Psychiatric Medication - antipsychotics Flashcards
Antipsychotics MOA
- 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
Schizphrenia positive vs negative symptoms cause in relation or mesolimbic and mesocortical pathway
- 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.
Where do unwanted effects of antipsychotics come from?
- Nigrostriatal (movement) –> Parkinsons syndrome
- Tuberoinfundibular (hypothalamic-pituitary-adrenal axis) –> raised prolactin
4 dopamine pathways in brain
- Mesocrotical
- Mesolimbic
- Nigrostriatal
- Tuberoinfundibular
Side effects antipsychotics
- Sedation
- Extra-pyramidal
- Weight gain
- Acute dystonia inc oculogyric crisis
Typical vs atypical antipsychotics
- 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
Examples of typical antipsychotics
- Haloperidol
- Flupenthixol
- Zuclopenthixol
- Chlorpromazine
- Sulpiride
- Aripiprazole - D2 partial agonist
Examples of atypical antipsychotics
- Clozapine
- Olanzapine
- Risperidone
- Quetiapine
- Amisulpride
Side effects of antipsychotics depending on type of
- All - sedation, weight gain and QTc prolongation
- Typical - extrapyramidal (eg bradykinesia, stiffness an tremor), dizziness, sexual dysfunction
- Atypical - weight gain, dyslipidaemia, diabetes
Monitoring for antipsychotics
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
Neuroleptic malignant syndrome - what is it and symptoms
- 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
Cause of death from NMS
- Rhabdomyolysis
- Renal failure
- Seizures
Risk factors for NMS
- High potency dopamine antagonists (typical)
- Antipsychotic naive
- High doses
- Young men - more muscle to break down
- Black ethnicity
Management of NMS
- 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
Extrapyramidal side effects - how are they treated
- 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
What can anticholinergics worsen?
Tardive dyskinesia - sudden uncontrollable movements in face and body
Examples of anticholinergics used for extra-pyramidal side effects
- Procyclidine - most common
- Benztropine
- Trihexphenidyl
What is acute dystonia?
- Sudden, often painful muscular spasms producing twisted abnormal postures
- 50% cases within first 48hrs, 90% within first 5 days of taking antipsychotic
Where can acute dystonias often occur?
- Neck
- Tongue
- Jaw
- Oculogyric crisis (neck arched and eyes rolled back)
Management of acute dystonia
- 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
Clozapine MOA and key points
- D2 antagonist - fairly weak
- 5HT-2 antagonist
- Most effective antipsychotic ever
- Improvements can continue for several months
When to consider Clozapine?
- 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)
Side effects Clozapine
- 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
How often FBC for agranulocytosis risk in Clozapine?
- Weekly for 18 weeks
- Every 2 weeks for 1 year
- Then monthly
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
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
Side effects Clozapine
- Myocarditis
- Constipation
- Hypersalivation
- Seizures
- NMS - less likely with Clozapine (if previously had, reccomended to consider Clozapine)
- Agranular cytosis
- Postural hypotension
Origin of EPSE of antipsychotics
Dopamine antagonist of nigrostriatal pathway
Atypical antipsychotics are more likely to be effective
:)
3 most common side effect of antipsychotic
- Weight gain
- Akathisia - unsupressable urge to move, can’t stay still
- Sedation
NMS RF
- Male
- Restraint of patient
- Antipsychotic naive
- Typical antipsychotic (more dopaminergic)
Timing for repeating baseline tests for antipsychotics
- At 3 months
- Yearly
Most appropriate administration of antipsychotic medication that someone is refusing
Long acting depot
