Antipsychotics

Question 1

Indications for antipyschotics

Answer 1

schizophrenia, schizoaffective disorder, bipolar disorder- for mood stabilization and/or when psychotic features are present, psychotic depression, augmenting agent in treatment resistant anxiety disorders

Question 2

Mesocortical pathway

Answer 2

projects from the ventral tegmentum (brain stem) to the cerebral cortex. This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise. Problem here for a psychotic patient, is too little dopamine.

Question 3

Mesolimbic pathway

Answer 3

projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system. This pathway is where the positive symptoms come from (hallucinations, delusions, and thought disorders). Problem here in a psychotic patient is there is too much dopamine.

Question 4

Nigrostritatal pathway

Answer 4

projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia. This pathway is involved in movement regulation. Remember that dopamine suppresses acetylcholine activity. Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia and dystonia.

Question 5

Tuberoinfundibular pathway

Answer 5

projects from the hypothalamus to the anterior pituitary. Remember that dopamine release inhibits/regulates prolactin release. Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia (gynecomastia/galactorrhea/decreased libido/menstrual dysfunction).

Question 6

Typical antipsychotics

Answer 6

Mostly D2 dopamine receptor antagonists.

Question 7

High potency typical antipsychotics

Answer 7

High potency typical antipsychotics bind to the D2 receptor with high affinity. As a result they have higher risk of extrapyramidal side effects

Question 8

Low potency typical antipsychotics

Answer 8

Low potency typical antipsychotics have less affinity for the D2 receptors but tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects including sedation, hypotension. Examples include chlorpromazine and Thioridazine.

Question 9

Atypical antipsychotics

Answer 9

atypical agents are serotonin-dopamine 2 antagonists (SDAs) They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain

Question 10

Risperidone

Answer 10

Available in regular tabs, IM depot forms and rapidly dissolving tablet
Functions more like a typical antipsychotic at doses greater than 6mg
Increased extrapyramidal side effects (dose dependent)
Most likely atypical to induce hyperprolactinemia
Weight gain and sedation (dosage dependent)

Question 11

Olanzapine

Answer 11

Available in regular tabs, immediate release IM, rapidly dissolving tab, depo form
Weight gain (can be as much as 30-50lbs with even short term use)
May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
May cause hyperprolactinemia (< risperidone)
May cause abnormal LFT’s (2% of all patients)

Question 12

Quetiapine

Answer 12

Available in a regular tablet form only
May cause abnormal LFT’s (6% of all patients)
May be associated with weight gain, though less than seen with olanzapine
May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain), however less than olanzapine
Most likely to cause orthostatic hypotension

Question 13

Ariprazole

Answer 13

Available in regular tabs, immediate release IM formulation and depo form
Unique mechanism of action as a D2 partial agonist
Low EPS, no QT prolongation, low sedation
CYP2D6 (fluoxetine and paroxetine), 3A4 (carbamazepine and ketoconazole) interactions that the manufacturer recommends adjusted dosing. Could cause potential intolerability due to akathisia/activation.
Not associated with weight gain

Question 14

Clozapine

Answer 14

Available in 1 form- a regular tablet
Is reserved for treatment resistant patients because of side effect profile but this stuff works!
Associated with agranulocytosis (0.5-2%) and therefore requires weekly blood draws x 6 months, then Q- 2weeks x 6 months)
Increased risk of seizures (especially if lithium is also on board)
Associated with the most sedation, weight gain and abnormal LFT’s
Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain

Question 15

Tardive dyskinesia

Answer 15

involuntary muscle movements that may not resolve with drug discontinuation- risk approx. 5% per year

Question 16

Neuroleptic Malignant Syndrome

Answer 16

Characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts. Potentially fatal.

Question 17

Extrapyramidal side effects

Answer 17

Acute dystonia, Parkinson syndrome, Akathisia

Question 18

Most common psychotic symptom

Answer 18

Lack of insight

Question 19

What should be considered in schizophrenic patients

Answer 19

Consider long acting intramuscular

Question 20

Atypical antipsychotics can cause

Answer 20

dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain

Question 21

What bloods should be done before starting atypical antipsychotics

Answer 21

Fasting lipid profile
Fasting blood sugar
Lfts
CBC

Question 22

Treatment of akathisia

Answer 22

Anticholinergic agent or propanolol