A.25 Flashcards
Antipsychotic
- 1st generation antipsychotic: Haloperidol, Droperidol, Tiapride
- 2nd generation antipsychotics: Clozapine, Olanzapine, Quetiapine, Risperidone, Aripiprazole, Cariprazine,
Psychosis
loss of reality control
Types of psychosis
Schizophrenia, Affective psychosis, other psychoses
ntipsychotics and DA receptors
- D1-like family (D1, D5), Gs-coupled
activation results in ↑adenylyl cyclase activity, ↑cAMP - D2-like family (D2, D3, D4), Gi-coupled
stimulation results in ↓adenylyl cyclase activity, ↓cAMP
Haloperidol
MOA: high selectivity for D2-R antagonism, weak binding to D1, 5-HT, α1, M-ACh-R;
ROA: i.m;
IND: management of acute psychotic disorders→ acute delirium, severe vomiting, hiccups;
Extra: good effect on + symptoms, no effect on - symptoms of schizophrenia, most widely used typical antipsychotic with EPS with high clinical potency;
SEs: EPS (dystonia, akathisia, parkinsonism, tardive dyskinesia), neuroleptic malignant syndrome, hyperprolactinemia, dry mouth, weight gain
Droperidol
MOA: D2>α1, H1;
Effect: has sedative effect;
IND: used in neuroleptanalgesia (together with fentanyl);
SEs: EPS, NMS, ↑Prolactin, dry mouth, weight gain
Clozapine
MOA: high affinity antagonist for 5-HT2A/C, M-AChR, adrenergic Rs, weak D2 antagonist;
IND: schizophrenic patients resistant to 1st generation antipsychotics, bipolar disorders;
SEs: seizures (rare), no EPS, Sedation, neuroleptic malignant syndrome, hyperprolactinemia, Cardiomyopathy, blood disorders, Agranulocytosis, QT↑, increased salivation, weight gain, metabolic effects (hyperlipidemia/↓glucose tolerance);
Extra: have effect on + and - symptoms, Dibenzepine structure, medium clinical potency, All antipsychotic decrease the seizure threshold - proconvulsive effect
Olanzapine
MOA: 5-HT2A/C>D2, M, H1, α1 antagonist→ improves negative symptoms;
Effect: pronounced action on mesolumbic system;
IND: 1st drug of choice in schizophrenia, also proven to be anti-maniac and have good mood stabilizing effect, bipolar disorders, unipolar depression (adjunctive therapy), Acute psychosis;
SEs: small EPS, Sedation, Weight gain, ↑QT interval, ↑Prolactin secretion ;
Extra: have effect on + and - symptoms, Dibenzepine structure, high clinical potency, All antipsychotic decrease the seizure threshold - proconvulsive effect
Risperidone
MOA: 5-HT2A/C ,D2, H1,α1,2 antagonist→ improves negative symptoms;
IND: acute and chronic schizophrenia, Tics of Tourette disorder in children;
SEs: EPS (dose related), hyperprolacinemia, modest weight gain and metabolic disorders, ↑QT interval; Extra: have effect on + and - symptoms, Benzisoxazole analog, high potency
Aripiprazole
MOA: 5-HT2A antagonist→ improves negative symptoms, 5HT1A and D2 partial agonist;
IND: Schizophrenia, bipolar disorders (adunctive therapy), major depressive disorder;
DOA: long acting, T1/2 up to 3 days;
SEs: small EPS, weight gain, akathisia, insomnia;
Extra: have effect on + and - symptoms, Dihydrocabostyril structure, high clinical potency
Quetiapine
MOA: 5-HT2A-R>D2 antagonist (lower affinity for D2); IND: schizophrenia, bipolar disorders, unipolar depression;
SEs: sedation, weight gain, low EPS, ↑QT interval;
Extra: have effect on + and - symptoms, Dibenzepines (tricyclic structure), low potency
Tiapride
MOA: atypical antipsychotic, D2/3 antagonist;
IND: management of alcohol psychosis, choreoathetoid movements (Tradiv dyskinesia);
Extra: have effect on + and - symptoms
Cariprazine
MOA: D3>D2 partial agonist»»5-HT2A/C inverse agonist, 5-HT7 antagonist, partial agonist of 5-HT1A; IND: Schizophrenia, bipolar disorders;
Extra: have effect on + and - symptoms, new Hungarian dicovery (!)
EPS (Extra Pyramidal Symptoms)
Dystonias (minutes),
Drug-induced parkinsonism,
Akathisia (days),
Neuroleptic malignant syndrome (NMS),
peiroral tremor,
lip smacking,
Tradive dyskinesia (weeks)
Endocrine symptoms:
Hyperprolactinemia
Tardive dyskinesia (TD)
a movement disorder that causes a range of repetitive muscle movements in the face, neck, arms and legs. TD symptoms are beyond a person’s control.
Akathisia
an inability to remain physically still.
Neuroleptanalgesia
the combination of a potent sedative analgesic agent (an opioid) and a tranquillizer
DA pathways in the brain and their function
- The nigrostriatal DA pathway: part of the extrapyramidal nervous system and controls motor functions
- The mesolimbic DA pathway: Delusions and hallucinations
- The mesocortical DA pathway: cognitive symptoms and affective symptoms of schizophrenia
- Tuberoinfundibular DA pathway: controls prolactin secretion
- The fifth DA pathway is from multiple sites, its function is unknown
The dopamine hypothesis
Amphetamines and L-DOPA can trigger psychosis
treatment for Dystonias induced by AP
Antihistamines
Which antipsychotic can cause Akathisia with high frequency?
Aripiprazole
Treatment: BDZs
most likely cause of Tradiv dyskinesia
upregulation of D2 receptors
Treatment: ↑dose of AP or give another D2 antagonist (e.g. Tiapride)
treatment for NMS (neuroleptic malignant syndrome)
stop the AP, give bromocryptine (DA agonist), stabilize BP, cool the patient, give BDZs
treatment for hyperprolactinemia
stop the AP, give bromocryptine (DA agonist)
The tuberoinfundibular pathway
a population of dopamine neurons that project from the arcuate nucleus(a.k.a. the “ infundibular nucleus”) in the tuberal region of the hypothalamus to the median emminence It is one of the four major dopamine pathways in the brain. Dopamine released at this site inhibits the secretion of prolactin from anterior pituitary gland lactotrophs by binding to D2 receptors.
Some antipsychotic drugs block dopamine in the tuberoinfundibular pathway, which can cause an increase in the amount of prolactin in the blood
The mesocortical pathway
a dopaminergic pathway that connects the ventral tegmentum to the prefrontal cortex. It is one of the four major dopamine pathways in the brain. It is essential to the normal cognitive function of the dorsolateral prefrontal cortex (part of the frontal lobe), and is thought to be involved in cognitive control, motivation and emotional response
Positive symptoms
delusion, hallucination, loss of contact with reality, thought disorder (loose associations), disorganized thinking, paranoia, bizzare behaviour, verbal or physical aggression
Negative symptoms
Bradyphrenia (reduced, poor thinking), blunted emotions, alogia (speechless, poverty of speech), anhedonia (absence of pleasure), ambivalence (mixed feelings), asociality (anti-social behaviours), decreased motivation, carelessness (poor social problem solving)
Cognitive deficit
short-term memory impairement, long-term memory impairement, verbal memory impairement, attention impairement, reduced ability to abstract, reduced viligance
Schizophrenia symptoms
The symptoms of schizophrenia are usually classified into: positive symptoms – any change in behaviour or thoughts, such as hallucinations or delusions. negative symptoms – where people appear to withdraw from the world around them, take no interest in everyday social interactions, and often appear emotionless and flat
Schizophrenia
paranoid, catatonic, hebephrenia (disorganized)
Affective psychoses
Bipolar disorders (type I and II) - manic phase is always considered psychotic, Major depression - only very severe cases are considred psychosis
Other psychoses
Schizoaffective, Drug induced, Psychosis from organic reasons (e.g. dementia, Parkinson psychosis)
Catatonia
a state in which someone is awake but does not seem to respond to other people and their environment
Hebephrenia
a form of schizophrenia characterized especially by incoherence, delusions lacking an underlying theme, and affect that is usually flat, inappropriate, or silly
- delusions, hallucinations, disorganized speech and thoughts, disorganized or catatonic behavior, negative symptoms, such as an inability to show emotion or perform routine tasks.
What is the best drug to treat negative symptoms of schizophrenia?
Cariprazine or Aripiprazole
note: Cariprazine is a distinctive AP agent due to its D3 preferential dopamine partial agonism, which makes it preferable with prominent negative symptoms
Which symptoms is most unlikely to be caused by antipsychotic drugs?
- hypotension
- nausea
- Tradive dyskinesia
- EPS
- Weight gain
- Nausea
