Antimicrobial Chemotherapy Flashcards
What’s the principle of antimicrobial therapy?
Selective toxicity - ability to kill an invading microorganism without harming the cells of the host
Desired properties of antimicrobials
Non toxic to host
Long plasma half life
Good tissue distribution
Low plasma protein binding
Non interference with other drugs
Classification of antibacterials
- Chemical- tetracycline, amino glycosides
- A.Target site- cell wall inhibitors(penicillin, vancomycin)
B.cytoplasm and protein synthesis inhibitors(aminoglycosides)
C.Nucleus inhibitors (quinolones) - Bacteriostatic vs Bactericidal
- chemotherapeutic spectrum
A. Narrow spectrum
B. Broad spectrum
C. Extended spectrum
Selection of antimicrobial agents
Organism identity
Site of infection(vascular perfusion,blood brain barrier )
Safety of agents
Patient factor(immune system,renal&hepatic function, pregnancy& lactation)
Cost of therapy
Disadvantages of combination antimicrobial therapy
Increases possibility of toxicity
Occurrence of resistant organisms
Possibility of superinfection
How does drug resistance occur?
By transfer of bacteria between people
Transfer of resistant genes between bacteria
Transfer of resistant genes between genetic elements within bacteria, on transposons
How do plasmids carry and transfer gene for resistance
Transduction or conjunction
Biochemical resistance to antibodies is by;
1.Production of enzymes that inactivate the drug e.g D-lactamase for penicillin, acteyltransferases- chloramphenicol, kinases-aminoglycosides
- Alteration of drug binding sites
- Reduction of drug uptake by bacteria e.g tetracycline
- Alteration of enzymes e.g DFHR becomes insensitive to trimethoprim
Uses of prophylactic antibiotics
- Prevention of streptococcal infections in patients with rheumatic heart disease
- Pretreatment of patients undergoing dental extractions who have prosthetic devices
- Prevention of tuberculosis in exposed people
- Pre surgical treatment in git procedures; c.s, joint replacement
Complications of antibiotic therapy
- Hypersensitivity
- Direct toxicity
- Superinfections
General mechanism of antimicrobial chemotherapy
- Inhibition of cell wall synthesis: penicillin, cephalosporin, vancomycin, bacitracin
- Inhibition of cellular membrane function; amphotericin b, Nystatin
- Nucleic acid synthesis inhibition; trimethoprim, nalidixic acid, rifampin
- Protein synthesis inhibition; chloramphenicol, erythromycin, tetracycline and aminoglycosides
Chloramphenicol card
Bind to 50s ribosomes, bacteriostatic, wide spectrum, Bactericidal to (S.penumoniae, H.influenzae, N.meningitidis)
Uses: typhoid,brucellosis, meningitis,rickettsia
Adverse effects: hypersensitivity, hematological toxicity, git probs, gray baby syndrome,
Tetracycline card
Bacteriostatic, bind to 30s ribosomes, complexation with diary products, e.g doxycycline, oxytetracycline,minocycline
Uses: rickettsia, Chlamydia, STI, brucellosis, acne, mycoplasma infection
Adverse effects: photosensitivity, hypersensitivity, decoloration of teeth, renal and hepatic toxicity, git probs
Macrolides card
Erythromycin
Macrolides card
E.g; erythromycin, clarithromycin, azithromycin
Bacteriostatic but Cidal in high doses.
Bind to 50s ribosomal units.
Uses: mycoplasma pneumonia, Chlamydia, diphtheria, pertussis,strep. Infection, tetanus, legionnaires disease, h.pylori
Adverse effects: skin eruption, eosinophilia, jaundice, git probs, cholestatic hepatitis
Aminoglycosides card
Bacteriocidal,
E.g streptomycin,gentamicin, neomycin,tobramycin,amikacin,
Binds to 30s ribosomal units and interfere with protein synthesis
Uses: bacterial endocarditis , UTI, plague, Tularemia, sepsis, meningitis
Side effects: ototoxicity, nephrotoxicity, neuromuscular blockade, hypersensitivity
Caution: neonatal infection, pregnancy, renal insufficiency
Quinolones card
Older Gen: nalidixic acid,pironidic acid
Newer gen: ciprofloxacin, levofloxacin, norfloxacin, trovafloxacij
Target Bacteria DNA gyrase(Gran -ve) and toposiomerase IV(Gram+ve)
Uses: UTI, prostatitis, STI, gastroenteritis,Respiratory infection, bone joint and soft tissue infection
Adverse effects: git probs, CNS probs, skeletal system probs, hypersensitivity
Sulphonamides card
E.g sulfadiazine, sulfamethoxazole, sulfadoxine
Structural analog and competitive inhibitors of PABA (folic acid)
Uses: toxoplasmosis, strep. Prophylactic, anti-protozoal, norcadiosis
Adverse effects: Hematopoietic probs, hypersensitivity, liver toxicity, git probs
Penicillin card
Inhibit peptidoglycan of bacteria cell wall
Bacteriocidal
Know types of penicillin, B-lactam ring
Uses: strep, staph and pneumonia infection, anaerobes, UTI, salmonella
Side effets: git probs, dizziness, headache,granulocytopenia, bone marrow suppression, hypersensitivity
Cephalosporin card
Bacteriocidal, inhibit peptidoglycan cell wall, B-lactam ring
First gen- cefazolin,
Second gen- cefuroxine, cefoxitin
Third gen- ceftriazone, ceftazidine
Fourth gen- cefepime
Uses: skins and soft tissue (1st Gen)
Gonorrhea,CSM(3rd Gen)
RTI(2nd Gen)
Noscomial infection (4th Gen)
Antifungal card
Mycotic infection, superficial.
Systemic ones are life threatening and difficult to treat due to rigid cell wall and eukaryotic
E.g: amphotericin b, fluconazole,ketoconazole, itraconazole
Amphotericin B
Bind to ergosterol found in cell membrane of fungi and allow leakage of electrolytes
Systemic mycosis treatment
Adverse affects: renal impairment, fever,anemia, hypotension, neurological effects
Griseofulvin
Superficial mycotic infection
Disrupt mitotic spindles and inhibit mitosis
Side effects : headache, nausea, teratogenic,
E.g Nystatin,miconazole,clotrimazole
Interferon card
Recombinant DNA technique
Human interferon: alpha, beta, gamma,
It stimulates NK cells, stimulates tumoricidal macrophages(gamma)
Side effects: renal, hepatic, hypersensitivity, neurologic probs, pulmonary toxicity.
