Tag Archives: drugs

Macrolides

Erythromycin, clarithromycin, azithromycin.

Bacteriostatic not bacteriocidal, but doesn’t necessarily mean inferior.

Broad spectrum, including things that aren’t even bacterial! eg Bordetella pertussis, syphilis.

Diarrhoea and vomiting as main side effects, not an allergy as such. True allergy is virtually unheard of! Other important issues:

  • Risk of pyloric stenosis in neonates
  • Prolong QT, so beware other things that also prolong QT including electrolyte disturbance

Prolonged QT interval

An abnormal finding on ECG.

QT interval changes with heart rate, so usually calculated as corrected QT (QTc), where average QT is divided by square root of RR interval (ie 1 second, if heart rate 60).

Associated with dysrhythmia, especially torsades de pointes (polymorphic ventricular tachycardia).

Seen with:

  • Genetic predisposition – Long QT syndrome
  • Certain drugs – antipsychotics (eg chlorpromazine, quetiapine), antiarrhythmics (!?), tricyclic antidepressants (eg amitriptyline), other antidepressants (eg citalopram, venlafaxine), antihistamines (terfenadine, but also loratadine, diphenhydramine, astemizole), macrolides, quinine.

Antihistamines

First generation have prominent CNS effects, usually drowsiness (which an be useful, eg to help sleep in chronic itch) but can be hyperactivity, paradoxically!

Second generation have lower incidence of these side effects.

Benadryl (brand name) can be either cetirizine or acrivastine.  Latter marketed as “fasted allergy capsule” – I suspect the only allergy capsule.

Tmax (plasma) lowest for Rupatadine (0.75hr), levocetirizine (0.8), cetirizine (1).  Chlorphenamine is 2.8, worse than diphenhydramine (best of the sedating antihistamines at 1.7).  Loratadine (1.2) and Acrivastine (1.4) not far behind; Desloratadine has a range of values from 1-3, which is unhelpful, Fexo is definitely slow at 2.6.

In terms of clinical effect on wheal (because tissue distribution different from plasma), cetirizine, acrivastine, levocetirizine equivalent (1hr), diphenhydramine, fexo, desloratadin 2 hrs, CPM 3hrs (!).  Rupatadine is 2 hrs, despite the short Tmax!

No particular reason to think formulation matters. Possibly liquid might work directly in the mouth and throat, but only if you don’t swallow it immediately (gargle!?).

Some examples of capsules beating liquids for specific drugs (!?) but prob not much difference between absorption from tablet, liquid etc. Prob easier to swallow liquid if oral angioedema, but liquid bolus might actually be harder than tiny tablet…

[J Investig Allergol Clin Immunol 2006; Vol. 16, Supplement 1: 3-12]

Macrolide allergy

The majority of cases reported are non immediate reactions eg maculopapular rash, urticaria. The incidence of anaphylactic reactions is extremely low.

Less than 15% of those suspected of having macrolide allergy are finally confirmed as allergic, mainly by direct provocation testing.

Cross-reactivity between the different macrolides is variable and little information is available.

Current Opinion in Allergy and Clinical Immunology 14(4), August 2014, p 278–285. DOI: 10.1097/ACI.0000000000000069

Penicillin allergy

Atanaskovic-Markovic et al found that cross-reactivity between cephalosporins and penicillins varied between 0.3 and 23.9%, being higher among penicillins and between first-generation and second-generation cephalosporins.

However, it has recently been shown that all penicillin allergic children can tolerate cefuroxime, presumably as it has a different side chain.

Cross-reactivity appears to be higher in immediate reactions, and when penicillins and cephalosporins are identical or similar in the R1 side chain, as happens with the first and second-generation cephalosporins.

Currently BNFc says to avoid cefalosporins if history of immediate penicillin hypersensitivity, but if use of cefalosporin is “essential” then can be used (but not cefalexin!).

See Testing for antibiotic allergy.

NSAID hypersensitivity

Ibuprofen etc are a common cause of reactions, but mostly non immune mediated, via COX -1 inhibition. Previously called pseudo-allergy or intolerance, best called hypersensitivity, then subdivided into allergic or non-allergic. Often occurs in patients with underlying problem eg asthma, chronic urticaria, rhinosinusitis – exacerbates underlying condition. Hypersensitivity can be to a single drug, or cross-reactive, ie to unrelated drugs from different families (salicylates ie aspirin, propionic derivatives eg ibuprofen, acetic acid derivatives eg diclofenac, etc). Cross reactivity suggests a non-immune mechanism. Without history to support single drug (or family) hypersensitivity, you would have to advise the patient to avoid all NSAIDs.

Testing

  • Skin testing with culprit drug is appropriate if you have an acute urticarial or angioedema reaction in a single drug/family.
  • Oral challenge is appropriate to confirm all types of hypersensitivity, esp in equivocal histories. At the same time, challenge with aspirin to check cross-reactivity, and with next best alternative NSAID. Start 1/10 dose, increase every 2 hours.
  • For nasal/bronchial symptoms, inhaled lysine aspirin is safer and faster, but only 77-90% sensitive cf 90% for oral. Intranasal is equivalent if inhaled/oral not possible.
  • If patient is on long term steroids, or else has been well controlled for a long time, sensitivity seems less!
  • Consider proceeding to challenge with COX2 (coxib) if challenge positive.

Aspirin desensitization works for NSAID exacerbated respiratory disease, and NSAID induced (cross reactive) skin disease, controversial for chronic urticaria and no data for single drug skin disease or anaphylaxis. But needs maintenance dosing so only really useful for chronic conditions eg needing antiplatelet therapy.

Allergy 2013:68;1219

Allergic Rhinitis

Under-recognized, particularly when chronic blockage (without itch/sneezing) rather than sneeze/discharge. Late phase reactions involving Eosinphil induction by T cells tends to produce chronic swelling and non-specific irritability eg cold air. Nose problems impact with everything connected eg eyes, sinuses, middle ear, lungs. Differential is wide eg CF/PCD, deviated septum, polyps.

ARIA= allergic rhinitis in asthma report (WHO).

Swimming and asthma

For competitive swimmers, note FINA doping control rules (based on the World Anti-Doping Agency regulations). Most asthma medications are on the Prohibited List including inhaled steroids and inhaled Beta2 agonists.

Therefore, elite athletes with asthma must apply for special permission to use these medications, known as the “Therapeutic Use Exemption” (TUE) program.  If competing at FINA events, then you apply directly to the FINA Doping Control Review Board to have their applications considered. Lower level athletes should apply to their national anti-doping body.