Tardive Dyskinesia & Refeeding Syndrome Flashcards
The hospitalized alcoholic patient is prone to severe ______ due to decreased intestinal absorption and increased urinary excretion
Hypophosphatemia
Serum phosphate concentration can fall to less than 1 mg/dL 12-36 hours after admission due to shift of extracellular phosphate into the cells due to IV therapy with ________. Another contributing factor can be the acute ______ ______ (acid/base disturbance) resulting from alcohol withdrawal
Dextrose-containing solutions; respiratory alkalosis
Serial monitoring of serum ______ is required when alcoholic pts are admitted to the hospital
Phosphate
Hypophosphatemic alcoholic pts may have a myopathy due to both phosphate depletion and alcohol toxicity, and are at risk for clinically significant _______
Rhabdomyolysis
________ and hypophosphatemia, commonly seen in chronic alcoholics, may potentiate muscle toxicity
Hypokalemia
Best known neurologic complication of thiamine deficiency
Wernicke-Korsakoff syndrome
Thiamine is a cofactor for what 3 key enzymes important in energy metabolism?
Transketolase
Alpha-ketoglutarate dehydrogenase
Pyruvate dehydrogenase
Thiamine requirements depend on metabolic rate, with the greatest need during periods of high metabolic demand and high glucose intake. This is manifested by the precipitation of Wernicke encephalopathy in susceptible pts by administration of IV ______ before thiamine supplementation
Glucose
Classic triad of Wernicke encephalopathy
Encephalopathy — characterized by profound disorientation, indifference, and inattentiveness
Oculomotor dysfunction — nystagmus, lateral rectus palsy, and conjugate gaze palsies
Gait ataxia — primarily involves stance gait and is likely d/t combination of polyneuropathy, cerebellar involvement, and vestibular dysfunction
Detailed clinical and neuropathological data from many pts indicated that all features of the Wernicke encephalopathy triad were only present 1/3 of the time. What finding was common to 82% of those pts?
Mental status abnormalities — hence the importance of the mental status exam!
______ was the most common presenting symptom of Wernicke encephalopathy, followed by staggering gait and ocular problems
Confusion
Commonly affected brain areas in Wernicke’s encephalopathy
Third ventricle Aqueduct Fourth ventricle Mamillary bodies Dorsomedial thalamus Locus ceruleus Periaqueductal gray Ocular motor nuclei Vestibular nuclei Cerebellum
[less frequently affected areas include colliculi, fornices, septal region, hippocampus (medial temporal lobe), and cerebral cortex]
T/F: there are no lab studies that are diagnostic of wernicke’s encephalopathy
True — a thiamine blood level may not accurately reflect brain thiamine levels
If the potential for Wernicke encephalopathy is suspected, immediate thiamine replacement takes precedence over lab diagnosis
Which should be administered first in a pt in whom Wernicke encephalopy is suspected — glucose or thiamine?
Thiamine!!
Late neuropsychiatric manifestation of Wernicke encephalopathy in which there is a striking disorder of selective anterograde and retrograde amnesia
Korsakoff syndrome
Adverse effects of antipsychotic drugs may include extrapyramidal syndromes (EPS), what are some examples?
Acute dystonic reactions
Drug-induced Parkinsonism
Akathisia
Antipsychotic-induce catatonia
Tardive dyskinesia
Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by sudden tonic contractions of muscles of tongue, neck, back, mouth, eyes
Acute dystonic reaction
Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by cogwheel rigidity, bradykinesia, tremor, loss of postural reflexes, mask-like facies, drooling
Drug-induced parkinsonism
Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by motor restlessness, may involve entire body (typically inability to keep legs and feet still)
Akathisia
Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by withdrawal, mutism, motor abnormalities (rigidity, immobility, waxy flexibility)
Antipsychotic-induced catatonia
Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by fasciculations of the tongue, lingual-facial hyperkinesias, choreoathetotic movements of the extremities and trunk
Tardive dyskinesia
Adverse effect of antipsychotic drugs characterized by muscular rigidity, autonomic instability, and altered level of consciousness
Neuroleptic malignant syndrome
Tardive dyskinesia is a medication-induced hyperkinetic movement disorder caused by exposure to drugs with what MOA?
Dopamine receptor blockers (most often antipsychotics)
To be considered tardive dyskinesia, the hyperkinetic movement disorder must persist for at least ______ after dicontinuation of the offending agent
1 month
Various manifestations of tardive dyskinesia
Chorea Athetosis Stereotyped behaviors Dystonia Akathisia Tics Respiratory dyskinesias Tremor
Rating scale used to detect tardive dyskinesia and follow its severity over time
Abnormal Involuntary Movement Scale (AIMS)
[assesses characteristic abnormal involuntary movements of face, mouth, trunk, or limbs]
Early antipsychotic drug withdrawal results in a better prognosis for recovery, therefore pts on antipsychotic drugs should be frequently monitored with the __________________ for signs of TD
Abnormal Involuntary Movement Scale (AIMS)
What is withdrawal-emergent TD?
Dyskinesia in children that occurs transiently (<1 month) immediately following the discontinuation of an antipsychotic drug
What is withdrawal dyskinesia TD?
Dyskinesia in adults that occurs immediately after discontinuing or reducing the dose of a dopamine receptor-blocking agent
What is “masked” TD?
Tardive movements that resolve when a dopamine receptor-blocking agent is resumed or its dose is increased
Medications besides first/second gen antipsychotics known to cause TD
Metoclopramide
Antiemetics: prochlorperazine, chlorpromazine
What 2 antipsychotics carry highest risk for tardive dyskinesia?
Paliperidone
Risperidone
[aripiprazole, lurasidone, olanzapine, and ziprasidone carry intermediate risk]
What antipsychotics carry low, or low-to-absent risk for tardive dyskinesia?
Risk is lower for iloperidone
Low or absent risk in pimavanserin, quetiapine, and clozapine
T/F: second generation antipsychotics carry significantly lower risk for tardive dyskinesia when compared to first gen
False — the difference between the two classes is not as significant as previously thought
Risk factors for developing tardive dyskinesia
Pts who develop extrapyramidal symptoms early-on with antipsychotic drug therapy
Pts with schizophrenia
Pts who are older, are heavy smokers, or have diabetes mellitus are also at higher risk of TD
How does the dopamine-hypothesis explain the slightly lower tendency of second gen antipsychotics to cause TD?
Dopamine hypothesis refers to imbalance between D1 and D2 receptor-mediated effects
First gen antipsychotics preferentially block D2, resulting in excess activity of D1-mediated striatopallidal output
Second gen antipsychotics like clozapine produce relatively less D2 and more D1 blockade, leading to less incidence of TD
The serotonin hypothesis relating to tardive dyskinesia cites polymorphisms in the _______ receptor gene have been linked to susceptibility to TD
5-HT2A
[Note that Clozapine is a serotonin antagonist with strong binding to 5-HT2A/2C receptor subtype, and is associated with lower incidence of TD and may even have favorable effect on TD]
Pharmacologic treatment options for TD involve discontinuation of offending drug, potentially switching from first to second gen antipsychotic drugs, noting that _____ and _____ may have ameliorating effects on TD severity.
Use of benzodiazepines, botox injections, valbenazine, or tetrabenazine to control symptoms of TD. Also potential paradoxical effect with resuming treatment with antipsychotic drugs in order to suppress TD
Clozapine; quetiapine
In a randomized controlled trial from China including pts with schizophrenia and TD, a standardized extract of Ginkgo biloba leaves known as ______ was effective treatment for TD
EGb-761
What effect do anticholinergic drugs have on choreiform dyskinesias vs. tardive dystonia?
Trihexyphenidyl, benztropine, and other anticholinergics are usually ineffective or may even exacerbate choreiform dyskinesias
Anticholinergic drugs are sometimes helpful in ameliorating tardive dystonia
