You are in: eMedicine Specialties > Emergency Medicine > TOXICOLOGY Toxicity, Medication-Induced Dystonic ReactionsArticle Last Updated: Sep 30, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Geofrey Nochimson, MD, Consulting Staff, Department of Emergency Medicine, Sentara Careplex Hospital Geofrey Nochimson is a member of the following medical societies: American College of Emergency Physicians Editors: Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital Author and Editor Disclosure Synonyms and related keywords: medication-induced dystonic reactions, dystonic reaction, neuroleptic drug therapy, drug treatment, neuroleptics, neuroleptic agents, dyskinesia, acute dystonic reaction, neuroleptic drugs, involuntary muscle contractions INTRODUCTIONBackgroundDystonic reactions are adverse extrapyramidal effects that often occur shortly after the initiation of neuroleptic drug therapy. These reactions may occur with a wide variety of medications. Dystonic reactions (ie, dyskinesias) are characterized by intermittent spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, and extremities. Dystonic reactions are rarely life threatening, yet are very uncomfortable and often produce significant anxiety and distress for patients. Fortunately, treatment is extremely effective, and motor disturbances resolve within minutes. PathophysiologyAlthough dystonic reactions are occasionally dose related, these reactions are more often idiosyncratic and not predictable. They appear to result from drug-induced alteration of dopaminergic-cholinergic balance in the nigrostriatum (ie, basal ganglia). Most drugs produce dystonic reactions by nigrostriatal dopamine D2 receptor blockade, which leads to an excess of striatal cholinergic output. High-potency D2 receptor antagonists are most likely to produce an acute dystonic reaction. Agents that balance dopamine blockade with muscarinic M1 receptor blockade are less likely to produce a dystonic reaction. Paradoxically, an alternative cause of dystonic reactions may be increased nigrostriatal dopaminergic activity that occurs as a compensatory response to dopamine receptor blockade. FrequencyUnited StatesIncidence of acute dystonic reactions varies according to individual susceptibility, drug identity, dose, and duration of therapy. For patients on neuroleptics, the overall incidence of dystonic reactions is approximately 2%. Mortality/Morbidity
SexIncidence of dystonic reactions is greater in males than in females. Age
CLINICALHistoryDystonic reactions most often occur shortly after initiation of drug treatment; 50% occur within 48 hours and 90% occur within 5 days of initiation of treatment. Risk factors include family history of dystonia, recent history of cocaine or alcohol use, or treatment with a potent dopamine D2 receptor antagonist (eg, fluphenazine, haloperidol).
Physical
Causes
DIFFERENTIALSConversion Disorder Dislocations, Mandible Hypocalcemia Hypomagnesemia Meningitis Status Epilepticus Stroke, Hemorrhagic Stroke, Ischemic Tetanus Toxicity, Anticholinergic Toxicity, Carbamazepine Toxicity, Phenytoin Toxicity, Valproate
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| Drug Name | Benztropine (Cogentin) |
|---|---|
| Description | By blocking striatal cholinergic receptors, may help in balancing cholinergic and dopaminergic activity. |
| Adult Dose | 1-2 mg PO/IV/IM qd or bid; IV has most rapid onset |
| Pediatric Dose | <3 years: Not established >3 years: 0.02-0.05 mg/kg PO/IV/IM; not to exceed 2 mg/d |
| Contraindications | Documented hypersensitivity; angle-closure glaucoma; stenosing peptic ulcers; prostatic hypertrophy or bladder neck obstructions; myasthenia gravis; pyloric or duodenal obstruction; achalasia (megaesophagus); megacolon |
| Interactions | Decreases effects of levodopa; increases effects of narcotic analgesics, phenothiazines, quinidine, tricyclic antidepressants, and anticholinergics |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | May exacerbate hypertension, tachycardia, cardiac arrhythmias, liver or kidney disorders, hypotension, prostatic hypertrophy, urinary retention, and obstructive disease of GI/GU tracts; may cause toxic psychosis in psychiatric patients with extrapyramidal reactions resulting from phenothiazine |
| Drug Name | Diphenhydramine (Benadryl) |
|---|---|
| Description | Although an antihistamine, also possesses significant anticholinergic properties. Mechanism of action is identical to that of benztropine. |
| Adult Dose | 50-100 mg IV/IM repeat prn |
| Pediatric Dose | 1-2 mg/kg IV/IM repeat prn |
| Contraindications | Documented hypersensitivity; MAOIs; angle-closure glaucoma |
| Interactions | Potentiates effect of CNS depressants; alcohol content of syrup dosage form may cause disulfiramlike reaction in patients taking medications that can cause these reactions |
| Pregnancy | A - Fetal risk not revealed in controlled studies in humans |
| Precautions | May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction |
Normal balance between dopamine and acetylcholine in the basal ganglia involves modulation from GABA-containing striatonigral neurons. GABA-ergic neurons are inhibitory and antagonize excitatory dopaminergic neurons. GABA agonists (eg, benzodiazepines) may be helpful for acute dystonic reactions.
| Drug Name | Diazepam (Valium) |
|---|---|
| Description | Some recommend using for patients with dystonic reactions refractory to anticholinergic therapy or when such therapy is contraindicated. |
| Adult Dose | 2.5-10 mg IV slow push |
| Pediatric Dose | 0.1 mg/kg IV slow push repeat prn |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma |
| Interactions | Phenothiazines, barbiturates, alcohols, and MAOIs may increase CNS toxicity |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity) |
Toxicity, Medication-Induced Dystonic Reactions excerpt
Article Last Updated: Sep 30, 2008