Types of Antimicrobial Agents Cell Wall Inhibitors lactam
Types of Anti-microbial Agents
Cell Wall Inhibitors β- lactam These drugs interfere with cell wall synthesis process. § These consist of B lactam inhibitors. § And they consider as Bactericidal in nature §
Summary of antimicrobial agents affecting cell wall synthesis.
β-lactam / 1 - Penicillin's least toxic drugs known, but increased resistance has limited their use. Stable to stomach acid. 1 -Natural penicillin's / penicillin G (Germs ) Penicillin G is less stable to acid (so given Injections ). Inactivated by β- lactamase enzyme. 2 -Anti-staph penicillin's: E. g. , oxacillin, cloxacillin Stable to gastric acidity. Stable to β-lactamase enzyme.
β-lactam /Penicillin's 3 -Extended-spectrum penicillin's : e. g. amoxicillin. Stable to gastric acidity. Inactivated by β -lactamase (may be combined with β-lactamase inhibitors e. g. . clavulanic acid or sulbactam ). 4 -Anti-Pseudomonal penicillins: E. g. carbenicillin which is the most potent. Unstable to gastric acidity (so given parentrally). Ø Inactivated by β-lactamase enzymes. combined with β-lactamase inhibitors e. g. clavulanic acid or sulbactam ).
β- lactamase enzymes inhibitors: e. g. , Clavulanic acid. They don't have significant antibacterial effect. Inhibit β-lactamase so protect antibiotics which are inactivated by this enzyme. Combinations of these agents with β-lactam antibiotics are effective against β-lactamase producing organisms, e. g. Amoxicillin + clavulanic acid Ampicillin + sulbactam.
Adverse effects: 1 - Hypersensitivity (most common): Rashes, angioedema (marked swelling of lips, tongue) and allergy due to antigenic metabolic penicillinoic acid (metabolite of penicillin. 2 - Diarrhea: Due to disruption of normal balance of intestinal microorganisms. It occurs more with incompletely absorbed and extended spectrum agents, e. g. ampicillin. 3 - Nephritis: With all penicillins, but methicillin cause acute interstitial nephritis and that's why it is no longer used.
Summary of the adverse effects of penicillin.
β-lactam / 2 - Cephalosporin β- lactam antibiotics similar to penicillin's in their mode of action but are more resistant to β-lactamase. Adverse effects: 1 - Hypersensitivity reactions. Should not be used inpatients that have anaphylactic reaction with penicillin 2 -Nephrotoxicity especially when used with aminoglycosides. 3 - Local irritation: severe pain after IM injections and injections.
cephalosporin's Antibacterial spectrum First generation as cephazoline Broad spectrum especially against Gm+ve organisms. Not effective against pseudomonas. Resistant to b-lactamase enzyme. Do not cross the meninges so not effective in meningitis. Second generation as cefuroxime Broader spectrum than first generation. Effective against Gm-ve bacilli, but not pseudomonas OR enterococci. Do not penetrate meninges. All second generation cephalosporins are less active against gm+ve bacteria than first generation cephalosporins. Third generation as Cefotaxime Cefdinir. Ceftriaxone Wider spectrum of activity. Highly effective against Gm-ve bacilli and Anaerobic Microbs. Effective against pseudomonas. Highly resistant to beta -Lactamase. High concentration in CSF useful in Gm-ve meningitis. Not effective orally. Fourth generation as cefepim - Similar to third generation agents. More resistant to hydrolysis by beta-lactamases Its clinical role is similar to that of third generation except it is useful in treatment of infections caused by enterobacter.
β- lactam / 3 - Carbapenems Broadest spectrum β-lactams. Effective against gm +ve and –ve organisms especially penicillinase producing organisms and anaerobes(Important in empiric therapy) Resistant to β-lactamase. Adverse effects: 1. Extensive cross allergy with penicillin. 2. Imipenem nausea, Vomiting and diarrhea.
β-lactam / 4 - Monobactams: ØE. g. Aztreonam ØNarrow spectrum. ØEffective against aerobic gram–ve organisms , not gram +ve and anaerobes. ØResistant ØGiven IV and IM. ØRelatively ØNo to β-lactamase. non toxic. cross allergy with other B-lactam antibiotics
Other agents inhibiting cell wall synthesis
Vancomycin Mechanism of action: inhibits cell wall synthesis at an earlier stage than β-lactam antibiotics Adverse effects: 1. Fever, chills, rigors, phlebitis. 2. Shock on rapid infusion (red man syndrome due to histamine release)
Some adverse effects of vancomycin.
to be continued
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