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Drug Interactions

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Drug interactions are a common problem in the NHS. This resource is composed of 10 self assessment questions, is designed tests your knowledge on common drug interactions that occur in day to day practice. Complete the 10 questions to obtain a certificate awarding you 1hr of CPD which can be added to your portfolio.


1. To understand and recognise of the common interactions that occur between prescribed and Over the Counter (OTC) medications.

2. To have a better comprehension of the effect of more common herbal remedies and homeopathic therapies on prescribed drugs.


Drug Checker http://www.drugs.com/drug_interactions.html

Medscape drug checker http://reference.medscape.com/drug-interactionchecker

Health Line - drug interactions http://www.healthline.com/druginteractions

Prescribing

A 58 year old woman presented to her GP with tremor and agitation. She has a past history of depression for which she has been on long term lithium therapy which has provided effective control. More recently, her GP noted that she was hypertensive and commenced new therapies. Initiation of which of the following is most likely to have precipitated her lithium toxicity?

Lithium is a drug used for bipolar affective disorder. It is a drug that needs to be kept within a narrow therapeutic range. If the drug level goes above this range, lithium toxicity occurs. Lithium toxicity ranges in severity from mild tremors, agitation, and confusion to ataxia, convulsions and arrhythmias. Interactions can occur between lithium and other agents that precipitate toxicity; in particular, diuretics both loop and thiazides through sodium depletion and reduction of excretion can increase the potential for lithium toxicity. ACE inhibitors may also cause lithium toxicity as can NSAIDs.

http://www.patient.co.uk/doctor/Lithium.htm

http://emedicine.medscape.com/article/815523-overview

Question 1

A 68 year old man presents to his GP with a two week history of profound tiredness and falls. He has a history of hypertension and type 2 diabetes for which he attended a review two weeks ago, where changes to his medication were made. He is a non smoker and drinks occasionally. On examination, he is apyrexial, has a regular heart rate of 42 bpm, a blood pressure of 112/72 mmHg and a respiratory rate of 14 breaths per minute.

His ECG reveals a rate of 42 bpm with no p waves preceding the QRS complexes

What drug interaction may have caused this problem?

Verapamil should not be prescribed together with a β-blocker, because it can cause produce problematic hypotension, heart failure as well as precipitate bradycardia and complete heart block. The more profound reactions tend to happen with IV verapamil, but it is relatively contra-indicated for use together with a β-blocker even when given by mouth. It is thought that the negative inotropic and chronotropic effects of beta blockers and verapamil combine synergistically to cause the heart failure.

Question 2

An 80 year-old man presents with a three day history of shortness of breath and ankle swelling. He has a past history of hypertension and diabetes for which he takes rosuvastatin, losartan, aspirin, amlodipine and metformin. Recently his HbA1c has deteriorated to 57 mmol/mol (it was previously less than 53 mmol/mol) and he was commenced on pioglitazone.

On examination, he has bilateral ankle oedema with a blood pressure of 134/86 mmHg and pulse of 80 bpm.
Interaction between pioglitazone and which of the following is likely to be responsible for this patient’s presentation?.

Explanation: Thiazoldinediones such as pioglitazone may have an antagonistic effect on myocardial calcium channels, thereby enhancing the effect of calcium channel blockers and may exacerbate oedema associated with either agent or may indeed precipitate heart failure.

Buse JB. Glitazones and heart failure: critical appraisal for the clinician. Circulation. 108(8):e57, 2003 Aug 26 

http://www.ncbi.nlm.nih.gov/pubmed/12939247

Arikawa M. Takahashi N. Kira T. Hara M. Saikawa T. Sakata T. Enhanced inhibition of L-type calcium currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes. British Journal of Pharmacology. 136(6):803-10, 2002 Jul

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573409/

Question 3

A 35 year old woman presents to the practice for annual thyroid function tests. She has been treated with thyroxine 100 micrograms for the last 5 years for hypothyroidism and all previous TFTs have been normal. She informs you that she is compliant in taking her thyroxine. On this occasion her thyroid function tests reveal:

Which of the following drugs that she is taking is likely to have contributed to the adverse change in thyroid function test results?

This patient has had stable thyroid function on 100 micrograms of thyroxine but her most recent TFTs reveal that the dose is now inadequate. Of the drugs listed, the use of 

 may be responsible for reduced absorption of thyroxine through chelation of thyroxine in the stomach. It is important to remind patients to take their thyroxine 2 hours before taking ferrous sulphate.

http://www.nhs.uk/medicine-guides/pages/MedicineOverview.aspx?medicine=Ferrous%20sulphate%20tablets

Question 4

Following discharge from hospital, a 77 year old woman was reviewed by her GP and found to have the following urea and electrolytes:

She has a history of osteoarthritis, ischaemic heart disease, hypertension, and atrial fibrillation, does not smoke and drinks a glass of wine daily. She takes warfarin, bumetanide, isosorbide mononitrate, bisprolol, co-codamol, spironolactone, simvastatin and ramipril. On examination, she had a BMI of 31, a heart rate of 72 bpm irregular and a blood pressure of 130/84mmHg. Her pulse was irregularly irregular.

Which drug interaction is most likely to be responsible for her U+E results?

This patient has hyperkalaemia with a potassium of 5.3 mmol/l. This is likely to be a consequence of the co-prescription of an ACE inhibitor together with spironolactone. Spironalactone is a potassium sparing diuretic. It acts on the late distal tubule in the nephron, by blocking the action of aldosterone - an aldosterone antagonist. It binds to the aldosterone dependent receptors at the sodium-potassium exchange site and causes increased amounts of sodium and water to be excreted while potassium excretion is inhibited. Consequently, the reabsorption of sodium (in exchange for potassium) is inhibited. ACE inhibitors such as lisinopril enhance this effect because of reduced levels of angiotensin II results in reduced aldosterone secretion.

ABC of heart failure: Management: diuretics, ACE inhibitors, and nitrates M K Davies, C R Gibbs, G Y H Lip. BMJ;2000;320:428-431.

Question 5

A 24 year old female presents to clinic after becoming pregnant. She has been taking Microgynon for five years. She insists that she has never missed a pill. She also takes salbutamol and beclomethasone inhalers and has recently used several over-the-counter medications, for various reasons as she has previously had problems with irritable bowel syndrome and depression.

Which over-the-counter drug is likely to have interfered with her contraception?

It is important to be aware of the herbal remedies that a patient might take, not only to be in a position to advise them as to whether they are likely to achieve the desired effect, but also because they have adverse reactions, and are known to interact with numerous conventional drugs.St John’s wort, or hypericum, is an inducer of the cytochrome P450 system, particularly isoenzyme CYP 3A4, which is important in the metabolism of a significant number of drugs. Inducing this system reduces their plasma concentration because they are metabolised more rapidly. It has more urgent consequences in patients who take warfarin or digoxin, but it should still be avoided by those who take oral contraception. Unwanted pregnancy is obviously a very significant problem, with serious physical, psychological and socioeconomic consequences.

http://www.netdoctor.co.uk/diseases/depression/stjohnswort_000316.htm

Question 6

A 58 year old man attends clinic complaining of muscle aches and pains. He does not smoke and drinks only occasionally. On examination, he is obese, has some muscle tenderness, heart rate 62 bpm and blood pressure is 142/88 mmHg
His medical history includes hypertension and type 2 diabetes for which he has taken stable medication for the last six months including amlodipine 10 mg daily, metformin 500mg tds, ramipril 5mg daily, aspirin 75 mg daily and atorvastatin 40 mg daily.
On further discussion, the only other piece of information that is relevant is that over the last month or so, he has begun to take his diet more seriously and has substituted fruit juices for some of his usual tea and coffee beverages.
Which of the following foodstuffs is likely to be responsible for his presentation?

Statins can cause mylagia/myositis and in its most severe form, rhabdomyolysis. The most likely cause of this patient?s presentation is mylagia related to statins. Many patients experience these symptoms without any drug interaction taking place.
Statins are metabolised by cytochrome P450. Grapefruit juice is known to inhibit this, resulting in increased concentrations of atorvastatin if taken concurrently. Consequently, there is a greater risk of adverse reactions such as myositis.
The patient should be advised to stop drinking grapefruit juice immediately, and temporarily, to stop the atorvastatin. He or she can be reassured that the benefit conferred by statins is greater than that of taking grapefruit juice, assuming that the patient has some other source of vitamin C. Other citrus juices are not reported to cause this effect and are safe to take. This illustrates the importance of understanding the pharmacological effects of common foods.

http://www.patient.co.uk/medicine/Simvastatin.htm

Question 7

A 66 year old female presents to clinic for regular monitoring of INR. She has taken warfarin for approximately 2 years as anticoagulation for atrial fibrillation with the INR kept around 2.5 on a dose of 3-4 mg of warfarin daily. Her only other treatment includes losartan and amlodipine for hypertension.
On this occasion, her INR is 4.1. On further discussion, she informs her GP that she has most recently embarked on lifestyle and dietary changes. Which of the following products is likely to be responsible for this change in INR?

There is some evidence to suggest that cranberry juice enhances the anticoagulant effect of warfarin. It is important to recall that many patients take cranberry juice as prophylaxis against urinary tract infection. It is also taken by some for the flavinoids (‘antioxidants’) that it contains, which are thought to reduce the risk of developing various malignancies. Unfortunately, they are also known to inhibit cytochrome P450 enzymes. Warfarin is predominantly metabolised by P450 CYP2C9 and if this is inhibited, the INR will obviously rise.
Patients taking warfarin should avoid cranberry juice, at least until more is known about this potential interaction. It should be noted, however, that the potential interaction was observed in a patient who had consumed extremely large quantities of cranberry juice and very little else for several days. Consumed in moderation, the juice is probably unlikely to interfere with warfarin.

Possible interaction between warfarin and cranberry juice. Rafe Suvarna, Munir Pirmohamed, Leigh Henderson. BMJ;2003;327:1454, doi:10.1136/bmj.327.7429.1454.

http://www.patient.co.uk/medicine/Warfarin.htm

Question 8

A 55 year old female presents to her GP with nausea, vomiting, headache and sweating.
On examination, she is apyrexial, has a heart rate of 98bpm, a blood pressure of 138/90mmHg and a respiratory rate of 18.
Four months ago, she was found to have hypertension, and was prescribed ramipril and atenolol.
Three days ago, she was prescribed amoxicillin, metronidazole and omeprazole in response to a positive urea breath test.
What drug interaction may have occurred?

Metronidazole can cause the disulfiram reaction when taken with alcohol.
Alcohol is metabolised by the enzyme alcohol dehydrogenase, to acetaldehyde. Acetaldehyde is further metabolised by acetaldehyde dehydrogenase; both metronidazole and disulfiram inhibit this enzyme therefore acetaldehyde accumulates. Unfortunately, acetaldehyde produces the rather unpleasant symptoms described above. For most, overindulging significantly is required before achieving a relatively mild hangover, but if alcohol is consumed even in small quantities while a patient is taking metronidazole, they will rapidly experience severe symptoms. Therefore, it is important to warn patients not to drink alcohol whilst taking it.
This effect is utilised deliberately in disulfiram therapy, which alcoholics take to overcome the temptation to drink.

http://www.drugs.com/pro/metronidazole.html

http://www.netdoctor.co.uk/ate/medicines/207474.html

Question 9

A 65 year-old man presents with a three year history of erectile dysfunction. His libido is unimpaired but he has been unable to have intercourse with his wife for some months, which they both find distressing. He has a history of angina and hypertension. Today, he has a heart rate of 80 bpm and a blood pressure of 144/94mmHg.
Which of the following concomitant therapies would be a contraindication to sildenafil (Viagra) treatment?

Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor, drugs that are well known to interact with nitrates, resulting in dramatic hypotension. These drugs should not, therefore, be used in patients who also use a GTN spray.

Drug Interactions

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