First generation antipsychotics represented a great advance in the psychopharmacological management of mental illness. The drugs are not perfect, of course. The "first" first generation antipsychotic was chlorpromazine (Thorazine), which was actually used at the time by anesthesiologists as an anti-emetic (First generation antipsychotics are reasonable anti-emetics, such as prochlorperazine). Some psychotic patients were calmer after surgery and hence the evolving use of chlorpromazine in psychiatry.
First generation antipsychotics are sometimes referred to as neuroleptics. This label is only properly applied to first (and not second) generation antipsychotics as it refers to the way in which such drugs were developed and identified. Namely, if a medication led to Parkinsonian signs (i.e., neurolepsis) in animal models, then it tended to work as an antipsychotic in humans. This principle, and the subsequent determination of the role of the dopaminergic D2 receptor, governed the development of antipsychotic medications for some time.
Considerations
With a first-generation antipsychotics one of the major considerations is the occurrence of extrapyramidal symptoms, which can occur in as many as 50-75% of the patients taking such medications. High potency antipsychotics, such as fluphenazine and haloperidol are more strongly associated with extrapyramidal symptoms that are low potency antipsychotics, such as thioridazine or chlorpromazine. At first, this may make low potency antipsychotics appear to be a better choice, but they are associated with fairly significant anticholinergic side effects. Because anticholinergic effects can exacerbate or even cause delirium, low potency of the psychotics are very poor choice for treating delirium in the medically ill.
Extrapyramidal symptoms
Although extrapyramidal symptoms can be uncomfortable, they can generally be addressed with the medications such as been benztropine, diphenhydramine, or trihexyphenidyl. However, these medications have anti-cholinergic side effects that can be undesirable, especially in older adults.
More worrisome than extrapyramidal symptoms, however, is the occurrence of acute dystonic reactions. The first generation of the psychotics dysthymic reactions tend to be more common in younger, African-American, antipsychotic naive males. One of the most common causes of the stomach reactions on inpatient services (other than psychiatry), is the use of high-dose phenothiazines agents, such as metoclopramide.
Lowering the seizure threshold
Especially at higher doses, first-generation antipsychotics can lower the seizure threshold. This becomes especially relevant in brain injured populations or in patients with epilepsy. The increase in seizure risk from phenothiazines, for example, is approximately tenfold relative to the general population. ★Of note, the second-generation antipsychotic, clozapine, is associated with features at higher doses and typically requires prophylactic valproic acid.
Sedation is a common side effect of first-generation antipsychotics, especially low potency antipsychotics.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is the most serious complication associated with first-generation antipsychotic therapy. Neuroleptic malignant syndrome is fortunately rare and is not unique to psychiatric populations, as it can even occur in non-psychiatrically ill patients receive phenothiazines, such as metoclopramide. Nearly malignant syndrome usually develops over 1-3 day period and can last for 5-10 days after the antipsychotic is discontinued. If a patient is taking a long-acting antipsychotic, obviously neuroleptic malignant syndrome can be prolonged. The mortality from neuroleptic malignant syndrome is high and the neighborhood of about 20% (it would be much higher, but the detection rate has been improving. The classic signs of neurological in its interim or provided in this table.
Cardiovascular effects
Haloperidol is known for prolonging the QTc interval, especially when given intravenously. However, a other first-generation antipsychotics also prolong the QTc interval, such as thioridazine, mesoridazine, and droperidol. In addition, some second-generation antipsychotics can prolong the QTc interval, it usually to a much lesser degree. As discussed elsewhere, an EKG should be obtained prior to the administration of haloperidol intravenously.
Impaired thermoregulation
Antipsychotics can interfere with thermoregulation. This is more common with low potency first-generation antipsychotics. Consequently, patients should limit their exposure to heat and midday sun to avoid heat stroke. Almost all psychiatric facilities are air-conditioned (there is a time when few were), so this helps a great deal.
Endocrine & metabolic effects
the second-generation antipsychotics receive the most number to riot he for effecting plasma lipid levels, weight gain, and glucose tolerance, the first-generation psychotics are not free of such effects. For example, phenothiazines can elevate serum cholesterol and triglycerides. Among first-generation antipsychotics, hyper prolactin anemia is relatively common especially among the high potency first-generation at a psychotic's. Although weight gain may be more pronounced and second-generation medications, first-generation psychotics also have this as a nation with subsequent weight gain.
The syndrome of inappropriate anti-diuretic hormone (SIADH) secretion can occur with first generation antipsychotics. SIADH is characterized by reduced ability to excrete water. To differentiate between SIADH and polydipsia, one can check urine osmolality, which would be relatively high in SIADH as compared to polydipsia.
Overdose
First-generation antipsychotics are generally not futile and overdose. Typically, patients experience increased sedation, although some medications can result in QTc prolongation and sometimes anticholinergic delirium.
Dosing
Although the consultation service treats psychotic illnesses and medical patients, one of the more common uses of antipsychotics in in consultation psychiatry is in connection with delirium. The logic behind antipsychotic choice and dosage and delirium as discussed elsewhere. In general, medication dosage in the medically ill is started lower than in settings of acute psychiatric illness and titrated upward more slowly. This is especially true amongst older adults, who It's a may have many complicating medical conditions and experience difficulties metabolizing the first-generation antipsychotics.