L51 - Anti-psychotics Flashcards
Define psychosis?
A spectrum of symptoms from mental health problems that stop the person from thinking clearly, telling the difference between reality and their imagination and acting normally
List the positive symptoms of psychosis?
Hallucination
Delusion
Agitation
Disorganized thinking
Define Hallucination?
Perceive something that does not exist in reality (feeling)
Can occur in any of the 5 senses
Define delusion?
cannot separate real from unreal experiences
strongly believe things that, when examined rationally, are not true/rational
Define agitation
unpleasant state of increased tension and irritability
Symptoms of unorganized thoughts?
Rapid, constant speech
Random speech content: Switch from one topic to another in the middle of a sentence
Train of thoughts may suddenly stop = abrupt pause in conversation / activity
List the negative symptoms of psychosis?
Lack of emotional response Social withdrawal/ depression Apathy (Experience feelings of emptiness) Lack of drive Lack of insight and self- awareness
Explain how lack of insight and self-awareness impacts a psychosis patient’s behavior ?
Totally unaware that they act in strange ways or have hallucinations / delusions
Can recognize abnormal behaviors of others
3 major causes of psychosis?
- Psychological conditions
- General medical conditions causing secondary psychosis
- Drugs
List psychological conditions that cause psychosis?
Schizophrenia (repeated psychosis)
Bipolar disorder (extreme mood swings)
Severe stress or anxiety
Lack of sleep
Severe depression
List some general medical conditions that cause psychosis?
Metabolic diseases: Vit B12 deficiency** >> Acute onset of psychosis Hyponatremia Hyperadrenalism Hyper- or hypothyroidism Hepatic encephalopathy
Brain diseases:
- Stroke
- Huntington’s
- Wilson’s
- Tumour
- Encephalitis or CNS infections
List some substances that can trigger psychosis?
- Severe alcohol intake
- Chronic Cannabis use
- Cocaine
- Amphetamine
- Meth, LSD, Ketamine, MDMA, Mephedrone
Compare the general MoA of antipsychotics vs antidepressants
Antidepressant = Increase monoamine neurotransmitters
Antipsychotics = BLock Dopamine
Which neurotransmitter in excess is key to psychosis?
Dopamine
Excess = interrupts specific brain pathways responsible for normal functions (e.g. memory, emotion, social behavior, self-awareness) = psychosis
Differentiate the types of dopamine receptors?
5 different dopamine receptors (D1-D5):
D1, D5: activate adenylate cyclase
D2, D3, D4: inhibit adenylate cyclase
List the structures of the brain with the most D2 receptors?
Cerebral cortex Corpus striatum (caudate nucleus, putamen) Limbic system Basal ganglia Pituitary gland Hypothalamus
List some non-medication treatment options for psychosis?
- Psychological therapies
- Social support
- Family therapy
- Self-help groups
Formulation/ preparations of antipsychotics? When are the diff. formulations indicated?
- Oral pills or syrups
- Rapid- disintegrated forms for buccal absorption for non-adherent patients - Injections:
- Slow-release antipsychotics for non-compliant patients
Distinguish the MoA between typical and atypical anti-psychotics? Can they cure schizophrenia or bipolar disorder?
Typical = high affinity for Dopamine D2 receptors
Atypical = High affinity for 5-HT2 receptors
Both types do not cure schizophrenia and bipolar, but can ameliorate the symptoms
Outline the dopamine hypothesis for psychosis development?
increased dopamine release cause aberrant salience: influence behavior inappropriately*****
> > psychosis
Evidence supporting the dopamine hypothesis?
1) Many antipsychotic drugs block brain dopamine receptors (especially D2 receptors)
2) Dopamine agonists (e.g. amphetamine, levodopa, cocaine, cannabis) exacerbate psychosis
3) Untreated schizophrenics have increased density of dopamine receptors in certain brain regions
Evidence against dopamine hypothesis?
Antipsychotic drugs are not effective in all patients: other transmitters involved
Atypical antipsychotics work despite not blocking D2 receptor
List the 3 dopaminergic tracts in the brain?
Nigrostriatal pathway: substantia nigra to striatum
Mesolimbic and mesocortical pathways: ventral tegmental area to nucleus accumbens, amygdala, hippocampus, prefrontal cortex
Tuberoinfundibular pathway: hypothalamus to pituitary gland
Function of the 3 dopaminergic tracts?
Nigrostriatal = Extrapyramidal** motor control/ modulation
Tuberoinfundibular = Hormonal regulation (e.g. control prolactin release)**, maternal behavior, pregnancy
Mesolimbic and Mesocortical = Regulate memory, motivation, emotion, addiction, reward and desire
Blockage of Nigrostriatal pathway causes what disease?
Parkinsons
Blockage of mesolimbic and mesocortical pathways cause what diseases?
Hallucinations
Schizophrenia
Effects of D2 receptor blocker on the Nigrostriatal pathway?
Extrapyramidal symptoms
Effects of D2 receptor blockage by typical antipsychotics on the 3 dopaminergic pathways?
Block mesolimbic and mesocortical pathways = GOOD, Antipsychotic effect
Block nigrastriatal pathway = EXTRAPYRAMIDAL SYMPTOMS
Block Tuberoinfundibular pathways = PROLACTIN dysregulation
List the side effects of typical antipsychotics? (4)
D2 receptor blocker interrupt normal dopaminergic pathways:
Extrapyramidal symptoms
Hyperprolactinemia symptoms
Drowsiness
Neuroleptic malignant syndrome (NMS): temperature regulation center to fail
List the symptoms under Extrapyramidal symptoms caused by typical anti-psychotics?
1) Acute dystonia = hyperkinetic movement disorder
2) Akathisia (restlessness)
3) Parkinsonism (muscle regidity, tremor, cognitive impairment)
4) Tardive dyskinesia (inoluntary mouth movement)
Describe the effects of D2 receptor blocker on the Tuberoinfundibular pathway?
Loss of inhibition on pituitary prolactin
> > high prolactin levels / hyperprolactinemia (both men, women)
> > pseudopregnancy
1) Gynecomastia (swollen breasts)
2) Galactorrhea (milk discharge)
3) Loss of libido
4) Low FSH and LH cause sexual dysfunction
What are some symptoms under neuroleptic malignant syndrome caused by typical antipsychotics?
Motor / behavioural:
- Rigidity, muscle breakdown
- Immobility
Autonomic
- Fever ***
- Tachycardia
- Dilation of pupils
- Elevated / unstable blood pressure
Explain why atypical antipsychotics have less side effects seen in typical antipsychotics?
5HT2 receptor binding mostly
Quickly dissociate from D2 receptor thus reduces side effects:
Less neuroleptic malignant syndrome + less extrapyramidal signs + less hyperprolactinaemia
Compare the psychotic signs treated by typical vs atypical antipsychotics?
Typical = only Positive signs
Atypical = BOTH positive and negative signs
List examples of typical antipsychotics
Haloperidol**
Chlorpromazine**
fluphenazine, trifluoperazine
List examples of atypical antipsychotics
Olanzapine, clozapine, ziprasidone
Riseperidone
quetiapine **
Aripiprazole**
** = most prescribed
ADR of atypical antipsychotics?
- Increase risk of high blood sugar= Increased risk of diabetes ***
- Elevated lipids and cholesterol = Severe weight gain *** (obesity)
Other side effects:
- Block α1 adrenergic receptors
- Block muscarinic receptors
- Block histaminergic receptors
***COMMON
Do atypical antipsychotics suffer from side effects of typical antipsychotics?
Yes, but much, much rarer than in typical antipsychotics
Neuroleptic malignant syndrome + Hyperprolactinaemia + Extrapyramidal signs
List all the receptors blocked by atypical antipsychotics?
- 5HT2 receptor mainly
- D2 receptor
- α1 adrenergic receptors
- muscarinic receptors
- histaminergic receptors
List the ADR from the non serotonin receptors blocked by atypical antipsychotics?
Block:
α1 adrenergic receptors»_space; reflex tachycardia and postural hypotension
muscarinic receptors = anticholinergic symptoms: hyperthermia, tachycardia, mydriasis, dry mouth, constipation, urinary retention
histaminergic receptors»_space; sedation and slowness
Risks of long-term prescription of atypical antipsychotics to children?
Brains are still developing – unclear adverse effects of antipsychotic to brain
Severe weight gain, 2-4x increased risk of diabetes in youth
What can cause anti-psychosis withdrawal symptoms?
Dosage reduction / discontinuation
Suddenly Switching one drug to another
List some antipsychotic withdrawal symptoms?
Tardive dyskinesia Nausea and vomiting) Anorexia Anxiety/ Agitation Insomnia Psychosis *** relapse
Explain the physiology of super-sensitive psychosis?
Antipsychotics block dopaminergic receptors
> > compensatory increase number, sensitivity of dopamine receptors, drug withdrawal cause super-activation of dopamine receptors
> > super-sensitivity psychosis
List one antipsychotic used to treat autism
risperidone
Treat irritability in children, adolescents with autism
Do antipsychotics work on depression or anxiety?
Works for depression
Doesnt work for anxiety
List some off-label uses of antipsychotics?
- Autism spectrum disorders **
- Alzheimer’s disease **
- Depression **
- Dementia