topic 7 Flashcards
what percentage of the EU population suffer from a mental disorder?
38.2%
what are the most common mental disorders?
anxiety insomnia major depression drug and alcohol dependence adhd dementia
what are the 3 symptom domains of schizophrenia?
positive (psychosis), negative (asociality, unmotivated) , cognitive
what is the incidence rate of schizophrenia
1%
what neurotransmitter is implicated in schizophrenia
overactivity of dopamine
also evidence for the involvement of glutamate and serotonin
what is the dopamine hypothesis of schizophrenia
- an increase in dopaminergic neurotransmission in the mesolimbic pathway
- this leads to abnormally high levels of dopamine in the nucleus accumbens and striatum
- this is thought to underlie the positive symptoms of psychosis
- there is also thought to be a decrease in dopamine transmission in the mesocortical pathway, projecting from the VTA to cerebal cortex
- this is associated with the negative and cognitive symptoms
what are the 3 categories of antipsychotics
Typical/1st generation
Atypical/2nd generation
partial agonists
what is the distinction between different types of antipsychotics based on?
receptor binding profile
incidence of extrapyramidal symptoms
efficacy against negative symtpoms
efficacy in treatment resistant patients
what symptoms do antipsychotics treat
positive symptoms
not generally effective at negative or cognitive symptoms
what is treatment faliure?
loss of efficacy over time
how do most antipsychotic drugs work?
most are antagonists or partial agonists at D2 dopamine receptors - thought to determine potency
there is also activity at some other receptors such as muscarinic receptors - thought to determine side effect profile
how many dopamine d2 receptors must be blocked for the maximum therapeutic effect of antipsychotics
60-80%
what are extrapyramidal symptoms of antipsychotics
diskinesia and other movement disorders
what are 3 antipsychotic side effect clusters
sedation
metabolic
extrapyramidal (motor side effects)
what does it mean when an affective disorder is unipolar
mood swings are in the same direction
what proportion of major depression cases are reactive or endogeneous (genetic)
75% reactive
25% endogeneous
what is the monoamine theory of depression?
- depression results from functional deficit in monoamine neurotransmitters (dopamine, noradrenaline, serotonin)
- mania results from an excess in monoamine neurotransmitters
- tricyclic antidepressent drugs are effective and boost monoamine neurotransmisison
what are two categories of antidepressant drugs?
slow acting anti depressants and fast acting antidepressants
what are 3 categories of slow acting antidepressants?
monoamine uptake inhibitors
monoamine oxidase inhibitors
atypical antidepressants
what are 3 rapid action antidepressants?
ketamine
scopolamine
pscilocybin
how do tricyclic antidepressants work
they non selectively inhibit both NA and Serotonin reuptake into nerve terminals
what are side effects of tricyclic antidepressants
sedation postural hypotension dry mouth, blurred vision, constipation occasional mania risk of cardiovascular side effects
why might SNRI’s be better than SSRIs
fewer side effects
What are side effects of SSRIs
nausea
insomnia
sexual dysfunction
what is the difference between SSRis and SNRis
ssris block serotonin reuptake
snris block noradrenaline reuptake
are monoamine oxidase ihibitors irreversible or reversible
most of the time the monoamine oxidase inibition is irreversible
what are the main side effects of monoamine oxidase ihibitors
postural hypertension
weight gain
restlessness
how do MAO inhibitors work
inhibit monoamine oxidase
these are ezymes that degrade monoamines
this increases ctyosolic stores of 5HTP and NA in nerve terminals
describe atypical antidepressants
- refer to a heterogeneous group of drugs that are known to improve mood but have no common mechanism of action
- they mainly act at presynaptic receptors, perhaps to enhance monoamine release
describe lithium as a mood stabilizer
- lithium is an inorganic ion taken as lithium carbonate
- 2 possible mechanisms of action:
1. interference with inositol phsophate formation
2. interferance with cAMP formation - it has a long plasma half life
- side effects are common
what are 3 categories of CNS stimulants
- convulsants and respitory stimulants - little effect on mental function
- psychomotor stimulants - alter mental function and behaviour
- psychotomimetric drugs - alter perception and cognition
what are 3 proposed mechanisms for amphetat=mine
- inhibition of dopamine reuptake by acting as a competitive antagonist of dopamine transporters
how does cocaine work?
inhibits dopamine reuptake
how do psychedelic drugs work
5HT21 agonism
what are the 5 main types of drugs that are abused
narcotic analgesics (e.g morhpine) general cns depressents anxiolytic drugs (e.g benzodiazepines) psychomotor stimulants (e.g amphetimines) psychotominetric drugs (psychedelic)
what are the common features of abused drugs
all produce rewarding effects that lead to stimulants
they are accompanied by habituation/adaptatio when used repeatedly
what is the dual diagnosis for substance abuse?
there is a statistically significant overlap between genes that confer risks for schizophrenia and drug dependence
how many pharmocologically active cannaboids are in cannabis?
over 60
what are the best known constituents of cannabis
THC and CBD
how do cannoboids work
they act on cannaboid receptors
CB1 receptor activation reduces neuronal activity
what are the endogenous ligands of cannaboid receptors?
anandamide and 2-AG (released from the post synaptic terminal, travelling to the pre)
functions in memory, synaptic depression, immune system, sleep, stress response, pain relief
what are the two cannaboid receptors
CB1 receptors are abundant in the hippocampus, cerebelleum, substantia nigra, mesolimbic dopamine pathway and the cortex
CB2 receptors are in the peripheral lymphoid system (potential immune role?)
- they are both g protein coupled receptors
- they are present in the presynaptic neurons (retrograde messengers)
where is the expression of CB1 receptors highest?
prefrontal cortex, amygdala, hippocampus,
all thought to be involved in cognition
there is also expression in the meso-corticolimbic system thought to be associated with its rewarding effects
what are 3 effects of cannabis exposure in the CNS?
- increased dopamine released
- reduces GABA and Glutamate release in nucleus accumbes
- increases opiod peptide release in the nucleus accumbens
what is it thought that the disruptions in cognition due to cannabis are due to
- Decrease ACh release in the hippocampus and the prefrontal cortex
- reduced GABA release and increased Glutamate release in the prefrontal cortex
- increased NA release in HIPP and frontal cortex
what are some adaptive changes due to chronic cannabis exposure in the CNS
- decreased regional cannabis receptor 1 expression
- deficiets in cortical and hippocampus CBR1 associated with impaired memory and cognition
- disruption of reward related signalling associated with reduced DA cell density and firing in the VTA and reduced dopamine release in the nucleus accumbens
- these effects are more prominent in those meeting the criteria for dependence
