Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Antipsychotic agents
Class Summary
These agents are useful, perhaps owing to their sedating properties.
Haloperidol (Haldol, Haldol Decanoate, Halperon)
Antipsychotic and strong tranquilizer; butyrophenone used in treatment of acute psychosis, acute schizophrenia, manic phases, control of aggression, agitation, and disorganized and psychotic thinking. May be used to help treat false perceptions (eg, hallucinations, delusions), Gilles de la Tourette syndrome, and psychosis associated with dementia, depressions, or mania.
More likely to cause adverse effects such as tardive dyskinesia than most other antipsychotic drugs.
Risperidone (Risperdal)
Benzisoxazole derivative, novel antipsychotic drug. Well absorbed after PO administration, has high bioavailability, and exhibits dose proportionality in therapeutic dose range, although interindividual plasma concentrations vary considerably. Food does not affect extent of absorption, thus can be administered with or without meals.
Peak plasma concentrations of parent drug reached within 1-2 h after intake. Mainly metabolized via hydroxylation and oxidative N-dealkylation. Major metabolite is 9-hydroxy-risperidone, which has similar activity to parent drug; clinical effect brought about by active moiety, namely risperidone plus 9-hydroxy-risperidone.
Hydroxylation depends on debrisoquine 4-hydroxylase (ie, metabolism of risperidone is sensitive to debrisoquine hydroxylation-type genetic polymorphism). Consequently, concentrations of parent drug and active metabolite differ substantially in extensive and poor metabolizers. However, concentration of active moiety (risperidone plus 9-hydroxy-risperidone) did not differ substantially between extensive and poor metabolizers, and elimination half-lives were similar in all subjects (approximately 20-24 h).
Rapidly distributed. Volume of distribution 1-2 L/kg. Steady-state concentrations of risperidone and active moiety were reached within 1-2 d and 5-6 d, respectively. In plasma, bound to albumin and alpha1-acid glycoprotein. Plasma protein binding of risperidone is approximately 88% and that of metabolite 77%. One wk after administration, 70% of dose excreted in urine and 14% in feces. In urine, risperidone plus 9-hydroxy-risperidone represents 35-45% of dose. Remainder is inactive metabolites.
Evaluated at dose range of 1-16 mg/d PO and compared to both placebo and haloperidol, studies indicated that risperidone is an effective antipsychotic agent improving both positive and negative symptoms.
Pimozide (Orap)
Diphenylbutylpiperidine derivative with neuroleptic properties. Relatively nonsedating and can be administered in single daily dose.
Appears to have selective ability to block central dopaminergic receptors, although it affects norepinephrine turnover at higher doses. Extrapyramidal effects also are observed, but it appears to have fewer autonomic effects. Peak plasma level in humans occurs 3-8 h after administration, and plasma levels decrease slowly to approximately 50% of peak level at 48-72 h after dosing.
Used to suppress severe motor and phonic tics in patients with Tourette disorder whose symptoms have not responded satisfactorily to standard treatment (eg, haloperidol). Use also extended to management of manifestations of chronic schizophrenia in which main manifestations do not include excitement, agitation, or hyperactivity. Not indicated in treatment of patients with mania or acute schizophrenia.
Anticonvulsants
Class Summary
These agents have proven useful in the management of severe muscle spasms and provide sedation.
Chloral hydrate (Noctec, Aquachloral)
Hypnotic and anxiolytic. At normal doses, this sleep induction does not affect breathing, blood pressure, or reflexes. When used in combination with analgesics, can help manage pain after surgery. Used for sedation for procedures (eg, CT scan) or for agitation that is interfering with ventilation.
Onset of action is 10-15 min. Metabolized to an active metabolite, trichloroethanol, which is excreted by kidney after conjugation to glucuronide salt. Plasma life is 8-64 h in neonates (mean 37 h). Protein binding is approximately 40%.
Available as supp, syr, or cap; mix syr with one-half glass (4 oz) water or fruit juice to minimize GI upset; cap should be swallowed whole followed by full glass (8 oz) of water or fruit juice.
Phenobarbital (Barbita, Solfoton, Luminal)
Barbiturate mostly used as anticonvulsant. Usually used in treatment of grand mal and focal motor epilepsy. In addition, used prophylactically for febrile seizures in children. Exact mode and site of action of phenobarbital (and other barbiturates) in suppression of seizure activity unknown. Believed to work by reducing neuronal excitability and by increasing motor cortex threshold to electrical stimulation.
Use also extends to suppression of anxiety and apprehension.
Valproic acid (Depakote, Depakene)
Anticonvulsant whose activity may be related to increased brain concentrations of GABA. Peak serum levels occur approximately 1-4 h after single PO dose. Serum half-life typically 6-16 h. Primarily metabolized in liver to glucuronide conjugate. Elimination of valproic acid and its metabolites occur principally in urine, with minor amounts in feces and expired air.
Used as sole or adjunctive therapy in treatment of simple or complex absence seizures, including petit mal, and useful in primary generalized seizures with tonic-clonic manifestations. Also used for manic phase of depression and in migraine.
Carbamazepine (Tegretol)
Chemically similar to cyclic antidepressants. Also manifests antimanic, antineuralgic, antidiuretic, anticholinergic, antiarrhythmic, and antipsychotic effects. Anticonvulsant action not known but may involve depressing activity in nucleus ventralis anterior of thalamus, resulting in reduction of polysynaptic responses and blocking posttetanic potentiation. Due to potentially serious blood dyscrasias, undertake benefit-to-risk evaluation before drug instituted. Peak serum levels in 4-5 h. Half-life (serum) in 12-17 h with repeated doses. Therapeutic serum levels are 4-12 mcg/mL. Metabolized in liver to active metabolite (ie, epoxide derivative) with half-life of 5-8 h. Metabolites excreted through feces and urine.
Antiemetics
Class Summary
These agents are used to control symptomatic nausea and may have antipsychotic effects.
Chlorpromazine (Ormazine, Thorazine)
Blocks postsynaptic mesolimbic dopamine receptors, has anticholinergic effects, and depresses reticular activating system. Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones.
Benzodiazepines
Class Summary
By binding to specific receptor sites, these agents appear to potentiate effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.
Diazepam (Valium)
Anxiolytic sedative drug useful in symptomatic relief of anxiety and tension states. Also has adjunctive value in relief of certain neurospastic conditions. Peak blood levels reached within 1-2 h after single PO dosing. Acute half-life is 6-8 h with slower decline thereafter, possibly due to tissue storage. However, after repeated doses, blood levels increase significantly over 24-48 h.
In humans, comparable blood levels were obtained in maternal and cord blood, indicating placental transfer of drug.
Symptomatic management of mild-to-moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear, or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions, and anxiety states with somatic expression.
In acute alcohol withdrawal, may be useful in symptomatic relief of acute agitation, tremor, and impending acute delirium tremens.
As adjunct for relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and rare "stiff man syndrome."
While usual daily dosages meet needs of most patients, some may require higher doses. In first few days of administration, cumulative effect may occur; therefore, increase dosage only after stabilization is apparent.
Tables
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| Drugs/toxicity |
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| Infectious |
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| Inherited disorders of metabolism |
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| Metabolic/endocrine disorders |
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| Other systemic disorders |
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| Miscellaneous |
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