Antipsychotics Flashcards
Name the “Typical” aka Older Antipsychotic drugs.
Name some of the “Atypicals”
Older/Typical:
- Chlorpromazine, Fluphenazine, Perphenazine, Haloperidol
Atypical: “Heterocyclics”
- Clozapine, Quetiapine, Risperidone, Zotepine, Olanzapine
What are common adverse effects for the Typical Antipsychotics?
Anticholinergic Effects
Sedation
Orthostatic Hypotension
Tachycardia
EPS and movement disorders
Less Expensive
What are the common adverse effects for the Atypical Antipsychotics?
Less likely to have EPS
Instead associated with weight gain, hyperglycemia, and diabetes
Nausea, dizziness, HA and hypotension
**Clozapine – Agranulocytosis **
What is the main mechanism of action of Antipsychotic Medications? What are the 4 major pathways that they act on?
Block D2 Receptors!!!!
Nigrostrial
Mesolimbic – target for positive symptoms
Mesocortical – target for negative symptoms
Tuberoinfundibular
Which have higher affinity for D2 receptors: Atypicals or Typicals? What is the significance of affinity? How does it relate to potency?
Typicals have high affinity for D2 receptor
Atypicals are less “sticky” and have less affinity so can block both D2 and 5HT receptors – this allows them to act more for negative symptoms
Higher affinity then less you need for effective dose (higher potency) but also cause more EPS
Lower affinity/potency tend to cause more sedation, anti-Ach, orthostatic hypotension
Of the Typicals, which ones most block the M1 cholinergic receptors in addition to D2?
Which ones block Alpha 1 more than others?
Which ones block H1 more than others?
Which one has the highest affinity for blocking D2 and least affinity for other receptor subtypes?
M1 Bloc k Thioridazine
A1 and H1 – Chlorpromazine
Haloperidol is the best!
What are the effects of blocking D2 in the Tuberoinfundibular Pathway?
Tuberoinfundibular pathway controls Prolactin secretion (hypothal to arcuate nucleus)
Blocking D2 –> Increase in prolactin secretion
= Hyperprolactinemia!!! With breast secretions, amenorrhea and infertility
What are the effects of blocking D2 in the Mesocortical Pathway?
Mesocortical Pathway – mediates negative and cognitive symptoms likely through Da deficit
Blockade of D2 here where you already have deficit in Da leads to:
- Emotional blunting
- Cognitive problems
- Essentially, mimicking negative symptoms
What are the effects of blocking D2 in the Nigrostrial Pathway?
Blocking D2 here, from SN to BG, leads to EPS and movement disorders including:
- Dystonia
- Tremor
- Akinisia – decreased movement spontaneity
- Akathisia – Motor restlessness/constant urge to move
Tardive Dyskinesia – MAY BE PERMANENT
What is Tardive Dyskinesia? What causes this?
Hyperkinetic Movement Disorder characterized by repetitive, involuntary and purposeless movements
- Facial and Tongue movements – tics and jercs*
- Rapid movements of arms, trunk and legs may appear*
- Involuntary movements of fingers*
Mechanism: D2 Blockade leads to Up-Regulation of Receptors!!! Permanent reorganization unless blockade is removed early enough
What is the relationship between Da and Ach in the BG? How can imbalance cause EPS? How can you alleviate EPS?
Normally, there’s a balance between Da and Ach
Da suppresses activity of Ach neurons and limits release when acting through receptors, when you block Da receptors you get increased Ach release/activity associated with EPS (muscarinic rec in BG)
*Anticholinergic properties of typical antipsychotics help to overcome excess Ach activity and reduce EPS but does NOT alleviate the risk for Tardive Dyskinesia
What’s the general MOA for the heterogenous group of Atypical Antipsychotics?
What are their clinical effects?
Da Antagonism – lower affinity for D2 receptors and so only occupy and block a few of those
5HT2A receptor Blockade
Clinically – effective for negative symptoms from 5HT blockade and lessen positive symptoms with lower risk of EPS
What role does the Serotonin inhibition play in the different clinical effects of the atypical antipsychotics?
In most areas of the brain, serotonin inhibits Da release BUTTTTTT in the nigrostriatal pathway, 5HT2A antagonism results in an increase in Da activity and lowers the EPS
Also, bc the Da antagonism is weaker, Da release can compete with the atypicals
How do the atypicals work in the Mesocortical pathway? What is the significance?
5HT2A antagonism releases the brake on Da in the Mesocortical pathway
High density of 5HT2A in cerebral cortex leads to more effective block and an increase in Da release which can outcompete the D2 Antagonist part
What is Neuroleptic Malignant Syndrome?
Life-threatening illness associated with antipsychotic therapy occurs within 30 days of new medication or dose increase
Clinical Manifestation: F.E.V.E.R.
- Fever
- Encephalopathy – delirium, agitation, coma
- Vital Signs unstable – Autonomic instability: high BP, tachypnea, Diaphoresis
- Elevated enzymes – CPK increased
- Rigidity of Muscles
