Antipsychotic drugs - French Flashcards
Name and describe 4 dopamine pathways.
- Mesolimbic (VTA –> NAc)
- Mesocortical (VTA –> frontal cortex)
- Nigrostriatal (SN –> Striatum)
- Tuberoinfundibular (Hypothalamic release of dopamine prevents prolactin release)
Hyperactivity in the mesolimbic pathway accounts for what type of symptoms?
What category of drugs is useful for relieving these symptoms?
Positive symptoms (hallucinations, delusions)
Antipsychotic agents (via D2 dopamine receptor blockade)
Hypoactivity in the mesocortical pathway accounts for what type of symptoms?
What category of drugs is useful for relieving these symptoms?
Negative symptoms (flattening, disordered speech, disordered thought)
atypical antipsychotic agents such as CLOZAPINE or olanzapine (via additional BLOCK of 5HT2A receptors)
D2 receptor blockade often causes side effects related to the nigrostriatal and tuberoinfundibular pathways. What side effects stem from each?
Nigrostriatal–> extrapyramidal symptoms
Tuberoinfundibular–> blockade of dopamine receptors causes prolactin release. Leads to weight gain, hyperprolactinemia, and interferes with body temperature regulation (poikilothermia)
LSD and other hallucinogens act as ____ agonists and activation of _____ receptors leads to the hallucinogenic effects.
serotonin; 5HT2A
Activation of 5HT2A receptors on DA neurons in the PFC
will (INcrease or DECrease) DA release leading to (NEGative or POSitive) symptoms?
So would an antagonist or agonist be desired?
Decrease
Negative
Antagonist
Activation of 5HT2A receptors on glutamate pyramidal cells in the PFC result in stimulation of DA neurons in VTA will (increase or decrease) DA release in the mesolimbic pathway leading to (positive or negative) symptoms?
Treat with antagonist or agonist?
Increase
Positive
Antagonist
What is the glutamate hypothesis?
Account for both positive and negative symptoms.
HYPOfunction of NMDA receptors located on GABAergic interneurons in the PFC leads to decreased inhibitory tone, which INCREASES CORTICAL OUTPUT, resulting in:
1) increased mesolimbic DA release (+ symptoms)
2) decreased mesocortical DA release (- symptoms)
“Typical” agents (1st generation) are characterized by what? What is the adverse affect?
Characterized by a high D2 / 5HT2A ratio corresponding to good D2 block and good efficacy against positive symptoms of schizophrenia. But this good D2 block is also associated with a high incidence of extrapyramidal toxicity.
Name two typical agents. State their potency and the side effect fallout.
Haloperidol - High potency. Lower doses can be used with good efficacy, greater risk of extrapyramidal toxicity.
Chlorpromazine - Low potency. Higher doses required leads to antimuscarinic, α1-blockade, and antihistamine side effects.
What explains the most significant pharmacologic effects of antipsychotic agents?
D2 blockade.
[BUT efficacy has been found in antipsychotic agents that block 5HT2 receptors without possessing potent blockade of D2 receptors]
What characterizes “atypical” agents (2nd generation)?
Characterized by a low D2 / 5HT2A ratio corresponding to poor D2 block yet… good efficacy in schizophrenia
Mnemonic: (an “atypical” observation).
Good efficacy against NEGATIVE symptoms of schizophrenia.
Name 3 atypical agents. [4 bonus]
Aripiprazole (Abilify)
Clozapine
Olanzapine
[Bonus: Quetiapine]
Will antipsychotic agents cross the placenta? Will they distribute into breast milk?
Yes, and yes.
As a general rule, what can guide selection of a typical vs atypical antipsychotic, with regard to control of positive/negative symptoms?
Both are effective at controlling positive symptoms.
Atypical are more effective at resolving negative symptoms.
______ is effective in majority of schizophrenic patients that are refractory to other drugs. It should be reserved for this specific indication because of frequency of substantial increases in weight and lipids as well as a 1-2 % incidence of agranulocytosis.
Clozapine
What is the side effect profile of Chlorprozamine?
1) Dry mouth, constipation ( Autonomic - Muscarinic blockade)
2) orthostatic hypotension (α1-adrenergic blockade)
3) Sedation (Muscarinic blockade, antihistamine activity)
What is the main side effect of note for Haloperidol?
Considerable EPS profile
What are two main side effects of Risperidone? (Atypical)
Extrapyramidal dysfunction, hypotension with high dose
What are two main side effects of Olanzapine (Atypical)
EPS, lowering of seizure threshold.
Your patient is concerned about feeling “sleepy” while taking antipsychotic meds. What two might you consider?
Aripiprazole
Risperidone
Your patient is concerned about weight gain. What antipsychotic medications might you avoid prescribing?
What might you prescribe?
Olanzapine
Clozapine
Try aripiprazole.
This drug is generic and inexpensive, but has many autonomic side effects.
Chlorpromazine
This drug is generic, but causes severe extrapyramidal syndrome
Haloperidol
This drug should be considered for treatment-resistant patients, and has few EPS side effects. However, it is associated with agranulocytosis or seizures in a small percent of patients.
Clozapine
This drug has broad efficacy, with little or no EPS effects at low dose. At high doses the EPS profile increases, and patients may be at risk of hypotension.
Risperidone
This drug is effective against both positive and negative symptoms, with little EPS dysfunction. However, it lowers the seizure threshold and can cause weight gain.
Olanzapine.
This drug has a lower weight gain risk, longer half life, and has few known side effects.
Aripiprazole
