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PHARMACOLOGY
2.1D ANTIMICROBIALS

AMINOGLYCOSIDES CLINICAL USES

 From Streptomyces inhibit protein synthesis GENTAMYCIN, TOBRAMYCIN AND AMIKACIN
 Serious infections caused by aerobic gram (-) bacteria.
 Natural and semi-synthetic o E.Coli
 Produced from Streptomyces o Klebsiella
 Poor oral absorption; no PO forms o Providencia
 Very potent antibiotics with serious toxicities. o Serratia
 Bactericidal o Enterobacter
 Kill mostly gram-negative; some gram-positive also. o Proteus
 Used to kill gram-negative bacteria such as Pseudomonas o Pseudomonas
spp., E.Coli, Proteus spp., Klebsiella spp., Serratia spp.
 Used for the following but is not the drug of choice.
 Often used in combination with other antibiotics for synergistic
effect. o H. Influenzae
o M. Catarrhalis
MECHANISM OF ACTION o Shigella species
 Bacteriocidal (irreversible) inhibition of protein synthesis.
 Penetration of bacterial cell wall is partly dependent on O2 ANTIBACTERIAL SYNERGY
dependent active transport.  Not effective for gram (+) cocci when used alone.
 Minimal activity ahainst strict anaerobes.  Combination of aminoglycosides and cell wall synthesis
 Transport is enhanced by cell wall synthesis inhibitors. inhibitors.
o Antimicrobial synergism.  Combined with penicillin in the treatment
 Bind to 30s ribosomal unit. o Pseudomonal
 Interfere with protein synthesis. o Listerial
1. Block formation of initiation complex. o Enterococcal infections
2. Cause misreading of the code on the mRNA template.
3. Inhibit translocation. STREPTOMYCIN
 Tuberculosis
MECHANISM OF RESISTANCE  Plague
1. Resistant due to failure to penetrate into the cell.  Tularemia
 Streptococci, including S. Pneumoniae  Multi-drug-resistant (MDR) strains of M. TB resistant to
 Enterococci Streptomycin maybe susceptible to Amikacin.
2. Plasmid-mediated formation of inactivating enzymes.
 Transferases produced by enterococci can inactivate: NEOMYCIN
- Amikacin  Used topically
- Gentamicin  Locally
- Tobramycin o In the GIT
- Not Streptomycin o Eliminate bacterial flora
 Netilmicin is less susceptible and is active against more strains
of organisms SPECTINOMYCIN
 Aminocylitol related to aminoglycosides.
ANTIBIOTICS : AMINOGLYCOSIDES  Back-up drug
 Gentamicin (Geramycin)  Intramuscular as single dose for gonorrhea.
 Kanamycin
 Neomycin SIDE EFFECTS
 Streptomycin  3 most common (systemic) Gentamicin, Tobramycin, Amikacin
 Cause serious toxicities:
 Tobramycin
o Nephrotoxicity (renal failure)
 Amikacin (amikin) o Ototoxicity (auditory impairment and vestibular (8th
 Netilmicin cranial nerve)
 Must monitor drug levels to prevent toxicities.
PHARMACOKINETICS  Ototoxicity and nephrotoxicity:
 Structurally related amino sugars attached by glycosidic o The most significant
linkages.  Headache
 Paresthesia
 Polar compounds  Neuromuscular blockade
 Not absorbed orally.  Dizziness
 Given intravenously or intramuscularly for systemic effects.  Vertigo
 Limited tissue penetration.  Skin rash
 O not readily cross the blood-brain barrier.  Fever
 Superinfection
 Major mode of excretion
o Glomerular filtration SULFONAMIDES
 Plasma levels are affected by changes in renal function. FOLIC ACID SYNTHESIS
 Sulfonamides (sulfa drug) and trimethroprim
o Analog of PABA
o Competitive inhibition of enzymes
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Pharmacology 2.1D ANTIMICROBIALS

o Prevents the metabolism of DNA, RNA and amino SIDE EFFECTS

acid. BODY SYSTEM EFFECT
Blood Hemolytic and aplastic anemia,
COMPETITIVE INHIBITORS thrombocytopenia
SULFONAMIDES (SULFA DRUGS) Integumentary Photosensitivity, exfoliative
 Inhibit folic acid synthesis dermatitis, Stevens- Johnson
 Broad spectrum syndrome, epidermal necrolysis
 One of the first groups of antibacterial agents GI Nausea, vomiting, pancreatitis,
o Sulfadiazine diarrhea
o Sulfamethizole Other Convulsions, Crystalluria, toxic
o Sulfamethoxazole nephrosis, headache, peripheral
o Sulfasoxazole neuritis, urticaria
 Sulfonamides compete with PABA for the active site on the
enzyme. DISPENSING ISSUES
o The sulfonamide Sulfamethoxazole is commonly  Avoid the sun
used in combination with Trimethoprim.  Maintain adequate fluid intake

MECHANISM OF ACTION QUINOLONES

BACTERIOSTATIC ACTION  Ciprofloxacin (Cipro)
 Prevent synthesis of folic acid required for synthesis of purines  Enoxacin (Penetrex)
and nucleic acid  Lomefloxacin (Maxaquin)
 Doesn’t affect human cells or certain bacteria – they can use  Norfloxacin (Noroxin)
preformed folic acid.  Ofloxacin (Floxin)
STRUCTURE OF SULFONAMIDES  Excellent oral absorption
 Absorption reduced by antacids
CLASSIFICATION OF SULFONAMIDES  First oral antibiotics effect against gram (-) bacteria
SHORT ACTING MEDIUM DURATION
Streptocid Sulfamethoxazole – is a part of co- MECHANISM OF ACTION
Sulfadimezine trimoxazole  Inhibition of bacterial DNA gyrase (Topoisomerase I)
Aethazole o Formation of quinolone DNA gyrase complex
Norsulfazole o Induced cleavage of DNA
Urosulfan
 Inhibition of bacterial Topoisomerase IV
Sulfizoxazole
o Mechanism poorly understood
Sulfacyl-sodium
LONG ACTING SUPER LONG ACTING
 Bactericidal
Sulfadimethoxyn Sulfalen
 Effective against Gram (-) organisms and some Gram (+)
Sulfapirydazin Sulfadoxyn – is a part of fansidar
organisms
Sulfamonomethoxyn
 Alter DNA of bacteria, causing death
 Do not affect human DNA
SULFAMETHOXAZOLE THERAPEUTIC USES
AZO-GENTANOL
CLASSIFICATION
 Combined with phenazopyridine (an analgesic-anesthetic that QUINOLONES (1ST GEN)
affects the mucous of the urinary tract)
 Highly protein bound
 Used to treat urinary tract infections (UTI) and to reduce the
 Mostly used in UTI’s
pain associated with UTIs.
FLUOROQUINOLONES (2ND, 3RD, 4TH GEN)
BACTRIM
 Not highly protein bound
 Combined with Trimethoprim
 Wide distribution to urine and other tissues, limited CSF
 Used to treat UTIs, Pneumocystis carini pneumonia, ear
penetration
infections, bronchitis, gonorrhea, etc.

CO-TRIMOXAZOLE (BACTRIM) DRUG NAMES

 480 – for adults 1ST Nalidixic acid Gram (–) but not
Cinoxacin Pseudomonas
 960 – for adults
species
 120 – for children
2ND Norfloxacin Gram (-) including
 240 – for children
Ciprofloxacin Pseudomonas
o Orally 2x daily
Enoxacin species and some
Ofloxacin Gram (+) S.Aureus
SULFISOXAZOLE THERAPEUTIC USES and some atypicals.
AZO-GANTRISIN 3RD Levofloxacin Same as 2nd gen with
 Combined with phenazopyridine Sparfloxacin extended Gram (+)
 Used for UTIs Moxifloxacin and atypical
Gemifloxacin coverage.
PEDIAZOLE 4TH Trovefloxacin Sam as 3rd gen with
 Combined with Erythromycin broad anaerobic
 Used to treat Otitis Media coverage.

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Pharmacology 2.1D ANTIMICROBIALS

 May damage growing cartilage resulting in arthropathy (but

that’s reversible so may be used in pseudomonal infections in
C.F where benefit outweighs the risk.)
 Tendonitis and tendon rupture is rare but very serious.
 Phototoxicity – avoid excessive sun exposure.
 Leukopenia, eosinophilia (rare)
 Mild elevation in transaminases (rare)

CONTRAINDICATION
 Children (not absolute)
 Pregnancy
 Lactation
 Epilepsy
 QTc prolongation

SUMMARY OF TARGETS
Inhibition of cell wall synthesis Penicillin, Bacitracin,
Cephalosporin, Vancomycin
Disruption of cell membrane Polymyxin
function
Inhibition of protein synthesis Tetracycline, Erythromycin,
Streptomycin, Chlorampenicol
Inhibition of nucleic acid synthesis Rifamycin (transcription),
Quinolones (DNA replication),
Metronidazole
Action as antimetabolites Sulfonilamide, Trimethoprim
THERAPEUTIC USES
 Lower respiratory tract infections
 Bone and joint infections
 Infectious diarrhea
 Urinary tract infections
 Skin infections
 Sexually transmitted disease
DISPENSING ISSUES
 Not be given with Theophylline
 Antacids interfere with absorption
 Avoid exposure to sun
END OF TRANS
“You don’t have to be great to start, but you have to start to be great.”
~ Zig Ziglar

DRUG INTERACTIONs
Drugs increasing levels of FQL FQL increasing the levels of:
Theophyline Antidepressants
NSAIDS Imipramine
Corticosteroids Caffene
Theophylline
Warfarin (INR –monitored)

INDICATIONS
UTI and PROSTATIS STDS -GI and abdominal
- 7 day course of infections.
Ofloxacin and -Traveller’s diarrhea
Sparfloxacin for -Cholera
chlamydial -Enteric fever
infection -Shigellosis
- 14 day course
Oflaxocin for
PID.
RTI BONE AND JOINT OTHERS
-3rd and 4th -Osteomyelitis (weeks -Multi drug resistant
generations FQL have – months) tuberculosis
excellent activity -Diabetic foot (in -Prophylactically in
against S. Pneumonia combination with anti- neutropenic patient.
-Very effective in anaerobic agent)
clearing H.I and M.
Catt from sputum

ADVERSE EFFECTS
 Generally safe antibiotics
o GI - Nausea, vomiting, diarrhea and antibiotic
associated colitis have been reported.
o Neuro – Confusion, insomnia, dizziness, anxiety and
seizures (displacement of GABA from its receptors)
o Cardio – Torsade de pointes, prolonged QTc interval

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