Chapter 18_Psychopharmacology Flashcards
Typically how long to antidepressants take to see an effect?
Most require a trial of at least 3-4 weeks, some as little as 1-2 weeks others needing 6-8 weeks.
What are the most common class of antidepressants used and why?
SSRIs.
Low incidence of side effects (most resolve with time), no food restrictions, much safer in overdose
Mechanism of SSRIs
inhibit presynaptic serotonin pumps that take up serotonin -> increased availability of serotonin in synaptic clefts.
FDA blackbox warning for all SSRIs?
potential to increase “suicidal thinking and behavior” in children and young adults (under 25). Can happen to adults as well
T/F: You can have withdrawal from antidepressants
True. “withdrawal phenomena” - dizziness, headaches, nausea, insomnia, malaise…depends on dose and half-life they may need to be tapered
Give some examples of commonly used SSRIs
Fluoxetine (prozac), sertraline (zoloft), paroxetine (paxil), citalopram (celexa), escitalopram (lexapro),fluvoxamine (luvox)
Which SSRI is only approved for OCD and has multiple drug interactions due to CYP inhibition?
fluvoxamine
Whih SSRI has few drug interactions but higher risk for GI disturbance?
sertraline (zoloft)
Which SSRI has the fewest drug drug interactions, but has dose dependent QtC prolongation?
citalopram (celexa)
Which is a levo-enantiomer of citalopram but has fewer side effects, does not need to be tapered?
escitalopram (lexapro)
Which SSRI has several drug-drug interactions, has anticholinergic effects, and a short-half life leading to withdrawal phenomena if not taken correctly?
Paroxetine (paxil)
Why do SSRI’s have fewer side effects than TCAs or MAOIs?
serotonin selectivity (they don’t act on histamine, adrenergic or muscarinc receptors
Some side effects of SSRIs
GI disturbance (nausea/diarrhea, taking with food helps
insomnia; vivid drems
headache
anorexia, weight loss
USUALLY RESOLVE AFTER A FEW DAYS AS BODY GETS USED TO IT
Other side effects that are more serious/rare/won’t usually resolve?
Sexual dysfunction (30-40%) - decreased libido, norgasmia, delayed ejaculation
restlessness
serotonin syndrome (usually seen when combined with MAOIs) = autonomic instability, delirium, hyperreflexia
seizures, hyponatremia
Name two SNRIs
venlafaxine (effexor), duloxetine (cymbalta)
Good SNRI for depression and neuropathic pain, and fibromyalgia?
duloxetine
What advantage does buproprion (Wellbutrin) have over SSRIs? (norepi/dopamine reuptake inhibitor)
Lack of sexual side effects, some efficacy in treatment of ADHD
BUT…can lower seizure threshold, so don’t give to epilepsy or eating disorder patients
ALSO WORKS AS A GOOD SMOKING CESSATION AID
Which antidepressant is useful for treating major depression with insomnia, due to sedative effects?
trazodone!! (serotonin receptor antagonist)
just watch out for priapism
Which antidepressant is useful in treating major depression in patients with significant weight loss and/or insomnia?
mirtazapine (a2-adrenergic receptor antagonist)
MURTAZA LIKES TO SLEEP AND EAT!
Why are TCAs rarely used as first line agents?
LETHALITY IN OVERDOSE, side effect profile, tiration of dosing
Treatment for TCA overdose?
sodium bicarbonate
Name some TCAs
Amitriptyline, imipramine, clomirpamine, doxepin, nrotriptyline
“Anti” side effects of TCAs
Antihistaminic - sedation and weight gain
Anticholinergic - dry mouth, constipation, urinary retention, blurred vision
Antiadrenergic - CARDIOVASCULAR side effects ( orthostati hypotension, dizziness reflex tachcardia, widening QRS QT PR intervals, arrhythmias
3 C’s - cardiotoxicity, convulsions, coma
Mechanism of MAOIs l
prevent inactivation of biogenic amines (NE, serotonin, dopamine, tyramine) by irreversibly inhibiting enzyymes MAO-A and -B.
In what situations are MAOIs better than TCAs for depression?
Depression with atypical features (hypersomnia, increased appetite, interpersonal rejection sensitivity, leaden paralysis,
Name some MAOIs
phenelzine, tranylcypromine, isocarboxazid
Two big side effects to watch out for with MAOIs
serotonin syndrome - usually when SSRIs and MAOIs taken in close proximity due to increased serotonin. Lethargy, restlessness, progress to hyperthermia, hypertonicity, rhabdo.
hypertensive crisis - when MAOIs taken with tyramine-rich foods or sympathomimetics (excessive catecholamines)
Treatment when serotonin syndrome is suspected?
d/c meds, provide supportive care with benzos and serotonin antagonist cyproheptadine
MAO-A preferentially deactivates…
serotonin and norepinephrine (blocking this with MAOI helps with depression)
MAO-B preferentially deactivates…
phenethylamine (acts on tyramine and dopamine along with MAO-A)
Difference between typical and atypicals
typical (aka neuroleptics) - block dopamine (D2 receptors) -> EPS!
atypicals - block dopamine (D2, D4,) and serotonin (2A) receptors (less EPS, more metabolic syndrome); better at treating negative symptoms?
Low potency typicals vs high potency typicals
Compared to high potency typicals, low potency typicals have…
- lower affininty for dopamine receptors, meaning you need a higher dose for effect (not the same as lower efficacy)
- higher incidence of antiadrenergic, -cholinergic, and -histamine side effecs
- lower incidence of EPS and possibly neuroleptic malig syndrome (NMS)
Name one low potency typical
chlorpromazine (thorazine)
Side effects of chlorpromazine
- orthostatic hypotension
- blu-gray skin discoloration
- photosensitivity
Name some high potency typicals
haloperidol (decanoate long acting), fluphenazine, trifluoperazine, pimozide
Compared to low potency typicals, high potency typicals…
- have greater affinity for dopamine -> lower doses needed
- greater risk for EPS, NMS, and tardive dyskinesia
- less sdation, orthostatic hypotension, anticholinergic effects
What are anti-HAM effects and what medication classes typically cause them?
Antihistamine - sedation, weight gain
Antiadrenergic - orthostatic hypotension, cardiac abnormalities, sexual dysfunction
antimuscarinic - dry mouth, constipation, tachycardia, urinary retention, blurry vision, precipitation of narrow-angle glaucoma
typically caused by TCAs (amitriptyline, nortriptyline, doxepin) and low potency antipsychotics
What are the antidopaminergic effects seen in antipsychotics?
- EPS!!! (parkinsonism, akathisia, dystonia)
- hyperprolactinemia - decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea
How does EPS occur?
antipsychotics block dopamine pathways in the NIGROSTRIATUM
Positive symptoms of schizphrenia are treated by the actions of medications in the….pathway
mesolimbic dopamine pathway
Negative symptoms of schizophrenia are thought to occur due to decreased dopaminergic action in the …. pathway
mesocortical
Atypical least likely to cause EPS
clozapine
Most weight friendly atypicals
aripriprazole and ziprasodone
Atypical most likely to cause EPS
risperdone
Besides schizophrenia, what else can atypicals treat?
bipolar, acute mania, adjunct to dpression, PTSD and borderline, tics also
LAST resort antipsychotic for refractory schizophrenia
clozapine
Only antipsychotic known to reduce suicide risk
clozapine
which atypical has risk for agranulocytosis and myocarditis
clozapine
What makes aripiprazole unique compared to other atypicals?
unique mechanism of partial D2 agonism -> can be more activating (akathisia) and less sedating, but less potential for weight gain
Which atypical is associated with qtc prolongation
ziprasidone; must be taken with food
Which atypical can cause increased prolactin
risperdone
Therapeutic and toxic range of lithium
therapeutic - 0.6 - 1.2
toxic - >1.5
What labs to regularly monitor for patient on lithium
lithium level, thyroid , CBC, renal function
Side effects lithium
teratogen (Ebstein’s anomaly), nephrogenic DI, thyroid enlargement (hypo), GI disturbance, weight gain/sedation, benign leukocytosis, ECG changes, fine tremor (altered mental status, seizures, delirium, coma, death)
How long before checking first lithium level?
5 days, then every 2 days after that
Good anticonvulsant treatment for mania with mixed features and rapid cycling bipolar?
carbemazepine!
Most serious side effect of lamotrigine?
steven johnson syndrome
mechanism of benzos?
potentiate GABA in order to reduce anxiety; can treat akathisia
how to treat benzo OD?
flumazenil; but don’t induce withdrawal too quickly
treatment for restless leg syndrome?
dopamine agonists and benzos
what lab to check of restless leg syndrome?
ferritin, iron replacement if low
