#Comparison of Metronidazole and Erythromycin

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Comparison of Metronidazole and Erythromycin

Excretion of the Drugs

The elimination of the drug from the body is an important process. The main path of elimination of metronidazole and its metabolites is[PS1]  through the renal system. Urine contains about 60% to 80% of the dose whereas faecal excretion accounts for 6% to 15% of the dose (Lofmark, Edlund & Nord, 2010). The metabolites that exist in the urine are products of side chain oxidation and glucuronide conjugation. Unchanged metronidazole also form part of the content eliminated from the body and it accounts for approximately 20% of the whole.

Erythromycin is only partly excreted in urine and only about 2.5% of an orally administered dose and 15% of a parenterally administered does is recoverable from the urine in the active form. The concentration of this drug in its active form in urine is normal low and variable. The main path for elimination of erythromycin is through bile after being mobilised in the bile. The elimination of this drug through the bile occurs by demethylation and oxidation of the aminated sugar. Studies reveal that some erythromycin excreted through this means is reabsorbed in the intestine. Nevertheless, large proportion of this drug is inactivated in the body in liver (Woo & Robinson, 2013).

Comparison of Pharmocodynamics of the Drugs

Mechanism of Action of the Drugs

The mechanism of action of metronidazole and erythromycin bear some semblance and differences. The ways in which these drugs enter into the cells of the pathogens tend to differ and this defines nature of reaction into the body.

Erythromycin like other macrolide antibiotic inhibits protein synthesis. It binds to the 23srRNA molecule of the bacterial ribosome thus blocking the exit of the growing peptide chain of the pathogens. However, certain microorganism with mutational changes fails to bind with erythromycin. Erythromycin exhibit reversible association with ribosome and this occurs when 50S subunit is free from tRNA molecules containing the nascent peptide chain. Studies reveals that gram-positive bacteria tend to accumulate erythromycin about 100 times more than gram-negative microorganisms (Sun, Huang, Frassetto, & Benet, 2004). The non-ionised molecules from the drug are notably more permeable to cells. The increased antimicrobial activity usually occurs in alkaline pH.

Metronidazole inhibits activity of a variety of protozoa and bacteria[PS2] . It enters the cell via passive diffusion. Afterword, it is activated in cytoplasm of the bacteria or[PS3]  organelles of the protozoa. As such, it interferes with the activities of the specific protozoa and bacteria. However, in cells that are resistant to the drug, it fails to activate. During the reaction, metronidazole molecule is converted to free radical, nitroso (Davey, Wilcox, Irving, & Thwaites, 2015). The process leads to transfer of electron to nitro group. The action of the drug[PS4]  includes inhibition of DNA synthesis and DNA damage[PS5] . This it causes a single strand and double strand bleaks that influence the death of the cell. The activated reduced metronidazole tends to bind non specifically to bacteria DNA thereby deactivating the activity of the bacteria consequently leading to death of bacteria.

Adverse Reaction Linked to Mechanism of Action

The interaction of the drug to the body cells and the pathogens may result into adverse reaction. Erythromycin and metronidazole tend to show varied adverse reactions to the cells and body even though both dugs are antibiotics. Perhaps the reason behind this observation is that these drugs belong to different groups of antibiotics. As such, their reaction and function tend to differ.

The adverse reaction of metronidazole includes headache about 18%, dizziness about 4% and sometimes one may experience seizures in the form of optic and peripheral neuropathy, poor coordination of nerve activities, irritability, and insomnia (Davey, Wilcox, Irving, & Thwaites, 2015). Some people experience pruritis such as skin irritation, itching or rash, dryness and burning. It may also lead to thrombophlebitis, urticaria, flushing, allergic reaction including contact dermatitis and transient redness (Lofmark, Edlund & Nord, 2010). It reacts to produce metallic taste, blockage of the nose, and pharyngitis. To some people, it leads to reactions such as nausea, abdominal pain, constipation, and epigastric distress. Further, users may experience vaginitis such as vaginal discharge, abnormal urine, and incontinence and reduced libido.

The administration of erythromycin often leads to about 5% to 30% of causes of gastrointestinal pain such as vomiting, gastric pain, nausea, and abdominal cramp (Jjemba, 2008). It is not advisable to take high single doses because they lead to adverse reactions. The reactions are more frequent in children than in adult. Nevertheless, all forms of erythromycin preparations results into hepatotoxic reactions; however, the condition is reversible once the person using the drug stops (Sun, Huang, Frassetto, & Benet, 2004). Some people show transaminases increase while jaundice and ototoxic effects remain infrequent and reversible. Skin reactions, colitis, fever, and pancreatitis are among other rare effects of this drug.

References

Davey, P., Wilcox, H. M., Irving, W., & Thwaites, G., (2015). Antimicrobial Chemotherapy. London: Oxford University Press.

Jjemba, K. P., (2008). Pharma-Ecology: The Occurrence and Fate of Pharmaceuticals and Personal Care Products in the Environment. New Jersey: John Wiley & Sons.

Lofmark, S., Edlund, C., & Nord, E. C., (2010). Metronidazole Is Still the Drug of Choice for Treatment of Anaerobic Infections. Clinical Infectious Diseases. 50(1), S16-S23.  

Smith, A. D., Allerton, C., Kubinyi, H., Walker, H., & Walker, K. D., (2012). Pharmacokinetics and Metabolism in Drug Design. New Jersey: John Wiley & Sons.

Sun, H., Huang, Y., Frassetto, L., & Benet, Z. L., (2004). Effects of Uremic Toxins on Hepatic Uptake and Metabolism of Erythromycin. Drug Metabolism and Disposition, 32(11), 1239-1246.

Woo, M. T., & Robinson, V. M., (2013). Pharmacotherapeutics For Advanced Practice Nurse Prescribers. New York: F.A. Davis.

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 [PS1]Possible source: http://cid.oxfordjournals.org/content/50/Supplement_1/S16.full

 [PS2]Possible sources: http://cid.oxfordjournals.org/content/50/Supplement_1/S16.full http://www.medicinescience.org/pdfs/journals/vol3/no2/53-1376335919.pdf

 [PS3]Possible sources: http://cid.oxfordjournals.org/content/50/Supplement_1/S16.full http://www.medicinescience.org/pdfs/journals/vol3/no2/53-1376335919.pdf

 [PS4]Possible source: http://cid.oxfordjournals.org/content/50/Supplement_1/S16.full

 [PS5]Possible sources: http://cid.oxfordjournals.org/content/50/Supplement_1/S16.full http://ijpsr.com/wp-content/uploads/2014/11/16-Vol.-4-Issue-7-July-2031-IJPSR-RA-2425-Paper-16.pdf

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Comparison of Metronidazole and Erythromycin

Introduction

Metronidazole belongs to the class of antibiotic family, but suitable for treatment of[PS1]  conditions caused by single celled bacteria and specific parasites. The anaerobic bacteria have a tendency of living in regions with limited or little oxygen supply. Some of the areas where these bacteria live include abdomen, liver, and pelvis. Apart from treating health conditions caused by anaerobic bacteria, it treats conditions caused by internal parasites that affect the abdomen. On the other hand, erythromycin also belongs to the family of antibiotics, but used in treatment of conditions caused by acute bacterial infections. It has a wide range of application in treating complicated bacterial infections. Importantly, while metronidazole and erythromycin belong to the same group of antibiotics, the fall in different classes thus meant to treat different bacterial infections and conditions caused by specific types of parasites. The purpose of this essay is to compare and contrast the similarities and differences of metronidazole and erythromycin.

Pharmacokinetics

Administration Route: Gastric acid easily inactivates erythromycin. As such, erythromycin comes in form long acting capsule, tablet, and liquid. It is given as enteric coated, esters, and more stable salts. The body easily absorbs erythromycin and diffuses in the body tissues and phagocytes. Its high concentration in the phagocytes and body tissues makes it to be transported by blood to infection sites (Jjemba, 2008). Here, active phagocytises occur thus allowing the large concentration of erythromycin to be released.  

Metrodinazole disposition in the body is same for intravenous dosage and oral one. When administered orally, the body absorbs it well and it achieves peak concentration in the plasma after one to two hours. Usually, the concentration of metrodinazole in the plasma is proportion to the dose consumed. While studies indicate no considerable bioavailability difference between women and men, due to weight differences, the plasma levels is lower in male (Woo & Robison, 2013).

Bioavailability and Half-life of the Drugs

Studies reveal that bioavailability of metronidazole is 100% and has a half-life of 7.5 hours (Woo & Robinson, 2013). In instances of impaired liver function, the elimination of metronidazole tends to be slower than the above. In case of renal failure, its half-life remains constant, however that of metabolites tends to increase.

Erythromycin has variable and erratic bioavailability because its lability to stomach acid. However, studies show that its derivatives with modified acid lability tend to show increased bioavailability and extended plasma half-life. Some studies show that bioavailability of oral erythromycin base is poor and highly variable because of inactivation gastric acidity Sun, Huang, Frassetto, & Benet, 2004). The long terminal half-life of erythromycin is the main reason behind its administration once in a day.

Distribution of the Drugs in the Body

Oral metronidazole is readily absorbed and distributed widely into the body tissues and fluids including breast milk, liver abscesses, bone, vaginal secretion, and seminal fluids. Major component of metronidazole appear in the plasma with low quantities of metabolites. Plasma proteins bind about 20% of circulating metronidazole in the body tissues (Smith, Allerton, Kubinyi, Walker, & Walker, 2012). Once a person consumes metronidazole, it circulates in the body tissues and usually appears or present in cerebrospinal fluid, breast milk, and saliva. The concentration of metronidazole in these body fluids is similar to the quantity found in the plasma. Bactericidal concentration of metronidazole also found in pus.

Erythromycin is distributed through the body fluids and tends to penetrates easily into body tissues where it remains longer than the blood. It also accumulates in the cells, attaining cellular and extracellular concentrations of around ten. This property is usually so because of erythromycin molecule exhibit high diffusibility.  Erythromycin stearate is less like to destroyed in the stomach than erythromycin base and it dissociates in the duodenum thus releasing active erythromycin (Woo & Robinson, 2013). The peak serum level for erythromycin stearate and erythromycin base are usually the same, but the absorption of the base might take a bit longer. Once absorbed in the body tissues, its concentration tends to appear in the body fluid including urine.

Metabolism of the Drugs

The body metabolizes metronidazole into numerous degradation products with large percentage, about 60% to 80%, being eliminated through the renal. The liver partially metabolises metronidazole by hydroxylation, glucuronide conjugation, and acid side chain oxidation.

Erythromycin undergoes extensive hepatic metabolism. Majority of metabolism of erythromycin occur in the liver by CYP3A4 to N-demethyl erythromycin (Smith et al 2012). It is bacteriostatic and it exhibit increased activity in alkaline condition. It large diffusion into tissues serves as an advantage for treatment of several infections. It reaches peak levels in serum after four hours of dosing.

 [PS1]Possible source: http://www.medicinescience.org/pdfs/journals/vol3/no2/53-1376335919.pdf