pharmacology of antipsychotics

Question 1

what causes positive symptoms in schitzophrenia?

Answer 1

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)

Question 2

what is the mesolimbic dopamine pathway?

Answer 2

from the Ventral Tegmental Area (VTA) -> Nucleus Accumbens (NA)

Question 3

What causes negative symptoms in schitzophrenia?

Answer 3

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

Question 4

what is the mesocortical pathway?

Answer 4

from the Ventral Tegmental Area -> Cortex

Question 5

what is used to treat positive symptoms?

Answer 5

Dopamine antagonist antipsychotics
-because positive symptoms are due to dopamine hyperactivity in the subcortical area (mesolimbic pathway from VTA-> nucleus acumbens)

Question 6

what dopamine pathway is involved in movement?

Answer 6

Nigrostriatal pathwy
Substantia Nigra -> Striatum (caudate + putamen)

Question 7

What is the nigrostriatal pathway?

Answer 7

Dopamine pathway controlling movement

From Substantia Nigra -> Striatum (caudate + putamen)

Question 8

What affect can antipsychotics have on the nigrostriatal pathway and how may it present?

Answer 8

Antipsychotics decrease dopamine levels in the nigrostriatal pathway and can induce Parkinsonism (extrapyramidal motor symptoms)

Question 9

What is the tuberoinfindibular pathway?

Answer 9

Hypothalamus -> Pituitary gland

Question 10

what releases prolactin?

Answer 10

pituitary gland

Question 11

what is the relationship between dopamine and prolactin?

Answer 11

inverse relationship

increase in dopamine leads to a decrease in prolactin

Question 12

what affect can antipsychotics have on the tuberoinfundibular pathway and how may this present?

Answer 12

Antipsychotics decrease levels of dopamine in Hypothalamus causing increase levels of Prolactin in Pituitary

Increase Prolactin:
-Decrease FSH and lead to Amenorrheoa
-Galactorrhoea

Question 13

examples of typical/ first generation antipsychotics?

Answer 13

-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine

Question 14

MofA of antipsychotics?

Answer 14

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!

Question 15

SE of histamine (H1) receptor antagonist?

Answer 15

weight gain + sedation

Question 16

SE of adrenoceptor (alpha 1) receptor antagonist?

Answer 16

-hypotension
-priapism (prolonged erection)

Question 17

SE of muscarinic (M1) receptor antagonist?

Answer 17

anticholinergic SE:
-dry mouth
-constipation
-dilated pupils

Question 18

What type of antipsychotics are more likely to give you extrapyramidal symptoms?

Answer 18

1st generation AKA typical

Examples:
-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine

Question 19

what type of antipsychotics are more likely to cause Neuroleptic Malignant Syndrome?

Answer 19

1st generation AKA typical

Examples:
-Haloperidol
-Chlorpromazine
-Zuclopenthixol
-Flupentixol
-Trifluoperazine
-Prochlorperazine

Question 20

examples of 2nd generation AKA atypical antipsychotics?

Answer 20

-Clozapine
-Olanzapine
-Quetiapine
-Risperidone
-Paliperidone
-Lurasidone
-Ariprazole

Question 21

what receptors do second generation drugs bind to that first generation drugs dont?

Answer 21

they bind to both:
-Dopamine (D2) receptors
-Seretonin 2a Receptor (5HT2a)

First generation drugs do not bind to serotonin 2a receptors

Question 22

what SE is risperidone (2nd generation) likely to cause?

Answer 22

hyperprolactinaemia

Question 23

what SE is Clozapine (2nd generation) more likely to cause?

Answer 23

Agranulocytosis

Question 24

what antipsychotic needs monitored closely and why?

Answer 24

Clozapine as it can cause agranulocytosis
-need to routinely check bloods

Question 25

what is the most effective antipsychotic and why is it not first line?

Answer 25

Clozapine= most effective antipsychotic -Not first line as risk of agranulocytosis

Question 26

what are examples of Extrapyramidal symptoms?

Answer 26

-Dystona -Akathisia -Parkinsonism -Tardive Dyskenesia

Question 27

How does Dystonia present?

Answer 27

-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)

Question 28

who usually experiences dystonia after being given antipsychotic?

Answer 28

-young men

Question 29

when after administering antipsychotic would people normally experience dystonia?

Answer 29

-soon after treatment

Question 30

what is the management for dystonia?

Answer 30

IM anticholinergics

Question 31

what is akathasia? (EPSE)

Answer 31

unpleasant restlessness

Question 32

when will akathasia occur in relation to antipsychotic ? (ESPSE)

Answer 32

within 2 weeks of taking antipsychotic

Question 33

treatment for akathasia? (EPSE)

Answer 33

-reduce dose (beta bloxker/ benzodiazepine)

Question 34

presentation of Parkinsonism? (EPSE)

Answer 34

-bradykinesia, rigidity and tremor

Question 35

how long after taking an antipsychotic will parkinsonism occur ?

Answer 35

months after taking antipsychotic

Question 36

management of Parkinsonism? (EPSE)

Answer 36

antiparkinson medication

Question 37

presentation of Tardive dyskensia (EPSE)?

Answer 37

-face and extremities make involuntary movements

Question 38

when does Tardive dyskenisia occur in relation to antipsychotics? (EPSE)

Answer 38

-with prolonged use

Question 39

what is the managment of tardive dyskenesia?

Answer 39

stop the drug

Question 40

how does neuroepilelptic malignant syndrome present?

Answer 40

-motor, mental and autonomic dysfunction with hyperpyrexia

Question 41

when would neuroepileptic malignant syndrome occur in relation to taking an antipsychotic?

Answer 41

within a few weeks

Question 42

management of neuroepileptic malignant syndrome?

Answer 42

-stop drugs -supportive (10% mortality)

Question 43

what is monitored for antpsychotics?

Answer 43

Fasting blood glucose, prolactin, ECG, FBC

Question 44

why is fasting blood glucose monitored for antipsychotics?

Answer 44

-Antipsychotics act on glucose and insulin homeostasis -they impair glucose tolerance and increase the risk of T2DM

Question 45

why is prolactin monitored for antipsychotics?

Answer 45

-Antipsychotics decrease dopamine in the tuberoinfindibular pathway (Hypothalamus -> pituitary) -Dopamine and prolactin have an inverse relationship (decrease dopamine increase prolactin)

Question 46

why is an ECG used to monitor antipsychotics?

Answer 46

-as they can cause QT prolongation

Question 47

why is a FBC done to monitor antipsychotics?

Answer 47

-Clozapine can cause agranulocytosis (would appear as decreased neutrophils on FBC)

Question 48

why should a patient make you aware if they smoke- antipsychotics?

Answer 48

smoking increases the levels of clozapine -so patient should let doctor know if they are stopping smoking too

Question 49

which antipsychotic has best SE profile?

Answer 49

Aripiprazole

Question 50

what antipsychotic has highest T2DM risk and why?

Answer 50

Olanzapine has -it causes most weight gain

Question 51

what antipsychotic should be given to someone with Parkinsons?

Answer 51

-No antipsychotics should be given to someone with Parkinsons -Give Lorazepam instead

Question 52

SE clozapine?

Answer 52

-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