hospital with fever, diaphoresis, shivering, tachycardia, hypertension, delirium and neuromuscular excitability, what happened?
Serotonin syndrome from taking OTC cough medications
What are the most common side effects of the SSRIs?
sexual dysfunction in 25-30% (typically do not resolve) Nausea/diarrhea (so take with food) Insomnia and vivid dreams headache anorexia and weight loss restlessness seizures at 0.2%
What are the three main options for dealing with the sexual side effects of the SSRIs
- augment with buproprion
- switch to a non-SSRI
- add sildenafil for men
Why do the SSRIs have a black box warning from the FDA?
increased suicidal thinking and behavior in children and adolescents, but may be accurate for adults as well
(theory is that it decreases the indecisiveness and lack of energy before it improves mood, so they’re more likely to carry out suicide plans that were already present)
What are the two SNRIs?
venlafaxine (Effexor)
desvenlafaxine (pristiq) - just the active metabolite
duloxetine (Cymbalta)
Besides depression, what is venlafaxine typically used for?
anxiety disorders (especially GAD) and may have some use in ADHD
Venlafaxine shouldn’t be used in patients with which chronic medical condition?
hypertension - it can increased blood pressures
Besides depression, what is duloxetine often used for?
neuropathic pain and fibromyalgia
The side effects of duloxetine are similar to the SSRIs with what minor differences?
constipation instead of diarrhea and more dry mouth
Why shouldn’t you use duloxetine in patients with heavy alcohol use?
it can have liver side effects
What is the norepinephrine-dopamine reuptake inhibitor?
buproprion
Bupropion is usually very well tolerated, but what are the worrisome side effect potentials?
increased seizure risk
psychosis at high doses
increased anxiety in some
In what patients is bupropion contraindicated
patients with a hx of seizures, patients with active eating disorders and in those currently on an MAOI
What are the two serotonin receptor mixed antagonists/.agonists
trazodone and nefazodone
Trazodone isn’t a great antidepressant, so what do we use it for?
primarily insomnia
What are the side effects of trazodone and nefazodone?
nausea, dizziness, orthostatic hypotension, cardiac arrhythmias, sedation and priapism (trazobone)
Why does nefazodone carry a black box warning?
rare, but serious liver failure
What’s the antidepressant that works as an alpha-2 adrenergic receptor antagonist?
mirtazapine
Who are the best patients to use mirtazapine for?
little old ladies with depression who need to gain some weight
Mirtazapine has the typical antidepressant side effects with the addition of what rare effect?
agranulocytosis
How do TCAs work?
they inhibit the reuptake of NE and 5HT
What are the 6 main TCAs?
amitriptyline imipramine clomipramine doxepin nortriptyline desipramine
Which TCAs are used in chronic pain and migraines?
amitryptiline and nortryptiline
Which TCA is helpful in enuresis?
imipramine
Which TCA is used mainly in OCD?
clomipramine
The danger with TCAs is their risk for lethal overdose. What is the mainstay treatment for TCA OD?
IV sodium bicarbonate
What are the major complications of the TCAs? Hint: triCs….
cardiotoxicity (orthostatic hypotension, dizziness, reflex tachy, arrhythmias, widening QRS, prolonged QT and PR)
convulsions
coma (in OD)
How do MAOIs work?
they block the inactivation of biogenic amines like NE, 5HT, DA, etc., so these NTs increase in the synapse
MAOIs are not classically first line, but in what type of depression are they particularly useful?
atypical depression characterized by hypersomnia, increased appetite, increased sensitivity to interpersonal rejection and a leaden sensation in the legs
What are the three main MAOIs?
phenelzine
selegiline
tranylcypromine
isocaboxazid
How long do you need to wait to switch from an SSIR to an MAOI to avoid serotonin syndrome?
at least 2 weeks (but actually 5-6 with fluoxetine because of the long half life)
What is the management for serotonin syndrome?
stop the drug
you can also try calcium channel blockers like nifedipine
if carefully monitored, try chlorpromazine or phentolamine
People on MAOIs can have hypertensive crisis if they eat tyramine rich foods. Besides the elevated BP, what side effects do they often have?
headache, sweating, nausea, vomiting, photophobia, autonomic instability, chest pain, arrhythmias
What type of receptors are blocked by the first generation, or typical, antipsychotics?
D2 receptors
What receptors are blocked by the second gen, or atypical, antipsychotics?
D2 and Serotonin (2A) receptors
Although atypical antipsychotics are used to treat the symptoms of dementia and delirium, why is their use in the elderly controversial?
they are associated with an increased risk for all-cause mortality and stroke
What are the two low-potency typical antipsychotics?
chlorpormazine and thoridazine
The low-potency typicals have lower incidence of PS and NMS than the high-potency typicals, but what do they have an increased risk for?
anticholinergic and antihistaminic side effects
also more lethality in overdose due to QTc prolongation and potential for heart block and vtach
Chlorpromazine is associated with what unique side effects?
orthostatic hypotension
bluish skin discoloration
photosensitivity
What is chlorpromazine also used for besides psychosis?
nausea, vomiting and intractable hiccups
What side effect is associated with thioridazine?
retinitis pigmentosa
What are the four midpotency typical antipsychotics?
loxapine
thiothixene
trifluoperazine
perphenazine
What are the three high-potency typical antipsychotics?
haloperidol
fluphenazine
pimozide
The antipsychotics treat the symptoms of schizophrenia through action in the medolimbic dopamine pathway. What are the brain structures included in this pathway?
nucleus accumbens
fornix
amygdala
hippocampus
The negative symptoms are thought to occur to dopamine action in what pathway?
mesocortical
The extrapryamidal side effects are from the medication effects on what pathway?
nigrostriatum
What are some of the hyperprolactinemia effects from the blockage of dopamine in the tuberoinfundibular pathway?
decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea and osteoporosis
How many cases of tardive dyskinesia will spontaneously remit?
50%, but many cases are permanent
Which atypical antipsychotic is the least likely to cause TD?
clozapine
What is the treatment for NMS?
stop the drug
supportive therapy: hydration, cooling
sodium dantrolene, bromocriptine, amantadine
True or false: if the patient develops NMS on a drug, they shouldn’t take that drug ever again
false - they can actually go back on it without an increased risk of recurrence
Although atypical antipsychotics have lower risk for EPS, TD and NMS, what do they have an increased risk for?
metabolic syndrome
If a patient on an atypical antipsychotic develops metabolic syndrome, what are the options?
switch to a more weight-neutral atypical antipsychotic like aripiprazole or ziprasidone
or switch to a typical antipsychotic
Clozapine has been shown to be the most efficacious antipsychotic (30% of treatment-resistant psychosis will respond and it’s the only one to decrease suicide risk), but why don’t we use it as first line?
risk of agranulocytosis and need for weekly monitoring
note - it also has increased anticholinergic side effects, mayocarditis and higher seizure risk
At what absolute neutrophil count do you need to stop clozapine?
less than 1500/microL
What is the particular side effect of risperidone?
increases prolactin more than the others, so more risk for galactorrhea, etc.
also orthostatic hypotension and reflex tachy
Which atypical antipsycotic has the highest risk for weight gain?
olanzapine
How is aripiprazole’s mechanism of action special among the atypicals?
it has partial D2 AGONISM
means if can be more activating and less sedating
also less potential for weight gain
What are the four mood stabilizers?
lithium
valproid acid (depakote)
lamotrigine
carbamazepine
Which is the only mood stabilizer shown to decreased suicidality?
lithium
Besides mania, what can lithium be used for?
cyclothymia and as an adjunct in unipolar depression
How is lithium metabolized?
in the kidneys, so you have to adjust the dose and monitor levels closely in patients with renal dysfunction
Prior to initiating lithium, what lab tests should a patient receive?
ECG, basic chemistries, thyroid function test, CBC and a pregnancy test
How long is onset of action for lithium?
5-7 days
Blood levels actually correlate with clinical efficacy for lithium, so how often should you check them when starting?
at 5 days and then every 2-3 days until therapeutic
What is the major drawback to lithium?
low therapeutic range (0.6-1.2; toxic over 1.5 and lethal over 2)
What are some side effects of lithium?
altered mental status, coarse tremors, convulsions and death
thyroid dysfunction kidney damage nephrogenic diabetes insipidus GI distrubance weight gain sedation ECG changes benign leukocytosis
What is the birth defect caused by lithium?
epstein’s anomaly
What are some factors that will affect Lithium levels?
NSAIDs will decrease aspirin dehydration will increase salt deprivation will increase sweating (salt loss) will increase impaired renal function will increase diuretics and thiazides
Carbamazepine is particularly useful in treating mixed episodes and rapid-cycling bipolar disorder. What are the sommon side effects?
GI effects, drowsiness, ataxia, sedation, confusion
skin rash - stevens-johnson syndrome
leuopenia, hyponatremia, aplastic anemia, thrombocytopenia, agranulocystosis
neural tube defects if used in pregnancy
What are some of the side effects of valproic acid?
GI weight gain sedation alopecia pancreatitis hepatotoxicity!! thrombocytopenia teratogenic - neural tube defects
What are the anxiolytics used for besides anxiety?
muscle spasms seizures sleep disorders alcohol withdrawal anesthesia induction
In chronic alcoholics or liver disease, you need to use benzos that are not metabolized by the liver. What are some examples? (mnemonic: there are a LOT of them)
Lorazepam
oxazepam
temazepam
Why aren’t benzos a great idea for anxiety?
many patients become dependent on them and require increasing doses for the same clinical effect
Which two benzos are long acting?
diazepam
clonazepam
Diazepam isn’t really used to treat anxiety much anymore, so what do we use it for?
detox from alcohol or sedative-hypnotic anxiolytics
and for seizures
What are the 4 intermediate acting benzos? (mnemonic: A LOT)
alprazolam
lorazepam
oxazepam
temazepam
Which drug do we use in benzo OD?
flumazenil
Which two benzos are short acting?
triazolam
midazolam (versed)
What are the side effects of benzos?
drowsiness
impaired intellectual function
reduced motor coordination (so careful in elderly)
anterograde amnesia
Why is withdrawal from benzos life threatening?
seizures
How do the z-hypnotics work?
they bind to the benzo receptor 1, which is responsible for the sedation, but not the euphoria.
Rank the three z-hypnotics by half life, shortest to longest.
zaleplon > zolpidem > eszopiclone
How does ramelteon work for sleep?
selective melatonin MT1 and MT2 agonist
How does buspirone work?
partial agonist at the 5HT-1A receptor
How long does it take for buspirone to take effect?
1-2 weeks
Buspirone is not as effective as other options, so what do we usually combine it with?
an ssri
So if buspirone doesn’t work as well as the benzos, why do we use it?
because it doesn’t potentiate the CNS depression of alcohol and has a low potential for abuse/addiction
If someone wants a quick-acting short-term medication (unlike buspirone) that isn’ta benzo, what is the best option?
hydroxyzine (atarax)
Why don’t we use barbs hardly ever anymore?
risk of lethal OD and bad side effect profile
Which hypertension med is useful in treating the autonomic effects of panic attacks or performance anxiety?
propranolol
Propranolol is also used to treat what side effect of the typical antipsychotics?
akathisia
