Controversies about Cardiotoxicity Effect of Second-Generation Antihistamines

What medicines are they?
Five examples of famous second-generation antihistamines are cetirizine, terfenadine, astemizole, ebastine, and loratadine.

What are their advantages compared to first-generation antihistamines?
First-generation antihistamines have several weaknesses; namely their tendency to cross blood-brain barrier and consequent sedative-anticholinergic side effects. Their half-life is also shorter, thus limiting their efficacy against allergic symptoms. These weaknesses have been "covered" by the second-generation antihistamines.
Overall, antihistamines are rapidly and completely absorbed after oral administration with peak plasma concentration reached within 1-4 hours. Most of second-generation antihistamines undergo an extensive first-pass metabolism via cytochrome P450 (Cyp3A4). But several of them (e.g. mizolastine) is not metabolized by this pathway, but by glucuronidation enzyme.

FDA Pregnancy Safety Index

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United States Food and Drug Administration (US FDA) has used pregnancy safety index categories to determine the potential of a medicine to harm a pregnancy. The harm means birth defects or termination of pregnancy. FDA created this guideline in 1975 for pharmaceutical companies, and then revising the labeling method in 1997.

The categories are determined by the reliability of documentation from animal and human study; and the risk to benefit ratio of using this medicine in pregnancy (according to life-saving factor vs pregnancy factor). For your information too, these categories does not include any risks of breastfeeding-related risk.

Fluoroquinolones: Behind the Famous Broad Spectrum Antibiotic

Fluoroquinolone is one of antibiotic/antimicrobial class with the highest prescriptions rate worldwide. This antibiotic works as an inhibitor of gyrase enzyme, and/or topoisomerase II/IV. These enzymes are vital for bacterial DNA synthesis or replication process.

There are four generations of quinolones:

First generation: nalidixic acid, nitrofurantoin. Usually used in urinary tract infection. This group was called old quinolones.
Second generation: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, and lomefloxacin. From this generation on, the next groups are called new quinolones/fluoroquinolones; due to their systemic effect.
Third generation: gatifloxacin, gemifloxacin, grepafloxacin, sparfloxacin
Fourth generation: moxifloxacin, trovafloxacin

Ciprofloxacin: How is the safety in Children?

Ciprofloxacin, just like other fluoroquinolones, is not recommended for infectious diseases children; due to concern of potential arthropathy and development disturbances risk. All ciprofloxacin labels worldwide list children and adolescent under age of 18 as contraindication of all fluoroquinolones. But how about the experiences?

Phases in Clinical Trial

Clinical trial is needed to support effectivity and safety claims of a medicine, and also to support data for approval need by regulatory system. Before a clinical trial is conducted in human, a compound (experimental medicine) is tested to animals first, to show whether the compound gives benefit or not. Animal study is using several dose level, from small to large doses. This is needed to determine how high is lethal dose, how low is an effective dose, how high is safe dose, and how wide/narrow is the safety margin, etc. When the animal trial data would be extrapolated into propose human trial with same agent, dose should be calculated by scientist so that human dose is much smaller than animal dose.

There are four phases of clinical trials: phase I, II, III, and IV. Phase I-III are called experimental trials, and phase IV is postmarket study.