Antibiotics : Mechanism of Action, Uses, Side effects

Antibiotics are substances which are derived from one microorganism in order to kill another microorganism.

Antibiotics are effective against bacterial, fungal and parasitic infections. But, antibiotics are not helpful against viral infections.

Pathogenic bacteria can be killed by synthetic components at low concentration. Examples: Ampicillin and amoxicillin.

Penicillin :-

Penicillin was the first antibiotic to be used clinically in 1941. It was originally obtained from the fungus Penicillium notatum.

Mechanism of Action=

Penicillin kills bacteria through binding of the beta-lactam ring to DD transpeptidase, inhibition its cross linking activity and preventing new cell wall formation. Without a cell wall, a bacterial cell is vulnerable to outside water and molecular pressures, and quickly dies.

• Penicillin-g (benzyl penicillin)

Antibacterial spectrum PnG is a narrow spectrum antibiotic, activity is limited primarily to gram-positive bacteria, few gram negative ones and anaerobes.

Bacterial resistance– Many bacteria are inherently insensitive to PnG because in them the target enzymes and PBPs are located deeper under lipoprotein barrier where PnG is unable to penetrate or have low affinity for PnG. The primary mechanism of acquired resistance is production of penicillinase.

Penicillinase

It is a narrow spectrum Beta-lactammase which opens the Beta-lactam ring and inactivates PnG and some closely related congeners.

Majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, H. influenzae and few other bacteria produce penicillinase.

The gram-positive penicillinase producers elaborate large quantities of the enzyme which diffuses into the surroundings and can protect other inherently sensitive bacteria.

In gram-negative bacteria, penicillinase is found in small quantity, but is strategically located in between the lipoprotein and peptidoglycan layers of the cell wall.

Staphylococcal penicillinase is inducible, and methicillin is an important inducer; while in gram-negative organisms, it is mostly a constitutive enzyme.

Pharmacokinetics=

Penicillin has low protein binding in plasma, the bioavailability of penicillin depends on the type; Penicillin G has a low bioavailability, below 30%. Penicillin has a short half life and is excreted via the kidneys.

Side effects of Penicillin=

Includes diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis).

Includes fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis.

Uses of penicillin G=

Penicillin G is the drug of choice for infections caused by organisms susceptible to it, unless the patient is allergic to this antibiotic.

1. Streptococcal infections– Like pharyngitis, otitis media, scarlet fever, rheumatic fever respond to ordinary doses of PnG because Strep. pyogenes has not developed significant resistance.
2. Pneumococcal infections– PnG is not used now for empirical therapy of pneumococcal (lobar) pneumonia and meningitis because many strains have become highly penicillin resistant. However, PnG 3-6 MU i.v. every 6 hours is the drug of choice if organism is sensitive.
3. Meningococcal infections– are still mostly responsive; meningitis and other infections may be treated with intravenous injection of high doses.
4. Gonorrhoea- PnG has become unreliable for treatment of gonorrhoea due to spread of resistant strains.
5. Diphtheria– Procaine penicillin 1-2 MU daily for 10 days is used to prevent carrier state.
6. Tetanus and gas gangrene- Antitoxin and other measures are more important; PnG 6-12 MU/day is used to kill the causative organism and has adjuvant value.
7. Penicillin G is the drug of choice for rare infections like anthrax, actinomycosis, rat bite fever and those caused by Listeria monocytogenes, Pasteurella multocida.

Semi-synthetic Penicillins

The various compounds are the product of the addition of various prosthetic groups to a basic building block, 6- aminopenicillanic acid.

Although penicillinase rapidly inactivated penicillin G, the addition of larger prosthetic groups to 6-aminopenicillanic acid protects the molecule from penicillinase action.

The group of semisynthetic penicillins which are resistant to the action of penicillinase constitutes a new frontier in the clinician’s war against Staphylococcus aureus.

Classification=

• Acid-resistant alternative to penicillin G Phenoxymethyl penicillin (Penicillin V).
• Penicillinase-resistant penicillins Methicillin, Cloxacillin, Dicloxacillin.
• Extended spectrum penicillins Aminopenicillins. Ampicillin, Bacampicillin, Amoxicillin.
• Carboxypenicillins: Carbenicillin
• Ureidopenicillins: Piperacillin, Mezlocillin.
• B-lactamase inhibitors Clavulanic acid Sulbactam, Tazobactam

Drugs used; in Detail =

1. Phenoxymethylpenicillin used to treat bacterial infections, including ear, chest, throat and skin infections. It can also be used to prevent infections if you have sickle cell disease, or if you have had chorea (a movement disorder), rheumatic fever.
2. Methicillin also called methicillin, antibiotics formerly used in the treatment of bacterial infections caused by organisms of the genus Staphylococcus.
3. Cloxacillin is used for the treatment of certain bacterial infections. It is most commonly used to treat infections of the skin, bone, heart valve, blood, and lung.
4. Dicloxacillin fights bacteria in your body. Dicloxacillin is used to treat many different types of infections caused by bacteria such as bronchitis, pneumonia, or staphylococcal infectiona.
5. Ampicillin is a penicillin antibiotic that is used to treat or prevent many different types of infections such as bladder infections, pneumonia, gonorrhea, meningitis, or infections of the stomach or intestines.
6. Amoxicillin is used to treat certain infections caused by bacteria, such as pneumonia; bronchitis (infection of the airway tubes leading to the lungs); and infections of the ears, nose, throat, urinary tract, and skin.
7. Bacampicillin It fights bacteria in the body. Bacampicillin is used to treat many different types of infections, such as tonsillitis, pneumonia, bronchitis, urinary tract infections, gonorrhea, and infections of the skin.
8. Piperacillin and tazobactam are a combination penicillin antibiotics that are used to treat many different infections caused by bacteria, such as stomach infections, skin infections, pneumonia, and severe vaginal infections.
9. Mezlocillin to treat serious gram-negative infections of the lungs, urinary tract, and skin.

CEPHALOSPORINS :-

Cephalosporins are a type of beta-lactam antibiotics.

They can be taken orally or injected into a vein (intravenous injection), depending on the infection.

Oral cephalosporins are generally used for simple infections that are easy to treat.

For example a routine case of strep throat might be treated with a course of oral cephalosporins.

Intravenous (IV) cephalosporins are used for more severe infections.

Specification =

There are very few indications for the use of cephalosporins as first-line antibiotic treatment. Ceftriaxone is used for the treatment of gonorrhoea, pelvic inflammatory disease and epididymo orchitis. It is also an alternative to benzylpenicillin in patients with suspected meningitis.

Cefaclor may be considered as a second-line treatment for infections such as otitis media, sinusitis, cellulitis, diabetic foot infection and mastitis.

Cephalexin is a third-line treatment for urinary tract infection in pregnant women.

Cefaclor, Cefuroxime axetil, Cefprozil Cefixime, Cefpodoxime proxetil, Cefdinir, Ceftibuten, Ceftamet pivoxil, Cefepime, Cefpirome, Cefotaxime Ceftizoxime, Ceftriaxone, Ceftazidime, Cefoperazone.

TETRACYCLINE :-

Tetracycline is used to treat many different bacterial infections of the skin, intestines, respiratory tract, urinary tract, genitals, lymph nodes, and other body systems.

It is often used in treating severe acne, or sexually transmitted diseases such as syphilis, gonorrhoea, or chlamydia.

Tetracycline is also used to treat infections you can get from direct contact with infected animals or contaminated food.

In some cases, tetracycline is used when penicillin or other antibiotics cannot be used to treat serious infections such as Anthrax, Listeria, Clostridium, Actinomyces, and others.

Side effects=

1. Increased sensitivity of skin to sunlight (rare with minocycline)
2. Bulging fontanel (soft spot on head)
3. Abdominal pain
4. Headache
5. Nausea and vomiting
6. Loss of appetite
7. Yellowing skin
8. Greatly increased frequency of urination or amount of urine.

Administration=

Oral capsule is the dosage form in which tetracyclines are most commonly administered. The capsule should be taken 2 hr before or 2 hr after food. .

Tetracyclines are not recommended by i.m. route because it is painful and absorption from the injection site is poor. Slow i.v. injection may be given in severe cases, but is rarely required now.