Which ONE of the following medications is LEAST likely to cause serotonin syndrome in overdosage?
Answer: B: Serotonin syndrome is a toxic state caused mainly by excess serotonin (5HT) within the CNS, causing excessive stimulation of serotonergic receptors. It results in a variety of mental, autonomic and neuromuscular changes, which can range in severity from mild to life threatening. Most cases are self-limiting. Severe serotonin syndrome is nearly always caused by a drug interaction involving two or more ‘serotonergic’ drugs, at least one of which is usually a SSRI or monoamine oxidase inhibitor (MAO). Management involves withdrawal of the offending drugs, aggressive supportive care and occasional use of serotonin antagonists such as cyproheptadine. Treatment of the condition for which the serotonergic drugs were prescribed should be reviewed.
Numerous drugs are implicated in the development of serotonin syndrome, of which the most important ones are:
Although it is possible for levodopa to cause serotonin syndrome, as it releases 5HT from stored vesicles, it is more commonly associated with neuroleptic malignant syndrome.
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Regarding lithium toxicity, which ONE of the following statements is TRUE?
Answer: D: The hallmark feature of acute lithium toxicity is acute gastrointestinal symptoms including vomiting and diarrhoea, leading to significant fluid losses. The hallmark feature of chronic toxicity is neurotoxicity, which may lead to permanent neurological damage. Acute toxicity is typically due to deliberate overdose, whereas chronic toxicity typically occurs in patients who are on chronic lithium therapy when renal excretion of lithium is impaired. Although rare, a delayed onset of neurotoxicity may occur in acute toxicity if renal functions are impaired due to any cause, including significant fluid losses. In chronic toxicity the neurological symptoms can progress from tremor, hyperreflexia, weakness and ataxia to agitation, muscle rigidity and hypertonia. In severe neurotoxicity altered level of consciousness, convulsions and coma may occur.
In chronic toxicity serum lithium levels do not correlate well with the clinical severity. However, when an unwell patient who is on lithium presents to the ED, serum lithium level should be done as this may aid in early diagnosis. In both toxicities serum lithium levels are important to confirm the diagnosis and to monitor the progress of treatment. The neurological symptoms may persist even after the lithium level returns to normal.
The mainstay of treatment in acute toxicity is fluid resuscitation and maintaining hydration to achieve normal renal function with good urine output and normal electrolyte balance. This enhances lithium excretion from the body. Similarly, in chronic toxicity it is important to maintain good hydration and renal function to enhance renal lithium excretion. However, enhanced elimination with haemodialysis may be necessary in the face of neurotoxicity and established renal failure.
Cardiac monitoring is not indicated in lithium toxicity unless for other reasons including co-ingestants.
Regarding risk assessment in patients with paracetamol overdose after a single acute ingestion, which ONE of the following statements is TRUE?
Answer: C: The threshold single dose of paracetamol ingestion that could produce hepatotoxicity is variable both in adults and children, but is considered as 150 mg/kg in adults and 200 mg/kg in children. The risk of hepatotoxicity from a single acute ingestion when untreated is predictable when a serum paracetamol level obtained 4–15 hours from the time of ingestion is plotted on the Rumack-Matthew nomogram. When this level is >300 mg/L at 4 hours the probability of hepatotoxicity reaches 90% when not treated.
Hepatotoxicity is defined if the peak AST or ALT exceeds 1000 IU/L. With toxic serum paracetamol levels due to single ingestions, the probability of hepatotoxicity depends on the time taken to commence NAC from the time of ingestion. If the time of commencement of NAC is within 8 hours, 100% survival can be expected. The benefits are reduced when NAC is commenced 8–24 hours from the time of single ingestion. Usually there is no demonstrable benefit when NAC is commenced >24 hours later.
In a patient who presents >8 hours from the time of a single ingestion, a toxic paracetamol level together with elevated hepatic transaminase levels indicate early hepatotoxicity. When a patient presents >24 hours from the time of a single ingestion, if the serum paracetamol level is normal and has normal transaminases, the risk of developing hepatotoxicity is minimal.
A child <8 years of age who has accidentally taken <200 mg/kg of paracetamol as a single dose or over a period of 8 hours does not require decontamination or serum paracetamol or liver function tests done.
Regarding the use of NAC in paracetamol toxicity, which ONE of the following statements is TRUE?
Answer: B: NAC is the intravenous sulfhydryl donor used in paracetamol toxicity in Australasia. It protects against paracetamol-induced hepatotoxicity. It is given as three infusions of fixed duration over a 20-hour period and this duration can be extended further in relevant patients. The contraindications for the antidote are almost non-existent. It can be used in a pregnant woman with paracetamol toxicity. It should be started immediately without waiting for serum paracetamol results for any patient who had taken a toxic dose (>150 mg/kg for an adult) and presenting >8 hours later. Beyond the usual 20-hour infusion, NAC should be continued in patients:
The incidence of mild anaphylactoid reaction is 10–50% and usually occurs during the initial infusion or shortly after that. The typical symptoms are flushing, rash, mild hypotension and angioedema at times and should be treated accordingly. If the patient gets severe symptoms the NAC infusion can be ceased temporarily until symptoms resolve and it should be restarted early when the patient is stable.
Regarding severe toxicity secondary to a large ingestion of aspirin, which ONE of the following statements is TRUE?
Answer: D: In large ingestions of aspirin, as well as with enteric coated tablets, delayed absorption may occur mainly due to bezoar formation in the stomach and the intestine. If the serum salicylate level is rising after the initial dose of activated charcoal a second dose is indicated after a few hours.
These patients typically have a mixed metabolic acidosis and respiratory alkalosis. Alkalaemia should be maintained to prevent salicylate from entering the CNS because it increases ionization of aspirin. Urinary alkalinization increases the renal excretion of aspirin. For the above mentioned reason, even after intubation alkalaemia should be maintained with hyperventilation. Ventilatory settings should not be adjusted to correct this alkalaemia. Lack of meticulous attention to maintain alkalaemia can be catastrophic to the patient.
Aspirin has a low volume of distribution (it is distributed mainly in the intravascular compartment), low protein binding, a low molecular weight and high water solubility, and therefore it can be eliminated with HD. Patients should be considered for HD after intubation if the indication for intubation is severe salicylate toxicity and not co-ingestants.
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