Antipsychotic drugs

Question 1

Antipsychotics generally exert influence on which dopaminergic pathways?

Answer 1

Mesocortical and mesolimbic

Question 2

First-generation (typical) antipsychotics?

Answer 2

Haloperidol (high potency), perphenazine (mid potency), chlorpromazine (low-potency)

Question 3

First-generation (typical) antipsychotics: MOA

Answer 3

High-affinity dopamine (D2) receptor antagonists

Question 4

First and second generation antipsychotics: Indications

Answer 4

Treats Sx of psychosis.
Primarily used to treat
schizophrenia and
schizoaffective
disorder. Also used to
treat other psychoses
(e.g., psychosis
secondary to mood
disorders, delirium, and
intoxication).

Question 5

How are first and second generation antipsychotics different?

Answer 5

1st and 2nd
Gen are differentiated by
their potency, R affinity,
and SE’s. Not, however,
vastly different in their
antipsychotic efficacy
with one key exception (clozapine).

Question 6

Which antipsychotic has been proven to be consistently efficacious for schizophrenia? What is the dangerous side effect of this medication?

Answer 6

Clozapine is consistently
more efficacious for
schizophrenia

(Note:
Clozapine has potentially
life-threatening SE of
agranulocytosis ->
makes it a 2nd-line
agent; mainly used for treatment of refractory schizophrenia.

Clozapine also has side effects of myocarditis and metabolic syndrome.

Question 7

What are the second-generation (atypical) antipsychotics?

Answer 7

Aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone.

Question 8

What are general side effects of ALL antipsychotics?

Answer 8

1. General:
   a. All delay cardiac conduction (thus prolong the QTc interval), putting Pts
   at slightly higher risk of developing torsades de pointes.
   b. All have a black box warning that they increase the rate of death in elderly
   patients with dementia-related psychosis

Question 9

What are anticholinergic side effects of antipsychotics? What’s the difference between high-potency and low-potency antipsychotics in terms of side effects?

Answer 9

2. Anticholinergic effects: As the antipsychotic potency changes, so do the
   side effects.
   a. Lower-potency antipsychotics (such as chlorpromazine) have more
   anticholinergic side effects: blurred vision, constipation, dry mouth,
   orthostatic hypotension, sedation, and urinary retention.
   b. Higher-potency antipsychotics (such as haloperidol) exhibit stronger
   dopaminergic antagonism and thus have more extrapyramidal symptoms
   (see below).

Question 10

What causes extrapyramidal symptoms?

Answer 10

2/2 negative effects of D2 antagonism along the

nigrastriatal pathway

Question 11

What is acute dystonic reaction? What is the treatment? What’s the time of onset?

Answer 11

Tends to develop over hours to days. A dystonia
is the sustained contraction of muscles, usually in the neck, mouth, or tongue.
Treatment: intramuscular diphenhydramine or benztropine

Question 12

What is akathisia? What is the time of onset?

Answer 12

Tends to develop over days to weeks. Defined as a feeling of
inner restlessness that manifests in both a subjective (anxiety, agitation, etc.)
and objective (pacing, rocking, etc.) manner.

Question 13

What is Parkinsonism? What is the time of onset of sx? What is treatment?

Answer 13

Tends to develop over weeks to months. Clinically
indistinguishable from idiopathic Parkinson’s disease → manifested by
tremor, cogwheel rigidity, and/or hypokinetic movements. Treatment: lower
dose of antipsychotic and administer diphenhydramine or benztropine

Question 14

What is tardive dyskinesia? What is time of onset? What is treatment?

Answer 14

Develops after 6+ months as a result of chronic D2
blockade. Characterized as an abnormal, irregular, hyperkinetic movement
disorder involving the head, limbs, and trunk. Perioral movements (tongue,
facial grimacing, and lip puckering) are the most common form. While
traditionally thought to be irreversible, the course is variable and may even be
reversible if caught very early on in its development. Treatment: if on first-generation
drug → change to second-generation; if already on second-generation
drug → change to clozapine

Question 15

What causes hyperprolactinemia? What symptoms does hyperprolactinemia cause in patients? What two drugs are the most likely to cause hyperprolactinemia?

Answer 15

a. Excessive dopamine blockade along the tuberoinfundibular pathway
stimulates prolactin release.
b. Can result in osteoporosis, amenorrhea, galactorrhea, gynecomastia,
and sexual side effects.
c. Haloperidol and risperidone are the most common offenders.

Question 16

Which class of antipsychotics is associated with metabolic syndrome?

Answer 16

Second-generation antipsychotics are associated with metabolic
syndrome, characterized by weight gain, diabetes, hyperlipidemia, and
hypertension.
b. These drugs induce insulin resistance and dyslipidemia independent of
the associated weight gain, which overall elevate patients’ cardiovascular risk
factors/events.

Question 17

What is neuroleptic malignant syndrome?

Answer 17

a. A rare but potentially fatal idiosyncratic reaction to the dopamine blockade.
Can occur after any duration of treatment, although two thirds of cases occur
within the first week.
b. Characterized by confusion, vital sign instability, extreme
hyperthermia, rhabdomyolysis, renal failure, cardiovascular collapse,
and eventually (if untreated) death.

Question 18

What is malignant hyperthermia? How is this different from NMS? What is the treatment for both of these conditions?

Answer 18

similar, but malignant hyperthermia is a reaction to succinylcholine or inhaled
anesthetics, not antipsychotics. Their fundamental pathophysiology is also
different. In both cases, the hyperthermia/rhabdomyolysis/etc. is caused by
extreme muscle rigidity.

In NMS, however, this rigidity is secondary to
dopaminergic blockade in the brain; in MH, the pathophysiologic mechanism
of rigidity occurs at the level of the muscle. In both NMS and MH, the
treatment is dantrolene.

Question 19

Second-generation antipsychotics: MOA

Answer 19

Second-generation or atypical antipsychotics have two distinct mechanisms of action: Weaker affinity dopamine receptor antagonists (D2) and potent serotonin (5HT-2) receptor antagonists.

Question 20

Antipsychotics: Metabolism

Answer 20

LIVER!!!!