Drug therapy and poisoning

Published on 05/05/2015 by admin

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16 Drug therapy and poisoning

Questions

Question 1

How should the body surface area be calculated when giving drugs for which doses are given per square metre of body surface area?

Question 2

Where can I find a reference table that shows drugs that can safely be prescribed and avoided during pregnancy and during lactation? Might this be included in the next edition of Kumar and Clark’s Clinical Medicine?

Question 3

Where might I find a reference table showing paediatric drug doses?

Question 4

My question is concerned with the practical use of steroids. In inflammatory bowel disease, what doses are used and when is the dose reduced?

Question 5

What is the safe dosage/length of treatment for the drug dexmethasone so that its destructive effects are avoided?

Question 6

1. Please explain ‘odds ratio’ and ‘risk ratio’.
2. What is meant by saying that diabetics have a 3.3 risk ratio of developing dementia?

Question 7

I’m a medical student from the Faculty of Medicine, Peradeniya, Sri Lanka. I have a question about the management of aspirin poisoning. Is it reasonable to carry out a postalkaline diuresis in these patients?

Question 8

What is meant by intermediate syndrome in organophosphorus poisoning?

Question 9

What are the pulmonary manifestations of Pink’s disease and how common are they relative to the usual cerebral, skin and renal effects?

Question 10

Is it necessary to administer antivenom to a person bitten by a snake 6 hours previously, presenting only with local leg swelling over the bitten site and so far no other systemic feature of poisoning?

Question 11

What is the ideal management for scorpion bite?

Question 12

In acute anaphylaxis, you recommend IM adrenaline (epinephrine). Surely in such an acute situation intravenous adrenaline would be better?

Question 13

Why should patients avoid grapefruit juice if they are taking terfenadine?

Question 14

Many older drug therapies, e.g. penicillin in streptococcal sore throat, have never been submitted to rigorous trials such as a randomized controlled trial (RCT). Do you think they should be?

Question 15

Please explain why some drugs are teratogenic in the first trimester and some in the second?

Question 16

What is the difference between compliance and concordance?

Question 17

The rates of paracetamol (acetaminophen) self-poisoning have decreased in the UK. Why is this?

Question 18

Is N-acetylcysteine of any use in a case of paracetamol overdosage taken 16 hours previously?

Question 19

What is meant by primary end point and secondary end point?

Question 20

Can chronic exposure to organophosphorus compounds (in farmers) cause axonal radiculoneuropathy persisting for years? Is this disease reversible?

Answers

Answer 1

Body surface area is mainly used in children. The body surface area of a 70-kg man is 1.8m2. To calculate the dose in a child use the following formula:

image

However, the best way to ensure the correct dose in children is to use reference tables or the manufacturer’s guidelines.

Answer 2

In the UK, the British National Formulary (BNF) contains the data you ask for, as does the reference book Martindale: the Complete Drug Reference, edited by Sean C Sweetman. The information can also be found in Kumar and Clark’s Handbook of Medical Therapeutics.

Answer 3

In the UK, this information can be found in the British National Formulary (BNF) and in the reference book Martindale: The Complete Drug Reference. In addition, it is also available in paediatric textbooks and manufacturers’ information sheets.

Answer 4

There are no hard and clinically proven rules for the use of steroids (usually prednisolone) in inflammatory bowel disease; there is also no fixed way to reduce the dose. In moderate/severe inflammatory bowel disease we start with 45mg prednisolone as a single dose daily for 1 week, reducing this to 30mg daily for 2 weeks and then by 5-mg decrements, depending on the clinical condition of the patient and the changes in inflammatory markers, e.g. erythrocyte sedimentation rate and C-reactive protein.

Answer 5

There is no safe dosage/length of treatment, particularly with a potent steroid like dexmethasone. For example, ischaemic necrosis of bone has been described after three doses of dexmethasone 4mg. You must always keep the dose as low as possible for as short a time as possible.

Answer 6

1. The odds ratio (OR) is the ratio of the probability of an event occurring to the probability of an event not occurring. The probability itself is an estimate of the likelihood of an event, usually expressed as a number between 0 and 1.

Thus, when calculating the OR, it is the odds of, for example, an adverse event occurring in the treated group, i.e. the number with an adverse event (a) divided by the number without the event (b), divided by the odds of the event occurring in the placebo group, i.e. the number of controls with adverse events (c), divided by the number without (d). Thus:

image

The risk ratio (RR) is the ‘rate’ of the event occurring in the treated group, i.e. the number on treatment with, for example, a drug getting an adverse reaction (a) divided by the total number (a number with no reactions) (b). This is divided by the rate of the event occurring in the control group on a placebo – again, the number on placebo getting an adverse event (c) – divided by the total number on treatment (c and d (number with no reaction). Thus, the RR or relative risk is:

image

(See K&C 7e, p. 931 for an explanation of odds ratio.) In the same example, the risk ratio would be [a/(a b)] [c/(c d)].

2. A risk ratio of 3.3 means a 3.3 increased risk of developing dementia in this case.

Answer 7

Plasma salicylate levels should be performed in all patients suspected of aspirin overdosage.

Plasma salicylate levels of 500–700mg/L (3.62–5.07mmol/L) at 2 hours, 4 hours (or later) after aspirin ingestion should have urine alkalinization (see K&C 7e, p. 938) with 225mL of an 8.4% bicarbonate infused over 1 hour. Forced alkaline diuresis should no longer be used.

Answer 8

The intermediate syndrome consists of cranial nerve and brainstem lesions with a proximal neuropathy, which starts 1–4 days after acute intoxication and lasts 2–3 weeks. Respiratory failure due to muscle weakness can occur. The aetiology is uncertain but is probably due to inadequate treatment.

Answer 9

Pink’s disease is due to mercury ingestion in the old teething powders and therefore infants were affected. You will need to check with a paediatric specialist. The disease does not now occur in many countries because the compounds are no longer available.

Answer 10

Antivenoms are not usually required unless signs of systemic envenoming are present. There are, however, exceptions to this rule and rapid progression of swelling is one. If systemic signs are present it is never too late to give antivenom. You must get expert local advice.

Answer 11

Pain from the sting can be helped by local anaesthetic (local infiltration or ring block). Parenteral analgesia is also required frequently. The use of antivenom is controversial.

Answer 12

Adrenaline has a rapid onset of action. It is well absorbed from the IM route, even in shocked patients. For these reasons it is a much safer option than IV adrenaline, which can be dangerous.

Answer 13

Grapefruit juice inhibits the P450 enzyme CYP3A4. This is due to the interaction between flavinoids and other chemicals that are found in grapefruit. Interaction between the antihistamine terfenadine means that the two should never be given together. However, this is academic because terfenadine has been withdrawn because of its cardiac effects.

Answer 14

Let us not forget that many patients’ lives have been saved by antibiotics such as penicillin. Good observational studies are still relevant. It would, of course, be extremely difficult to do an RCT now in many situations, e.g. penicillin for a streptococcal throat infection.

Answer 15

Teratogenicity only occurs in the first trimester (particularly 3rd-11th weeks), causing congenital malformation. Following this, drugs can affect growth and functional development of the fetus but this is not teratogenic.

Answer 16

Compliance simply means that patients are not taking the drug prescribed. Concordance is a more general term implying an implicit agreement between the doctor and the patient on the value of taking therapy.

Answer 17

There are many reasons; one being the education about the dangers of the drug. In addition, you cannot buy more than 16 tablets at any one time from drug outlets in the UK. Foil-wrapped drugs are also less likely to be taken for self-harm.

Answer 18

Yes there is evidence that continued infusion of N-acetylcysteine improves the morbidity and mortality of liver problems, even after 16 hours (Fig. 16.1 and Box 16.1).

Rights were not granted to include this Figure in electronic media. Please refer to the printed publication.

Fig. 16.1 Nomogram of paracetamol. From British National Formulary (1998) with permission.

Box 16.1 Antidote regimens for paracetamol poisoning

N-acetylcysteine (intravenously in 5% glucose)

• 150mg/kg in 200mL over 15min, then 50mg/kg in 500mL over the next 4 hours and 100mg/kg in 1000mL of 5% glucose over the ensuing 16 hours
• Total dose: 300mg/kg over 20.15 hours

Note: A 48-hour regimen is used in some US centres: patients receive a loading dose of 140mg/kg, followed by 70mg/kg every 4 hours for 12 doses, all infused over 1 hour

N-acetylcysteine (orally)

• 140mg/kg initially, then 60mg/kg every 4 hours for 17 additional doses
• Total dose: 1300mg/kg over 72 hours

Methionine

• Oral 2.5g followed by three similar doses every 4 hours if unable to give N-acetylcysteine

Answer 19

The main result is measured at the end of the study to see if the treatment has worked, e.g. mortality in the treatment group versus the placebo group. This primary end point should be clear before the study starts. The secondary end point refers to other variables, such as side-effects in the treatment group, which might affect the overall results.

Answer 20

There has been much debate about the effects of chronic exposure to organophosphate compounds. Chronic low exposure might cause neurological lesions, but these changes are subtle. Acute exposure does cause axonal damage to roots and peripheral nerves.

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