What are the 3 symptom dimensions of schizophrenia?
positive, negative, and cognitive
What are the positive symptoms of schizophrenia?
Distortions in language
Abnormal behavioral monitoring
What are the types of abnormal behavioral monitoring?
What are two other things that can induce psychosis?
Medical disorders (eg. Huntingtons, DLB, etc.) Drugs
What types of drugs can induce psychosis?
anticholinergics(e.g. L-DOPA, Benadryl)
What are the negative symptoms of schizophrenia?
Affect flattening Alogia Avolition Anhedonia Asociality
What are the cognitive symptoms of schizophrenia?
Thought disorder including incoherence, loose associations, neologisms
Impaired attention/information processing
Impaired verbal fluency
Impaired executive functioning
Aggressive and hostile symptoms
Depressive and anxious symptoms
What is the most studied DA receptor?
What terminates DA action?
Reuptake pumps (transporters) MAO inside presynaptic neuron and synapse
DA hypothesis of schizophrenia
DA overactivity in mesolimbic pathway (VTA to nucleus accumbens) leads to positive symptoms of schizophrenia
Mesolimbic DA pathway
from bentral tegmental ares (VTA)
What is the difference in mechanism of action between cocaine and amphetamines?
Both block reuptake of DA, but only amphetamines increase the release of DA into the synaptic cleft, and in fact reverse the action of reuptake receptors.
How do all antipsychotic drugs act to decrease positive symptoms of schizophrenia?
They antagonize/block D2 receptors
Nigrostriatal dopamine pathway
From substantia nigra to basal ganglia/striatum (part of the extrapyramidal system); releases DA, which binds to D2 receptors
Painful spasms involving tongue, face, jaw, (facial grimacing); neck (spasmodic torticollis), back, eyes (oculogyric crisis), larynx (laryngospasms), hand (writer’s cramp), or foot
Severe restlessness, pacing, anxiety, agitation; patients often don’t tell doctors about this and just D/C on their own.
What system is the nigrostriatal pathway a part of?
Extrapyramidal System (EPS)
What does decreased activation of D2 receptors result in?
Parkinson's disease Extrapyramidal symptoms (ESP's)
Tuberoinfundibular DA pathway
From hypothalamus to anterior pituitary gland
Disinhibition of DA in the tuberoinfundibular pathway can cause what condition?
What does hyperprolactinemia lead to?
Decrease in testosterone & estrogen
What does DA normally block in the tuberoinfundibular pathway?
What does DA normally block in the nigrastriatal pathway?
Why is the 5HT2A receptor so important?
It inhibits DA release in all 4 pathways.
How is 5HT action terminated?
reuptake enzymatic degradation (MAO)
How do atypical AP’s work?
Antagonize 5HT2A receptors…
What are atypical AP’s also known as?
What type of drug is sometimes given in conjunction with atypical AP’s to treat affective symptoms of psychosis?
Anticonvulsants + atypicals are often used to treat what?
Behavioral dysfunction in children (e.g. children with ASD who have severe head banging)
What does the antagonism of H1 (histamine 1) receptor lead to?
Sedation (due to inhibition of histamine in the CNS)
Weight gain, especially if the 5HT2C receptor is also blocked
Antagonism of ACh-Mi (cholinergic, muscarinic) receptor leads to:
Memory problems Delirium Blurred vision Dry mouth Constipation Urinary hesitation/retention Reflex tachychardia
What’s the saying that is used to describe SE of AP’s?
Mad as a hatter, blind as a bat, dry as a bone, red as a beet.
Antagonism of a1 (alpha adrenergic) receptor leads to:
low blood pressure postural hypotension (orthostasis) dizziness increased heart rate (compensatory) Ejaculatory dysfunction, priapism (prolonged erection) Constricted pupils
What population are AP’s not FDA-approved for?
Elderly/geriatric due to increased risk of death
Prolongation of QTc can lead to what?
What is an important affect of AP’s on the cardiovascular system?
Some AP’s (thioridazine, Geodon) can prolong QTc, which leads to slower electrical activity in heart, which can lead to hearth arrhythmia.
What are some side effects associated with atypicals?
Cardiometabolic effects Sedation Anticholinergic (includes sexual dysfunction) Orthostasis & dizziness Sexual dysfunction Rashes Photosensitivity & temperature deregulation Liver effects Seizures
What is the most serious SE of atypicals?
What are cariometabolic effects also known as?
What are the symptoms of cardiometabolic effects/metabolic syndrome?
Hyperglycemia (risk of Type 2 diabetes)
Which atypicals have the worst cardiometabolic effects?
Clozaril & Zyprexa
Which atypicals have the least cardiometabolic effects?
Geodon & Abilify (although some of the newer atypicals are touting less cardiometabolic effects)
What is the main reason for partial/non-responses and relapses in schizophrenia?
What is poor adherence usually due to?
What are some of the main consideration regarding adherence that should be addressed?
Pts must not skip doses.
Pts should tell doctors about any SE’s
Involve significant others when possible (helpful in maintaining adherence)
Options for Inadequate responses
Switching drug classes (i.e. atypical vs typical)
Check DDI’s, including drug abuse
Increase dose (perhaps beyond those used in studies)
Increase for therapeutic effects
What is the most common type of optimization?
Increasing dosage (perhaps beyond those used in studies)
Adding a non-psychotic (e.g. antidepressants, anxiolytics, mood stabilizers)
Switching to another AP, hopefully rationally based on symptoms & SEs of specific patient
Adding another AP (usually adding an FGA to an atypical, since atypicals are usually prescribed first); Not as common (or as justified) as for bipolar