Amoxicillin belongs to a class of antibiotics called the Penicillins. The chemical structure of the Penicillin antibiotics contain a highly reactive β-lactam ring. This ring can be opened in neutral or basic solutions which can result in an inactive drug. The ring is also acted on by β-lactamase, which is an enzyme produced by some bacteria that can degrade Penicillin antibiotics.
Introduction to Amoxicillin Amoxicillin belongs to a class of antibiotics called the Penicillins. The chemical structure of the Penicillin antibiotics contain a highly reactive β-lactam ring. This ring can be opened in neutral or basic solutions which can result in an inactive drug. The ring is also acted on by β-lactamase, which is an enzyme produced by some bacteria that can degrade Penicillin antibiotics. Therefore, Penicillin antibiotics need to have chemical structures added to increase their acid stability and their β-lactamase resistance. Adding an electron withdrawing group onto the 6-position amide group (located on the β-lactam ring) can increase its acid stability by making the amide oxygen less nucleophillic. This ensures that the amide oxygen will not attack the β-lactam ring's carbonyl group to open it.
Adding a bulky substituent (like a benzene ring) to this same position, covers the β-lactam ring’s carbonyl group and can increase the drugs β-lactamase resistance. To increase the spectrum of the penicillin, a polar group can be added to the 6-position amide group. This allows the drug to be active against gram negative bacteria as well as gram positive. The polar groups allow the drug to cross the gram negative cell wall through porins. Amoxicillin has an electron withdrawing group with a polar hydroxyl group added to the 6-position amide. This increases its spectrum of action and acid stability when comparing it to other Penicillins, like Ampicillin. However, Amoxicillin's substituent does not cover the β-lactam ring. This makes it susceptible to β-lactamase and it can be degraded by resistant bacteria.
Mechanism of Action The Penicillins were one of the first antibiotics discovered and they act on bacteria by preventing the cross linking of peptidoglycan in the bacterial cell wall. Peptidoglycan is the “backbone” of the bacterial cell that gives the cell its rigidity. Without the peptidoglycan the cell wall cannot handle the pressure and will rupture and the cell will die. The Penicillin antibiotics resemble the transition state of the cross linking reaction and the Ala-Ala terminal of the peptidoglycan therefore, they are acted on by the transpeptidase enzyme.
Resistance As mentioned before, resistance tends to occur if the bacteria produce and enzyme called β-lactamase. This enzyme is located between the bacteria’s outer membrane and peptidoglycan in gram negative bacteria. The enzyme attacks the carbonyl group of the β-lactam ring and degrades the drug. This can be avoided if a bulky substituent is added to the 6-position to cover the reactive ring. However, Amoxicillin does not have a bulky group attached, therefore, it can be used in combination with a β-lactamase inhibitor. Amoxicillin is normally added to Clavulanic Acid, a β-lactamase inhibitor that is acted on by the β-lactamase and is used up allowing the Amoxicillin to kill the bacteria without getting degraded. Resistance still occurs with Amoxicillin which has limited its use. There are other medications with less resistance and a broader spectrum available for use.
Clinical Uses of Amoxicillin The most common trade names of Amoxicillin are Amoxil, Amoxicot, DisperMox, Moxilin, and Trimox. It is also used with Clavulanic Acid in Augmentin. Clavulanic acid is a β-lactamase inhibitor which gets used up and Amoxicillin is not degraded by the bacteria’s β-lactamse. Amoxicillin can be used for many different indications. Some of them include: urinary tract infection, respiratory tract infection, and infections of the skin. Also, bacterial infections caused by E. coli, streptococci, H. influenzae, and N. gonorrhoeae (Amoxicillin is not the drug of choice for a gonorrhea infection).(7)
Doses and Dosage Forms Amoxicillin is available in many dosage forms including: 250 and 500 mg capsules,oral powder for suspension in concentrations 125 mg/5ml, 200mg/5ml, 250mg/5ml, 50mg/ml, and 400mg/5ml; 500 and 875 mg tablets; 125, 200, 250, 400 mg oral chewable tablets; and 200, 400, 600 mg tablets for suspension. Amoxicllin can be taken with or without food. The suspension needs to be shaken before the dose is given. The dose given depends on the type of infection, but it is normally given every 8 to 12 hours a day.(7)
Adverse Effects Amoxicillin should not be taken if the patient is allergic to Penicillin. They should also be careful if they are sensitive to Cephalosporins. The most common adverse effects are rash, diarrhea, nausea, and vomiting. The most serious side effect is an allergic reaction (itching, redness, or inflammation). If an allergic reaction occurs, Adrenaline should be given.(7)
Drug Interactions Some drug interactions that should be known are Methotrexate, Warfarin, Ethinyl Estradiol, and Norgestrel. The most serious drug interactions are with Methotrexate and Warfarin. Amoxicillin causes the Methotrexate levels to increase and can cause toxicity. When Amoxicillin is used with Warfarin there is a greater risk of bleeding. The patient should have the INR and prothrombin times monitored. It is important to talk to a doctor before starting Amoxicillin therapy. The patient should tell the doctor any other medications, herbal therapies, or non-prescription medications that they are taking before taking Amoxicillin.(7)
Other InformationAmoxicillin is a pregnancy category B which means that either animal testing has shown no side effects to the fetus or that there have been some animal studies that have shown some fetal risk, but there have not been any controlled studies in humans.(7)
Future of Amoxicillin In the future Amoxicillin will probably not be used very often due to bacterial resistance. This drug has been used for many years and sometimes used when it is not needed. This increases the risk of resistance and Amoxicillin is already sensitive to β-lactamase. There are many new antibiotics that are more resistant to β-lactamase and have broader spectrums against bacteria, therefore the use of Amoxicillin will decrease in the future.