Adverse Drug Reactions

Question 1

What is the effect of Amiodarone on Warfarin?

Answer 1

Amiodarone is an enzyme inhibitor leading to decreased clearance of Warfarin and consequently an increased INR.

Question 2

What side effect is associated with beta blockers?

Answer 2

Insomnia is a commonly reported side effect of all beta blockers.

Question 3

What are the well known side effects of Phenytoin?

Answer 3

Dupuytren’s contracture is a well recognised side effect of Phenytoin.

Other important SEs:

• Coarsening of facial features
• Hirsutism
• Gingival hyperplasia
• Tremor
• Vomiting
• Ataxia
• Peripheral neuropathy

Question 4

What SE of cetirizine is most likely seen in children?

Answer 4

Drowsiness. Cetirizine is considered to be a non-drowsy antihistamine as it penetrates the blood brain barrier to a lesser extent than older antihistamine. Despite this, it can cause some drowsiness in children.

Question 5

Which antibiotic should be given as an alternative to amoxicillin in penicillin allergic patients for a chest infection?

Answer 5

Clarithromycin (Macrolide).

Question 6

Why is trimethoprim contraindicated with methotrexate?

Answer 6

Trimethoprim acts to block folate from being used in deoxyribonucleic acid (DNA) synthesis, as does methotrexate. Use of these two drugs together can cause bone marrow suppression and neutropenia. It is essential to monitor for any signs or symptoms of infection, such as sore throat and fever, in these patients for this reason.

Question 7

What medications can cause erythema multiforme?

Answer 7

Erythema multiforme is an acute hypersensitivity reaction of the skin that results in classic target lesions (a rim of erythema surrounding a paler area and a vesicle or bullae).

Although 90% of cases are caused by infections (such as herpes simplex virus, human immunodeficiency virus and Mycoplasma), medications make up 10% of cases. Many drugs have been reported to cause erythema multiforme and this list includes:

• Penicillins
• NSAIDs
• Nitrofurantoin
• Sulfonamides
• Anticonvulsants.

Stevens-Johnson syndrome is a potentially fatal drug reaction that causes sheet-like skin and mucosal loss. It was previously thought to be a severe form of erythema multiforme, but it is now considered a distinct entity. It is nearly always caused by medications and 40% of cases are associated with antibiotics

Question 8

Does steroids cause fluid retention?

Answer 8

Yes. Systemic corticosteroids can cause increased salt and water retention, especially when used in high doses. For this reason, they should be used with caution in patients who have pre-existing conditions such as heart failure or hypertension.

Over-treatment with exogenous corticosteroids can cause Cushing syndrome which presents with the characteristic features of truncal obesity, buffalo hump, moon facies and skin atrophy. It can also contribute to psychological problems such as depression.

Question 9

Common side effects of steroids?

Answer 9

Common side-effects include:

• Fluid retention
• Abdominal pain
• indigestion
• feeling sick
• mood/behavioural changes
• difficulty sleeping
• feeling confused
• increased weight
• thrush
• muscle weakness
• feeling tired
• irregular periods.

Question 10

SEs of memantine?

Answer 10

Memantine is a glutamate receptor antagonist. SEs include constipation, drowsiness, headache and hypertension. can also cause hallucinations and balance problems.

Question 11

What medications cause anti-cholinergic SEs? (dry mouth, constipation, visual changes and urinary retention)

Answer 11

Tricyclic antidepressant (Amitryptiline)
Atropine
Oxybutynin
Ipratropium

Question 12

What medication can cause bilateral ankle swelling?

Answer 12

Amlodipine. Peripheral oedema is a known SE of amlodipine. ACEi can be considered if SE not tolerated.

Question 13

Most common SE caused by bisoprolol?

Answer 13

Headache and dizziness are common symptoms of bisoprolol use.

Bisoprolol is a selective inhibitor of beta-1 adrenergic receptors with little or no effect on beta-2 receptors. But can cause bronchospasm in reactive airways (asthma).

Question 14

SE associated with entacapone (COMT inhibitor)?

Answer 14

Red-brown urine.

Question 15

What is a SE of bleomycin?

Answer 15

Pulmonary fibrosis.

Question 16

Common SE of gentamicin toxicity?

Answer 16

Vertigo.

Gentamicin is an intravenous (IV) aminoglycoside. The primary toxicities of aminoglycosides are nephrotoxicity and ototoxicity.

Aminoglycoside-induced ototoxicity may result in either vestibular or cochlear damage. Vestibular toxicity manifests as vertigo, light-headedness, nausea, vomiting and ataxia.

Cochlear toxicity manifests as tinnitus and bilateral sensorineural hearing loss. In many cases, ototoxicity is irreversible. Ototoxicity is more likely to occur with courses lasting more than one week but can occur irrespective of dose, blood concentration measurements and renal function. An audiogram should be considered if therapy is anticipated to continue for more than seven days.

Question 17

What drug exacerbates Parkinsonian symptoms?

Answer 17

Metoclopramide. It is a dopamine antagonist which crosses the blood brain barrier. It can cause a reduction in dopamine level therefore exacerbating parkinson’s symptoms.

Question 18

What adverse effect is likely caused by Seretide?

Answer 18

Oral candidiasis.

Seretide is a combination of fluticasone (corticosteroid) and salmeterol (LABA). Candidiases is a common SE of inhaled corticosteroids. The risk can be reduced by encouraging rinsing with water after using the inhaler and use of a spacer driver.

Question 19

Common SE of codeine?

Answer 19

Constipation.

Codeine is thought to act on receptors in the gastrointestinal (GI) tract by inhibiting gastric emptying, delaying peristalsis and decreasing the amount of fluid available in the intestine. These effects contribute to the hardening of stool and increased difficulty in passing stool.

Question 20

What drugs need to be used with caution in asthmatics?

Answer 20

• NSAIDs
• Beta blockers
• Adenosine

Around 10-20% of patients with asthma experience bronchospasm / worsening of asthma control after ingesting NSAIDs. The risk is increased in patients with nasal polyps and also those who are middle-aged. Surprisingly, NSAID-induced asthma is uncommon in children.

If alternative analgesics are not available and there is no history of hypersensitivity to NSAIDs it is acceptable to give asthmatic patients a trial of NSAIDs after informing them of the risks.

Again beta-blockers may cause bronchospasm and are best avoided. They are not however absolutely contraindicated and if no alternatives are available a low-dose may be initiated under specialist supervision. Some beta-blockers are more cardioselective (e.g. nebivolol) so in theory may induce less bronchospasm.

The BNF states that asthma / chronic obstructive pulmonary disease (COPD) are contra-indications to adenosine. Verapamil may be used as an alternative.

Caution should be exercised when prescribing large doses of opioid based medications on benzodiazipines to patients with COPD as these medications may act as respiratory depressants.

Question 21

What drugs can exacerbate heart failure?

Answer 21

The following medications may exacerbate heart failure:
- Thiazolidinediones: Pioglitazone is contraindicated as it causes fluid retention

• Verapamil: negative inotropic effect
• NSAIDs/glucocorticoids: should be used with caution as they cause fluid retention.
  low-dose aspirin is an exception; many patients will have coexistent cardiovascular disease and the benefits of taking aspirin easily outweigh the risks.
• Class I antiarrhythmics: Flecainide (negative inotropic and proarrhythmic effect).

Question 22

Drugs that worsen seizure control in epilepsy?

Answer 22

The following drugs may worsen seizure control in patients with epilepsy:

• alcohol, cocaine, amphetamines
• ciprofloxacin, levofloxacin
• aminophylline, theophylline
• bupropion
• methylphenidate (used in ADHD)
• mefenamic acid

Some medications such as benzodiazepines, baclofen and hydroxyzine may provoke seizures whilst they are being withdrawn.

Other medications may worsen seizure control by interfering with the metabolism of anti-epileptic drugs (i.e. P450 inducers/inhibitors).

Question 23

Drugs harmful in pregnancy?

Answer 23

Antibiotics:

• tetracyclines
• aminoglycosides
• sulphonamides and trimethoprim
• quinolones
• ACE inhibitors, ARBs
• Statins
• Warfarin (Most women are switched to LMWH for the duration of the pregnancy)
• Sulfonylureas
• Retinoids (including topical)
• Cytotoxic agents

The majority of antiepileptics including valproate, carbamazepine and phenytoin are known to be potentially harmful. The decision to stop such treatments however is difficult as uncontrolled epilepsy is also a risk.

Question 24

Regarding dosing of gentamicin, what should be done if the peak (post dose) level is high?

Answer 24

Due to the significant ototoxic and nephrotoxic potential of gentamicin it is important to monitor plasma concentrations.

Both peak (1 hour after administration) and trough levels (just before the next dose) are measured:

• If the trough (pre-dose) level is high the interval between the doses should be increased.
• If the peak (post-dose) level is high the dose should be decreased.

Question 25

Beta blockers should not be combined with what drug due to risk of life threatening bradycardias?

Answer 25

Beta-blockers and Verapamil (CCB) should never be prescribed together due to the risk of life-threatening bradycardias.

Question 26

What drugs should be avoided in renal failure?

Answer 26

Drugs to avoid in renal failure:

• Antibiotics: tetracycline, nitrofurantoin
• NSAIDs
• Lithium
• Metformin

Drugs likely to accumulate in CKD; need dose adjustment:

• Most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
• Digoxin, atenolol
• Methotrexate
• Sulphonylureas
• Furosemide
• Opioids

Question 27

Drugs to avoid in patients with ischaemic heart disease?

Answer 27

The following drugs should be used with caution in patients with ischaemic heart disease:

• NSAIDs
• Oestrogens: e.g. COCP, hormone replacement therapy
• Varenicline

Question 28

List 3 common side effects from calcium channel blockers?

Answer 28

• Headache
• Ankle swelling
• Flushing

Question 29

Adverse effects of tamoxifen?

Answer 29

• Menstrual disturbance: vaginal bleeding, amenorrhoea
• Hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects
• Venous thromboembolism
• Endometrial cancer

Question 30

What is the management for a paracetamol overdose?

Answer 30

The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.

Acetylcysteine should be given if:

• There is a staggered overdose (an overdose is considered staggered if all the tablets were not taken within 1 hour) or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration;

OR

the plasma paracetamol concentration is on or above the treatment line (joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours) regardless of risk factors of hepatotoxicity.

Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction. Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.

Question 31

Symptoms of lithium toxicity?

Answer 31

Features of toxicity:

• Coarse tremor (a fine tremor is seen in therapeutic levels)
• Hyperreflexia
• Acute confusion
• Polyuria
• Seizure
• Coma

Question 32

Digoxin monitoring (read further on passmedicine)

Answer 32

Digoxin is a cardiac glycoside now mainly used for rate control in the management of atrial fibrillation. As it has positive inotropic properties it is sometimes used for improving symptoms (but not mortality) in patients with heart failure.

Monitoring

• digoxin level is not monitored routinely, except in suspected toxicity
• if toxicity is suspected, digoxin concentrations should be measured within 8 to 12 hours of the last dose

Plasma concentration alone does not determine whether a patient has developed digoxin toxicity. Toxicity may occur even when the concentration is within the therapeutic range. The BNF advises that the likelihood of toxicity increases progressively from 1.5 to 3 mcg/l.

A classic precipitating factor is hypokalaemia.

Question 33

Acute management for a supraventricular tachycardia (SVT)? one of the most common arrhythmias encountered in younger patients

Answer 33

Acute management:

1. Vagal manoeuvres: e.g. Valsalva manoeuvre, carotid sinus massage
2. Intravenous Adenosine 6mg → 12mg → 12mg: contraindicated in asthmatics - Verapamil is a preferable option
3. Electrical cardioversion

Prevention of episodes:

• beta-blockers
• radio-frequency ablation

Question 34

Does ACE-i need to be stopped if creatinine goes up on starting the drug?

Answer 34

A small rise in creatinine (<20%) is to be expected when starting an ACEi and does not require investigation or a change in prescription.