Chapter 15: Schizophrenia and Bipolar Affective Disorder Flashcards
what are the 2 categories of antipsychotics?
typical / 1st generation antipsychotics and atypical / second generation antipsychotics
mania or a manic episode is characterized by:
enhanced mood, increased activity, grandiosity (increased self-esteem), racing thoughts and decreased need for sleep
as mania persists, it may develop into ___ as the person loses sleep and mood may dip
psychosis
patients with bipolar affective disorder experience periods of ___ and periods of ___
mania and depression
what is psychosis?
altered state of mind with the inability to distinguish real from delusions or hallucinations and disorganized or paranoid thoughts may also be present
___ is the most common clinical presentation of psychosis?
schizophrenia
how does psychosis present in schizophrenia?
duration and severity may vary, but usually psychosis is not continuous and patients may have long periods w/o symptoms and lead normal lives
there is a strong ___ link in schizophrenia and most patients w/ the disease also have a ___ who has the disease
genetic; relative
schizophrenia occurs in ~__% of the population
1
___ psychosis can occur in response to severe illness or drug use
acute
___ drugs are used to treat conditions where psychosis occurs
antipsychotic
the 2 important NT involved in schizophrenia are __ and __
DA and 5-HT
the DA hypothesis of schizophrenia proposes:
excess DA in certain brain regions causes the development of positive symptoms of schizophrenia
the serotonin hypothesis of schizophrenia proposes:
positive and negative symptoms of schizophrenia is caused by increased signalling by the 5-HT receptors which modulate levels of DA in many brain regions
the glutamate hypothesis of schizophrenia proposes:
modified glutamate signalling contributes to dystregualtion of neuronal circuits
what is the general consensus around the hypotheses of schizophrenia?
that serotonin and DA are imbalanced (not linked significantly to glutamate)
what are 2 important pathways to consider the roles of 5-HT and DA in schizophrenia?
- mesolimbic
2. mesocortical
in schizophrenia, in the mesocortical pathway, ___DA is released, causing the symptoms of: ______ (which are the ____(+/-) symptoms of schizophrenia
less; apathy, social withdrawal, reduced interest and motivation. Negative symptoms
in schizophrenia, in the mesolimbic pathway, ___DA is released into the nucleus accumbens and activates ___ receptors. This causes the ____(+/-) symptoms of schizophrenia
increases; D2; +
what are the + symptoms of schizophrenia that are caused by excess DA release into the nuclei accumbens?
delusions and hallucinations
in the mesolimbic pathway, excess DA is released into the ___ (brain region)
nucleus accumbens
the mesocortical pathways can ___(directly/indirectly) influence mesolimbic pathways
indirectly
reduced DA input into mesocortical neurons can result in ___ of the mesolimbic circuits
disinhibition
what brain region is commonly associated with the positive symptoms of schizophrenia?
nucleus accumbens
the ____ is the site of dopaminergic synapses from the mesolimbic pathway
nucleus accumbens
what DA type receptor is highly found in the nucleus accumbens?
D2
blocking ___receptors is the primary MOA of typical antipsychotics
D2
D2 receptors are expressed in brain regions other than the nucleus accumbens, what is the issue with this interns of antipsychotic use?
attempted to lower DA signalling in the mesolimbic pathway may also affect other pathways
the nigrostriatal pathway goes from the ___ to the ___
substance nigra to the striatum
antipsychotics acting on the D2 receptors along the nigrostriatal pathway leads to what types of ADR?
Parkinson’s-like movements
the tuberoinfundibulnar pathway goes from the ___ to the ___
hypothalamus to pituitary
the tuberinfundibular pathway is involved in regulation of ___hormones
endocrine
blocking D2 receptors in the pituitary can lead to increase in ___hormone which can cause ____effects
prolactin; low libido, infertility, enlargement of breast tissue
most ___ antipsychotics also act in the striatum, causing Parkinson’s like effects, often called ___ symptoms
typical; extrapyramidal
the ADR of typical antipsychotics are often results in ___to medication regimens
poor adherence
the first antipsychotic to be used clinically was ___ in the 1950’s
chlorpromazine
chlorpromazine has significant ____effects when administered to agitated patients, which lead to its wide-spread institutional use in the ‘50’s and ‘60’s
calming
chlorpromazine was the first ___ antipsychotic agent in use
typical
what happened that made the DA theory of schizophrenia really take off?
it was found that chlorpromazine blocked DA receptor s
the ability of an agent to block ___receptor and produce ___effecst are the primary characteristic of a typical antipsychotic
DA; psychosis
the primary action of typical antipsychotics is to block ___
DA recepts
how does blocking the DA receptors in the nucleus accumbens help schizophrenia?
reduces DA signalling, which alleviates hallucinations and delusions
Haloperidol is an example of a ___ type drug
typical antipsychotic
Haloperidol is typically used bc of its ability in ___ (what is the formulation?)
long-acting depot formulation (IM injections)
why is an IM injection of Haloperidol beneficial?
makes admin easier for patients who forget or are non-aderhent with medications
which has a higher potency as a D2 receptor antagonist, Haloperidol or chlorpromazine?
Haloperidol
how often is an IM injection of Haloperidol given?
monthly
typical antipsychotics are unique in that their clinical potency is directly proportional to their ____
binding affinity at the D2 receptor
the potency of an antipsychotic used to treat schizophrenia is measured by its ability to __
resolve the positive symptoms of schizophrenia
the potency is measured by what phamacokinetics term?
ED50
affinity is measured by what pharmacokinetics term?
K
on a graph of D2 R affinity vs Potency, chlorpromazine and haloperidol both land very close to the line on the graph, meaning ___
their potency is directly related to their binding affinity
in typical antipsychotics, drugs with a higher D2 receptor affinity will have a ____potency
higher (lower ED50)
do atypical agents such as clozapine follow the same affinity/potency relationship as typical antipsychotics?
no
Clozapine’s (an atypical antipsychotic) potency is much higher than would be expected based on its affinity for the D2 receptor, what does this mean in terms of hypotheses for schizophrenia?
it means dopamine is not the only contributor
the serotonin hypothesis if schizophrenia suggests that blocking ___ receptors will increase ___ release in the cortex which is beneficial for the negative symptoms of schizophrenia a
5-HT; DA
the serotonin hypothesis involves blocking 5HT receptors in what part of the brain?
mesocortical pathway
atypical antipsychotics have more activity at ___ receptor that __ receptors
5HT; DA
t/f the atypical antipsychotics do still have some D2 blocking which helps alleviate the positive symptoms of schizophrenia
t
atypical antipsychotics restore ___ inputs into the mesolimbic pathway
inhibitory
clozapine and Olanzapine are examples of ____antipsychotics that block both __ and ___ receptors
atypical; 5HT and DA
the use of the clozapine and olanzapine results in management of both ___ and ___
+ and - symptoms of schizophrenia
MOA of Aripiprazole
atypical antipsychotic which is a 5HT antagonist and D2 partial agonist
t/f partial agonists produce some agonist activity, but to a lesser extent
t
what is the benefit of Aripiprazole being a partial agonist of D2?
when the partial agonist binds, the full agonist (DA) cannot bind, so competitive antagonism happens, but some physiologic effect is maintained, This reduces the effects that lead to Parkinson’s like ADR
many ADR common to most antipsychotics are related to ___
blocking D2 in unintended regions of the brain
one of the most common and most treatment-limiting effects of antipsychotics is ____ effects that occur when D2 is blocked in the striatum
extrapyramidal (EPS) which cause Parkinson-like effects
antipsychotics that have lower ____ to the d2 receptor cause fewer EPS effects and may be better tolerated
affinity
what branch of antipsychotics has reduced affinity for D2 receptors?
atypical
aside from EPS effects, what are some ADR associated with activating off-target D2 receptor?
sedations, restlessness, elevated prolactin which can lead to sexual dysfunction and infertility
off-target effects of antipsychotics can be predicted based on their ____ profiles at off-target receptors
binding
t/f there do not seems to be patterns between typical and atypical antipsychotics in terms of binding profiles
t
the most common ADR are ___ and ___ with drugs that also block histamine receptors
sedation and weight gain
t/f anticholinergic effects are common with several antipsychotics
t
hypotension may occur when drugs are used that block ___ receptors
alpha 1 adrenergic
what off-target receptors can chlorpromazine bind to?
alpha 1, H1 and muscarinic
what off-target receptors can haloperidol bind to?
alpha 1
what off-target receptors can clozapine bind to?
alpha 1, H1, muscarinic
what off-target receptors can olanzapine bind to?
H1
what off-target receptors can aripiprazole bind to?
alpha 1, H1
lithium has been used for many years as a ___
mood stabilizer
lithium is used in the management of _____
bipolar affective disorder
t/f the precise mechanism of how lithium stabilzes mood is unknown
t
lithium can interact with ion ___ and ___. Why?
channels and transporters; bc it is a small monovalent cation like Na and K
the proposed therapeutic mechanism of lithium involves the depletion of intracellular ____which influences many neuronal signalling pathway and also inhibiting ___which is involved in energy usage of cells
inositol; glycogen synthase kinase
lithium is a classic example of a drug with a ___ therapeutic window
narrow
too much lithium can lead to significant toxicity, including ___
life-threatening arrhythmias
the neuronal ADRs of lithium are likely extensions of their therapeutic effects; by modifying neuronal function, ___ and ___ can occur
tremors and drowsiness
at high levels of lithium, ___ can occur and in severe toxicity: ___ and ___ are possible
delirium, coma and death
some ADR of lithium are related to its structural similarity to ___
sodium and potassium
lithium’s ability to influence water and electrolyte balance in the kidneys can cause __ and ___
water retention and weight gain
what are some cardiovascular effects that can occur wit high lithium doses? what is the severity?
tachycardia, hypotension, arrhythmias (life-threatening)
what is the therapeutic range for lithium (in mEq/L)?
0.6-1.4
t/f the ADR and need for constant monitoring with lithium use have made other antipsychotics and antidepressants more popular
treu
