Antipsychotic Medications

I. Typical or first-generation antipsychotics, sometimes referred to as neuroleptics, are classified

by potency and block dopamine (D2) receptors.
a. Potency refers to the action on dopamine receptors, not the level of efficacy. Both low and
high potency antipsychotics have the same level or efficacy, but to reach that level different
dosages are required.
b. Highly lipid soluble & stored in body fat, thus, very slow to be removed from the body.
II. Indications:
a. Schizophrenia, acute or chronic psychosis, bipolar disorder, dementia, postpartum
psychosis, delirium, acute confusional states, and treatment resistant depression.
III. More effective at treating the presence of positive psychotic symptoms, such as hallucinations
& delusions.
IV. Low-Potency, Typical Antipsychotics
a. Higher incidence of anticholinergic & antihistamine side effects than high-potency
traditional antipsychotics.
b. Have a lower incidence of EPS & neuroleptic malignant syndrome.
c. More lethality in overdose due to QT prolongation and the potential for heart block &
ventricular tachycardia.
d. Rare risk for agranulocytosis (failure of the bone marrow to make white blood cells), &
they have a slightly higher seizure risk than higher-potency medications.
e. Chlorpromazine (Thorazine):
i. Commonly causes orthostatic hypotension (low blood pressure that occurs when
you stand up from a sitting or lying down position).
ii. Can cause bluish skin discoloration
iii. Can cause photosensitivity
iv. Can cause deposits in lens & cornea.
v. Can treat nausea & vomiting, as well as intractable hiccups.
f. Thioridazine (Mellaril):
i. Associated w/ retinitis pigmentosa (irreversible retinal pigmentation).
V. Midpotency, Typical Antipsychotics
a. Have midrange properties.
b. Loxapine (Loxitane):
i. Higher risk of seizure
ii. Metabolite is an antidepressant
c. Thiothixene (Navane):
i. Can cause ocular pigment changes
d. Trifluoperazine (Stelazine):
i. Can reduce anxiety
e. Perphenazine (Trilafon)
VI. High-potency, Typical Antipsychotics
a. Have a greater affinity for dopamine receptors, & therefore a relatively low dose is needed
to achieve effect.
b. Cause less sedation, orthostatic symptoms & anticholinergic effects.
c. Greater risk for extrapyramidal symptoms & tardive dyskinesia.
d. Haloperidol (Haldol): Decanoate form available
e. Fluphenazine (Prolixin): Decanoate form available
i. Decanoate means that they are available in a long-acting intramuscular form that is
useful if patients dont like taking oral medications.
f. Pimozide (Orap):
i. Associated w/ heart block, ventricular tachycardia, & other cardiac effects.
VII. Antidopaminergic effects:
a. Extrapyramidal Symptoms (EPS):
i. Parkisonism bradykinesia, masklike facies, cogwheel rigidity, pill-rolling tremor.
ii. Akathisia subjective anxiety & restlessness, objective fidgetiness. Patients may
report a sensation of inability to sit still.
iii. Dystonia sustained painful contraction of muscles of neck (torticollis), tongue,
eyes (oculogyric crisis). Life-threatening if they involve the airway or diaphragm.
iv. Treatment:
1. Reduce dose of the antipsychotic.
2. Administer an anticholinergic medication such as benztropine (Cogentin), an
antihistaminergic medication such as diphenhydramine (Benadryl), or an
antiparkinsonian medication such as amantadine (Symmetrel).
b. Hyperprolactinemia decreased libido, galactorrhea (milky discharge from the nipple),
gynecomastia (enlargement of breast tissue in males), impotence, amenorrhea,
osteoporosis.
c. Anti-HAM effects (Histaminergic, Adrenergic, & Muscarinic Receptor action)
i. Antihistamine results in sedation, weight gain.
ii. Anti-alpha adrengic results in orthostatic hypotension, cardiac abnormalities, &
sexual dysfunction.
iii. Antimuscarinic anticholinergic effects (dry mouth, tachycardia, urinary retention,
blurry vision, constipation, & precipitation of narrow-angle glaucoma).
d. Tardive dyskinesia (TD):
i. Choreoathetoid (writhing) movements of mouth & tongue that may occur in
patients who have used neuroleptics for > 6 months.
ii. 50% of cases will spontaneously remit, but many cases may be permanent.
iii. There is roughly a 1% chance of developing tardive dyskinesia for each year on a
typical antipsychotic.
iv. Treatment: discontinue current antipsychotic and switch to a medication w/ less
potential to cause tardive dyskinesia.
e. Neuroleptic malignant syndrome:
i. Rare, most often occurs in young males early in treatment with both atypical &
typical antipsychotics.
ii. It is a medical emergency and has a 20% mortality rate if left untreated.
iii. Characterized by the following (FALTERED):
1. Fever (most common presenting symptom)
2. Autonomic instability (tachycardia, labile hypertension, diaphoresis
[excessive sweating])
3. Leukocytosis
4. Tremor
5. Elevated creatine phosphokinase
6. Rigidity
7. Excessive sweating (diaphoresis)
8. Delirium
iv. Treatment: discontinuation of current medication and supportive medical care.
v. This does not mean that the patient cannot restart the same neuroleptic at a later
time.
vi. Antipsychotics lower seizure thresholds.
1. Low-potency antipsychotics are more likely to cause seizures than high
potency.