Psychiatric Medication - antipsychotics Flashcards
1
Q
Antipsychotics MOA
A
- Reduce level of dopamine activity at D2 receptors
- All are D2 antagonists or partial agonists
- Target dopaminergic pathways in the brain are mesocortical and mesolimbic - want slightly different effects at each - WHAT
2
Q
Schizphrenia positive vs negative symptoms cause in relation or mesolimbic and mesocortical pathway
A
- Increased dopaminergic activity in the mesolimbic pathway accounts for the production of positive symptoms
- Decreased dopaminergic activity in the mesocortical pathway is postulated to account for the negative symptoms and cognitive impairments seen in patients with schizophrenia.
3
Q
Where do unwanted effects of antipsychotics come from?
A
- Nigrostriatal (movement) –> Parkinsons syndrome
- Tuberoinfundibular (hypothalamic-pituitary-adrenal axis) –> raised prolactin
4
Q
4 dopamine pathways in brain
A
- Mesocrotical
- Mesolimbic
- Nigrostriatal
- Tuberoinfundibular
5
Q
Side effects antipsychotics
A
- Sedation
- Extra-pyramidal
- Weight gain
- Acute dystonia inc oculogyric crisis
6
Q
Typical vs atypical antipsychotics
A
- Typical - older and more likely to cause extra-pyramidal side effects, dizziness and sexual dysfunction
- Typical - tend to bind more to muscarinic and histaminic receptors
- Atypical - more serotonergic activity (also called second generation), more likely to cause weight gain, dyslipidaemia and diabetes
7
Q
Examples of typical antipsychotics
A
- Haloperidol
- Flupenthixol
- Zuclopenthixol
- Chlorpromazine
- Sulpiride
- Aripiprazole - D2 partial agonist
8
Q
Examples of atypical antipsychotics
A
- Clozapine
- Olanzapine
- Risperidone
- Quetiapine
- Amisulpride
9
Q
Side effects of antipsychotics depending on type of
A
- All - sedation, weight gain and QTc prolongation
- Typical - extrapyramidal (eg bradykinesia, stiffness an tremor), dizziness, sexual dysfunction
- Atypical - weight gain, dyslipidaemia, diabetes
10
Q
Monitoring for antipsychotics
A
Baseline:
* FBC - bone marrow supression
* Lipids - dyslipidaemia
* LFT - steatohepatitis
* HbA1C - can cause diabetes, know baseline
* Weight - weekly idealy
* ECG - QTc prolongation
* BP and pulse - check risk of metabolic syndrome
repeat at 3 months and 1 year
11
Q
Neuroleptic malignant syndrome - what is it and symptoms
A
- Rare life-threatenig reaction to antipsychotics - hard to tell between serotonin syndrome
- Fever
- Confusion
- Muscle rigidity
- Sweating
- Autonomic instability
- High CK can differentiate between Serotonin syndrome
12
Q
Cause of death from NMS
A
- Rhabdomyolysis
- Renal failure
- Seizures
13
Q
Risk factors for NMS
A
- High potency dopamine antagonists (typical)
- Antipsychotic naive
- High doses
- Young men - more muscle to break down
- Black ethnicity
14
Q
Management of NMS
A
- Emergency referral to A&E
- Stop antipsychotics
- Give benzodiazepine for acute behavioural disturbance
- Fluid resuscitation
- Reduce temperature - cooling blankets (autonomic instability, temp changes)
- O2 if needed
- Rhabdo - fluids and sodium bicarbonate - alkalise urine (ITU needed?)
- Relax muscles - dantrolene or lorazepam or bromocriptine
- Don’t need serum antipsychotic level
15
Q
Extrapyramidal side effects - how are they treated
A
- Bradykinesia, tremor and rigidity
- Ratio of dopamine:acetylcholine in nigrostriatal pathway is important cause of side effect
- If give anticholingergic (Procyclidine) - reduce acetylcholine as you have reduced dopamine
16
Q
What can anticholinergics worsen?
A
Tardive dyskinesia - sudden uncontrollable movements in face and body
17
Q
Examples of anticholinergics used for extra-pyramidal side effects
A
- Procyclidine - most common
- Benztropine
- Trihexphenidyl
18
Q
What is acute dystonia?
A
- Sudden, often painful muscular spasms producing twisted abnormal postures
- 50% cases within first 48hrs, 90% within first 5 days of taking antipsychotic
19
Q
Where can acute dystonias often occur?
A
- Neck
- Tongue
- Jaw
- Oculogyric crisis (neck arched and eyes rolled back)
20
Q
Management of acute dystonia
A
- Stop antipsychotic
- Administer IM or IV procyclidine (anticholinergic) - NOT ORAL as often can’t swallow
- Continue for 1-2 days after dystonia and consider long term prophylactic
- New antipsychotic - less dopamine strong
21
Q
Clozapine MOA and key points
A
- D2 antagonist - fairly weak
- 5HT-2 antagonist
- Most effective antipsychotic ever
- Improvements can continue for several months
22
Q
When to consider Clozapine?
A
- If someone tried two antipsychotics and not effective
- Some psychiatrists recommend trialling after 1 ineffective - sooner intervention in psychosis = less psychogenic brain (easier to treat)
23
Q
Side effects Clozapine
A
- Significant potential for agranulocytosis - severe leukopenia especially neutrophils = CLOSE monitoring of FBC needed (drug companies sometimes do not issue if no FBC)
- GI hypomobility - constipation –> fatal bowel obstruction
- Hypersalivation
- Urinary incontinence
24
Q
How often FBC for agranulocytosis risk in Clozapine?
A
- Weekly for 18 weeks
- Every 2 weeks for 1 year
- Then monthly
25
How is Clozapine started?
* Dose titrated slowly upward over two weeks and vital signs monitored for autonomic dysregulation
* Titrated slowly due to autonomic instability - body then adapts to it quite quickly
* = reduced postural hypotension
26
Management of agranulocytosis caused by Clozapine
* Stop Clozapine
* Stop any other potentially marrow supressing drugs eg Sodium Valproate
* Avoid antipsychotics for a couple of weeks where possible - if needed use Aripiprazole (less bone marrow suppression)
* Call on-call consultant haematologist as emergency
* Avoid sources of infection - consider prophylactic broad spec abx
* Sometimes lithium used to increase WCC and neutrophil count
* Granulocyte colony stimulating factor (G-CSF) - can be used - causes peaks and troughs of levels
27
Side effects Clozapine
* Myocarditis
* Constipation
* Hypersalivation
* Seizures
* NMS - less likely with Clozapine (if previously had, reccomended to consider Clozapine)
* Agranular cytosis
* Postural hypotension
28
Origin of EPSE of antipsychotics
Dopamine antagonist of nigrostriatal pathway
29
Atypical antipsychotics are more likely to be effective
:)
30
3 most common side effect of antipsychotic
* Weight gain
* Akathisia - unsupressable urge to move, can't stay still
* Sedation
31
NMS RF
* Male
* Restraint of patient
* Antipsychotic naive
* Typical antipsychotic (more dopaminergic)
32
Timing for repeating baseline tests for antipsychotics
* At 3 months
* Yearly
33
Most appropriate administration of antipsychotic medication that someone is refusing
Long acting depot
34
