Sedation with antipsychotics

Neuroleptic malignant syndrome D2-blocking antipsychotics Acute severe parkinsonism hypertension, hyperthermia, normal or reduced bowel sounds, onset over 1-3 days Diphenhydramine (parenteral), cooling if temperature is very high, sedation with benzodiazepines... 

Antihistamines are to varying degrees sedative, the more sedating members ( older antihistamines ) of the class interacting with other sedating drugs (antipsychotics, BZDs, opioids,barbiturates). 

I Sedation and Cognition. Sedation must be recognized as an antipsychotic side effect and not as an indication of therapeutic effect. It occurs more frequently with antipsychotics with antihistaminic properties. Chlorpromazine, thioridazine, mesoridazine, clozapine, olanzapine, and quetiapine are most frequently implicated. Administration of most or all of the daily dosage at bedtime (depending on the drug half-life) can decrease daytime sedation and in some patients eliminate the need for hypnotic agents. Sedation occurs early in treatment... 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

In high dose, injection of metoclopramide can cause sedation and facial muscle spasms due to effects on dopamine receptors in the brain. This is similar to the adverse reactions seen with antipsychotic drugs (see Chapter 11). 

Many of the side effects associated with antipsychotic agents can be attributed to their antagonist activity at a variety of CNS receptors, which include histamine Hi, adrenergic 01/02, cholinergic Mi receptors, serotonin 5-HT2, and dopamine D2 receptors in the brain. For example, antipsychotic drug side effects such as sedation. 

There is an increased risk of sedation and delirium with increased age. There is also an increased risk of antidopaminergic effects such as parkinsonism due to antipsychotic drugs. Many other drugs that pass the blood-brain barrier may cause adverse effects in the elderly. The response of opioids may be increased in the elderly, resulting in oversedation (Turnheim 1998). 

These medications cannot be dosed solely based on their dopamine receptor blocking potency, because they also have effects on other receptors that must be factored into their dosing (see Table 4.6). For example, it is not unusual to begin treatment of a psychotic patient with a 5 mg dose of haloperidol. In terms of dopamine receptor blocking potency, 5 mg of haloperidol is more or less equivalent to 500 mg of chlorpromazine. If a patient were immediately treated with 500 mg of chlorpromazine, however, he/she would likely have side effect problems such as dizziness and excessive sedation. This is because the medications with the lowest dopamine receptor blocking potency are the most potent at other receptor systems responsible for these side effects. (See Table 4.7) The evolution of antipsychotics from low to medium to high potency has been driven not only by the desire to find... 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

The impact of antipsychotic agents on consciousness is immediately apparent from the frequency with which sedation and drowsiness are reported as side effects (Tune et ah, 1991), a property which historically has been used as a treat-... 

Atypical antipsychotics have advantages in tolerabihty and safety over the older drugs. They have a lower incidence of extrapyramidal movement disorders, but may cause sedation and weight gain. Their metabolism by CYP450 enzymes leads to a potential for interaction with many co-prescribed drugs. 

Sedation is common after use of all antipsychotic drugs and is especially notable with the low-potency phenoth-iazines this is a result of their activity at aj-adrenergic and Hi-histaminergic receptors. However, sedation decreases during long-term treatment, and many patients become tolerant to this effect. Single daily doses given at bedtime minimize this problem. 

High-potency antipsychotic with a relatively high incidence of EPS, but a low incidence of sedation, anticholinergic effects, and cardiovascular effects... 

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