Antipsychotic Agents & Lithium Flashcards
What are the essentials of dx for schizophrenia? (6)
Social withdrawal
Loose thought associations
Autistic absorption in inner thoughts
Auditory hallucinations
Delusions
Sx ≥ 6 months duration
What plays a role in schizophrenia?
Serotonin: 5-HT2A receptor blockade
Dopamine: blockade of postsynaptic D2 receptors
Glutamate: hypofunction of NMDA receptors
Out of all of the first generation antipsychotics (FGAs), which causes the most wt gain?
Chlorpromazine
Which FGA causes significant QT prolongation?
Thioridazine
Which 2nd-gen antipsychotics should be taken w/ food? How many calories are required?
Lurasidone: ≥ 350 calories
Ziprasidone: ≥ 500 calories
Which 2nd generation antipsychotics cause wt gain?
Olanzapine (avoid in 1st antipsychotic episode)
Quetiapine (dose related)
All antipsychotics should be tapered slowly before discontinuation to avoid cholinergic rebound.
Which drug is this especially important for?
Clozapine
What is the MOA of lithium?
Increase the volume of brain structures involved in emotional regulation
S/a the prefrontal cortex, hippocampus, & amygdala (reflecting its neuroprotective effects)
What does lithium do at a neuronal level?
Reduces excitatory (dopamine & glutamate) but increases inhibitory (GABA) neurotransmission
Which 2 drug classes cause decreased clearance of lithium?
Thiazides & NSAIDs
What are ADEs of lithium?
Tremor
Edema
Hypothyroidism*
Renal dysfunction
Pregnancy category D*
What are 3 newer drugs used for bipolar disorder?
Carbamazepine
Lamotrigine
Valproic acid
What is an ADE of lamotrigine (1 of the newer drugs for bipolar d/o)?
Rash*
How do you initially treat hypomania?
Initiate mood stabilizer: lithium, valproate, carbamazepine, or SGAs
If initial tx for hypomania fails, what is your next step?
Consider 2 drug combo:
Lithium + an anticonvulsant or SGA
Anticonvulsant + another anticonvulsant or SGA
How do you initially treat mania?
2 or 3 drug combos + a benzo &/or antipsychotic for short term adjunctive tx of agitation or insomnia
If initial tx for mania fails, what is your next step?
Consider 3 drug combo:
Lithium + anticonvulsant + antipsychotic
Anticonvulsant + another anticonvulsant + antipsychotic
If 3-drug therapy fails in the tx of mania, what is your next step?
Consider ECT or add clozapine
How do you initially treat a mild to moderate depressive episode?
Initiate mood-stabilizer: lithium, quetiapine, lurasidone
How do you initially treat a severe depressive episode?
Optimize current mood stabilizer or initiate: lithium, quetiapine, or lurasidone
If initial treatment for severe depressive episode fails, what is your next step?
Consider carbamazepine or adding antidepressant
If second form of tx fails for severe depressive episode, what is the 3rd step?
Consider 3-drug combo:
Lithium + lamotrigine + antidepressant
Lithium + quetiapine + antidepressant
If 3rd form of tx fails for severe depressive episode, what is the 4th step?
Consider ECT
What are the 4 dopaminergic pathways?
Mesolimbic: + sx
Mesocortical: - sx
Nigrostriatal: EPS & tardive dyskinesia
Tuberophypophyseal: hyperprolactinemia
What are overall characteristics of antipsychotics?
Well absorbed
Lipid soluble
Bound to plasma proteins
Metabolized by liver enzymes, renally eliminated
Long 1/2 lives
What are relative side effects of antipsychotics?
Sedation EPS Anticholinergic Orthostasis Wt gain Prolactin
What agents are used to treat EPS?
Antimuscarinics Antihistaminic Dopamine agonist Benzos B-blockers
How long should you continue antipsychotic therapy after remission of the 1st episode?
At least 12 months
Many recommend tx for at least 5 yrs
How do you switch from 1 antipsychotic to another?
Taper & discontinue the 1st over at least 1-2 wks while the 2nd antipsychotic is initiated & tapered upward
What is lithium used for?
Manic phase of bipolar d/o
Prevents mood swings
What 2 classes of meds may need to be included during the initiation of lithium or valproic acid for bipolar d/o?
Antipsychotics & benzos due to slow onset of lithium & valproic acid
What can precipitate mania in bipolar pts?
Monotherapy w/ antidepressants
What are ADEs of carbamazepine (1 of the newer drugs for bipolar d/o)?
Hematotoxicity & induction of drug metabolism
What are ADEs of valproic acid (1 of the new drugs for bipolar d/o)?
Hepatic dysfunction
Wt gain
Inhibition of drug metabolism
