COMMON TYPES OF ANTIBIOTICS AND THEIR MECHANISM OF ACTION

 

1. PENICILLINS: Penicillin is one of the oldest and most commonly used antibiotics in many countries because of it's effectiveness and affordability. It is effective against a wide range of bacterial infections and is often used to treat strep throat, pneumonia, and other respiratory infections. In the past before the coming of newer and more effective antibiotics, it was also one of the first lines in treatment of syphilis and gonorrheal infection.  Some of the examples of penicillins include but not limited to; Amoxicillin, Cloxacillin, Penicillin V, and Penicillin G.

Mechanism of action: Penicillin and derivatives are taken in a broad class of antibiotics known as Beta-lactam antibiotics; they work by inhibiting the synthesis and development of the bacterial cell wall.

Drawbacks: Although penicillin is still used in many countries due to it’s affordability and spectrum of activity, the on-going emergence of antimicrobial drug resistance limits their use in many scenarios. In addition, there are many individuals who develop allergic reactions to penicillin compared to new and safer antibiotics.  I already discussed penicillin and it's use in medicine in details and if you would like to read more about it you can follow the link below;  Use of penicillin and it's derivatives in clinical medicine.

2. FLOROQUINOLONES: Some of the drugs in this sub class of antibiotics include; Ciprofloxacin, Levofloxacin among others. Ciprofloxacin which is one of the most commonly available and prescribed, is a powerful antibiotic that is effective against a wide range of bacteria. It is often used to treat urinary tract infections, respiratory infections, and skin infections.

Mechanism of action: These drugs produce their effects by interfering with the DNA replication process and we shall therefore collectively term them; DNA synthesis inhibitors or in other wards, antimetabolites.  I made a detailed discussion on the pharmacology of this class of drugs and you can read more about the from the link below; Fluroquinolones and their use in clinical medicine.

3. TETRACYCLINES: Some of the drugs in this sub class of antibiotics include; Tetracycline, Oxytetracycline, Doxycycline and others. Doxycycline one of the most common, is an antibiotic that is used to treat a variety of bacterial infections, including acne, respiratory infections, and sexually transmitted diseases.

Mechanism of action:  These drugs act by inhibiting the process of protein synthesis in the bacterial cell.

Drawbacks: Because of their spectrum of activity which is broad, irrational use of these drugs can read to clearance of part of the human microbiome, something that can lead to opportunistic infection and super infections or even rendering other antibiotics ineffective. 

Their use is known to cause development of pseudomembranous colitis by Clostridium deficile and some fungal manifestations for that purpose. They are also discouraged from usage in young children due to their teeth discoloration effects and may lead to borne development problems.

4. MACROLIDES: In this class of antibiotics we have examples such as Azithromycin, Erythromycin and Clarithromycin. Azithromycin one of the most common is often used to treat respiratory infections, skin infections, and sexually transmitted diseases. The dosage and formulation of Azithromycin allows good compliance because of a three days regimen and a single tablet daily.  I discussed Azithromycin in a separate discussion in details you can read more about it from the link below;  Use of Azithromycin in clinical medicine.

5. VANCOMYCIN: Vancomycin is a glycopeptide antibiotic that is used to treat serious bacterial infections, including sepsis and endocarditis. Although it’s self is not a beta lactam antibiotic like penicillin and cephalosporines, it shares the mechanism of action with them; Inhibits the synthesis and development of the bacterial cell wall.

6. METRONIDAZOLE - Metronidazole is an antibiotic that is effective against a wide range of bacterial and parasitic infections, including vaginal infections, skin infections, and gastrointestinal infections. In brief we shall say; it is both antibacterial and antiprotozoal and therefore can be used as a prophylaxis for bacteremia and treatment of amebiasis. It is one of the most effective antibiotics against Entamoeba histolitica.

Mechanism of action: Metronidazole when used against protozoa, is DNA synthesis inhibitor and therefore we can say; it is an antimetabolite. In bacteria it acts as a proton sink, depriving the bacteria cell of oxidative equivalents

Drawbacks: Metronidazole have several side effects including but not limited to; Nausea and vomiting, a metallic taste, and it also has a disulfiram-like effect when taken together with alcohol.  I discussed about Metronidazole alone and it's use in details you can read about it from  here;  Use of metronidazole in clinical medicine.

7. SALFONAMIDES: Some of the most common examples of sulfonamides include; sulfamethoxazole and salfadoxine.  These drugs are frequently combined with non-salfonamide molecules with which they share some mechanism of action including but not limited to; Pyrimethamine and Trimethoprim.  Such combinations has greater synergistic effects and they can be used in treatment of a wide range of infections.

Trimethoprim-sulfamethoxazole, is one of such combination antibiotic that is often used to treat urinary tract infections, respiratory infections, and gastrointestinal infections.  This combination has been used widely in immunocompromised and HIV/AIDS patients for prophylactic prevention of opportunistic infections especially related to protozoa.  

The other common application of such combinations is the use of a combination of Pyrimethamine and salfadoxine in brand names like "Fansidar", one of the current malarial prophylaxis therapy in pregnant mothers.  I have recently discussed more about sulfonamides and you can read about them from  the link below; Sulfonamides and their use in clinical medicine

In our next discussion, I will be looking at the rest of the antibiotic classes I have not discussed briefly here including but not limited to; Cephalosporines such as Ceftrioxone, Carbapems such as Imepenem, Rifamycins such as Rifampicin and Rifampin and many others.  You can also feel free to subscribe to my YouTube channel where I discuss some of these pharmacotherapy from the link below;  Mega Mover Empire on YouTube.

RELATED;

1.  PNEUMONIA

2.  ANTIMICROBIAL DRUG RESISTANCE

3.  THE ORIGIN OF ALLERGIC REACTIONS IN THE HUMAN BODY

4.  PHARMACOLOGY OF PENICILLIN AND IT'S DERIVATIVES

5.  FLOROQUINOLONES AND THEIR USE IN CLINICAL MEDICINE

6.  THE HUMAN MICROBIOME

7.  USE OF AZITHROMYCIN IN CLINICAL MEDICINE

8.  USE OF METRONIDAZOLE IN CLINICAL MEDICINE

REFERENCES

METRONIDAZOLE (FLAGYL)

 

Introduction:  Metronidazole also sometimes referred to as fragyl, is one of the most commonly prescribed and used drugs because of availability, being cheap and broad spectrum of activity.  This drug can act against both bacteria, and protozoa.

Therapeutic Class: Anti-infective, antiprotozoan, and Antibacterial

Pharmacologic Class: Drug that disrupts nucleic acid synthesis and sometimes act as a proton sink, by depriving the microbe of oxidative potential.

Actions and uses: Metronidazole is the prototype drug for most forms of amebiasis, being effective against both the intestinal and hepatic stages of the disease. Resistant forms of E. histolytica have not yet emerged as a clinical problem with metronidazole therapy. Metronidazole is also a preferred drug for giardiasis and trichomoniasis. 

Metronidazole is unique among antiprotozoan drugs in that it also has antibiotic activity against anaerobic bacteria and thus is used to treat a number of respiratory, bone, skin, and CNS infections. 

Topical forms of metronidazole (MetroGel, MetroCream, MetroLotion) are used to treat rosacea, a disease characterized by skin reddening and hyperplasia of the sebaceous glands, particularly around the nose and face.

ADMINISTRATION ALERTS: The extended-release form must be swallowed whole and taken on an empty stomach. Metronidazole is contraindicated during the first trimester of pregnancy. Pregnancy category B

ADVERSE EFFECTS: Although adverse effects occur relatively frequently, most are not serious enough to cause discontinuation of therapy. The most common adverse effects of metronidazole are anorexia, nausea, diarrhea, dizziness, and headache. Dryness of the mouth and an unpleasant metallic taste may be experienced. Although rare, metronidazole can cause bone marrow suppression. 

Contraindications: Metronidazole is contraindicated in patients with trichomoniasis during the first trimester of pregnancy and those with hypersensitivity to the drug. Metronidazole can cause bone marrow suppression; thus, it is contraindicated for patients with blood dyscrasias.

INTERACTIONS: Drug–Drug: Metronidazole interacts with oral anticoagulants to potentiate hypoprothrombinemia. In combination with alcohol, or other medications that may contain alcohol, metronidazole may elicit a disulfiram reaction. In patients who are taking lithium, the drug may elevate lithium levels.

RELATED;

1.  FLOROQUINOLONES  

2.  PENICILLINS  

3.  CEPHALOSPORINS

4.  DRUG USE IN RELATION TO PREGNANCY

5.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

SULFONAMIDES

 

INTRODUCTION: Sulfonamides with varying physical, chemical, pharmacologic, and antibacterial properties are produced by attaching substituents to the amido group (–SO₂–NH–R) or the amino group (–NH₂ ) of the sulfanilamide nucleus. Sulfonamides tend to be much more soluble at alkaline than at acid pH. Most can be prepared as sodium salts, which are used for intravenous administration.

MECHANISM OF ACTION & ANTIMICROBIAL ACTIVITY: Sulfonamide-susceptible organisms, unlike mammals, cannot use exogenous folate but must synthesize it from PABA. This pathway is thus essential for production of purines and nucleic acid synthesis. Nucleic acids  As structural analogs of PABA, sulfonamides inhibit dihydropteroate synthase and thus folate production.

SPECTRUM OF ACTIVITY: Sulfonamides inhibit both gram-positive and gram-negative bacteria, Nocardia sp, Chlamydia trachomatis, and some protozoa. Some enteric bacteria, such as Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, and Enterobacter sp are also inhibited. It is interesting to note however that rickettsiae are not inhibited by sulfonamides but are instead stimulated in their growth. The activity is poor against anaerobes. Pseudomonas aeruginosa is intrinsically resistant to sulfonamide antibiotics. Bacteriology: Antibiotics  Combination of a sulfonamide with an inhibitor of dihydrofolate reductase (trimethoprim or pyrimethamine) provides synergistic activity because of sequential inhibition of folate synthesis.

RESISTANCE: Mammalian cells and some bacterial cells lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate; therefore, they are not susceptible to sulfonamides. Sulfonamide resistance may occur as a result of mutations that; (1) cause overproduction of PABA, (2) cause production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides, or (3) impaired permeability to the sulfonamide.

CLINICAL USES: Sulfonamides are infrequently used as single agents. Many strains of formerly susceptible species, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant. Antimicrobial drug resistance  The fixed-drug combination of trimethoprim-sulfamethoxazole is the drug of choice for infections such as Pneumocystis jiroveci (formerly P. carinii) pneumonia, toxoplasmosis, nocardiosis, and occasionally other bacterial infections.

ORAL ABSORBABLE AGENTS: Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents used almost exclusively to treat urinary tract infections. The usual adult dosage is 1 g of sulfisoxazole four times daily or 1 g of sulfamethoxazole two or three times daily. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade. The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. Sulfadoxine is the only long-acting sulfonamide currently available in many countries including sub Saharan Africa, and only as a combination formulation with pyrimethamine (Fansidar), a second-line agent in the treatment of malaria.

ORAL NONABSORBABLE AGENTS: Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease.

TOPICAL AGENTS: Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma. Another sulfonamide, mafenide acetate, is used topically but can be absorbed from burn sites. The drug and its primary metabolite inhibit carbonic anhydrase and can cause metabolic acidosis, a side effect that limits its usefulness. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds.

ADVERSE REACTIONS: All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances, hepatitis, and, rarely, polyarteritis nodosa and psychosis.

RELATED;

1.  Artemisinin and its derivatives

2.  Antibiotics

3.  Metronidazole

4.  Pharmacology and therapeutics

REFERENCES

AZITHROMYCIN

 

Introduction: Azithromycin, a 15-atom lactone macrolide ring compound, is derived from erythromycin by addition of a methylated nitrogen into the lactone ring. Its spectrum of activity, mechanism of action, and clinical uses are similar to those of clarithromycin. Azithromycin is active against M. avium complex and T. gondii. Mycobacteria:  Azithromycin is slightly less active than erythromycin and clarithromycin against staphylococci and streptococci and slightly more active against H. influenzae. Azithromycin is highly active against Chlamydia sp. H.influenzae

Pharmacokinetic aspects of the drug: Azithromycin differs from erythromycin and clarithromycin mainly in pharmacokinetic properties. A 500-mg dose of azithromycin produces relatively low serum concentrations of approximately 0.4 mcg/mL. However, azithromycin penetrates into most tissues (except cerebrospinal fluid) and phagocytic cells extremely well, with tissue concentrations exceeding serum concentrations by 10- to 100-fold. The drug is slowly released from tissues (tissue half-life of 2–4 days) to produce an elimination half-life approaching 3 days. These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases. For example, a single 1-g dose of azithromycin is as effective as a 7-day course of doxycycline for chlamydial cervicitis and urethritis.

Pharmacological Applications: Community-acquired pneumonia can be treated with azithromycin given as a 500-mg loading dose, followed by a 250-mg single daily dose for the next 4 days. A zithromycin is rapidly absorbed and well tolerated orally. It should be administered 1 hour before or 2 hours after meals. Aluminum and magnesium antacids do not alter bioavailability but delay absorption and reduce peak serum concentrations. Azithromycin does not inactivate cytochrome P450 enzymes and, therefore, is free of the drug interactions that occur with erythromycin and clarithromycin.  

RELATED;

1.  The cytochrome P450 enzyme system

2.  Pharmacology test questions

3.  Pharmacology and therapeutics

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