Tardive Dyskinesia & Refeeding Syndrome

Question 1

The hospitalized alcoholic patient is prone to severe ______ due to decreased intestinal absorption and increased urinary excretion

Answer 1

Hypophosphatemia

Question 2

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

Answer 2

Dextrose-containing solutions; respiratory alkalosis

Question 3

Serial monitoring of serum ______ is required when alcoholic pts are admitted to the hospital

Answer 3

Phosphate

Question 4

Hypophosphatemic alcoholic pts may have a myopathy due to both phosphate depletion and alcohol toxicity, and are at risk for clinically significant _______

Answer 4

Rhabdomyolysis

Question 5

________ and hypophosphatemia, commonly seen in chronic alcoholics, may potentiate muscle toxicity

Answer 5

Hypokalemia

Question 6

Best known neurologic complication of thiamine deficiency

Answer 6

Wernicke-Korsakoff syndrome

Question 7

Thiamine is a cofactor for what 3 key enzymes important in energy metabolism?

Answer 7

Transketolase

Alpha-ketoglutarate dehydrogenase

Pyruvate dehydrogenase

Question 8

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

Answer 8

Glucose

Question 9

Classic triad of Wernicke encephalopathy

Answer 9

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

Question 10

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?

Answer 10

Mental status abnormalities — hence the importance of the mental status exam!

Question 11

______ was the most common presenting symptom of Wernicke encephalopathy, followed by staggering gait and ocular problems

Answer 11

Confusion

Question 12

Commonly affected brain areas in Wernicke’s encephalopathy

Answer 12

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]

Question 13

T/F: there are no lab studies that are diagnostic of wernicke’s encephalopathy

Answer 13

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

Question 14

Which should be administered first in a pt in whom Wernicke encephalopy is suspected — glucose or thiamine?

Answer 14

Thiamine!!

Question 15

Late neuropsychiatric manifestation of Wernicke encephalopathy in which there is a striking disorder of selective anterograde and retrograde amnesia

Answer 15

Korsakoff syndrome

Question 16

Adverse effects of antipsychotic drugs may include extrapyramidal syndromes (EPS), what are some examples?

Answer 16

Acute dystonic reactions

Drug-induced Parkinsonism

Akathisia

Antipsychotic-induce catatonia

Tardive dyskinesia

Question 17

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

Answer 17

Acute dystonic reaction

Question 18

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

Answer 18

Drug-induced parkinsonism

Question 19

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)

Answer 19

Akathisia

Question 20

Extrapyramidal syndrome that may occur as an adverse effect of antipsychotic drugs; characterized by withdrawal, mutism, motor abnormalities (rigidity, immobility, waxy flexibility)

Answer 20

Antipsychotic-induced catatonia

Question 21

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

Answer 21

Tardive dyskinesia

Question 22

Adverse effect of antipsychotic drugs characterized by muscular rigidity, autonomic instability, and altered level of consciousness

Answer 22

Neuroleptic malignant syndrome

Question 23

Tardive dyskinesia is a medication-induced hyperkinetic movement disorder caused by exposure to drugs with what MOA?

Answer 23

Dopamine receptor blockers (most often antipsychotics)

Question 24

To be considered tardive dyskinesia, the hyperkinetic movement disorder must persist for at least ______ after dicontinuation of the offending agent

Answer 24

1 month

Question 25

Various manifestations of tardive dyskinesia

Answer 25

Chorea
Athetosis
Stereotyped behaviors
Dystonia
Akathisia
Tics
Respiratory dyskinesias
Tremor

Question 26

Rating scale used to detect tardive dyskinesia and follow its severity over time

Answer 26

Abnormal Involuntary Movement Scale (AIMS)

[assesses characteristic abnormal involuntary movements of face, mouth, trunk, or limbs]

Question 27

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

Answer 27

Abnormal Involuntary Movement Scale (AIMS)

Question 28

What is withdrawal-emergent TD?

Answer 28

Dyskinesia in children that occurs transiently (<1 month) immediately following the discontinuation of an antipsychotic drug

Question 29

What is withdrawal dyskinesia TD?

Answer 29

Dyskinesia in adults that occurs immediately after discontinuing or reducing the dose of a dopamine receptor-blocking agent

Question 30

What is “masked” TD?

Answer 30

Tardive movements that resolve when a dopamine receptor-blocking agent is resumed or its dose is increased

Question 31

Medications besides first/second gen antipsychotics known to cause TD

Answer 31

Metoclopramide

Antiemetics: prochlorperazine, chlorpromazine

Question 32

What 2 antipsychotics carry highest risk for tardive dyskinesia?

Answer 32

Paliperidone
Risperidone

[aripiprazole, lurasidone, olanzapine, and ziprasidone carry intermediate risk]

Question 33

What antipsychotics carry low, or low-to-absent risk for tardive dyskinesia?

Answer 33

Risk is lower for iloperidone

Low or absent risk in pimavanserin, quetiapine, and clozapine

Question 34

T/F: second generation antipsychotics carry significantly lower risk for tardive dyskinesia when compared to first gen

Answer 34

False — the difference between the two classes is not as significant as previously thought

Question 35

Risk factors for developing tardive dyskinesia

Answer 35

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

Question 36

How does the dopamine-hypothesis explain the slightly lower tendency of second gen antipsychotics to cause TD?

Answer 36

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

Question 37

The serotonin hypothesis relating to tardive dyskinesia cites polymorphisms in the _______ receptor gene have been linked to susceptibility to TD

Answer 37

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]

Question 38

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

Answer 38

Clozapine; quetiapine

Question 39

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

Answer 39

EGb-761

Question 40

What effect do anticholinergic drugs have on choreiform dyskinesias vs. tardive dystonia?

Answer 40

Trihexyphenidyl, benztropine, and other anticholinergics are usually ineffective or may even exacerbate choreiform dyskinesias

Anticholinergic drugs are sometimes helpful in ameliorating tardive dystonia