Antibacterial Drugs Mechanisms of action site of action

Antibacterial Drugs:

**Mechanisms of action ( site of action ) 1. Nucleic acid synthesis inhibition: e. g Sulphonamides, trimethoprim, quinolones, nitrofurantoin, refampicin.

• 2. Protein synthesis inhibition: e. g. • Macrolides, aminoglycosides, Chloramphenicol, tetracycline

3. Cell wall synthesis inhibition: e. g Vancomycin, cephalosporins, penicillins

** The β – lactam antibiotics: • These are the pencillines and cephalosporines whose basic structure include β – lactam ring

Resistance is commonly due to bacterial enzyme called β – lactamases (( pencillinase and cephalosporinase )) which can cleave the ring and inactivate the antibiotic.

** The penicillins: • All penicillins are bactericidal with wide range of activity for both gram +ve and certain gram –ve organism • It should never given interathecally

Their adverse effects include: • • • skin rash anaphylaxis drug fever interstitial nephritis haemolysis

** Benzylpenicllin: • It is rapidly absorbed following intramuscular injection and excreted by the kidneys withen few hours and addition of probenecid will delay its excreation and allow smaller doses with less frequent

** Procain Penicillin: • addition of procainamide, • given i. m, • Active against: streptococci, meningococci, anthrax, tetanus, syphilis and diphtheria.

** Phenoxymethyl penicillin (( Penicillin V )) • Incompletely absorbed from the stomach • Active against: streptococci.

** Cloxacillin & flucloxacillin • They are stable to staphylococcal β – lactimases • For oral therapy flucloxacillin is superior to cloxacillin

** Temocillin: • It is active against pencillinase producing gram –ve bacilli.

** Ampicillin; • It has a bactericidal action against both gram +ve and certain gram –ve organisms • It is susceptible to degradation by β – lactimase and not well absorbed with food. • Skin rash in patients with infectious mononucleosis

** Amoxycillin: • It is an analog of ampicillin which has similar antibacterial spectrum but it is more reliably absorbed from GIT

** Augmentin • It is a combination of amoxicillin and sodium clavulanate • Clavulanic acid is a potent inhibitors for many β – lactemases and it can protect amoxicillin from inactivation by them.

** Ticarcillin: • It is an analogue of carbencillin with more activity against Pseudomonus spp. • A combination of ticarcillin and clavulanic acid is called Timentin.

** Mezlocillin, azlocillin and pipracillin; • They have a wider range of activity and more effective against many gram –ve bacilli.

The Cephalosporins; • 1 st generation e. g cephalexin, cephradin • 2 nd generation e. g cephaclor, cefuroxime • 3 rd generation e. g cefotaxime, cephitrixone • 4 th generation e. g cefepime, cefpirome • Wide range of activity • 10 % of penicillin sensitive may als allergic to them

** Imipenem: • Β- lactam antibiotic with a very broad spectrum which include aerobic and anaerobic gram +ve and gram –ve organisms.

The Macrolide antibiotics

** Erythromycin: • Used in treatment of infection caused by gram +ve organisms in penicillin allergic patients. • It is effective in Whooping cough, pneumonia, mycoplasma and Chlamydia. • S/E : diarrhea, vomiting, abdominal pain, and cholestatic jaundice.

**Clarithromycin: • Greater activity than erythromycin and higher tissue concentration

** Azithromycin: • More activity against gram –ve organisms including H. Influenzae.

** Spiromycin: • A macrolide used in treatment of Txoplasmosis. • The Tetracyclines: is a bacteriostatic agent used in Brucellosis, mycoplasma, typhus fever, Q – fever • It should not prescribed for pregnant female, children and patients with renal failure.

The aminoglycosides: • They include gentamycin, streptomycin, amikacin • Active against gram –ve bacilli • Streptomycin has anti TB and used in treatment of Brucellosis • They are nephrotoxic and ototoxic • Neomycin is too toxic to be given parantraly and used orally in hepatic encephalopathy.

*** Chloramphenicol: • It is effective in enteric fever and against H. Influenzae • It may cause pancytopenia • It should never be given to premature infant or to the newborn because of the risk of development of gray baby syndrome.

*** Clindamycin / Lincomycin • Effective against most gram +ve organisms including penicillin resistant staphylococci • It pentrate well into bones so it is useful for osteomyelitis and effective in lung abscess • Common cause of pseudomembranous colitis

** Sodium fusidate • It is useful in infection caused by penicillin resistant staphylococci • It is well absorbed and the oral rout can be used instead the parenteral rout

** Spectinomycin • Used for treatment of gonorrhoea if penicillin is contraindicated because of allergy or bacterial resistance.

Vancomycin and teicoplanin: • Used for serious staphylococcal infection including methicillin resistant and it is used in antibiotic associated colitis. • They are nephrotoxic and ototoxic

** Sulphonamides/ Trimethoprim / Co – trimoxazol • Used in treatment of cystitis, UTI, typhoid fever and pneumonia • S/E skin rash, nephritis and haemolysis

*** Quinolone antibiotics • Ciprofloxacin is the most important one • Effective against aerobic gram –ve bacilli. • Used in treatment of typhoid fever, UTI, gonorrhoea • They are contraindicated in children and pregnancy

** Metronidazole • Effective against anaerobic bacteria and intestinal protozoa e. g Giardia Lambelia and Entameba histilytica.

** Tinidazole • It is similar to metronidazole but with longer half life

*** Antituberculous drugs • Refampicin, • INH, • Pyrazinamide, • Ethambutol and • Streptomycin

*** Antifungal drugs • For topical application: Nystatin, Clotrimazol • For oral administration: Ketoconazole, Grisofulvin • For intravenous infusion: Amphotericin, Flucytocin

*** Antiviral drugs • Acyclovir: effective against herpes simplex and H. zoster • Famciclovir: antiherpes agent with activity against E B virus and hepatitis B virus • Ganciclovir: antiherpes agent with activity against cytomegalovirus • Amantadine: used for prophylaxis of influenza A. • Ziduvidine used for HIV infection. • Ribavirine: against RNA viruses e. g Influenza, RSV

Antiparasitic drugs: • Antimalarial: Chloroquine, premaquine, proguanil • Anti intestinal protozoa: Metronidazole, tinidazole • Antihelmenth drugs: Mebendazole, Albendazole • Antibilharzial agents: Praziquantel.