unclear. possibilities include affecting second messengers/altering intracellular signaling, neuroprotective/antiapoptitic, alteration of neurotransmitter metabolism, or alteration of sodium transport across membrane of nerve/muscle cells.
narrow therapeutic index. takes 1-3 weeks to start working (like pretty much all other psych drugs).
renal/CV disease, dehydration/sodium depletion, pregnancy/breastfeeding (Cat D). black box warning for lithium toxicity (treat only if you can monitor it).
lithium + diuretics (both Na and Li are monovalent cations, so both get reabsorbed, can lead to toxicity).
lithium side effects
weight gain, nephrotoxicity, tremor (can be helped by co-prescribing propranolol).
Antagonize D2 receptors. In the mesolimbic tract, this results in a relief of psychosis (however in the nigrostriatal tract, this can result in movement disorder SE).
highly lipophilic. haloperidol, chlorpromazine, and thioridazine have active metabolites. Injectables: IM formulations faster acting (onset <1h), depot formulations are long-acting (duration of 3 weeks).
psychosis. haloperidol acute agitaition/delerium/mania. haloperidol and pimozide Tourette's. haloperidol and chlorpromazine intractable hiccups. chlorpromazine and prochlorperazine nausea and vomiting (immediate).
not approved for dementia-related psychosis (black box). thioridazine and droperidol black box for proarrhythmic effects (QT prolongation).
FGA side effects
EPS and hyperprolactemia as a result of D2 anatagonism. Antagonism of other receptors includes muscarinic (dry mouth, constipation, blurred vision), histamine (sedation, haloperidol is the least sedating), alpha1 (hypotension).
parkinsonian (bradykinesia, rigidity, resting tremor), dystonia (muscular spasms), akathisia (feeling of motor restlessness), tardive dyskinesia (involuntary muscle movements, sometimes irreversible).
Antagonize dopamine and serotonin receptors (specifically 5HT2A). Better at treating "negative" symptoms than FGAs.
schizophrenia, bipolar, depression (adjunct). clozapine resistant schizophrenia or suicide prevention. rispiradone irritability in autistic kids. HOWEVER, about 60% of their use is off-label (no effect on insomnia, even though it is frequently used there).
clozapine black box warning for agranulocytosis (restricted distribution, CBC/ANC needed to dispense, 4wks at a time). antipsychotics in general increase stroke and mortality risk in elderly dementia pts, so save them for the really bad ones.
SGA side effects
weight gain/metabolic effects (worse c olanzapine, less so c aripiprazole), QT prolongation (worse c geodon). Lower likelihood of EPS than the FGAs (blockade of serotonin may lead to more dopamine release?). aripiprazole has the best tolerability profile, clozapine has the worst.
schizophrenia 150-750mg/d div BID-TID; bipolar 200-400mg/d div BID
schizophrenia 10-15mg qd
schizophrenia 10mg qd
aripiprazole is available as an injection (acute tx of agitation associated c schizophrenia/bipolar).
olanzapine depot (Zyprexa Relprevv) has a black box warning for post-injection delerium/sedation syndrome, pts should be observed for 3 hrs after each injection (restricted distribution).
Enhances the effects of GABA at the GABA-A receptor. This has a sedative, hypnotic, and anxiolytic effect.
non-BZ hypnotics MOA
also work via enhancement of GABA, however they bind to a different subunit than the traditional benzos. The exception in ramelteon, which is a melatonin receptor agonist
short acting BZ
triazolam (most likely to develop dependence/withdrawal sx)
intermediate acting BZ
alprazolam and lorazepam
long acting BZ
quick onset BZ
alprazolam and diazepam (most likely to be abused)
best BZ for the liver
lorazepam, oxazepam, temazepam
sedation, insomnia, acute seizure tx, EtOH withdrawal, muscle relaxation. best for short-term use.
pregnancy/lactation (Cat D). new black box for strange sleep-related behavior and severe allergic reactions (as early as the first dose).
Benzos side effects
respiratory depression, amnesia (may be beneficial).
anxiety 0.25-0.5mg TID
panic disorder 0.5-2mg BID
anxiety 2-10mg BID-QID
anxiety 2-6mg/d div BID-TID
CNS stimulants MOA
increase levels of dopamine and norepinephrine in the synapse by enhancing chatecholamine release, inhibiting reuptake, and inhibiting MAO. Increased dopamine in prefrontal cortex thought to be the reason it helps in ADHD, however increased dopamine in the nucleus accumbens leads to euphoria and helps explain why they are abused.