Antimicrobial Chemotherapy

Question 1

What’s the principle of antimicrobial therapy?

Answer 1

Selective toxicity - ability to kill an invading microorganism without harming the cells of the host

Question 2

Desired properties of antimicrobials

Answer 2

Non toxic to host
Long plasma half life
Good tissue distribution
Low plasma protein binding
Non interference with other drugs

Question 3

Classification of antibacterials

Answer 3

1. Chemical- tetracycline, amino glycosides
2. A.Target site- cell wall inhibitors(penicillin, vancomycin)
   B.cytoplasm and protein synthesis inhibitors(aminoglycosides)
   C.Nucleus inhibitors (quinolones)
3. Bacteriostatic vs Bactericidal
4. chemotherapeutic spectrum
   A. Narrow spectrum
   B. Broad spectrum
   C. Extended spectrum

Question 4

Selection of antimicrobial agents

Answer 4

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

Question 5

Disadvantages of combination antimicrobial therapy

Answer 5

Increases possibility of toxicity
Occurrence of resistant organisms
Possibility of superinfection

Question 6

How does drug resistance occur?

Answer 6

By transfer of bacteria between people
Transfer of resistant genes between bacteria
Transfer of resistant genes between genetic elements within bacteria, on transposons

Question 7

How do plasmids carry and transfer gene for resistance

Answer 7

Transduction or conjunction

Question 8

Biochemical resistance to antibodies is by;

Answer 8

1.Production of enzymes that inactivate the drug e.g D-lactamase for penicillin, acteyltransferases- chloramphenicol, kinases-aminoglycosides

2. Alteration of drug binding sites
3. Reduction of drug uptake by bacteria e.g tetracycline
4. Alteration of enzymes e.g DFHR becomes insensitive to trimethoprim

Question 9

Uses of prophylactic antibiotics

Answer 9

1. Prevention of streptococcal infections in patients with rheumatic heart disease
2. Pretreatment of patients undergoing dental extractions who have prosthetic devices
3. Prevention of tuberculosis in exposed people
4. Pre surgical treatment in git procedures; c.s, joint replacement

Question 10

Complications of antibiotic therapy

Answer 10

1. Hypersensitivity
2. Direct toxicity
3. Superinfections

Question 11

General mechanism of antimicrobial chemotherapy

Answer 11

1. Inhibition of cell wall synthesis: penicillin, cephalosporin, vancomycin, bacitracin
2. Inhibition of cellular membrane function; amphotericin b, Nystatin
3. Nucleic acid synthesis inhibition; trimethoprim, nalidixic acid, rifampin
4. Protein synthesis inhibition; chloramphenicol, erythromycin, tetracycline and aminoglycosides

Question 12

Chloramphenicol card

Answer 12

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,

Question 13

Tetracycline card

Answer 13

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

Question 14

Macrolides card

Answer 14

Erythromycin

Question 15

Macrolides card

Answer 15

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

Question 16

Aminoglycosides card

Answer 16

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

Question 17

Quinolones card

Answer 17

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

Question 18

Sulphonamides card

Answer 18

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

Question 19

Penicillin card

Answer 19

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

Question 20

Cephalosporin card

Answer 20

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)

Question 21

Antifungal card

Answer 21

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

Question 22

Interferon card

Answer 22

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.