What are antipsychotics indicated for?
- BiPolar Disorders
Name 2 typical Antipsychotics
- Haloperidol (Haldol)
- Flupentixol Decanoate (Depixol)
Name 5 A-typical Antipsychotics
Talk to me about the DA theory of Sz?
- Based on the Dopamine Theory of Schizophrenia that Sz caused by high levels of DA
- discovered by accident (amphetamine psychosis and parkinson medication Levadopa which lead to increased DA showed similar side effects)
- BUT neurochemical changes in brain occur immediately after taking APs, yet it can take days/weeks to see observable ('behavioural') changes (epigenetics?)
What is the mechanism of action of Typical Antipsychotics?
- Act predominantly by blocking (antagonising) D2 receptors in the brain.
- Not selective for any of the four dopamine pathways in the brain, hence side effects.
What is the mechanism of action of Atypical Antipsychotics?
- Similar to Typical APs
- However do not exclusively block DA but act on a range of receptors, including;
- D1, D2, 5-HT, H-1 R and alpha-adrenoceptor antagonists
- This could explain why Atypicals have an effect on negative symptoms when typicals do not
Which Atypical Antipsychotic has a slightly different mechanism of action?
Aripiprazole is a partial D2 agonist;
- acts as an antagonist where high concentration of DA
- acts as an agonist where low concentrations of DA
It also has weak 5-HT partial agonism
What is specific to Olanzapine and Clozapine?
- Mechanism of action; also antagonise muscarinic receptors (Acetylcholine-GPCRs, excitatory/inhibitory)
- increased risk of metabolic syndrome (more than just via increase in body weight)
What are the shared side effects of Antipsychotics, and main differences between the two types?
- Sleepiness and feeling 'slowed down' in thinking
- Hypotension (and linked dizziness)
- Main concern with Typicals is EPSEs
- Main concern with Atypicals is metabolic syndrome
- but both share both!
What are the shared side effects of Typical Antipsychotics?
- Sexual side effects (reaching climax, difficulty achieving arousal for both)
- Hyperprolactinaemia (sexual dysfunction, reduced bone density, menstrual disturbances)-n.b. DA inhibits prolactin release!
What are the shared side effects of Atypical Antipsychotics?
- dry mouth
- weight gain (suggested average long term weight increase of >25%)-NOT Aripiprazole
- increased risk of metabolic syndrome (more than just via increase in body weight)-particularly Olanzapine and Clozapine
What are some of the side effects specific to Aripiprazole?
- blurred vision
What are the four main types of Extra Pyramidal Side Effects?
- Dystonia (sudden involuntary movement and muscle contractions, hypersalivation, mouth/tongue movements, abnormal eye rolling 'oculogyric crisis'). Usually within 1st week
- Akathisia (motor restlessness, inability to sit still)
- Pseudo Parkinsonism (cogwheel rigidity, drooling, shuffling gait, tremors). stop if drug withdrawn.
- Tardive Dyskinesia (irregular/jerky movements, lip smacking, chewing, slow and aimless arm movements). Usually after 6+ months and are hard to reverse
What are the nursing actions for EPSEs?
For Dystonia/Akathesia/Pseudo Parkinsonism;
- Reducing dose
- Switching to atypical
- anticholinergic medication-procyclidine
- use of a benzodiazepine
- increase vitamin e
Dangerous complications of all Antipsychotics
- High risk of cardiac complications
- Neuroleptic Malignant Syndrome
Tell me more about the cardiac complications linked with Antipsychotics?
- APs can interfere with electrical rhythm of heart, especially QTc interval.
- There is also a link between APs and Sudden Arrhythmic Death Syndrome (SADS).
- Therefore ECGs before starting/dose changes and every 1-3 months.
Tell me more about the risk of Neuroleptic Malignant Syndrome?
- APs affect bone marrow and lead to decrease in white blood cells
- in rare cases the body can suddently stop producing any-NMS crisis! Ireeversible
- 10-15% mortality rate!
- Symptoms? Sudden increase in temp and sweating, muscle pain, rigidity/stiffness, irregular pulse, increase/decrease bp, high resps, severe confusion.
- More likely to occur at start of AP, change of AP, change of dose or change of administration.
What are the contraindications of Typical Antipsychotics?
- CNS depression
What are the contraindications of Atypical Antipsychotics?
- Dementia-related psychosis
What is metabolic syndrome?
A group of risk factors which, taken together, increase the risk of T2DM and heart disease
- Key features: insulin resistance, visceral obesity and increased cholesterol levels
- Signs: High BMI, increased BP, increased blood glucose and increased waist measurement (>40 inches)
- Specifics: excess fat creates an additionally metabolic organ, free radicals, oxidative stress, inflammation (and IR)
What are some of the side effects specific to Clozapine?
- hypersalivation (consider using anticholinergic such as hyascine)
- blurred vision
- increased heart rate and linked increased sweating
What are the blood test requirements for Clozapine and what is a normal range?
- weekly for 18 weeks
- fortnightly for rest of year (<52 weeks)
- monthly forever (and one month after discontinuation)
- White cell count less than 3.5 x10^9/L=cause for concern!
When should Clozapine use be considered?
- When two other APs have been trialled (including at least one atypical)
- (People should receive APs for 4-6 weeks before deemed ineffective)
- Clozapine is effective in 30-60% of such 'treatment-resistant' cases! And prolongued use can increase insight!
Patient Education points for Clozapine?
- continued blood tests (holidays, needles etc)
- smoking-the hydrocarbons in smoke speed up the body's ability to metabolise clozapine therefore smokers need higher doses-therefore changes in smoking or even caffeine consumption can have a big effect
- Fall in neutrophil levels at any time, more likely in 18 weeks (neutropenia = 2%, agranulocytosis = <1%) Need to be alert for signs of infection! (Differences in ethnic backgrounds, for example Afro-Caribbean naturally lower)
What drug interactions can influence effectiveness and safety of most Antipsychotics?
-Clozapine/other antipsychotic use
-Many react with ADs
What are some nursing actions for constipation?
This can quickly lead to bowel blockages, blood poisoning and death.
- Bristol stool chart
- Fibre (fruit/veg)
- Exercise (stimulates bowel)
- Consider natural sedative (e.g. Senna)
Which Antipsychotic may be the safest to use during pregnancy?
- however evidence of gestational diabetes
- and NO breastfeeding
What could you use in conjunction with APs regarding side effects and why?
- Glasgow Antipsychotic Side-effect Scale
- Specific Clozapine monitoring tools
- Side effects are most common reason for non-concordance
- May be an indication of non-concordance (if no side effects)
- May be an indication of need to stop medication