Question

A patient has returned from an overseas holiday suffering from heart palpitations, nausea, fatigue and abdominal pain. The emergency room staff confirmed that liver damage had occurred, and have instigated a toxicological analysis. Initial screens of patient samples were inconclusive, however it has emerged that while on holiday, the patient began suffering from flu-like symptoms and her local friend took her to visit a general practitioner, who prescribed the following three preparations:

1. Aspirin tablets: two tablets taken four times per day

2. Elixir: 25 ml taken four times per day

3. Tea: 5 g of tea per cup, as required for general relief of symptoms

The patient indicated that she complied with the dosage regimen for the tablets and elixir, and had at least 3 cups of tea per day. Based on the symptoms, it is suspected that one or more of the preparations may contain excessive levels of paracetamol, as well as either caffeine or ephedrine to account for the heart palpitations. Fortunately, the remains of all three preparations were brought back to Australia.

Table 1: Caption

Preparation	Aspirin	Paracetamol	Caffeine	Ephedrine
Tablet	39.07764167	330.1918	nd	nd
Elixir	nd	nd	5.150935	nd
Tea	nd	nd	0.1109843	0.248216

Insert text here

Table 2: Caption

Compound	Daily dose (mg)
Aspirin	1563.10 mg
Paracetamol	13207.68 mg
Caffeine	2060.3 mg
Ephedrine	124.1 mg

Answers to the following:

a) Relate the levels detected in each medicine to the symptoms experienced by the patient, focusing on the mechanism of action of each compound. (8 marks, 2 marks for discussion of each compound analysed)

b) What methodological limitations may have affected the accuracy of the data? (2 marks)

For any discussion of toxicity, you should use the following values:

• Paracetamol causes liver damage at doses above 6 g/day.

• Caffeine has a stimulant effect at single doses above 500 mg.

• Ephedrine has a stimulant effect at doses above 60 mg/day.

Answer 1

ANSWER A :-

Aspirin

1. Aspirin is suggested to have a daily dosage limit of around 4000mg. In the case of the patient, the dosage was given in the form of two tablets four times a day. So, the concentration of each tablet is around (1563.10 / 8 = 195.38 mg ). So, this dosage is not potential until a single dose exceeds around 600 mg per dosage and 4000 mg/day.
2. Aspirin usually acts on the enzymes namely cyclooxygenase 1 to inhibit the synthesis of thromboxane which plays an important role in increasing blood pressure by means of vasoconstriction. So, blood pressure would become normal in the presence of aspirin. It also inhibits activity of cyclooxygenase 2 that helps in the synthesis of prostaglandins that in involved in inflammatory response. Thus, it is anti-inflammatory.
3. Excessive dosage is associated with nausea and abdominal pain as stated by the patient. It is antipyretic. Fever is associated with increase in levels of prostaglandins which interfere with the activity of the hypothalamus neuronal that play a viral role in thermoregulation. When prostaglandins function is altered, there would be no stimulation of thermoregulatory mechanism thereby preventing fever. Although, Nausea occurs due to medicine uptake in excessive quantity. It is a common side effect apart from abdominal pain rarely seen. Aspirin is stated to interact with the substances that forms the internal coverings of the intestine thereby leading to abdominal pain if not taken along with food or other medicines that relieve side effects.

Paracetamol

1. The maximum does of paracetamol should not exceed beyond 4000 mg per day. Excessive dose is often associated with liver damage. It is also associated with nausea, pain in the upper stomach. The dose provided to the patient is around 13.2 grams which is lethal. It is stated to be hepatotoxic. In certain cases, the drug metabolising system converts in into a toxic intermediate such as N-acetyl-p-benzoquinoneimine. This if not converted into a non-toxic enproduct would start accumulating in the liver and the process speeds up in the presence of more concentration of paracetamol.
2. Stomach pain is associated as a side effect seen in the entire stomach during initial stages and gets restricted to the upper region during severe conditions.

Caffeine

1. Tea and other associated products contains caffeine. The prescribed amount should be less than 1000 mg/day. In this case, caffeine uptake is around 2.06 grams/day which is more than the drug dosage limit.
2. Caffeine acts as a stimulant by enhancing the release of Adrenaline which in turn is associated with increase in blood pressure and heart associated activity. (Heart beat and palpitations). Caffeine is associated with fatigue, common symptom in individuals who are not on a daily uptake of coffee. It disturbs the normal sleep cycle and leads to a rebound effect. In the initial cases of consumption, the fatigue or weakness levels go down although, after a particular time period, the fatigue level again rises and this is the rebound effect. This may be associated with physical exhaustion.
3. It stimulates release of gastrin from the intestinal tract. This in turn supports digestion. Ultimate effect is enhancement in metabolism.

Ephedrine

1. Ephedrine is associated with enhancement in heart related activities. It induces vasoconstriction thereby increasing blood pressure. It is also associated with nausea or feeling of vomiting. The adult daily limit is around 150 mg/day which in this case cannot be considered to be abnormal (124.1 mg).

Note :- Please provide information regarding the data accuracy as is doesn't seem to conclude a specific statement. For any doubt, prefer mentioning in the comment section.