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67 Cards in this Set
- Front
- Back
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Examples of pyschotic disordes
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delusions
hallucinations disorganized thought/speech bizarre behavior catatonic motor behavior |
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Notes of delusions- psychosis
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erroneous beliefs held in the absence of concrete evidence
Delusions of persecution Delusions of reference - certain gestures, comments, or mass media are aimed specifically at the person Delusions of granduer bizarre delusion - someone is putting/removing thoughts from the person's head, they are being controlled by someone else |
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Notes on hallucinations- psychosis
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imagined sensory perceptions in any sensory modality
generally not aware that they are not real |
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Notes on disorganized thought and speech - psychosis
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lots of jumping around
irrelevant answers to questions may be so bad that they are totally intelligible -- word salad |
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notes on bizarre behavior - pyschosis
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odd gestures/facial expressions
strange postures bizarre clothing odd laughing |
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catatonic motor behavior- psychosis
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unusual motor behavior
decreased reactivty to enviro (catatonic stupor) bizarre postures (catatonic posturing) excessive movement (catatonic excitement) |
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Schizoprhenia - positive symptoms
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excess/distortion of normal function
AKA "psychotic symptoms" Usual cause of referral for TRT |
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Schizoprhenia - negative symptoms
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reduction of function
blunted affect, poor eye contact, monotone poverty of speech (alogia) loss of drive/energy - avolition Not as noticeable, but very debilitating |
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Schizoprhenia - cognitive symptoms
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persistent decrease in IQ
impaired attention imparied (ST) memory impaired executive function - form/carry out plans |
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Schizoprhenia - other features
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ahedonia - reduced ability to experience pleasure
dysphoria - unpleasant internal sensations sleep disturbances - change night and day Lack of insight - dont recognize the disease suicide substance-related disorders |
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Course of Schizophrenia
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prodromal phase --> active phase
prodromal = low level +, -, and cognitive -may not be obvious onset can be gradual but often is "psychotic break" -- lots of positive symptoms can have remissions and exacerbations or chronic level can have stable level or progressively worse |
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Biological basis of schizophrenia
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physical or biochemical defect
interaction of genetics and enviro |
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Neurodevelopmental/neurodegenerative hypothesis
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Neurodevelopmental - enviro inult occurs in utero/early life --> no symptoms until adulthood after brain remodels and 'unmasks' it
Modified recently to include progressive damage- continuous/sporadic neurodegeneration |
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Iriginal Dopamine hypothesis of schizophrenia
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oldest theory
orginally: EXCESS DA in certain pathways Evidence: (a) AP drugs are DA receptor antagonists (b) drugs that up DA activity produce + symptoms mesolimbic pathway is affected: VTA, nucleus accumbens, amygdala, other subcortical limbic structures also affects meocortical |
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Modified DA hypothesis of schizophrenia - what we use
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EXCESS DA in meolimbic = positive symptoms
LESS DA in mesocortical = neg, cognitive symptoms |
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glutamate hypothesis of symptoms
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Newer
symptoms due to deficiency of glutaminergic tranmission in some CNS pathways glutamate NMDA antagonists produce almost +, -, and cognitive effects also modulates DA pathways, so this may be the cause of the other theories |
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Convetions AP's
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chlorpromazine
haloperidol |
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Atypical AP's
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clozapine
risperidone olanzapine quetiapine ziprasidone aripiprazole |
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chemical structures of APs
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phenothiazines
butyrophenones |
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Low potency AP's
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chlorpromazine
clozapine |
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high potency AP's
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haloperidol
resperidone potency does not mean effectiveness |
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pharmacological charactersistics of conventional AP's
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Antipsychotics activity
-improve + symptoms -no effect on neg, cog variable onset: 2-3 wks, or 1-7 days NEver have tolerance |
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mech of action for AP action
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block post-syn D2 receptors in mesolimbic
need to block 65% of receptors |
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explanation of delayed onset
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depolarization block of neurons
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What are the effects of blocking DA in:
Neotriatum/nigrostriatal hypothalamus limbic nuclei/mesolimbic pre-frontal cortex/meoscortical |
Neotriatum/nigrostriatal - Block = motor SE
hypothalamus - block = endocrine Se's limbic nuclei/mesolimbic - block = improve symptoms pre-frontal cortex/meoscortical - block = neg, cognitive symptoms |
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Acute effect of D2 Block
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antagonists = more effect on autoreceptors so more firing --> no net decrease in transmission
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chronic effect of D2 block
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persistent depolarization = depolarization block
adds to post-syn DA blockade |
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pharmacological activity - sedative effect
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drowsiness
from H1 and alpha-1 block, also muscarinic NOT related to AP effects -tolerance to sedation, not AP -sedation starts w/ dose 1, AP later |
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pharmacological activity - anti-agitation
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reduced aggressive, agitated, hyperactive behavior
old term = rapid tranquilization --> used to stop person when in physical restraints rapid onset Mech of Action: don't really know -sedative? -D2 block? |
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pharmacological activity -
anti-emetic activity |
blocks D2 receptors in CTZ
-not good at stopping vomitting from other causes possibly affects muscarinic and H1 effects (vestibular effects) |
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factors influencing the vomitting center
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cerebral cortex/limbic system = see something gross
chemoreceptor trigger zone = blood flow monitor vestibular apparatus = motion sickness visceral afferent nerves = from the gut |
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pharmacological activity -
Extrapyramidal effects |
disorders of movement
-from blocked D2 in striatum positively correlated with AP potency |
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pharmacological activity -
block of muscarinic, alpha-1, and H1 receptors |
NEG correlation w/ potency
mainly source of SEs BUT -Muscarinic and H1 may help with anti-emetics -M1 may protect against EPS |
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pharmacological activity -
5HT blocking activity |
mainly 5HT2
Adverse - wt. gain Therapeutic - up AP, down EPS |
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pharmacological activity -
lowering sz threshold |
mech of action = unknown
NEG correlation with potency |
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pharmacological activity -
thermoregulatory effects |
poikilthermia - inability to regulate body temp from enviro
NEG correlated with potency due to PNS block of alpha-1 and muscarinic, CNS thermoregulatory |
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pharmacological activity -
enhanced prolactin |
INHIBIT the tuberoinfundibular DA pathway that STOPS prolactin release
-D2 block in anterior pituitary immediate effect after 1 dose POS correlation with potency |
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pharmacological activity -
Abuse/dependence |
No PSYCH
No strong physical discontinuation effect can occur -transient hypnotic -don't DC too quickly |
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Kinetics of APs
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1st pass = poor F
irregular ss per person long t1/2 --> QD dosing after tolerance to SEs t1/2 is longer in brain than in bood |
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Side Effects of APs
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Cognitive/behavioral effects
CV effects Hypo/Hyperthermia Anticholinergic Endocrine effects Metabolic effects Sexual dysfunction Seizures EPS Neuroleptic malignant syndrome Acute poisoning Drug interactions |
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Side Effects of APs:
Cognitive/Behavioral |
Sedation
-sometimes desired effects -moderate tolerance develops -additive effects with other drugs - common with low potency Dysphoria AKA neuroleptic-induced deficit syndrome -down conc, emotional responsiveness, response to enviro, motivation, thinking speed, movement speed -common -hard to differentiate from neg/cognitive fx of disease -cause unknown confusion/disorientation -more common in old people |
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Side Effects of APs:
CV effects |
Postural Hypotension
-common, but tolerates -alpha-block (PNS)= vasodilation, plus baroreceptor (CNS) fx Prolonged QT interval -worst = thiaridazine -use caution with pts with CVD |
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Side Effects of APs:
Hypo/Hyperthermia |
most susceptible in kids/elderly
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Side Effects of APs:
Anticholinergic effects |
common, but tolerate
sucky, but not dangerous mydriasis, dry eyes, blurry vision constipation xerostomia urinary problems anhidrosis |
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Side Effects of APs:
Endocrine effects |
mostly from up prolactin
man-boobs, man-lactation down sperm production, up body hair menstrual irregularities, down bone density up risk of breast cancer --> basic effect of increased prolactin |
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Side Effects of APs:
Metabolic syndrome |
components= wt gain, glucose intolerance, insulin resistance, hyperlipidemia
body wt gain may be main cause NEG correlation with potency common, major cause of non-adherence possible causes - *H1 block = up appetite, down activity *5HT2C block = up appetite *hyperprolactinemia= up fat deposition |
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Side Effects of APs:
sexual dysfunction |
common in both sexes
from hyperprolactinemia, alpha-block, D2 block in pleasure pathway Symptoms: down libido, erectile dysfunction, retrograde ejaculation |
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Side Effects of APs:
Seizures |
decreased sz threshold -->TC sz results
dose dependent Not likely at normal doses |
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Side Effects of APs - EPS:
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Acute: (1h post-dose)
-dystonias -akathisia -pseudoparkinsonism Delayed: (60-90day post dose) -tardive dyskinesia |
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Side Effects of APs - EPS:
Dystonias |
breif or prolonged contractions
POS correlation with potency, dose NEG correlation with age - highest in teens TRT= effective: muscarinic antagonist, spontaneously stop -benztropine -triheyphenidyl -diphenhydramine |
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Side Effects of APs - EPS:
Akathisia |
uncontrollable restlessness, inner tension
No age influence POS correlation with potency, dose best TRT is propanolol often persistant |
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Side Effects of APs - EPS:
pseudoparkinsonism |
core symptoms:
-bradykinesia -rigidity -tremor POS correlation with potency, dose, and age TRT: muscarinic blockers amantidine |
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Side Effects of APs - EPS:
Tardive Dyskinesia |
involunatary movements
Onset: 3mo to years 5% per year NOT correlated with potency, but may be correlated with lifetime D2 block No TRT: Switch to atypical APs |
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Side Effects of APs - EPS:
Neurobiological EPS |
subcortical system --> modulates cortical system
thought to be based on ACh/DA balance - too little DA action= parkinson, akathisia, dystonia - too much DA action = Tardive dyskinseia |
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Side Effects of APs - EPS:
basis of Tardive dyskinesia |
1. development of DA supersensitivity in NEOSTRIATUM
2. Down GABAnergic inhibition |
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Side Effects of APs -
Neuroleptic malignant syndrome |
agruably EPS
Symptoms: hyperthermia, muslce rigidity, EPS, change in consciousness, major fluctuations in BP/HR POS correlation with potency TRT: dantrolene bromocriptine DC AP, support vital fcns |
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Side Effects of APs -
acute poisoning |
low acute toxicity
-hard but possible for suicide Symptoms: coma, resp arrest, cardiac arrhthmias, SZ |
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clinical applications of AP's
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psychoses
manic states depression N&V Tourettes syndrome |
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Clinical Applications of AP's:
psychoses |
All types
All equally effectively, but different potency very effective on + symptoms, not good on neg/cognitive High relapse, even with good compliance Wide Variation in dose due to potency -Megadose= stupid, only up SE's Non-adherence likely: confusion, SEs, lack insight into disease, paranoia 20% won't relapse if they stop taking it -no way to predict |
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Clinical Applications of AP's:
N&V |
prochlorperazine (COMPAZINE) for IP
droperidol (INAPSINE) for OP useful for CTZ mediated, not as good for GI disturbance, cancer, motion sickness |
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Clinical Applications of AP's:
Tourette's syndrome |
common = haloperidol
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Atypical AP's
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clozapine
risperidone olanzapine quetiapine ziprasidone aripiprazole |
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Clozapine
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low incidence of EPS
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Clozapine Potential Mech's of action
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1. high M-block
-rebalance ACh vs. DA, but doesn't account for Tardive Dyskinesia block or mechanism for other atypicals 2. selective action on mesolimbic vs. nigrostriatal No nigrostriatal DA block for ALL atypicals 3. low D2 affinity clozapine has lower affinity than than conventionals --> need higher conc in in nigrostriatum for effect and lower conc in mesolimbic --> lower affinity means not enough get blocked in NS Doesn't explain ALL atypicals 4. hihg 5HT2A/D2 block all atypicals except aripiprazole block more 5HT2A than D2, main competitor to D2 hypothesis |
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Clozapine other comments
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little effect on prolactin
agranulocytosis hypersalivation seizures wt gain/metabolic syndrom |
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shared characteristics
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5HT2A/D2 blocking ratio
low EPS/Tardive dyskinesia probably effective against some neg symptoms possibly effective against cog effects no agranulocytosis minimal prolactin elevation except risperidone metabolic syndrome similar to conventional agents |
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aripiprazole
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D2 PARTIAL agonist
5HT1A agonist |
