pharmacology of antipsychotics Flashcards
what causes positive symptoms in schitzophrenia?
Positive symptoms are caused by too much dopamine in the mesolimbic pathway
(subcortical dopamine hyperactivity)
Mesolimbic pathway is from:
Ventral Tegmental Area (VTE) -> Nucleus Accumbens (NA)
what is the mesolimbic dopamine pathway?
from the Ventral Tegmental Area (VTA) -> Nucleus Accumbens (NA)
What causes negative symptoms in schitzophrenia?
Negative symptoms are caused by a reduction of dopamine in the mesocortical pathway
(frontal dopamine hypoactivity)
Mesocortical pathway is from:
Ventral Tegmental Area (VTE) -> Cortex
what is the mesocortical pathway?
from the Ventral Tegmental Area -> Cortex
what is used to treat positive symptoms?
Dopamine antagonist antipsychotics
-because positive symptoms are due to dopamine hyperactivity in the subcortical area (mesolimbic pathway from VTA-> nucleus acumbens)
what dopamine pathway is involved in movement?
Nigrostriatal pathwy
Substantia Nigra -> Striatum (caudate + putamen)
What is the nigrostriatal pathway?
Dopamine pathway controlling movement
From Substantia Nigra -> Striatum (caudate + putamen)
What affect can antipsychotics have on the nigrostriatal pathway and how may it present?
Antipsychotics decrease dopamine levels in the nigrostriatal pathway and can induce Parkinsonism (extrapyramidal motor symptoms)
What is the tuberoinfindibular pathway?
Hypothalamus -> Pituitary gland
what releases prolactin?
pituitary gland
what is the relationship between dopamine and prolactin?
inverse relationship
increase in dopamine leads to a decrease in prolactin
what affect can antipsychotics have on the tuberoinfundibular pathway and how may this present?
Antipsychotics decrease levels of dopamine in Hypothalamus causing increase levels of Prolactin in Pituitary
Increase Prolactin:
-Decrease FSH and lead to Amenorrheoa
-Galactorrhoea
examples of typical/ first generation antipsychotics?
-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine
MofA of antipsychotics?
Antagonists of:
-Dopamine (D2) Receptor
-Histamine (H1) Receptor
-Adrenoceptors (alpha 1) Receptor
-Muscarinic (M1) Receptor
Dopamine - most obvious
HAM- these people be going ham so give them an antipsychotic!
SE of histamine (H1) receptor antagonist?
weight gain + sedation
SE of adrenoceptor (alpha 1) receptor antagonist?
-hypotension
-priapism (prolonged erection)
SE of muscarinic (M1) receptor antagonist?
anticholinergic SE:
-dry mouth
-constipation
-dilated pupils
What type of antipsychotics are more likely to give you extrapyramidal symptoms?
1st generation AKA typical
Examples:
-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine
what type of antipsychotics are more likely to cause Neuroleptic Malignant Syndrome?
1st generation AKA typical
Examples:
-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine
examples of 2nd generation AKA atypical antipsychotics?
-Clozapine
-Olanzapine
-Quetiapine
-Risperidone
-Paliperidone
-Lurasidone
-Ariprazole
what receptors do second generation drugs bind to that first generation drugs dont?
they bind to both:
-Dopamine (D2) receptors
-Seretonin 2a Receptor (5HT2a)
First generation drugs do not bind to serotonin 2a receptors
what SE is risperidone (2nd generation) likely to cause?
hyperprolactinaemia
what SE is Clozapine (2nd generation) more likely to cause?
Agranulocytosis
what antipsychotic needs monitored closely and why?
Clozapine as it can cause agranulocytosis
-need to routinely check bloods
what is the most effective antipsychotic and why is it not first line?
Clozapine= most effective antipsychotic
-Not first line as risk of agranulocytosis
what are examples of Extrapyramidal symptoms?
-Dystona
-Akathisia
-Parkinsonism
-Tardive Dyskenesia
How does Dystonia present?
-Involuntary movement of head/face
-often sustained muscle contraction e.g. eyes stuck looking up or neck stuck in one place
-commonly in young men
-usually happens straight after treatment (antipsychotic)
who usually experiences dystonia after being given antipsychotic?
-young men
when after administering antipsychotic would people normally experience dystonia?
-soon after treatment
what is the management for dystonia?
IM anticholinergics
what is akathasia? (EPSE)
unpleasant restlessness
when will akathasia occur in relation to antipsychotic ? (ESPSE)
within 2 weeks of taking antipsychotic
treatment for akathasia? (EPSE)
-reduce dose (beta bloxker/ benzodiazepine)
presentation of Parkinsonism? (EPSE)
-bradykinesia, rigidity and tremor
how long after taking an antipsychotic will parkinsonism occur ?
months after taking antipsychotic
management of Parkinsonism? (EPSE)
antiparkinson medication
presentation of Tardive dyskensia (EPSE)?
-face and extremities make involuntary movements
when does Tardive dyskenisia occur in relation to antipsychotics? (EPSE)
-with prolonged use
what is the managment of tardive dyskenesia?
stop the drug
how does neuroepilelptic malignant syndrome present?
-motor, mental and autonomic dysfunction with hyperpyrexia
when would neuroepileptic malignant syndrome occur in relation to taking an antipsychotic?
within a few weeks
management of neuroepileptic malignant syndrome?
-stop drugs
-supportive
(10% mortality)
what is monitored for antpsychotics?
Fasting blood glucose, prolactin, ECG, FBC
why is fasting blood glucose monitored for antipsychotics?
-Antipsychotics act on glucose and insulin homeostasis
-they impair glucose tolerance and increase the risk of T2DM
why is prolactin monitored for antipsychotics?
-Antipsychotics decrease dopamine in the tuberoinfindibular pathway (Hypothalamus -> pituitary)
-Dopamine and prolactin have an inverse relationship (decrease dopamine increase prolactin)
why is an ECG used to monitor antipsychotics?
-as they can cause QT prolongation
why is a FBC done to monitor antipsychotics?
-Clozapine can cause agranulocytosis
(would appear as decreased neutrophils on FBC)
why should a patient make you aware if they smoke- antipsychotics?
smoking increases the levels of clozapine
-so patient should let doctor know if they are stopping smoking too
which antipsychotic has best SE profile?
Aripiprazole
what antipsychotic has highest T2DM risk and why?
Olanzapine has
-it causes most weight gain
what antipsychotic should be given to someone with Parkinsons?
-No antipsychotics should be given to someone with Parkinsons
-Give Lorazepam instead
SE clozapine?
-agranulocytosis (1%), neutropaenia (3%)
-reduced seizure threshold - can induce seizures in up to 3% of patients
-constipation
-myocarditis: a baseline ECG should be taken before starting treatment
-hypersalivation
