L51 - Anti-psychotics Flashcards by Max Kam

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

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List the positive symptoms of psychosis?

Hallucination
Delusion
Agitation
Disorganized thinking

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Define Hallucination?

 Perceive something that does not exist in reality (feeling)
 Can occur in any of the 5 senses

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Define delusion?

cannot separate real from unreal experiences

 strongly believe things that, when examined rationally, are not true/rational

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Define agitation

unpleasant state of increased tension and irritability

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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

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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

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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

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3 major causes of psychosis?

Psychological conditions
General medical conditions causing secondary psychosis
Drugs

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List psychological conditions that cause psychosis?

Schizophrenia (repeated psychosis)

Bipolar disorder (extreme mood swings)

Severe stress or anxiety

Lack of sleep

Severe depression

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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

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List some substances that can trigger psychosis?

Severe alcohol intake
Chronic Cannabis use
Cocaine
Amphetamine
Meth, LSD, Ketamine, MDMA, Mephedrone

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Compare the general MoA of antipsychotics vs antidepressants

Antidepressant = Increase monoamine neurotransmitters

Antipsychotics = BLock Dopamine

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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

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Differentiate the types of dopamine receptors?

5 different dopamine receptors (D1-D5):
 D1, D5: activate adenylate cyclase
 D2, D3, D4: inhibit adenylate cyclase

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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

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List some non-medication treatment options for psychosis?

Psychological therapies
Social support
Family therapy
Self-help groups

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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

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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 >> reflex tachycardia and postural hypotension muscarinic receptors = anticholinergic symptoms: hyperthermia, tachycardia, mydriasis, dry mouth, constipation, urinary retention histaminergic receptors >> 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