BIOP211- Pharmacology- Research Assignment

Macrolides are class of antibiotic that comprise, roxithromycin, azithromycin, erythromycin, etc. used for treating condition like pneumonia, H. Pylori, and acute urethritis, this is useful medication for people who are allergic to penicillin or cephalosporin.  In this essay, we are going to discuss the mechanism of this drug, route to administration, side effect of the drugs, and understanding it in relation to human physiology. Macrolides are used to treat skin, respiratory, sexually transmitted, soft tissue issues and atypical mycobacterial infections, we will discourse the drug concisely and at end a conclusion relevant to it will be given.

Mechanism of action (pharmacodynamics) of macrolides

Macrolides are class of antibiotic that comprise, roxithromycin, azithromycin, erythromycin, etc. Macrolides are used to treat skin, respiratory, sexually transmitted, soft tissue issues and atypical mycobacterial infections (Fohner, Sparreboom, Altman & Klein, 2017).. These interfere with bacterial protein synthesis and rely on bacterial species and concentration, the drug either kill bacteria (bactericidal) or hinder growth of bacteria (bacteriostatic).  Macrolides comprise anti-inflammatory and immunomodulatory effects that are beneficial in few situation, for example, treatment of cystic fibrosis. Macrolides are beneficial against gram positive expect enterococci and some gram negative bacteria, they are also effective against Treponema pallidum, mycoplasma pneumoniae, Legionella spp, Chlamydia trachomatis, Bordetella pertussis, etc.  The first line indication for macrolides is suitable are given in table below, however the medication is also considered for second line treatment.

Table 1.   First Line and Second Line Treatment for Macrolides

Infection	First line treatment	Second line treatment
Pneumonia	Amoxicillin	roxithromycin, erythromycin and doxycycline
H. Pylori	Amoxicillin, omeprazole and clarithromycin	Omeprazole, metronidazole  and clarithromycin
Pertussis	Erythromycin	______
Acute urethritis	Azithromycin	Vancomycin

 

(Fohner, Sparreboom, Altman & Klein, 2017).

Based on chemical structure macrolides are divided into categories, clarithromycin and erythromycin are fourteen membered lactone rings, azithromycin is contained 15 member ring that prevents metabolism through mechanism endured by other macrolides, as azithromycin did note interact with SLCOB1 and CYP2A4 it has a longer half-life and less drug interaction compare to another macrolide.  Macrolides hinder bacterial growth by preventing protein synthesis, and by reversibly binding to 50S of the 70s bacterial ribosomes and it also blocks additional converting of the proteins (So & Nicolau, 2016), hence it is considered as effective in dividing organisms actively. Macrolides effectiveness is evaluated according to dosage concentration and time of dose interval this mechanism creates a low barrier for bacteria to show resistance to the medication if structure of ribosome or if drug efflux applied by a change in bacterial macrolide efflux.

Route of administration, adverse effect, and contradiction of selected drug

Macrolides are generally administrated orally, though erythromycin can be administered parenterally (Jose, 2017). The preparation of the drug involves a conversation with the administering worker, factors needed to be considered when administrating are dosage, route, strength, treatment goal, etc.  (Pereira, Sara & Fernandes, 2019) There are various forms for administrating macrolides that rely on its use and desired medication, however, it is generally used in oral form (e.g. tablet) but they also come in the intravenous form and as a topical cream.

Table 2. The common macrolides and their common formulation and dosage.

Clarithromycin : Oral tablet (125mg, 250mg , 500mg , 1000mg )

Azithromycin: Oral tablet (100mg, 250mg, 500mg, 600 mg)

Erythromycin:  oral tablet (250mg and 500mg)

 

(Jose, 2017).

Adverse effect:

Macrolide drug interactions are prone to pharmacokinetic drug are concern and effect the toxicity and efficacy. Macrolide adverse effect include gastrointestinal issues, for instance, cramp, and diarrhoea, abdominal discomfort, etc. (Hansen et al., 2019) Symptoms rely on dose and can be easily noticed in children, erythromycin is identified to be having more adverse effect than other macrolides, just like other antibiotics the drug carry risk of typical side effect such as vomiting, nausea, diarrhea, and abdominal pain that is due to drug being agonists increasing risk gastrointestinal issues (Dinos, 2017). Also, flora is susceptible to macrolide effects, thus, it can cause imbalance between human gut and bacteria, and other adverse effect of macrolide is that in cardiac cycle its tendency to extend QT interval that can put patient at risk of torsades de pointes, ventricular fibrillation and tachycardia, again erythromycin has higher tendency compare to other macrolides. Patient can also suffer from hearing loss that is identified to be occurred due to increased or standard doses.  Toxic epidermal necrolysis is other serious but rare side effect of the medication that needed to be taken into account when prescribing the medication.   In pregnant women, erythromycin has association with hepatotoxicity, and these drug might increase risk of pyloric stenosis in baby, thus, pregnant women should avoid this drug. Still, in general these medication are considered to be safe antibiotic with right prescription however, the contradiction of the drug exit and its ability to interact with other medication/drug. Due to arrhythmogenic factors patient with QT interval should avoid taking this drug.  Resistance status of pathogens needed to be consider by prescriber. Other side effect of macrolides comprise liver injury, inflammation, etc.

 Macrolides utilise their action to hinder caterial protein synthesis and avoid peptytansfyrase controlled attachment of peptyl to TRNA after amino acid (Sultan et al., 2018). The nutritional state absence on Azithromycin tablet proven to be slow disintegration in fed stomach, long gastric acid exposure increase descladinose.

Table 3. Interaction of macrolide with enzyme.

Absorption	Clarithromycin	Azithromycin	Erythromycin
Food	Induction	Inhibition ( greater than 150% AUC)	0
Antacid	Inhibition	-	-
P-gp	Inhibition (50-150%)	-	-
Metabolism
CYP2C19	Inhibition	-	-
CYP3A4	Inhibition	0	Inhibition
Excretion P-gp	-	Inhibition	-

(Sultan et al., 2018)

How to prevent adverse reactions between the selected drug and herb or nutritional supplement.

When prescribing medication monitoring needed to be done to monitor the side effects and cardiac effects who use macrolides. Prescribers must be aware of probable dermatologic adverse effects and hence should advise patients on/about the adverse effects. Monitoring of QT interval on ECG to patient who are at high risk of arrhythmias, it is vital to check electrolyte of patient before administration, such as potassium, calcium and magnesium.

A few instances of bleeeding have been accounted for in individuals who take anti-biotic such as macrolides. This symptom might be the consequence of decreased nutrient K action as well as diminished nutrient K creation by microscopic organisms in the colon. One examination indicated that individuals who had taken wide range anti-infection agents had lower liver centralizations of nutrient K2 (menaquinone), however nutrient K1 (phylloquinone) levels stayed typical. A few anti-toxins seem to apply a solid impact on nutrient K movement, while others might not have any impact. Thusly, one ought to allude to a particular anti-toxin for data on whether it associates with nutrient K. Specialists of regular medication in some cases prescribe nutrient K supplementation to individuals taking anti-microbials. Extra research is expected to decide if the measure of nutrient K1 found in certain multivitamins is adequate to forestall anti-infection incited dying. Additionally, most multivitamins don't contain nutrient K (Vázquez-Laslop & Mankin, 2018).

Taking probiotic microorganisms such as Bifidobacterium longum, and rahmnosus GG might support in preventing adverse effect such as diarrhoea. Also When doctor prescribe bromelain to be taken with amoxicillin, it has shown to increase absorption of amoxicillin in humans, 80 mg of bromelain was taken together with tetracycline or erythromycin it is effective as bromelain acts on drug metabolism remains unknown. Chewing herb like khat help in recuing side effects of anti-biotic like macrolides.  Aluminium containing antacid and magnesium interfere with azithromycin and help people to avoid interaction by taking azithromycin two hour before or after any magnesium or aluminium comprising product. Digitalis belongs to group of plants regularly considered foxglove that contain digitalis glycosides, synthetic concoctions with activities toxin levels like the physician recommended tranquilize digoxin. Erythromycin and clarithromycin drug related to azithromycin can expand the serum level of digitalis glycosides, increase the therapeutic effect and risk of adverse effect as well.

Though macrolides safe be done to class of antibiotics, appropriate administration can reduce adverse effect. Healthcare professional having knowledge about common side effects such as gastrointestinal and monitoring patients for common adverse effects as well as the rare symptoms. Pharmaceutical consult needed to be include when initiating macrolide therapy and proper dose, use, objective, and appropriateness of the drug and drug-drug interaction needed to be considered,  questioning patient about the therapy and using therapeutic skills to ensure patient also take part in understanding benefits of medication, its adverse effects, and support in monitoring side effects.

Conclusion

Macrolides are beneficial in treating skin, respiratory, sexually transmitted, soft tissue issues and atypical mycobacterial infections. These interfere with bacterial protein synthesis and rely on bacterial species and concentration, the drug either kill bacteria (bactericidal) or hinder growth of bacteria (bacteriostatic). Medication generally administrated orally, has both benefits and side effects, Macrolide adverse effect include gastrointestinal issues, for instance, cramp, and diarrhoea, abdominal discomfort, etc.  Macrolides utilise their action to hinder caterial protein synthesis and avoid peptytansfyrase controlled attachment of peptyl to TRNA after amino acid. The nutritional state absence on Azithromycin tablet proven to be slow disintegration in fed stomach, long gastric acid exposure increase descladinose. Taking probiotic microorganisms such as Bifidobacterium longum, and rahmnosus GG might support in preventing adverse effect such as diarrhoea, and natural herb like khat and Digitalis can help in reducing adverse effect of drug. Though macrolides safe be done to class of antibiotics, appropriate administration can reduce adverse effect.

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Reference:

Dinos, G. P. (2017). The macrolide antibiotic renaissance. British journal of pharmacology, 174(18), 2967-2983.

Fohner, A. E., Sparreboom, A., Altman, R. B., & Klein, T. E. (2017). PharmGKB summary: Macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics. Pharmacogenetics and genomics, 27(4), 164.

Hansen, M. P., Scott, A. M., McCullough, A., Thorning, S., Aronson, J. K., Beller, E. M., & Del Mar, C. B. (2019). Adverse events in people taking macrolide antibiotics versus placebo for any indication. Cochrane Database of Systematic Reviews, (1).

José, R. J. (2017). Next generation macrolides for community-acquired pneumonia: will solithromycin rise to the occasion?. Journal of Research Hospital, 2.

Pereira, D. E., Sara, W. U., & Fernandes, P. (2019). U.S. Patent No. 10,188,674. Washington, DC: U.S. Patent and Trademark Office.

So, W., & Nicolau, D. P. (2016). Pharmacodynamics of Macrolides, Azalides, and Ketolides. In Antibiotic Pharmacodynamics (pp. 345-366). Humana Press, New York, NY.

Sultan, S., Jahangir, A., Gussak, I. B., Kostis, J. B., JamilTajik, A., & Jahangir, A. (2018). Interactions between supplements and medications. Iatrogenicity: causes and consequences of iatrogenesis in cardiovascular medicine, 370-389.

Vázquez-Laslop, N., & Mankin, A. S. (2018). How macrolide antibiotics work. Trends in biochemical sciences, 43(9), 668-684.