You are in: eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases Chorea GravidarumArticle Last Updated: Jan 8, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Chief, Department of Neurology, Crouse Irving Memorial Hospital; Professor, Department of Neurology, State University of New York Upstate Medical University Tarakad S Ramachandran is a member of the following medical societies: American Academy of Clinical Electroencephalographers, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of Managed Care Medicine, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine Editors: Stephen T Gancher, MD, Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Nestor Galvez-Jimenez, MD, Program Director of Movement Disorders, Department of Neurology, Division of Medicine, Director of Neurology Residency Training Program, Cleveland Clinic Florida; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: CG, involuntary movement, abnormal movement, facial grimaces, systemic lupus erythematosus, SLE, Huntington disease INTRODUCTIONSection 2 of 10
  BackgroundChorea gravidarum (CG) is the term given to chorea occurring during pregnancy. This is not an etiologically or pathologically distinct morbid entity but a generic term for chorea of any cause starting during pregnancy. Chorea is an involuntary abnormal movement, characterized by abrupt, brief, nonrhythmic, nonrepetitive movement of any limb, often associated with nonpatterned facial grimaces. CG is regarded as a syndrome rather than a specific disease entity. Incidence Most of the more common and serious movement disorders rarely occur during reproductive years. Hence clinicians are not very familiar with CG. Willson and Preece (1932) found that the overall incidence of CG was approximately 1 case per 300 deliveries. According to them, the first description of chorea with onset during pregnancy (chorea gravidarum) was made by Horstius in 1661. The condition is much more rare now. Zegart and Schwartz (1968) found that one patient had been encountered in the course of 139,000 deliveries in 3 major Philadelphia hospitals. The decline is probably the result of a decline in rheumatic fever (RF), which was a major cause of CG before the use of antibiotics for streptococcal pharyngitis. In recent times, most cases of chorea appearing during pregnancy are caused by other diseases (eg, systemic lupus erythematosus [SLE], Huntington disease). In general, about half the cases are idiopathic, with rheumatic fever and antiphospholipid syndrome (APLS) underlying most of the remainder (Dike, 1997). Patient profile Most patients with CG are young; the average age is 22 years (Willson and Preece, 1932). Almost all reported patients have been Caucasians, although this may be due to a bias in the older literature, in which the vast majority of reported cases are among European patients. Of initial attacks, 80% occur during first pregnancies, and one half start during the first trimester (Willson and Preece, 1932). One third begin in the second trimester. Of afflicted women, 60% previously had chorea. Recurrences may occur in subsequent pregnancies, particularly if APLS is the cause. A family history of transient chorea is not unusual. PathophysiologySeveral pathogenetic mechanisms for CG have been offered, but none have been proven. Willson and Preece noted that nearly 70% of their patients gave a previous history of either RF or chorea. Of patients who present with chorea and no apparent carditis, 20% may develop rheumatic heart disease after 20 years. Interestingly, 50% of patients with oral contraceptive-induced chorea have a past history of chorea, which in 41% of cases is of rheumatic origin. The suggestion is that estrogens and progestational hormones may sensitize dopamine receptors (presumably at a striatal level) and induce chorea in individuals who are vulnerable to this complication by virtue of preexisting pathology in the basal ganglion. Pathologic changes found at autopsy in CG include perivascular degenerative changes in the caudate nucleus. Pathology of rheumatic brain disease is of a nonspecific arteritis with endothelial swelling, perivascular lymphocytic infiltration, and petechial hemorrhages. Aschoff bodies are not present in the brain (Greenfield and Wolfsohn, 1922; Winkelman and Eckel, 1932). These changes are evident to some extent throughout the cerebrum but are most prominent in the corpus striatum. Severe neuronal loss occurs in the caudate nucleus and putamen. The same pathologic changes have been reported for CG, but all those patients also had cardiac disease (Willson and Preece, 1932). Brain tissue from patients with acute RF with or without chorea has not been studied for the presence of antistreptococcal antibodies. Presumably, as the inflammation resolves, the chorea disappears and degenerative changes are left in small arterioles. Several lines of evidence suggest that heightened dopamine activity occurs either by denervation hypersensitivity or by aberrant sprouting of dopamine terminals on the remaining striatal neurons. A possible relationship between CG and moyamoya disease has been reported in a 16-year-old pregnant woman (Unno et al, 2000). The choreic movements may be caused by ischemia and/or enhanced dopaminergic sensitivity mediated by increased female hormones during pregnancy. CLINICALSection 3 of 10
HistoryEmotional stress aggravates the movements of CG. During sleep, the movements disappear. The chorea may be unilateral hemichorea. The patient may attempt to disguise chorea by incorporating it into a mannerism or gesture. Choreic movements largely affect the extremities but vary greatly in complexity and temporal expression from one patient to another. The patient may be restless and fidgety and often is unaware of it and may not complain about it; hence, the clinician might be misled or totally miss the diagnosis. Generally, the affected limb is hypotonic; joints are floppy, and knee jerks are pendular. Normally the arms dangle by the sides, but with chorea (ie, hypotonia), they flail about. Wrist and fingers assume the shape of a dinner fork with abduction of the thumb. At times, continuous involuntary movements may be impossible to sustain. Protruded tongue darts in and out uncontrollably. Varying hand strength is referred to as "milkmaid" grip. Choreic movements are rapid, purposeless, irregular, jerky movements that seem to randomly flow from one part of the body to another. Obtain a thorough past history including a history of RF and confidential inquiry about illicit drug use and any psychiatric treatment with neuroleptics or metoclopramide (ie, dopamine antagonists).
PhysicalPhysical examination includes a careful general, systemic, and neurologic examination. Look especially for involuntary movements and mental status changes. CausesThe most probable cause of CG is the reactivation by some mechanism of subclinical damage to basal ganglia resulting from previous rheumatic encephalopathy. Oral contraceptives and possibly other mechanisms may activate the same mechanism. In 2004, Miranda et al reported of a case of chorea associated with the use of the oral contraceptives, in which antibasal ganglia antibodies have also been detected, suggesting an immunological basis to the pathogenesis of this disorder. However, it should be noted that the presence of antibodies in serum does not necessarily infer pathogenicity; the antibodies could be produced as part of tissue damage (Dale, 2003). In order to demonstrate that a disorder is autoimmune, 5 criteria must be fulfilled (Archelos, 2000), which include (1) the presence of autoantibodies, (2) the presence of antibodies in target tissue, (3) the induction of disease in an animal model by passive transfer of the antibody, (4) the induction of disease in an animal model by autoantigen immunization, and (5) improvement of clinical symptoms after removal of the antibodies with plasma exchange. DIFFERENTIALSSection 4 of 10
Cerebellar Hemorrhage Hallervorden-Spatz Disease Huntington Disease Lesch-Nyhan Syndrome Lyme Disease Multiple System Atrophy Neuroacanthocytosis Neuronal Ceroid Lipofuscinoses Olivopontocerebellar Atrophy Pelizaeus-Merzbacher Disease Ramsay Hunt Syndrome Striatonigral Degeneration Systemic Lupus Erythematosus Torticollis Tourette Syndrome and Other Tic Disorders Viral Encephalitis Wilson Disease
|
| Drug Name | Haloperidol (Haldol, Haldol Decanoate, Halperon) |
|---|---|
| Description | 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. |
| Adult Dose | Actual dose must be determined by physician Typical dosage is as follows: 18-60 years: 0.5-30 mg/d PO >60 years: Lower dosage; increase cautiously |
| Pediatric Dose | <18 years: Administer only if under the care of a child psychiatrist |
| Contraindications | Documented hypersensitivity; Parkinson disease; impaired liver function (lower dosage prn); impaired kidney function (high dosage with caution and only prn); pregnancy (administer only if mother's or baby's life endangered); patients planning to become pregnant; breastfeeding; children may take this drug only under watchful eye of a physician; use in patients >60 y only in small doses at first and with close monitoring; patients >60 y must be careful when standing up because blood pressure may be lowered enough to impair balance |
| Interactions | Antacids containing aluminum or magnesium should not be taken 1 h before taking haloperidol and never right after; coadministration with heterocyclic antidepressants only with careful monitoring; caution if taking CNS depressants such as antihistamines, hay fever medicines, sedatives, narcotics, anesthetics, barbiturates, or muscle relaxants; caution if taking vasodilator (drug that dilates blood vessels); do not smoke and take this drug |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Common adverse effects include akathisia, akinesia, lethargy and/or sleepiness, low blood pressure, dry mouth, blurred vision, constipation, weight gain, difficulty urinating, or stiffness (acute dystonia) Rare adverse effects include dizziness, racing heartbeat and/or palpitations, weakness, sexual problems, restlessness, skin rash, seizures, low WBC count, tremors, or involuntary facial and/or tongue movements Patient should contact physician if any of the following occur: akathisia, akinesia, dizziness, severe lethargy or sleepiness, low blood pressure, racing heartbeat and/or palpitations, weakness, sexual problems, restlessness, skin rash, stiffness (acute dystonia), seizures, low WBC count, tremors, reduced urinary output, difficulty urinating, or involuntary facial and/or tongue movements, dry mouth, blurred vision, constipation, or weight gain |
| Drug Name | Risperidone (Risperdal) |
|---|---|
| Description | 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. |
| Adult Dose | Optimal therapeutic response observed in 4-8 mg PO qd, indicating bell-shaped dose-response relationship |
| Pediatric Dose | <18 years: Not established; use only under close supervision of child psychiatrist |
| Contraindications | Documented hypersensitivity |
| Interactions | Risk of potential interaction with other drugs has not been evaluated systematically; may enhance effects of alcohol, centrally acting drugs, and antihypertensive agents; because of potential for inducing hypotension, may enhance hypotensive effects of other therapeutic agents with this potential; may antagonize effects of levodopa and dopamine agonists; carbamazepine has been demonstrated to substantially decrease plasma levels of risperidone and its active metabolite, 9-hydroxy-risperidone; similar effects may be observed with other hepatic enzyme inducers; consider potential interaction between risperidone and drugs that are also substrates of this enzyme, namely phenothiazines, TCAs, SSRIs, and some beta-blockers |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May interfere with activities requiring mental alertness; therefore, caution patients not to drive or operate machinery until individual susceptibility known Conventional neuroleptics known to lower seizure threshold; caution in administering risperidone to patients with history of seizures or other predisposing factors (in clinical trials, seizures have occurred in a few risperidone-treated patients) Prolactin levels were considerably higher in risperidone-treated patients than in haloperidol-treated patients; since tissue culture experiments indicate that approximately one third of human breast cancers are prolactin dependent in vitro, administer risperidone to patients with previously detected breast cancer only if benefits outweigh potential risks; exercise caution when considering treatment in patients with pituitary tumors; possible manifestations associated with elevated prolactin levels are amenorrhea, galactorrhea, and menorrhagia; do not use during pregnancy unless expected benefits outweigh potential risks to fetus; not teratogenic in either rats or rabbits Most frequent adverse reactions observed during clinical trials were insomnia, agitation, extrapyramidal disorder, anxiety, and headache; in some instances differentiating adverse events from symptoms of underlying psychosis has been difficult; most serious adverse reactions include cases of syncope, cardiac arrhythmias, first-degree AV block, neuroleptic malignant syndrome, tardive dyskinesia, and seizures |
| Drug Name | Pimozide (Orap) |
|---|---|
| Description | 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. |
| Adult Dose | Chronic schizophrenia: 2-4 mg PO qd with weekly increments of 2-4 mg until satisfactory level of therapeutic effect attained or excessive adverse effects occur (initial recommended dose) Average maintenance dose: 6 mg/d PO; usual range is 2-12 mg/d PO Daily doses >20 mg not recommended; single morning dose recommended for all patients |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; CNS depression; comatose states; liver disorders; renal insufficiency; blood dyscrasias; depressive disorders; Parkinson syndrome; because prolongs QT interval of ECG, contraindicated in patients with congenital long QT syndrome, history of cardiac arrhythmias, or taking other drugs that prolong QT interval of ECG (see Interactions); tetrazine hypersensitivity (contained in 4-mg pimozide tab) |
| Interactions | Alcohol and other CNS depressants increase CNS depression; anticholinergic agents (eg, TCAs, atropine) increase anticholinergic effects; phenothiazines, TCAs, and antiarrhythmics increase risk of arrhythmias and heart block; antagonizes effects of anticonvulsants, with loss of seizure control; obtain ECG baseline data at initiation of therapy and check periodically, especially during period of dosage adjustment; can potentiate effects of amphetamine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Do not use in management of manifestations of chronic schizophrenia in which main symptoms include agitation, excitement, and anxiety Sudden unexpected deaths have occurred, mainly at doses >20 mg/d; ECG changes have been reported, and one possible mechanism for the deaths is prolongation of QT interval, predisposing patients to ventricular arrhythmia; perform ECG before treatment initiated and periodically thereafter, especially during period of dose adjustment or as dose approaches 20 mg/d; consider any indication of repolarization changes, such as prolongation of QT intervals beyond 0.52 s in adults, more than 25% above the patient's original baseline, or T wave or U wave changes, basis for stopping further increases, possibly lowering dose, and reviewing need for drug; exercise caution if use is necessary in patients with cardiovascular disorders; consider electrolyte imbalance, particularly hypokalemia, a risk factor Observe patients for evidence of hypotension; some individuals, especially elderly or debilitated individuals, have demonstrated transient hypotension for several hours following drug administration Occupational hazards include confusion; leukopenia, granulocytopenia, agranulocytosis, anemia, jaundice, convulsion, tardive dyskinesia, and neuroleptic malignant syndrome may occur Extrapyramidal symptoms consisting of akathisia, dystonia, and parkinsonism are the most commonly observed adverse effects; insomnia, restlessness, agitation, drowsiness, decreased attention, fatigue, and depression have been observed most commonly; menstrual irregularities (eg, amenorrhea, dysmenorrhea) and mild galactorrhea have been reported |
These agents have proven useful in the management of severe muscle spasms and provide sedation.
| Drug Name | Chloral hydrate (Noctec, Aquachloral) |
|---|---|
| Description | 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. |
| Adult Dose | Average dose: 500-1000 mg PO/PR initially; can repeat if needed; not to exceed 2000 mg/d |
| Pediatric Dose | Premature infants: 25 mg/kg/dose 25-50 mg/kg/dose PO/PR; well absorbed by PO route; may repeat in 30 min if inadequate effect |
| Contraindications | Documented hypersensitivity; colitis; esophagitis; liver or renal dysfunction; history of porphyria; allergy to tartrazine dye |
| Interactions | Coadministration of alcohol may result in flushing, headache, cardiac arrhythmia, and hypotension, particularly in patients with coronary artery disease; can affect ability of individual to drive safely; found in breast milk; American Academy of Pediatrics considers this medication usually compatible with breastfeeding |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use with extreme caution in conditions in which hepatic or renal dysfunction exists; if possible avoid use in patients in whom myocardial depression is present Adverse reactions include drowsiness, hypothermia, dysarthria, ataxia, excitability, and generalized weakness; other adverse effects include rash, nausea, vomiting, severe abdominal pain, cardiac arrhythmia, confusion, hallucinations, and, rarely, convulsions |
| Drug Name | Phenobarbital (Barbita, Solfoton, Luminal) |
|---|---|
| Description | 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. |
| Adult Dose | Loading dose: 1000 mg or 20 mg/kg IV Maintenance dose: 90-260 mg/d IV; adjust dose according to serum levels and patient's clinical status |
| Pediatric Dose | Loading dose: 10-15 mg/kg IV; administer at <1 mg/kg/min PO maintenance dose: Adjust on basis of patient's clinical status and serum levels |
| Contraindications | Documented hypersensitivity; porphyria; severe liver or respiratory disease |
| Interactions | Other anticonvulsants, CNS depressants, and MAOIs may potentiate effects; may increase action of acetaminophen; may decrease action of oral contraceptives and verapamil; antihistamines, corticosteroids, narcotic pain killers, tranquilizers, phenytoin, and valproic acid may increase action; other anticonvulsants may increase or decrease therapeutic effect |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Has potential for abuse; carefully monitor vital signs; may be substituted for other barbiturates as method of decreasing incidence of withdrawal symptoms while weaning patients off barbiturates; caution in patients with pulmonary, cardiovascular, hepatic, or renal insufficiency; treat hypoglycemic seizures with glucose, not phenobarbital, which does not resolve hypoglycemic state or prevent CNS injury; extravasation may cause tissue necrosis Long-term use may result in addiction; abrupt withdrawal may cause nightmares, forgetfulness, irritability, weight loss, and convulsions; avoid alcohol; because phenobarbital may impair physical and mental abilities, do not operate vehicle or other hazardous machinery while taking it; women should report pregnancy to their physicians promptly Adverse reactions include hypotension, bradycardia, respiratory depression, CNS depression, nystagmus, nausea, vomiting, pupillary constriction, and burning at site of injection |
| Drug Name | Valproic acid (Depakote, Depakene) |
|---|---|
| Description | 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. |
| Adult Dose | Recommended initial dose: 15 mg/kg/d PO, increasing at 1-wk intervals by 5-10 mg/kg/d until seizures controlled or adverse effects preclude further increases; not to exceed 60 mg/kg/d When total daily dose exceeds 250 mg, administer in divided regimen; 500-mg enteric-coated extended cap may be substituted for 2 250-mg cap |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; hepatic disease |
| Interactions | May increase effects of benzodiazepines (eg, diazepam, chlordiazepoxide, clorazepate, alprazolam) and warfarin; acetylsalicylic acid, other salicylates (eg, Alka Seltzer, bismuth subsalicylate, aspirin and caffeine [eg, Anacin]), and erythromycin may increase effects; carbamazepine, phenobarbital, phenytoin, and primidone may decrease effects; taken with alcohol and phenobarbital, may cause severe depression of CNS; concomitant phenobarbital may cause phenobarbital toxicity; clonazepam may cause absence seizures; any anticoagulants may result in excessive bleeding |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution during lactation and children aged 2 y or younger because they are at greater risk of developing fatal hepatotoxicity; use lower doses in elderly clients because they may have increased free unbound valproic acid levels in serum; safety and efficacy of divalproex sodium have not been determined for treating acute mania in children <18 y or for treating migraine in children <16 y Adverse effects include GI disturbances (most frequent), such as nausea and vomiting, indigestion, abdominal cramps, abdominal pain, dyspepsia, diarrhea, constipation, anorexia with weight loss, or increased appetite with weight gain CNS effects include sedation, psychosis, depression, emotional upset, aggression, hyperactivity, deterioration of behavior, tremor, headache, dizziness, somnolence, dysarthria, incoordination, and coma (rare) Ophthalmic effects include nystagmus, diplopia, and spots before eyes Hematologic effects include thrombocytopenia, leukopenia, eosinophilia, anemia, bone marrow suppression, relative lymphocytosis, hypofibrinogenemia, and myelodysplastic-type syndrome Dermatologic effects include transient alopecia, petechiae, erythema multiforme, skin rashes, photosensitivity, pruritus, and Stevens-Johnson syndrome Hepatic effects include hepatotoxicity and minor increases in AST, ALT, LDH, serum bilirubin, and serum alkaline phosphatase values Endocrine effects include menstrual irregularities, secondary amenorrhea, breast enlargement, galactorrhea, swelling of parotid gland, and abnormal TFTs Miscellaneous effects include asterixis, weakness, asthenia, bruising, hematoma formation, frank hemorrhage, acute pancreatitis, hyperammonemia, hyperglycinemia, hypocarnitinemia, edema of arms and legs, weakness, inappropriate ADH secretion, Fanconi syndrome (rare and observed mostly in children), lupus erythematosus, fever, enuresis, and hearing loss |
| Drug Name | Carbamazepine (Tegretol) |
|---|---|
| Description | 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. |
| Adult Dose | 200 mg bid on day 1 (100 mg qid susp) initial; increase by 200 mg/d or less at weekly intervals until best response attained; divide total dose and administer q6-8h; extended-release tab may be used for bid dosing instead of dosing tid/qid; not to exceed 1200 mg/d Maintenance: Decrease dose gradually to minimum effective level, usually 800-1200 mg/d |
| Pediatric Dose | <6 years: Not established; 10-20 mg/kg/d in 2-3 divided doses (qid with susp); can be increased slowly in weekly increments to maintenance levels of 35 mg/kg/d; not to exceed 400 mg/d 6-12 years: 100 mg bid on day 1 (50 mg qid of susp) initial; then, increase slowly at weekly intervals by 100 mg/d or less; divide dose and administer q6-8h; daily dose not to exceed 1000 mg Maintenance: 400-800 mg/d >12 years: Administer as in adults; not to exceed 1000 mg/d (12-15 y) or 1200 mg/d (>15 y) |
| Contraindications | Documented hypersensitivity to this drug or TCAs; history of bone marrow depression; lactation; MAOIs within 14d; use for relief of general aches and pains |
| Interactions | Since carbamazepine interacts with multiple drugs, use caution when combining with other medicines; phenobarbital, phenytoin, or primidone decrease levels; increases metabolism of warfarin, phenytoin, theophylline, and valproic acid, while erythromycin, cimetidine, propoxyphene, and calcium channel blockers increase levels; also increases metabolism (destruction) of hormones in oral contraceptives and can reduce their effectiveness (unexpected pregnancies have occurred in patients taking carbamazepine and oral contraceptives) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Safety and effectiveness not established in children <6 y; caution in glaucoma, hepatic, renal, and CV disease, and in patients with history of hematologic reaction; caution in patients with mixed seizure disorder that includes atypical absence seizures (carbamazepine is not effective and may be associated with increased frequency of generalized convulsions); use in elderly clients may increase incidence of confusion, agitation, AV heart block, syndrome of inappropriate antidiuretic hormone, and bradycardia Adverse effects include nausea, vomiting, diarrhea, constipation, gastric distress, abdominal pain, anorexia, glossitis, stomatitis, and dryness of mouth and pharynx Hematologic adverse effects include aplastic anemia, leukopenia, eosinophilia, thrombocytopenia, agranulocytosis, leukocytosis, pancytopenia, and bone marrow depression CNS adverse effects include dizziness, drowsiness, disturbances of coordination, headache, fatigue, confusion, speech disturbances, visual hallucinations, depression with agitation, talkativeness, hyperacusis, abnormal involuntary movements, and behavioral changes in children CV adverse effects include CHF, aggravation of hypertension, hypotension, syncope and collapse, edema, recurrence of or primary thrombophlebitis, aggravation of CAD, paralysis and other symptoms of cerebral arterial insufficiency, thromboembolism, and arrhythmias (including AV block) GU adverse effects include urinary frequency, acute urinary retention, oliguria with hypertension, impotence, renal failure, azotemia, albuminuria, glycosuria, increased BUN, and microscopic deposits in urine Pulmonary adverse effects include pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia Dermatologic adverse effects include pruritus, urticaria, photosensitivity, exfoliative dermatitis, erythematous rashes, alterations in pigmentation, alopecia, sweating, purpura, toxic epidermal necrolysis (ie, Lyell syndrome), Stevens-Johnson syndrome, aggravation of disseminated lupus erythematosus, alopecia, and erythema nodosum or multiforme Ophthalmic adverse effects include nystagmus, double vision, blurred vision, oculomotor disturbances, conjunctivitis, and scattered, punctate cortical lens opacities Hepatic adverse effects include abnormal LFTs, cholestatic or hepatocellular jaundice, hepatitis, and acute intermittent porphyria Other adverse effects include peripheral neuritis, paresthesias, tinnitus, fever, chills, joint and muscle aches, leg cramps, adenopathy or lymphadenopathy, inappropriate ADH secretion syndrome, frank water intoxication with hyponatremia, and confusion |
These agents are used to control symptomatic nausea and may have antipsychotic effects.
| Drug Name | Chlorpromazine (Ormazine, Thorazine) |
|---|---|
| Description | 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. |
| Adult Dose | 25-50 mg PO/IM tid/qid |
| Pediatric Dose | Children: Not established Adolescents: Administer as in adults |
| Contraindications | Documented hypersensitivity; bone marrow suppression, narrow-angle glaucoma; severe liver or cardiac disease |
| Interactions | Other CNS depressants, anticholinergics, or anticonvulsants; antihypertensives may cause additive effect; epinephrine may cause hypotension |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause pseudoparkinsonism; akathisia is common extrapyramidal reaction in elderly; lowers seizure threshold and increases risk of seizures in patient with history of seizures |
By binding to specific receptor sites, these agents appear to potentiate effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.
| Drug Name | Diazepam (Valium) |
|---|---|
| Description | 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. |
| Adult Dose | Individualize for maximum beneficial effect Symptomatic relief of anxiety and tension in psychoneurosis and anxiety reactions: 2-10 mg PO bid/tid/qid depending on severity of symptoms |
| Pediatric Dose | <6 months: Not recommended 1-2.5 mg PO tid/qid initially; increase gradually prn and as tolerated Because of varied responses, initiate therapy with lowest dose and increase as required |
| Contraindications | Documented hypersensitivity; myasthenia gravis; children <6 mo (due to lack of clinical experience); do not use during first trimester of pregnancy unless absolutely necessary |
| Interactions | Consider combining with other psychotropic agents, phenothiazines, barbiturates, MAOIs, and other antidepressants with care, because pharmacologic action of these agents may potentiate action of diazepam; since diazepam has CNS depressant effect, advise patients against simultaneous ingestion of alcohol and other CNS depressant drugs during therapy |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Most common adverse effects reported are drowsiness and ataxia; other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, and changes in libido; more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity, and paradoxic reactions (eg, hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances, stimulation); should these occur, discontinue drug |