antipsychotics

Question 1

what are the different types of amine transmitters in the CNS

Answer 1

-Noradrenaline
-Dopamine
-5-Hydroxytryptamine
-Acetylcholine

Question 2

whats the functional overview of amine transmitters in CNS

Answer 2

-Localized to small populations of neurons with cell bodies in the brain stem and basal forebrain
-Associated with ‘high level behaviours’ eg. emotion, cognition and awareness
-Many Anti-psychotic drugs, also known as ‘neuroleptics’, used in the treatment of schizophrenia
-anti-depressant drugs exert their actions by interfering with amine transmission- when NT released it can be referred to aerosol type transmission

Question 3

what are noradrenergic pathways in the CNS like

Answer 3

-a1 receptors widely distributed, involved in motor control, cognition, fear
-a2 involved in regulation of blood pressure, sedation and analgesia
-b1 in cortex, striatum and hippocampus(cells information about behavioural effects) contribute to long term effects of antidepressants
-Locus Ceruleus (sends projection into various areas of the cortex) neuronal activity is increased with behavioural arousal; =controls wakefulness and alertness
=control of mood (deficiency linked to depression)

Question 4

what are the functional aspects of dopaminergic pathways in CNS

Answer 4

1)Nigrostriatal pathway; fine motor control
=this pathway destroyed in Parkinson’s disease
2)Mesocortical and mesolimbic* pathways; behavioural effects, stereotypical, perserverance, pleasure-euphoria-reward (motivation), compulsion
=most prevalent and effective in schizophrenia
=project into the cortex
3)Tuberohypophyseal pathway; pituitary hormone secretion eg. Prolactin
=in the hypothalamus
=important in regulation secretion of hormone prolactin

Question 5

where is dopamine high

Answer 5

-striatum
-forms part of the ‘extrapyramidal motor system’ involved in coordination of movement

Question 6

how does tyrosine turn into adrenaline

Answer 6

-tyrosine– tyrosine hydroxylate > DOPA
-DOPA– DOPA decarboxylase > dopamine
-dopamine – dopamine b-hydroxylase -> noradrenaline
-noradrenaline– phenylethanolamine N-methytransferase > adrenaline

Question 7

where is PNMT only expressed

Answer 7

-adrenergic pathway

Question 8

what happens after the release of dopamine

Answer 8

-action is terminated by enzymes (COMT and MAO- both break down neurotransmitters) found both extracellularly and intracellularly and by action of re-uptake transporters.
-Reserpine (blocks dopamine storage, leads eventually depletion) , may be used to controls positive symptoms of schizophrenia

Question 9

what causes the release of neurotransmitter in dopaminergic receptors

Answer 9

-swelling when vesicles are located
-CO2 cause vesicles to fuse with membrane which then causes the release of NT

Question 10

what does L_DOPA do with Parkinson’s disease

Answer 10

-In Parkinson’s disease there is a loss of DA neurons of substantia nigra
-L-DOPA may be administered to increase DA synthesis (PA), however, can produce hallucinations

Question 11

what can Measurements of DA metabolic products be used to monitor

Answer 11

-used to monitor DA release in patients & animals

Question 12

what acids can be found in urine

Answer 12

-DOPAC
-HVA
-tested for disfunction

Question 13

what are the 2 families of dopaminergic receptors

Answer 13

1) D1, D5- Gs coupled receptors, stimulate adenylyl cyclase, increase cAMP, PKA and protein phosphorylation
=increase excitability of neurons
2)D2, D3, D4 - Gi coupled receptors, inhibit adenylyl cyclase, activate potassium channels which. causes hyper polarisation and found on presynaptic terminals, Inhibit Voltage Gated Calcium Channels, Oppose effects of D1 receptor activation, causes inhibition of neurons firing

Question 14

where are D2 receptors found

Answer 14

-in pituitary and on dopamine neurons
-more pharmacologically important

Question 15

Distribution and function of dopamine receptors

Answer 15

-cortex- role= arousal, mood, D1, D2, D4
-limbic system- role= emotion, stereotypic behaviour, D1, D2, D3, D4, D5
-stratium- role= prolactin secretion, D1, D2, D3, D4, D5
-ventral hypothalamus and anterior pituitary - role= prolactin secretion, D2, D3

Question 16

why can there be side effects with dopaminergic receptors

Answer 16

-Lack of selectivity of DA receptor agonists and antagonists

Question 17

what does amphetamines do

Answer 17

-stimulate secretion of DA (and NA), displace DA and NA from vesicles, cause re-uptake transporters to work in reverse, leading to increased DA and NE in brain and periphery
-Increased DA signaling leads to increased motor activity,
-In animals ‘stereotypic behaviours’, activation of reward pathways & feelings of euphoria- leads to drugs getting abused

Question 18

what are amphetamine like drugs used for

Answer 18

-to treat narcolepsy
-low doses= ADHD -D1 and a2 adrenoreceptors

Question 19

what does cocaine do

Answer 19

Cocaine inhibits DA transporter
-amine signalling blocks action on transporters on the plasma membrane

Question 20

what are Symptoms-characterized by disturbances in the areas of the brain associated with

Answer 20

-thought
-perception
-attention
-motor behavior
-emotion

Question 21

whats the prevalence rate of schizophrenia

Answer 21

-1.1% over 18

Question 22

what drugs can be used to help schizophrenia

Answer 22

-drugs that interfere with dopaminergic signalling

Question 23

what are the symptoms of schizophrenia

Answer 23

-Positive(more likely in young) : Hallucinations (voices), delusions (paranoid), thought disorders (irrational/wild, delusions of grandeur, garbled sentences) , defects in selective attention, bizarre behaviour, aggression, stereotyped movements, catatonia
-Negative: blunting of emotions, withdrawal from social contacts, flattening of emotional responses, anhedonia, reluctance to perform everyday tasks

Question 24

what are the causes of schizophrenia

Answer 24

-can be hereditary - no single gene is responsible
-Consumption of cannabis in adolescence is one of the environmental factors

Question 25

whats the difference between a schizophrenic brain and a normal brain

Answer 25

-Schizophrenic brains tend to have larger lateral ventricles and a smaller volume of tissue in the left temporal lobe -microscopic level, see decreased dendritic arborisation and spines. Synaptic dysfunction implicated -Drugs that enhance DA signaling increase positive schizophrenia-like symptoms, D2 blocking drugs reduce them -Glutamate signaling also arising, as NMDA antagonists also produce some psychotic symptoms, as do 5 HT2A receptor agonists (LSD)

Question 26

whats the Neuroanatomical and neurochemical basis of schizophrenia

Answer 26

-Overactivity of Mesolimbic pathway associated with +ve symptoms -increased D2 activity -Decreased activity in Mesocortical pathway, Associated with –ve symptoms- D1 receptors implicated

Question 27

what happens in mesolimbic areas with NMDA hypo function

Answer 27

-results in INCREASED DA signaling, because here the NMDA receptors are on inhibitory GABAergic interneurons

Question 28

what is the dopamine theory of schizophrenia

Answer 28

1)Amphetamine produces behaviours similar to acute schizophrenic episode 2)Hallucinations are side effect of treating Parkinson’s patients with levodopa 3)DA release in animals produces stereotypic behaviours 4)D2 receptor agonists induce stereotypic behaviours in animals AND like amphetamine, exacerbate symptoms of schizophrenia patients 5)DA antagonists and drugs that block DA storage (reserpine) control positive symptoms of schizophrenia and amphetamine induced behaviours

Question 29

what happens with reduced function of NMDA glutamate receptors

Answer 29

-implicatedDrugs which inhibit these receptors (eg. ketamine and phencyclidine) produce +ve , -ve and cognitive symptoms

Question 30

what are some antiphyschotic drugs

Answer 30

-Dopamine D2 antagonists used in the treatment of schizophrenia ~80% occupancy of receptors in the brain is needed to decrease positive symptoms -More than 80 antipsychotic drugs available for clinical use -First Generation Antipsychotics – referred to as Typical, Classical or Conventional” eg. chlorpromazine, haloperidol -Side effects include motor disturbances (extrapyramidal effects) and prolactin secretion -Second Generation Antipsychotics – referred to as atypical eg. clozapine, risperidone -Less extrapyramidal side effects

Question 31

what are some unwanted side effects of antipsychotic drugs

Answer 31

-Parkinson’s like symptoms, Acute reversible dystonias Slowly developing irreversible tardive dyskinesia (involuntary movements) -Increased prolactin release Sedation, Hypotension, Weight Gain Dry mouth, blurred vision