Typical Antipsychotics

Question 1

What do typical antipsychotics vary in?

Answer 1

Vary in potency but all have similar efficacy.

Question 2

What are the traits of Low-Potency, Typical Antipsychotics?

Answer 2

• Have a lower affinity for DA receptors and therefore a higher dose is required. Potency refers to the action on DA receptors, not the level of efficacy
• Higher incidence of anticholinergic and antihistaminic side effects than high-potency traditional antipsychotics
• Have a lower incidence of EPS and neuroleptic malignant syndrome
• As a group, they have more lethality in overdose due to QTc prolongation and the potential for heart block and ventricular tachycardia.
• Rare risk for agranulocytosis, and they have a slightly higher seizure risk than higher-potency medications

Question 3

What are the two main Low-Potency Typical Antipsychotics?

Answer 3

1. Chlorpromazine (Thorazine)

2. Thioridazine (Mellaril)

Question 4

What are the traits of Chlorpromazine (Thorazine)?

Answer 4

• Commonly causes orthostatic hypotension
• Can cause bluish skin discoloration
• Can lead to photosensitivity
• Can treat nausea and vomiting, as well as intractable hiccups

Question 5

What is the unique feature of Thioridazine (Mellaril)?

Answer 5

Associated with retinitis pigmentosa.

Question 6

What are the traits of Midpotency, Typical Antipsychotics?

Answer 6

Have midrange properties

Question 7

What are the four main Midpotency Typical Antipsychotics?

Answer 7

1. Loxapine (Loxitane)
2. Thiothixene (Navane)
3. Trifluoperazine (Stelazine)
4. Perphenazine (Trilafon)

Question 8

What are the traits of Loxapine (Loxitane)?

Answer 8

Higher risk of seizure, Metabolite is an antidepressant

Question 9

What is a trait of Thiothixene (Navane)?

Answer 9

Can cause ocular pigment changes

Question 10

What are the traits of High-Potency, Typical Antipsychotics?

Answer 10

• Have greater affinity for DA receptors, and therefore a relatively low dose is needed to achieve effect.
• Cause less sedation, orthostatic hypotension, and anticholinergic effects
• Greater risk for extrapyramidal symptoms and tardive dyskinesia

Question 11

What are the three main High-Potency Typical Antipsychotics?

Answer 11

• Haloperidol (Haldol)
• Fluphenazine (Prolixin)
• Pimozide (Orap)

Question 12

What is unique about Haloperidol (Haldol) and Fluphenazine (Prolixin)?

Answer 12

Decanoate (long term injection) form available

Question 13

What is unique about Pimozide (Orap)?

Answer 13

Associated with heart block, ventricular tachycardia, and other cardiac effects

Question 14

What are high-potency neuroleptics often used for?

Answer 14

Often given as IM injection to treat acute agitation or psychosis.

Question 15

Risperidone (Consta) and Paliperidone (Sustenna) also have…

Answer 15

…long-acting injectables, but they are more expensive.

Question 16

How do typical antipsychotics treat the positive symptoms of schizophrenia?

Answer 16

Positive symptoms are thought to be treated by action of medication in the mesolimbic dopamine pathway. The mesolimbic pathway includes the nucleus accumbens, the fornix, the amygdala and the hippocampus.

Question 17

What causes negative symptoms of schizophrenia?

Answer 17

Due to DA action in the mesocortical pathway

Question 18

What is the physiologic cause for extrapyramidal symptoms?

Answer 18

They are thought to occur through the DA pathways in the nigrostriatum

Question 19

What causes increased prolactin with typical antipsychotics?

Answer 19

Increased prolactin is related to dopamine action in the tuberoinfundibulnar area.

Question 20

What are the antidopaminergic effects of typical antipsychotics?

Answer 20

EPS (Parkinsonism - bradykinesia, masklike face, cogwheel rigidity, pill-rolling tremor, Akathisia - subjective anxiety and restlessness, objective fidgetiness. Patients may report a sensation of inability to sit still, Dystonia - sustained painful contraction of muscles of neck (torticollis), tongue, eyes (oculogyric crisis). Life-threatening if they involve the airway or diaphragm.)
Hyperprolactinemia - Can lead to decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea, osteoporosis

Question 21

What are the Anti-HAM effects of typical antipsychotics?

Answer 21

Cause by actions on Histamine, Adrenergic and Muscarinic receptors.

• Antihistaminic - results in sedation, weight gain
• Anti-alpha1 adrenergic - results in orthostatic hypotension, cardiac abnormalities, and sexual dysfunction
• Antimuscarinic - anticholinergic effects: results in dry mouth, tachycardia, urinary retention, blurry vision, constipation, and precipitation of narrow-angle glaucoma

Question 22

How do you treat EPS?

Answer 22

Reduce the dose of the antipsychotic and administer an anticholinergic medication such as benztropine (Cogent), an antihistaminergic medication such as diphenhydramine (Benadryl), or an antiparkinsonian medication such as amantadine (Symmetrel).

Question 23

What is unique about Clozapine?

Answer 23

It is the first atypical antipsychotic and is less likely to cause tardive dyskinesia.

Question 24

What important potentially permanent side effect can typical antipsychotics cause?

Answer 24

Tardive Dyskinesia (TD)

Question 25

What is Tardive Dyskinesia?

Answer 25

- Choreoathetoid (writhing) movements of mouth and tongue (or other body parts) that may occur in patient who have used neuroleptics for greater than 6 mo. - Most often occurs in older women - Though 50 percent of cases will spontaneously remit, many cases may be permanent.

Question 26

How do you treat Tardive Dyskinesia?

Answer 26

Discontinuing current antipsychotic if clinically possible and changing to a medication with less potential to cause tardive dyskinesia.

Question 27

What is a less common side effect of Typical Antipsychotics?

Answer 27

Neuroleptic Malignant Syndrome

Question 28

What is Neuroleptic Malignant Syndrome?

Answer 28

- Though rare, occurs most often in young males early in treatment with both atypical and typical antipsychotics - It is a medical emergency and has a 20 percent mortality rate if left untreated

Question 29

What are the symptoms of Neuroleptic Malignant Syndrome?

Answer 29

FALTERED: Fever (most common presenting symptom), Autonomic instability (tachycardia, labile hypertension, diaphoresis), Leukocytosis, Tremor, Elevated creatine phosphokinase (CPK), Rigidity (lead pipe rigidity is considered almost universal), Excessive sweating (diaphoresis), Delirium

Question 30

What is the treatment for Neuroleptic Malignant Syndrome?

Answer 30

Involves discontinuation of current medications and administration of supportive care (hydration, cooling, etc.)

Question 31

What is the chance of developing Tardive Dyskinesia?

Answer 31

There is a roughly one percent chance of developing TD for each year on a typical antipsychotic.

Question 32

What is the onset time line for Acute dystonia, EPS/Akathisia and TD?

Answer 32

``` Neuroleptic side effects: -Acute dystonia: Hours to days -EPS/Akathisia: Days to months -TD: Months to years Abnormal Involuntary Movement Scale (AIMS) can be used to quantify and monitor for tardive dyskinesia. ```

Question 33

Treatment for side effects:

Answer 33

Sodium dantrolene, bromocriptine and amantadine are infrequently used because of their own side effects and unclear efficacy.

Question 34

What should be remembered about typical antipsychotic side effects?

Answer 34

- This is not an allergic reaction. - Patient is NOT prevented from restarting the same neuroleptic at a later time - Elevated liver enzymes, jaundice

Question 35

What are ophthalmologic problems caused by typical antipsychotics?

Answer 35

Irreversible retinal pigmentation with high doses of thioridazine, deposits in lens and cornea with chlorpromazine

Question 36

What are dermatologic problems caused by typical antipsychotics?

Answer 36

Rashes and photosensitivity (blue-gray skin discoloration with chlorpromazine)

Question 37

Typical antipsychotics and seizures:

Answer 37

Antipsychotics lower seizure thresholds. Low-potency anti-psychotics are more likely to cause seizures than high potency.