Schizophrenia Spectrum & Other Psychotic Disorders- A&P Flashcards
What neurotransmitter systems are associated w/ all forms of psychosis
dopamine
serotonin
glutamate
psychosis
A syndrome (mix of sx) associated w/ many psych disorders but isn’t a specific disorder itself
At minimum hallmark sx= delusions and hallucinations (positive sx)
set of sx in which person’s mental capacity, affective response, and capacity to recognize reality, communicate and realate to others is impaired
delusions
fixed beliefs (often bizzare) that have an inadequate rational basis and cant be changed by rational arguments or evidence in the contrary
hallucinations
perceptual experiences of any sensory modality- esp. auditory= that occur without real external stimulus yet are vivid and clear just like normal perceptions but not under voluntary control
“other” sx of psychosis
disorganized speech or behavior, gross distortions of reality testing (perceptional distortions and motor disturbances)
neg sx= diminished emotional expression and decreased motivation
3 categories of psychosis
paranoid
disorganized/excited
depressive
perceptual distortions
being distressed by hallucinatory voices, hearing voices that accuse blame or threaten punishment, seeing visions, reporting hallucinations of touch taste or odor, or reporting that familiar things and people have changed
motor disturbances
peculiar, rigid postures, overt signs of tension, inappropriate grins/giggles, peculiar repetitive gestures, talking muttering or mumbling to oneself, or glancing around as if hearing voices
paranoid psychosis
paranoid projections, hostile belligerence, and grandiose expansiveness
often in schizophrenia and drug-induced
paranoid projection
preoccupation with delusional beliefs, believing that people are talking about oneself, believing one is being persecuted or being conspired against, and believing people or external forces control ones actions
ex: Parkinson’s disease psychosis common paranoid delusions= belief that one’s spouse is being unfaithful or that spouse or loved ones are stealing from them
hostile belligerence
verbal expression of feelings of hostility, expressing attitude of disdain, manifesting a hostile sullen attitude, manifesting irritability and grouchiness, tending to blame others for problems, expressing feelings of resentment, complaining and finding fault, as well as expressing suspicion of people
seen in schizophrenia and drug-induced psychosis
grandiose expansiveness
exhibiting an attitude of superiority, hearing voices that praise and extol, believing one has unusual powers or is a well know personality, or that one has a divine mission
schizophrenia and manic psychosis
disorganized/excited psychosis
conceptual disorganization, disorientation, and excitement
conceptual disorganization
giving answers that are irrelevant or incoherent, drifting off the subject, using neologisms, or repeating certain words/phrases
seen in any psychotic disorder
disorientation
not knowing where one is, the season of the year, the calendar year, or one’s own age and is common in psychoses associated with dementias and drug-induced
excitement
expressing feelings without restraint, manifesting speech that is hurried, exhibiting an elevated mood, an attitude of superiority, dramatizing oneself or ones sx, manifesting loud and boisterous speech, exhibiting overactivity or restlessness, excess of speech
mania or schizophrenia
depressive psychosis
psychomotor retardation, apathy, anxious self punishment and blame
psychomotor retardation and apathy
slowed speech, indifference to ones future, fixed facial expression, slowed movements, deficiencies in recent memory, manifesting blocking in speech, apathy toward oneself or ones problems, slovenly appearance, low or whispered speech, failure to answer questions
hard to distinguish from neg sx
anxious self punishment and blame
tendency to blame or condemn oneself, anxiety about specific matters, apprehensiveness regarding vague future events, attitude of self deprecation, manifesting depressed mood, expressing feelings of guilt and remorse, preoccupation with suicidal thoughts, unwanted ideas and specific fears, feeling unworthy or sinful, seen often in psychotic depression
3 major hypotheses of psychosis & their neurotransmitter
dopamine (DA)= hyperactive dopamine at D2 receptors in the mesolimbic pathway.
glutamate= NMDA receptor hypofunction
serotonin= 5HT2A receptor hyperfunction in the cortex
dopamine theory of psychosis main characteristics
mechanism= dopamine D2 agonist
hallucinations= auditory
freq. delusions= paranoid
no insightfulness
psychostimulants (cocaine, amphetamine)
glutamate/NMDA theory of psychosis main characteristics
mechanism= NMDA antagonist
hallucinations= visual
freq. delusions= paranoid
no insightfulness
dissociative anesthetics (PCP, ketamine)
serotonin theory of psychosis main characteristics
mechanism= serotonin 5HT2A agonist (lesser extent 5HT2c)
hallucinations= visual
freq. delusions= mystical
yes insightfulness
psychedelics (LSD, psilocybin)
two groups of dopamine receptors
D1-like receptors= excitatory and positively linked to adenylate cyclase. Includes both D1 and D5 receptors
D2-like receptors= inhibitory and negatively linked to adenylate cyclase. Includes D2, D3, D4
is dopamine excitatory or inhibitory
either or; depends on which DA receptor subtype it binds
what dopamine receptors can be located presynaptically and what does this mean
D2 and D3
due to inhibitory actions, can act as auto-receptors aka gatekeepers (a receptor that regulates, via positive or negative feedback processes, the synthesis and/or release of its own physiological ligand) to inhibit further DA release
where in the brain are there very minimal D2/D3 auto-receptors and what does this mean
prefrontal cortex
(mesocortical DA neurons arising from ventral tegmental area (VTA) in brainstem project to prefrontal)
without D2/D3 autoreceptors, DA release is not shit off by this mechanism and is thus freer to diffuse away from the synapse where released. Also have few/any DATs on presynaptic nerve terminals in prefrontal cortex allowing larger diffusion radius of DA away from presynaptic terminals
what postsynaptic receptor is predominant in prefrontal cortex & why is this good
D1
least sensitive to DA & requires higher concentration of DA to be present to be activated
5 classic dopamine pathways in brain
- tuberoinfundibular (hypothalamus to anterior pituitary)
- thalamic
- nigrostriatal (brainstem substantia nigra via axons terminating in the striatum)
- ** mesocortical (DA hypotheses psychosis; cell bodies in CTA to prefrontal cortex)
- ** mesolimbic (DA hypotheses psychosis; DA in VTA of brainstem to ventral striatum in limbic system)
Function of neurons in tuberoinfundibular DA pathway
hypothalamus to anterior pituitary
usually tonically active and inhibit prolactin release
postpartum= decreased activity > increased prolactin to increase lactation
lesions or drugs can disrupt= decreased activity > increased prolactin. SE: galactorrhea (breast enlargement), amenorrhea, sexual dysfunction
pathway maybe preserved in untreated schizophrenia
Function of neurons in thalamic DA pathway
under investigation
may be involved in sleep and arousal mechanisms by gating info passing through the thalamus to the cortex and other brain areas
no evidence of abnormal functioning in schizophrenia
Function of neurons in nigrostriatal DA pathway
brainstem substantia nigra via axons terminating in the striatum
part of extrapyramidal nervous system, control motor movements via connection to thalamus and CSTC loops
Normally BLOCKS motor movements but DA inhibits this action at D2 receptors and says “don’t stop” or “go more”
dopamine stimulates motor movements in both direct/indirect pathways
no evidence of abnormal function in schizophrenia but deficiencies of DA in these pathways cause movement disorders like Parkinson’s & can also cause akathisia (restlessness) & dystonia.
*Same disorders can be replicated w/ drugs that block D2DA receptors in this pathway= EPS. Chronic blockade can lead to tardive dyskinesia
hyperactivity of DA can cause hyperkinetic movement disorders like chorea, dyskinesias and tics (Huntington’s, Tourette syndrome)
Function of neurons in mesolimbic DA pathway
DA in VTA of brainstem to ventral striatum in limbic system
involved in motivation, pleasure, reward (ALL reward/reinforcement) including normal rewards (good food, orgasm), rewards too high (drug-induced), or too low
Too much DA= positive sx psychosis, drug-induced high of substance abuse
Too little DA= anhedonia, apathy, lack of energy (neg sx schizophrenia, unipolar and bipolar depression)
hyperDA in schizophrenia mesostriatal rather than purely mesolimbic because VTA-substantia nigra complex is integrative hub
Function of neurons in mesocortical DA pathway
cell bodies in CTA to prefrontal cortex
dorsolateral prefrontal cortex= cognition and executive functions
ventromedial= emotions and affect
still debate but belief= cognitive and some neg. sx schizophrenia may be due to deficit of DA in mesocortical projections to dorsolateral prefrontal cortex & affective and other neg sx d/t deficit of DA activity in mesocortical projections to ventromedial prefrontal cortex
underactivity/improper functioning= consequence of neurodevelopmental abnormalities in N-methyl-D-aspartate (NMDA) glutamate system
glutamate hypothesis of psychosis and schizophrenia
NMDA subtype of glutamate receptor is hypofunctional at critical synapses at specific site: certain GABA interneurons in prefrontal cortex
can lead to DA hyperactivity= psychosis
d/t neurodevelopmental abnormalities in schizophrenia, neurodegenerative in Alzheimer/dementia, and NMDA receptor blocking actions of drugs like dissociative anesthetics ketamine & PCP
glutamate
major excitatory neurotransmitter (& amino acid= primary use) in CNS, “master switch” of brain since can turn on/excite all CNS neurons
important glutamate pathways
- cortico-brainstem
- cortico-striatal
- hippocampal-striatal (theories link to schizophrenia)
- thalamo-cortical
- cortico-thalamic
- cortico-cortical (direct)
- cortico-cortical (indirect)
serotonin theory of psychosis
hyperactivity/imbalance of serotonin (5HT) activity, particularly at serotonin 5HT2A receptors can result in psychosis
disruption of 5HT functioning leading to positive sx psychosis can be hypothetically d/t neurodevelopmental abnormalities in schizophrenia, neurodegeneration in parkinson’s Alzheimer and other dementia, and drugs like LSD, mescaline, psilocybin
psychoses r/t serotonin= more visual hallucinations
serotonin vs dopamine hallucination
serotonin= visual
dopamine= auditory
what kind of neurotransmitter is serotonin
monoamine neurotransmitter (dopamine & norepinephrine as well) which regulates a brain network that is one of the most targeted by psychotropic meds
what enzyme does the synthesis of 5HT start with
tryptophan
difference between DA and 5HT and their transporters DAT & SERT
not all dopamine neurons contain DATs but all serotonin neurons contain SERTs
serotonin receptors vs those on dopamine and norepinephrine
dopamine & norepinephrine neurons have same receptors at both ends (axon terminals & dendrites, soma) while in serotonin neuron, axon-terminal receptors are different from somatodendritic receptors
presynaptic 5HT1A receptors
negative feedback receptors/inhibitory
detect serotonin released from dendrites which causes slowing of neuronal impulse flow through neuron and reduction of serotonin release from axon terminal
downstream effect can be excitatory
presynaptic 5HT2B receptors
feed forward receptors
activate serotonin neuron to cause more impulse flow and increased serotonin release from presynaptic nerve terminals
presynaptic 5HT1B/D receptors
aka terminal autoreceptor
negative feedback autoreceptors to detect presence of 5HT; causes blockade of 5HT release
serotonin inhibits release of dopamine, norepinephrine, histamine, and acetylcholine at 5HT1B receptors
postsynaptic serotonin regulation of other neurotransmitters
each neurotransmitter controls its own synthesis/release as well as actions of others via postsynaptic actions and networks of brain circuits
they act synaptically and trans-synaptically
does serotonin excite or inhibit
either or; depends upon the serotonin receptor subtype where it’s interacting and whether the postsynaptic neuron itself releases glutamate (excitatory) or GABA (inhibitory)
norepinephrine, dopamine, histamine, and acetylcholine can also receive direct input from serotonin or indirect through glutamate or GABA
*drugs acting on serotonin also have downstream effect on all other neurotransmitters
5HT2a receptors
excitatory but can be excitatory or inhibitory depending on where in brain
5HT2a antagonists= tx psychosis & mood disorders
agonists= hallucinogens
5HT2c receptors
excitatory neurons on GABA interneurons that generally inhibit release of downstream neurotransmitters
5HT2x agonists= tx obesity
antagonists= tx psychosis/mood disorders
5HT3 receptors
in brainstem chemoreceptor trigger zone outside of blood-brain barrier known for role in centrally mediated n/v
at other locations (especially prefrontal cortex) located on GABA interneuron= excitatory on GABA & therefore inhibit wherever GABA interneurons go like 5HT2c receptors
*inhibit acetylcholine & norepinephrine at cortical level
5HT3 antagonists enhance release of acetylcholine & norepinephrine. Reduces glutamate which in turn regulates serotonin (will decrease when normally excites d/t feedback loop)
5HT6 receptors
postsynaptic, key regulators of release of acetylcholine release and control of cognitive processes
blocking improves learning/memory
5HT7 receptors
postsynaptic, excitatory, localized on inhibitory GABA interneurons
inhibit release of downstream neurotransmitters especially glutamate at cortical level
regulate serotonin release at level of brainstem raphe
5HT7 antagonists= tx psychosis & mood
serotonin & dopamine in parkinsons
loss dopamine nerve terminals in motor striatum of niagrostriatal pathway= motor sx
loss of serotonin nerve terminals in prefrontal and visual cortex= up-regulation and too many 5HT2A receptors in cortex > imbalance in excitatory action on glutamate > psychosis
5HT2a antagonists block psychosis in parkinsons
serotonin in dementia
accumulation of plaques, tangles, & Lewy bodies, damage from strokes, knocks out cortical neurons > lack of inhibition of glutamate neurons; if GABA can’t counter= psychosis
selective 5HT2a antagonist decrease psychosis in dementia
link between psychosis hypotheses of serotonin hyperfunction at 5HT2a receptors and dopamine hypothesis
excessive 5HT2a stimulation at glutamatergic pyramidal neurons leads to dopamine hyperactivity & NMDA hypofunction > psychosis
length of time of sx to = schizophrenia
disturbance that lasts 6 months or more including at least 1 month of positive sx (delusions, hallucinations, disorganized speech, grossly disorganized/catatonic behavior) or neg sx
negative sx schizophrenia
- alogia- dysfunction in communication; restrictions in fluency/productivity of thought/speech
- affective blunting/flattening- restrictions in range/intensity of emotional expression
- asociality- reduced social drive/interaction
- anhedonia- reduced ability to experience pleasure
- avolition- reduced desire, motivation, or persistence; restrictions in initiation of goal-directed behavior
*more but these are the 5 classic types
can be before dx and neg sx can persist between psychotic episodes
prodromal neg sx schizophrenia
neg sx can be subsyndromal occurring before onset of full syndrome of schizophrenia, Important to detect/monitor over time in high-risk pt so tx can start at first sign psychosis
neg sx schizophrenia based solely on observation
reduced speech, poor grooming, limited eye contact, reduced emotional responsiveness, reduced interest, reduced social drive
what other (non diagnostic) sx of schizophrenia are there besides neg/pos sx
cognitive, affective, and aggressive sx
cognitive sx schizophrenia
impaired attention/information processing, manifesting as difficulties w/ verbal fluency, problems with serial learning, and impairment in vigilance for executive functioning
begin before onset first psychotic illness, manifest as lower IQ scored. Worsen during prodrome before full blown psychosis & progressively worsens throughout disease
*no short term memory disturbance; issues with executive functioning
affective sx schizophrenia
depressed mood, anxious, guilt, tension, irritability, worry
difficult to distinguish from neg sx and from comorbid mood/anxiety disorder
need to be treated; if not relieve dby drugs for positive sx psychosis, consider drugs to tx anxiety/depression to tx sx AND prevent suicide; will not be effective if sx are true negative sx
aggressive sx schizophrenia
ivert hostility, assaultiveness, physical abuse, violence, verbally abusive behaviors, sexually acting out, self injurious, arson/property damage
different from agitation because intentional harm
not common but more common than general population; stigma; more likely to experience violence against them
categories of violence in institutionalized schizophrenia pt pg. 148
impulsive (most common in institutions; precipitated by provocation as response to stress associated w/ neg emotions anger/fear)
predatory/organized (planned behavior; result of frustration/response to threat; common in psychopathic or antisocial personalities; associated w/ criminogenic more than psychotic sx)
psychotic (least common in institutions; positive sx psychosis)
genetics & schizophrenia
genes don’t = mental illness but do code for proteins and epigenetic regulators
Genes must conspire amongst themselves and environmental stressors to = mental illness
*genes= risk not cause per se
environmental stressors for schizophrenia
cannabis, emotionally traumatic experiences, sleep deprivation, being a migrant, etc.
environment puts load on neural circuits where risk genes expressed and cause circuits to malfunction under pressure. Same stressors can cause normal genes to malfunction > neuroplasticity and synaptogenesis
only half of all identical twins of pts w/ schizophrenia also have it
epigenetics
the study of how your behaviors and environment can cause changes that affect the way your genes work
normal genes can= mental illness if expressed when should be silenced or vice versa
neurodevelopment & schizophrenia
a bunch of neurons are made out of stem cells at conception but only a minority selected for inclusion in developing brain; abnormalities can occur w/ neuronal selection process leading to neurodevelopmental disorders
New neurons cont. to form, differentiation and myelination, synaptogenesis cont. throughout life & any disruption= neurodevelopmental illness
schizophrenia= neurodevelopmental process of synaptogensis/brain restructuring gone awry
What’s theory as to why schizophrenia manifests in adolescence
brain restructuring occur throughout life but most active during late childhood/adolescence (aka competitive elimination)
only 1/2 to 2/3 synapses from childhood left for adulthood
so elimination of compensatory critical synapses or formation of abnormal “weak” synapses could cause inefficient info processing in its circuit causing sx schizophrenia
neurodegeneration in schizophrenia
progressive downhill course
strengthening/weakening of synapses continues to occur throughout lifetime based off what’s used or not. “Use it or lose it”
abnormal synaptogenesis prevents normal synapses from functioning even if using and/or the wrong synapses are used/strengthened in schizophrenia
loss of brain tissue with recurrent episodes of psychosis
disorders where psychosis is defining feature
schizophrenia
substance/medication induced psychotic disorders
schizophreniform disorder
delusional disorder
brief psychotic disorder
shared psychotic disorder
psychotic disorder due to another medical condition
childhood psychotic disorder
disorders where psychosis is associated feature (not defining)
mania
depression
cognitive disorders
Alzheimer/other dementia
Parkinson’s
are sx of schizophrenia unique to schizophrenia
NO
several other illnesses can share same 5 sx dimensions
what is thought to lead to parkison’s disease psychosis (PDS)
accumulation of Lewy bodies in cerebral cortex and in serotonin cell bodies in midbrain raphe
why is it important to distinguish agitation from psychosis in dementia
can be difficult but neuronal pathways are different and so are treatments
neurolepsis
extreme slowness, absence of motor movements in animals; human counterpart= drugs that cause secondary neg sx: psychomotor slowing, emotional quieting, affective indifference
caused by blocking D2 receptors
what causes secondary neg sx
targeting dopamine D2 receptors in mesolimbic/mesostriatal and mesocortical pathways
what dopamine pathway causes hyperprolactemia w/ D2 antagonists
D2 receptors in the tuberoinfundibular dopamine D2 receptors
which causes gynecomastia, galactorrhea, amenorrhea therefore infertility, rapid demineralization of bones, sexual dysfunction, weight gain
what dopamine pathway causes motor side effets w/ D2 antagonists
targeting nigrostriatal dopamine D2 receptors
same pathway that degenerates in Parkinson’s
acute: drug induced parkinsonism (DIP)- tremor, muscular ridigity, bradykinesia, akinesia
EPS is old-fashioned/imprecise term for motor SE bc different sx= diff presentation/tx
chronic: tardive dyskinesia
tx drug-induced parkinsonism (DIP)
anticholinergics by blocking muscarinic cholinergic receptors, exploiting normal balance between dopamine and acetylcholine in striatum because dopamine neurons in nigrostriatal motor pathway make postsynaptic connections on cholinergic interneurons
anticholinergics block downstream release of acetylcholine
what causes DIP with D2 antagonists
dopamine normally blocks acetylcholine from postsynaptic nigrostriatal cholinergic neurons but D2 blockers cause acetylcholine release > excitation postsynaptic muscarinic cholinergic receptors on GABAergic neurons > movements/sx DIP
considerations for anticholinergics to treat DIP
peripheral and central SE
many drugs for psychosis also have anticholinergic SEs
concern for cognitive functioning and paralytic ileus
seek alternatives like drugs for psychosis w/o antichol. properties
alternative to anticholinergic for DIP
amantadine
can also help w/ TD and levodopa-induced dyskinesias
drug-induced acute dystonia
d2 blockers esp w/o serotonergic/anticholinergic properties
intermittent spasmodic or sustained involuntary contraction of muscles in face neck trunk pelvis extremities eyes
need IM anticholinergic
chronic late-onset can lead to TD & require diff tx
akathisia
syndrome of motor restlessness often seen with D2 blockers
subjective (inner restlessness, mental unease, dysphoria) objective (restless movements mostly lower-limb- pacing, rocking when stnading)
sometimes drug-induced sometimes d/t psychiatric disorder
tx with beta adrenergic blockers or BZOs; serotonin 2A antagonists also
neuroleptic malignant syndrome
rare fatal complication D2 blocker
extreme muscle rigidity, high fevers, coma, death
medical emergency > STOP d2 blocker > muscle relaxer (dantrolene or dopamine agonsists) intensive medical tx
conventional D2 antagonists (first generation antipsychotics)
not first line, use if don’t respond to newer drugs for psychosis
*agitation
psychiatric emergency
For agitated patients not willing or able to take oral medications, IM medications such as Olanzepine
and Haldol can be used
*when to use IM antipsychotics like olanzapine or haldol
For agitated patients not willing or able to take oral medications, IM medications such as Olanzepine
and Haldol can be used
*what should be administered with IM first generation antipsychotic like Haldol
IM haloperidol should be administered with benztropine or diphenhydramine to reduce the risk of severe EPS or dystonia.
severely agitated patients, we suggest using a benzodiazepine in combination with the antipsychotic
(e.g. Haldol + Lorazepam + Cogentin.
*what pathway do first generation antipsychotics block dopamine
Mesocortical
*main SE second generation antipsychotics
Can cause EPS but at a lower risk
* ↓ incidence of Tardive dyskinesia
* Metabolic side effects : Weight gain, HLD,
hyperglycemia, Diabetes, HTN, Cardiac and
respiratory S/E
* Some Antihistaminic, antiadrenergic and
antimuscarinic effects
* Elevated Liver function tests (LFTs)- check yearly
* QTC Prolongation
*time it take second generation antipsychotics to work
6-8 weeks
*main SE of typical antipsychotics
- High antiadrenergic, anticholinergic and antihistaminic s/e (e.g. sedation, weight gain)
- Elevated liver enzymes, jaundice
- Seizures – all antipsychotics lower the seizure threshold
- Orthostatic hypotension
- QTC prolongation – obtain baseline EKG
- Sexual dysfunction
- Rashes, photosensitivity
- Elevated liver enzymes, EPS (Akathisia, dystonia, Parkinsonism)
- **Hyperprolactinemia (decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea)
- Tardive dyskinesia
- Neuroleptic Malignant Syndrome (FALTERED)
*most effective tx akathisia (psychomotor restlessness)
β-adrenergic receptor antagonists (beta-blockers)
*should you co-order meds with antipsychotics to prevent EPS? Why/why no?
Do not co-prescribe drugs in efforts to prevent EPS. Associated w/ high anticholinergic side effects
If necessary, anticholinergics should be prescribed at the lowest dose possible.
*3 types EPS, sx, duration
Acute Dystonia, Akathisia, & Pseudo-Parkinsonism
*Acute dystonia sx/tx/when develops
- Sudden onset
- Fixed/Sustained painful
contraction of the neck muscles
(torticollis), tongue, eyes
(oculogyric crisis) - Can be life threatening if it affects
airway
Txt: Cogentin, Artane, Benadryl,
Benzos- Ativan
* Lower dose if possible
Hours to days
*Akathisia sx/tx/when develops
- Internal and external restlessness
- Subjective anxiety, restlessness,
inability to remain still - Constant need to pace or walk
Txt: Drug of choice= Beta blocker
(Propranolol), Benzos (Klonopin,
Ativan)
* Lower dose if possible
Days to months
*pseudo-parkinsonism sx/tx/when develops
Bradykinesia(shuffled gait),
masklike face, cogwheel rigidity,
pill-rolling tremor
- Txt: Cogentin, Artane, Benadryl,
Symmetrel (Amantadine) - Lower dose if possible
Days to months
*How many D2 receptors need to be blocked to cause EPS
Antipsychotics must occupy more than 80% of D2 receptors to cause EPS
*Clozapine(Clozaril)/Fazaclo (ODT)
Used to treat refractory schizophrenia(i.e., treatment
resistant)
- *****Only antipsychotic shown to decrease SI risk
-Less likely to cause TD
- Weight gain is most prominent
-More anticholinergic s/e- tachycardia, constipation etc.
- **Hypersalivation (sialorrhea) occurs in 30-80%
- Agranulocytosis( highest first 3 months of treatment)=
Monitor WBC and Absolute neutrophil count (ANC)
-D/C med if ANC is <1.5 (1500)
-ANC
Off label use
- Treatment resistant bipolar disorder
- Dementia
- Parkinson’s related psychosis or agitation
Common adverse effects
- HTN
- Hypotension
- Tachycardia
- Dislipidemia
- Weight gain
- Constipation
- Sialorrhea
- Drowsiness/sedation
*Only antipsychotic shown to decrease SI risk
Clozapine(Clozaril)*
*Management of Sialorrhea
- Chew sugarless gum
- Place towel over pillow especially if nocturnal sialorrhea is a
problem - Med: Glycopyrrolate (Robinul) -fewer Anticholinergic side
effects) - Benztropine, Artane etc.
*What med for parkinson-related psychosis
Pimavanserin =Nuplazid =Used in Parkinson’s related psychosis (newer med)
first-in-class atypical antipsychotic that does not induce clinically significant antagonism of dopaminergic, adrenergic, histaminergic, or muscarinic receptors.
*considerations for metabolic syndrome r/t antipsychotics
H1 receptor antagonism is associated with sedation and weight gain
❖Weight gain – Metformin can be used to reduce or prevent
❖Hyperlipidemia
❖Hyperglycemia
*** > Monitor Baseline and ongoing(i.e. 3 months etc.)
* Weight
* Waist circumference
* BP
* HbA1c
* Fasting lipids
NOTE: For patients established on antipsychotic medications, yearly labs should be considered.
see page 15 of study guide for table w/ monitoring freq. for metabolic syndrome with olanzapine, quetiapine, & clozapine
*Characteristics of metabolic syndrome
- Abdominal obesity
- Elevated triglycerides
- Low HDL levels
- BP higher than 135/85 mm Hg
Alogia, Anhedonia, Avolition and cognitive symptoms =
negative sx
Delusions, hallucinations, hostility, grandiosity = ___
positive sx
This class is associated with fewer neurological side effects and effective
for both positive and negative symptoms
second generation antipsychotics
This class is effective for only positive symptoms and can in fact worsen
negative symptoms due to decrease DA in the Mesocortical pathway
first generation antipsychotics
Associated with metabolic side effects =
atypical/second generation
What are the metabolic side effects associated with Atypical
antipsychotics
hyperglycemia, weight gain, risk metabolic syndrome, elevated triglycerides
Includes medications such as Haloperidol, Chlorpromazine, Fluphenazine, Perphenazine=
first generation antipsychotics
Medications for acute agitation or psychosis=
BZO
FGA reduce dopamine transmission by blocking _______________ receptors.
D2
SGA block both ______________ and ________________ receptors
D2 & 5HT2a
H1 blockade leads to symptoms of __________________ and __________
?
Safest and best tolerated anticonvulsant for patients taking clozapine
who experience dose related seizures =_
?
Less incidence of antiadrenergic, anticholinergic and antihistaminic side
effects but greater EPS =__________________________________________
