M6: Antibiotics

Question 1

Spectrum of Antibiotics

Answer 1

1. Narrow spectrum: e.g.,
   Gram +ve cocci: penicillin G
   Gram –ve bacilli: aminoglycosides
2. Broad spectrum:
   Gram +ve & –ve: tetracyclines

Question 2

Effects of Antibiotics

Answer 2

1. Bacteriostatic:
   - Inhibit growth and reproduction of bacteria without killing them
   DRUGS = tetracyclines – sulfonamides
2. Bactericidal:
   - Kill the bacteria
   DRUGS = penicillins – cephalosporins

Question 3

(3) ADDITIONAL COMBINATION

Answer 3

1. ADDITION (1+1 = 2)
2. SYNERGISM (1+1 = 3) = WE WANT
   - Activity of combined agents is greater than sum of agents if given separately

• E.g.,:
• Drugs acting at sequential steps in a metabolic pathway:
  Sulfonamides + trimethoprim
• One drug prevents inactivation of the second:
  Amoxicillin + clavulanate
  Imipenem + cilastatin

3. ANTAGONISM (1+1 = 0)
   - One antibiotic interferes with the effects of another antibiotic
   - E.g., tetracycline + penicillin:
   tetracycline inhibits action of penicillin

Question 4

ANTIBIOTIC RESISTANCE

Answer 4

1. Altered receptors and enzymes
2. Altered rates of entry or removal
3. Enhanced inactivation
4. Synthesis of resistant pathways
5. Failure to metabolize drug

Question 5

(6) EXAMPLES OF ANTIBIOTICS

Answer 5

1. Penicillin’s
2. Cephalosporins
3. Tetracyclines
4. Aminoglycosides
5. Sulphonamides
6. Quinolones

Question 6

PENECILLINS
- Structure
- Mechanism of Action
- Pharmacokinetics
- Types
- Adverse Effects
- Penecillin Resistance

Answer 6

Derived from Penicillium fungus
Discovered by Alexander Fleming

STRUCTURE:
1. Core of 6-aminopenicillanic acid
2. Beta lactam ring:
- Active part
- Destroyed by Beta-lactamase enzyme
3. + side (R) group:
- Determines type of penicillin

MECHANISM OF ACTION:
1. Inhibit the formation of peptidoglycan cross-links in bacterial cell wall
2. Spectrum:
G +ve G –ve
3. Bactericidal

PHARMACOKINETICS:
1. Absorption: variable
2. t½ = 30-60 min
3. Excretion:
- Through the kidney (90% tubular secretion)
- Delayed by probenecid
4. Route of administration:
Oral, IV, IM

TYPES OF PENECILLINS:
1. Penicillin G (benzylpenicillin):
- Spectrum: mainly Gram +ve
- Acid labile – only parenteral
- Short acting

2. Penicillin V (phenoxymethylpenicillin):
   - Similar to penicillin G … but: acid stable – taken orally
3. Benzathine benzylpenicillin:
   - Long-acting penicillin (2-4 weeks) – IM injection
4. β-lactamase resistant penicillins:
   DRUGS = coloxacillin – dicloxacillin – methicillin
5. Broad spectrum penicillins:
   DRUGS = ampicillin and amoxicillin

ADVERSE EFFECTS:
1. Hypersensitivity (Anaphylaxis):
- Might be severe → anaphylactic shock
- Cross-allergy

2. GI symptoms: nausea, diarrhea
3. Superinfection: e.g., candidiasis
4. Drug resistance

PENECILLIN RESISTANCE:
1. Destruction by Beta-lactamase enzyme:
- Synthesized by certain bacteria:
e.g., staphylococci

2. Avoided by:
   Clavulanic Acid:
   - Potent β-lactamase inhibitor
   - Combined with some penicillins e.g., amoxicillin

β-Lactamase Resistant Penicillins:
- E.g., cloxacillin – dicloxacillin - methicillin

Question 7

CEPHALOSPORINS

Answer 7

1. Another Beta-lactam antibiotics
2. Derived from Acremonium (Cephalosporium) fungus
3. Action → similar to penicillins
4. Adverse effects → similar to penicillins
5. Resistance → similar to penicillins

CLASSES OF CEPHALOSPORINS:
1. First = Cefadroxil, Cephalexin
- gram (+)

2. Second = Cefaclor, Cefuroxime
   - gram (-)
3. Third = Cefotaxime, Ceftriaxone
   - broad spectrum with gram (-)
4. Fourth = Cefepime, Cefpirome
   - broad spectrum
5. Fifth = Ceftaroline
   - broad spectrum + MRSA

Question 8

SULFONAMIDES
- Mechanism of Action
- Pharmacokinetics
- Adverse Effects
- Route of Admission

Answer 8

First antimicrobial drug discovered

Structure:
1. Derivatives of p-aminobenzoic acid (PABA)
2. Different “R” groups → different types

Bacteriostatic

Spectrum: Gram +ve & -ve

MECHANISM OF ACTION:
1. Reversible competitive:
- Decrease dihydropteroate synthetase enzyme →
- Decrease conversion of PABA to dihydropteroate
- Decrease Folic Acid Synthesis

2. Co-trimoxazole:
   - Sulfamethoxazole + Trimethoprim: Decrease in DHFR

PHARMACOKINETICS:
1. Absorption: variable
2. Carried by albumin
3. Metabolized in the liver
4. Excreted through the kidney

ADVERSE EFFECTS:
1. Hypersensitivity
2. Urinary tract obstruction
3. Hemolytic anemia

ROUTE OF ADMISSION:
1. Oral, topical

Question 9

QUINOLONES
- Mechanism of Action
- Indications
- Adminerstration

Answer 9

DRUG = ciprofloxacin

Synthetic antibiotics

MECHANISM:
1. Inhibit bacterial topoisomerase II (DNA gyrase) enzyme (required for transcription and DNA replication)

BROAD SPECTRUM (including β-lactam resistant strains)

INDICATIONS:
- Complicated UTI – serious G -ve infections

ADMINERSTRATION: oral