Pharmacological emergencies Jacob Alexander February 2016 TAPPP

Range of side effects from commonly prescribed medication Medication Induced Movement Disorders Serotonergic Syndrome Drug Induced Weight Gain Drug induced dysphoria, negative syndrome like symptoms Drug related anticholinergic side effects Drug induced cardiac complication- QTc prolongation

Medication Induced Movement Disorders

Extra pyramidal system Anatomical Neural Network that is part of the motor system Reticular formation of the pons and the medulla Nigrostriatal pathway Basal Ganglia Cerebellum Cerebral cortex- motor and sensory areas Functional Causes involuntary reflexes and movements Locomotion Complex movements Postural control

Extrapyramidal Tracts

Extrapyramidal Side Effects (EPSEs) The first generation (conventional) antipsychotics may cause significant extrapyramidal side effects, more so than the second generation antipsychotic agents. Risperidone and Ziprasidone more likely to cause EPSEs amongst second generation antipsychotic agents EPSEs require careful assessment and management

Objectives Objectives Early Identification Encourage and alleviate anxiety for patient and carers Be able to explain causes Be able to explain treatments Be able to choose/ prescribe treatment options

Types of EPSEs Dystonia Parkinsonism Akathisia Tardive Dyskinesia Acetylcholine-Dopamine dysregulation syndromes

EPSEs time to onset Immediately after use 48 hours from initiation of drug or increase in dose 3 weeks from initiation of drug or increase in dose 6 months or more of use Hypersensitivity reactions Dystonia Parkinsonian symptoms Tardive dyskinesia / dystonia/ akathisia Akathisia

Dystonia Occurs usually within 48 hours of initiation of the medication Involves bizarre and severe muscle contractions Can be painful and frightening Characterized by odd posturing and strange facial expressions

Drug-induced Parkinsonism Usually occurs after 3 or more weeks of treatment Characterized by: Cogwheeling rigidity Tremors Rhythmic oscillations of the extremities Pill rolling movement of the fingers

Akathisia Usually occurs after 3 or more weeks of treatment Subjectively experienced as desire or need to move Described as feeling like jumping out of the skin Mild: a vague feeling of apprehension or irritability Severe: an inability to sit still, resulting in rocking, running, or agitated dancing

Tardive Dyskinesia Tardive Dyskinesia Usually occurs late in the course of long-term treatment Characterized by abnormal involuntary movements (lip smacking, tongue protrusion, foot tapping) Often irreversible

Complications of Tardive Dyskinesia Inability to wear dentures Impaired respirations Weight loss Impaired gait Impaired posture

Dopamine-Acetylcholine Imbalance in the Extrapyramidal System A rare side effect Characterized by hallucinations, dry mouth, blurred vision, decreased absorption of antipsychotics, decreased gastric motility, tachycardia, and urinary retention Neuroleptic Malignant Syndrome

Methods to Improve Assessment of EPSEs Use rating scales. AIMS Simpson Neurological Rating Scale Videotape the exam for comparison at a later date

Treatment Treatment of EPSEs Titrate dose Switch to AP less likely to cause extra-pyramidal side-effects Evaluate need for EPSE causing other meds- metaclorpromide, amoxapine, SSRIs Anticholinergic agents- benztropine, trihexyphenidyl, benadryl Akathisia- benzodiazepines and beta blockers

http://youtu.be/pSXzuCNlI6Q akathisia http://youtu.be/2krwEbm5hBo dystonia http://youtu.be/_s1lzxHRO4U catatonia http://youtu.be/FUr8ltXh1Pc tardive dyskinesia http://youtu.be/j86omOwx0Hk parkinsonism

Serotonergic Syndrome

Drugs implicated in severe serotonin syndrome Mechanism L-tryptophan SSRIs TCAs MOAIs Pethidine Tramadol LSD Buspirone Amphetamines and anorectics Atypical Antidepressant St John’s wort Lithium Serotonin precursor Inhibits serotonin reuptake Inhibit Metabolism of 5-HT Serotonin agonist Partial serotonin agonist Increased 5_HT release and decreased reuptake Various All of the above? Unknown

Clinical features of serotonin syndrome Cognitive Autonomic Neuromuscular Confusion, agitation, hypomania, hyperactivity, restlessness Hyperthermia, sweating, tachycardia, hypertension, mydriasis, flushing, shivering Clonus(spontaneous/inducible/ocular), hyperreflexia, hypertonia, ataxia, tremor Hypertonia and clonus are always symmetrical and are often much more dramatic in the lower limbs

Sternbach Criteria Mental state changes (confusion, hypomania) Agitation Myoclonus Hyperreflexia Diaphoresis Shivering Tremor Diarrhoea Inco-ordination Fever Hunter Serotonin Toxicity Criteria

Treatment Cessation of offending agent Mild to moderate – resolves spontaneously in 24-72 hours Supportive care , temperature management, benzodiazepines In severe cases- cyproheptadine, propranolol, chlorpromazine

Dealing with drug induced QTc prolongation <400 ms (men) <470 ms (women) >500 ms (men or women) No action required, referral to cardiologist based on specific concerns Consider: Dose reduction Medication change Repeat ECG Cardiology referral? Stop suspected causative agent and switch to alternative that is less cardio offensive Refer to cardiologist as a matter of priority Abnormal T Wave Morphology- review treatment: reduce dose, switch to drug of lower effect, cardiologist referral