Antipsychotics

Question 1

What are antipsychotic medications used for?

Answer 1

1. Schizophrenia
2. Delusional disorders
3. Bipolar
4. Depressive psychoses

Question 2

First generation VS Second generation antipsychotics
- MOA

Answer 2

First generation:
- MOA - these medications all cause a strong blockade of dopamine in the CNS. Due to this strong blockade, all of these medications have the potential to cause EPS symptoms, similar as to what is seen in Parkinson’s disease.

Second generation:
- MOA - moderate blockade of dopamine in the CNS, strong blockade of serotonin in the CNS. The reduction in dopamine inhibition results in reduced risk for EPS symptoms. Increase in serotonin blockage leads to the major drawbacks of weight gain, diabetes, and dyslipidemia.

Question 3

What is schizophrenia?
What are the three types of symptoms?

Answer 3

Chronic psychiatric illness that is characterized by disordered thinking and reduced ability to comprehend reality.

Schizophrenia symptoms can manifest as three main types:
1. Positive symptoms - exaggeration or distortion of normal function (hallucinations, delusions, agitation, tension, or paranoia)
2. Negative - loss or reduction of normal functioning (lack of motivation, poverty of speech, blunted affect, poor self-care, withdrawal).
3. Cognitive - Disordered thinking, reduced ability to focus, prominent learning and memory difficulties.
3. Cognitive

Question 4

Haloperidol
- Drug classification
- MOA
- Indications
- Adverse effects

Answer 4

Haloperidol is a first generation antipsychotic

Creates a blockade of varying receptors both in and outside the CNS. Dopamine, acetylcholine, histamine, and norepinephrine are all blocked to varying degrees. The thought is that overall, these receptors being blocked leads to a reduction in mesolimbic area of the brain (reward center of the brain, largely attributed to dopamine activation).

Indications - Schizophrenia is the primary indication for use. Improvements of symptoms can take a couple of days to start and full improvement or effect is not felt for up to months after initial use.

Adverse effects:
- Development of EPS symptoms is the primary worry when taking first generation antipsychotics. With tardive dyskinesia being the worst of adverse effects.
+ Acute dystonia
+ Parkinson’s symptoms
+ Akathisia
- Neuroleptic malignant syndrome
- Anticholinergic effects
- Sedation
- Neuroendocrine effects
- Seizures
- Sexual dysfunction
- Dysrhythmias

Question 5

What is acute dystonia? How does it present with antipsychotic use? Treatment?

Answer 5

Acute dystonia is the development of severe muscle spasms of the tongue, face, neck, or back. Oculogyric crisis (involuntary upward deviation of the eyes) and opisthodomos (tetanic spasms of the back) can occur. Spasms can be so severe that dislocation can occur.

These symptoms can occur within the first couple hours or days of initial therapy with first generation antipsychotics.

Treatment - IV or IM administration of anticholinergic medication for intense symptoms.

Question 6

Parkinsonism? How does it relate to antipsychotic use? Treatment?

Answer 6

Parkinson’s disease like symptoms that occur with first generation antipsychotic as a potential adverse effect.

Symptoms:
- Drooling
- Bradykinesia
- Tremor
- Rigidity, shuffling gait
- Stooped posture

Treatment is through use of anticholiergic medications for a brief period of time (up to months).

Question 7

Akathisia

Answer 7

Pacing, squirming, inability to sit still. Profound restlessness. Treated with BBlockers, benzos., and anticholinergics.

Question 8

Tardive dyskinesia

Answer 8

Potential adverse effect that can occur with long-term use of first generation anti-psychotics. This is a potentially permanent disorder characterized by choreoathtoid (twisting, worm-like, writhing motions).

Question 9

Neuroleptic Malignant Syndrome
- what does it occur with? Treatment?

Answer 9

NMS can potentially occur with first generation antipsychotic use.

Characterized by “lead pipe rigidity”, sudden high fevers, sweating, autonomic instability, and fluctuations in blood pressure. Seizures and coma may develop.

Treatment - dantrolene and pramipexole can be used to treat the condition. Supportive therapy is also indicated with management of temperature, blood pressure.

Question 10

What neuroendocrine effects can occur with antipsychotic use?

Answer 10

First-generation antipsychotics can increase prolactin levels by decreasing the normal inhibition caused by dopamine. Since dopamine is blocked, prolactin is increased and can lead to gynecomastia and galactorrhea and menstrual irregularities.

Question 11

What change can first generation anti-psychotics cause to CBC?

Answer 11

Agranulocytosis - neutrophils drop dangerously low, leaving the body exposed to infections and illnesses.

Question 12

What cardiac changes can occur with first generation antipsychotic use?

Answer 12

QT prolongation

Question 13

What psychiatric illness sees an almost x2 increase in mortality when treated with antipsychotics? Why?

Answer 13

Dementia - most deaths occur due to cardiovascular issues (HF or sudden death) or infection.

Question 14

How can antipsychotics affect the skin?

Answer 14

Antipsychotics can increase the risk for damage from sun exposure, caution patients to use sunscreen when outside.

Handling of anti-psychotics can result in contact dermatitis.

Question 15

Second-generation antipsychotics
- Example
- MOA
- Indications
- Adverse effects

Answer 15

Example - Clozapine, Quetiapine, Olanzapine

MOA - Moderate degree of dopamine blockage, severe degree of serotonin blockage. Also causes a degree of norepinephrine, histamine, and acetylcholine blockade.

Indications - schizophrenia, less chance of EPS symptoms that are seen with FGA.

Adverse effects:
- metabolic effects
- Neutropenia
- Seizures
- EPS symptoms
- Orthostatic hypotension

Question 16

How does weight gain, diabetes, and HLD come about with second generation anti-psychotic use?

Answer 16

Weight gain - histamine blockage. Decreased body temperature.

These same mechanisms can cause the other symptoms. Regular monitoring should be performed in patients that are recieveing these medications.