case 8 Flashcards
with SZ non adherence is predicted by
not seeing a medical benefit, not predicting relapse, not liking the medication, poor insight into their condition
cognitive remediation
restorative or compensative. strategy based instructions.
SZ
inc DA in nigrostriatal pathway. Knock on effects from abnormalities in glutamate or GABA systems. Dec DA in DLPFC. psychosis-loss contact with reality. hallucinations, delusions, dosorganised speech and behaviour, flattened effect, cog deficits, occupational social dysfunction. 1% prevalence. more common men. higher in lower socioeconomic classes. age onset 20-30 in woman, 15-25 men.
dopamine
hormone-catecholamine and phenthylamine. motivation reward and reinforcement. tyrosine - tyrosine hydroxylase - LDOPA - DOPA decarboxylase - Dopamine. Reuptake Na ion dependent DA transporter DAT. MOA and COMT catabolise. Activate G protein coupled receptors. D1 type (D1 and D5) D2 type (D2,3,4). D1 coupled to G protein GSalpha activated adenylyl cyclase inc cAMP. D2 coupled G protein Gialpha inhibits formation cAMP.
nigrostriatal dopamine pathway
projects from substantia nigra to basal ganglia or striatum. Extrapyramidal nervous system. controls motor function and movement. hyperactivity is associated with pos symptoms, delusions and hallucinations. pleasure, hyperkinetic movement. SZ occurs in associative striatum of NS pathway. can be detected 3 yrs before first episode.
mesocortical dopamine pathway
from ventral tegmental area of brainstem to prefrontal cortex. cog symptoms in DLPFC, neg symptoms in DLPFC and VMPFC. deficit of DA. may be consequence of neurodevelopmental abnormalities in NMDA glutamate system.
mesolimbic dopamine pathway
ventral tegmental area to limbic areas, mainly nucleus accumbens in ventral striatum. deficient in this area leads to anhedonia and lack of pleasure.
tuberoinfundibular dopamine pathway
from hypothalamus to anterior pituitary gland. inhibit prolactin release. When pregnant Da neurons dec so prolactin levels rise for breast feeding. This can occur with antipsychotics that block D2.
3 functional pathways of striatum
sensorimotor-input from SNc, D1/2 receptors. Associative-learning, memory, attention, emotion, input from DLPFC, DA from SNc. D1/2/3. Limbic-reward. DA from VTA. D1/2/3.
causes and risk factors
thought to have a biological basis as enlarged ventricles, thinning of cortex, dec hippocampus, changes in DA and glutamate. Genetic componant. environmental-stressers can cause reacurance but not causative. neurodevelopment vulnerability, substance abuse. cannabis doubles the risk. cocaine can give psychotic sympt.
signs and symptoms
abnormal ideas-delusion. abnormal perceptions-hallucinations in all semses, auditory most prominent. motor and behavioural disorders-stereotypies(purposeless acts repetitivly) strange mannerisms, bizzare behaviour, catatonia, catalepsy(limbs can be manipulated) hyperactivity, impuslive behavious. thought disorders-unintelligible speech, neologism. emotional disorders-affective flattening, innapropriate affect.
types of delusions
persecution-somones trying to harm them. reference-everythings directed at and about them. control-something else is controling them. grandiose-divine purpose. hypochondrical-body is rotten. delusional mood.
positive symptoms
delusions, hallucinations, thought disorder, bizarre behavious. acute episodes
Negative symptoms
absence or reduction in normal function. apathy, affective blunting, poverty of speech, anhedonia, lack of desire for relationships, social withdrawl, avolition, impaired cog. chronic sympt.
phases
premorbid-may show no symptoms. predromal-symptoms. middle phase, late illness phase.
viscious cycle
dec DA in DLPFC feedbacks to associative striatum to inc, inc in striatum fec in DLPFC. this is secondary to other dysfuntions of brain.
glutamate hypothesis
diminished activation of NMDA receptors in brain. Phencyclidine caused hallucination and paranoia. PCP inhibits NMDA. low glutamate receptors found in SZ patients.
types of SZ
paranoid-auditory hallucinations and delusions. Disorganised-disorganised thought processes, emotional effects. catatonic. Undifferentiated. Residual-when symptoms lessen.
Diagnosis
DSM V, 2 or more of delusions hallucinations disorganised speech and behavious, neg symptoms. for 1 month, must include 1 of first 3.
ICD10 at least 1 first rank symptom for 1 month, thoughts delusions hallucinations. at least 2 second rank. Tests to rule out other causes of psychosis like substance abuse, mood disorders.
cannabis
most widely abused drug, dried female flower cannabis sativa. contains psychoactive substances-THC. leads to dec BP blood shot eyes feeling dizzy inc appetite.
cannabinoid receptors involved in psychosis
CB1 most effect of cannabinoids on CNS, appetite pain mood, euphoric and anticonvulsant. CB2 found in periphery expresed in immune system. activated by THC through production of endocannabinoid-anadamide.
plant canabinoids THC and ligand anadamide
THC acts on reward system releasing dopamine. stim D2 receptors in striatum. Inc in release anandamide, activates cannabinoid receptors, euphoria. distort balance by binding CB1 in cerebellum and basal ganglia.
endocannabinoids
substances produced in the brain. reduce the amount of neurotransmitter release. produced in post synaptic GABA neurons. GABA binds endocannabinoid source, production, bind CB1 cause reduction in GABA release, so less inhibit in brain cause euphoria. EC mediated depol induced suppression of inhibition.
conventional antipsychotics
halperidone, chlorpromazine, fluphenazine. act primarily to block D2 but also block cholinergic histamine adrenergic and seratonin. high - low potency. high is most for D2, low is opposite. fatigue due H and A. extrapyramidal effects in nigrostriatal pathway-parkinsonism. akathisia. tardive dyskinesia. seizures. inc prolactin. hepatotoxicity. cardiovasc effects. weight gain, sexual dysfunction.
risperidone
atypical 2nd gen antipsychotic. High affinity for seratonin in mesocortical (inc DA eliminate neg sympt) and D2 receptors in ventral part striatum (aleviates pos symptoms) not effect nigrostriatal so avoid extrapyramidal effects-happen at 78% occupancy. weight gain. neuroleptic malignant. syndrome. hyperprolactinemia happen at 72% occupancy. treatment begins to work when 60% occupancy.
clozapine
given when 2 other AP fail. many SE like sedation hunger diabetes. binds best to D4.
efficacy threshold
want 65% DA occupancy, typical have narrow dose range to overdose. atypical wider dose range.
main SE
Major Side Effects of Antipsychotics
- Elevated serum prolactin levels – antagonism of dopamine receptors in the tuberoinfundibular pathway
- Parkinsonian symptoms – antagonism of dopamine receptors in the nigrostriatal pathway
- Weight gain – antagonism of histamine H1 and serotonin 5-HT2c receptors plus effects on leptin
- Deterioration in working memory – antagonism of dopamine receptors in the mesocortical pathway
- Blurred near vision – antagonism of muscarinic M1 acetylcholine receptors
- Sedation – antagonism of H1 and alpha-adrenergic receptors
CB1 receptors
located on the presynaptic nerve terminals. anandamide and 2-arachidonoylglycerol (also stim CB2) activates it. linked to appetite.
