Antimicrobials in GIS

DR. PRASAD
FALL 2018
Objectives
 Classification of fluroquinolones based on their spectrum; Mechanism
of action; Mechanism of resistance; Indications of fluroquinolones

 Drugs used in treatment of Amebiasis

 Drugs used in treatment of Giardiasis

 Drugs used in treatment of Parasitic infestations

Fluroquinolones: Classification
 Ciprofloxacin, Ofloxacin:- excellent activity
against Gram(-) aerobic organisms including
Enterobacteria, Pseudomonas, Neisseria,
Hemophilus

 Levofloxacin, Sparfloxacin, Gatifloxacin:-

Additional organisms causing CAP, Atypical
organisms (Chlamydiae, Mycoplasma, Legionella)

 Moxifloxacin:- additional activity against

anaerobes
 Mechanism of action
 Inhibit DNA gyrase enzyme (for gram negative
bacteria)
 Inhibit topoisomerase IV (for gram positive
bacteria)
 Pharmacokinetics
 Well absorbed orally
 Penetrates inside the cells (effective against
intracellular pathogens)
 Antacids (Ca and Mg salts) reduce
absorption
 Moxifloxacin is eliminated by liver (all other
FQ’s by kidneys)
Mechanism of resistance
 Resistance
is due to - Alterations in the
DNA gyrase

 Enzymes that inactivate fluroquinolones

(acetyltransferase)
 Fluoroquinolones: Adverse effects

1. Phototoxicity: Lomefloxacin and Sparfloxacin

2. Prolongation of the QT interval: Sparfloxacin and moxifloxacin
3. P450 enzyme inhibitors can increase concentrations of
warfarin: Ciprofloxacin
4. **Achilles tendon rupture or tendinitis occurs rarely

Not recommended for use in patients younger than 18 years or in

pregnant or lactating women: can cause cartilage damage
and arthropathy
Therapeutic uses of FQs: Summary
 Ciprofloxacin: Drug of choice for prevention and treatment of
anthrax
 UTI: caused by pseudomonas-- Ciprofloxacin
 Bacterial diarrhea - by Shigella, Salmonella, toxigenic E coli, and
Campylobacter
 Typhoid fever: FQs, 3rd cephalosporin's, Co-trimoxazole
(Respiratory fluoroquinolones)
 Community acquired Pneumonias: Levofloxacin, ofloxacin
 Atypical pneumonia: Chlamydiae, Mycoplasma, and Legionella

 Delafloxacin: FDA approved for MRSA

 Which of the following group of AMA is associated with
cartilage damage and Achilles tendon rupture?
A. Beta lactam
B. Sulfonamiodes
C. Fluoroquinolones
D. Aminoglycosides
 Mechanism
Binds to 30S
Inhibits formation of initiation complex; misreading the
mRNA and formation of abnormal proteins (cidal);
premature termination – Aminoglycosides
Inhibits docking of tRNA to A site - Tetracycline

Binds to 50S
Inhibits formation of initiation complex – Linezolid
Inhibits peptidyl transferase – Chloramphenicol
Inhibits translocation – Macrolides and Clindamycin

Only aminoglycosides are cidal

 Aminoglycosides
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

 Bactericidal: concentration dependent killing; post

antibiotic effect
 O2 dependent uptake; (Would it work in abscess or
against anaerobes??)
 Severe gram ⊝ rod infections
 Synergistic with beta lactams against enterococci
and P. aeruginosa (penicillin inactivate AG if added
in same bottle)
 Aminoglycosides
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

 Not absorbed orally; dose reduction needed in renal

dysfunction
 Nephrotoxicity (usually reversible); Ototoxicity from hair
cell damage, includes deafness (irreversible) and vestibular
dysfunction (reversible); Neuromuscular blockade:↓ release
of Ach (enhance effects of skeletal muscle relaxants);
Dermatitis for neomycin
 Resistance: Bacterial transferase enzymes inactivate the
drug
Aminoglycosides: Uses

 Streptomycin for TB and DOC for bubonic plague and

tularemia
 Oral Neomycin: Neomycin for bowel surgery; for
Hepatic encephalopathy ( 1st drug of choice is
Lactulose)
 Ampicillin+ Gentamicin- against E. faecalis
 Vancomycin+ Gentamicin against E. Faecium
 Macrolides
Azithromycin, clarithromycin, erythromycin

 Atypical pneumonias (Mycoplasma, Chlamydia,

Legionella), STIs (Chlamydia), Campylobacter jejuni,
Mycobacterium avium-intracellulare (MAC), H. pylori
 Erythromycin: microsomal enzyme inhibitor, cholestatic
hepatitis, QT prolongation-- not used
 Azithromycin- long acting, no drug interaction, single dose
administration
 Macrolides
Azithromycin, clarithromycin, erythromycin

 Clarithromycin used in eradication therapy against H.

pylori
 Macrolides increase GI motility by stimulating motilin
receptors
 Resistance: Methylation of 23S rRNA-binding site prevents
binding of drug
Metronidazole, Tinidazole
 Metronidazole is a synthetic, nitroimidazole-derivative
 antibacterial and antiprotozoal agent

Mechanism of Action:
Reduced to active
metabolites, which inhibits
DNA
Metronidazole, Clinical Uses

 Amebiasis
 Anaerobic bacterial infection
 H. pylori
 Giardiasis
Metronidazole
Adverse Effects
Nausea, vomiting, diarrhea, epigastric distress,
abdominal cramping and constipation. Taking the
drug with meals lessens gastrointestinal irritation
Metallic taste
Disulfiram like reaction with alcohol- nausea,
vomiting, headache after alcoholic drinks due to
accumulation of acetaldehyde in blood
Drugs used in Amebiasis

 Metronidazole: drug of choice in the treatment of

extraluminal amebiasis.
 It kills trophozoites but not cysts of E histolytica and
effectively eradicates intestinal and extraintestinal tissue
infections.
 Tinidazole – related to metronidazole with similar efficacy
Drugs used in luminal Amebiasis
 Used only for intestinal amebiasis
 Not absorbed significantly into blood
 Are amebicidal (luminal amebicides), but not effective against trophozoites

IODOQUINOL
 Used with caution in patients with optic neuropathy, renal or thyroid disease

DILOXANIDE FUROATE
 Is split into diloxanide and furoic acid; Diloxanide is the active antiamebic

PAROMOMYCIN
NITAZOXANIDE
 Used against Giardia lamblia and cryptosporidium parvum
 Active metabolite, tizoxanide, inhibits the pyruvate-
ferredoxin oxidoreducse pathway (essential to anaerobic
energy metabolism)
ANTHELMINTIC DRUGS 22

BENZIMIDAZOLES
ALBENDAZOLE, Mebendazole
 Broad spectrum
 Drug of choice (primary therapeutic
application) for treatment of hydatid
disease and cysticercosis, Mixed worm
infestation with ascariasis, tricurasis and
strongyloidiasis, pinworm, hookworm
Albendazole contd.. 23

 Mechanism of action: It inhibits microtubule

synthesis in nematodes(intestinal round worms)
that irreversibly impairs glucose uptake,
intestinal parasites are immobilized and die
slowly.
 Long term administration causes
pancytopenia
Praziquantel
 Increase the permeability of trematode and cestode cell
membranes to calcium, resulting in paralysis, dislodgement,
and death

 Uses:
 Flukes: Schistosomiasis, Clonorchiasis
 Tape worms: Taeniasis and diphyllobothriasis
 Hydatid disease
Ivermectin
 Paralyzes by intensifying γ-aminobutyric acid (GABA)-mediated
transmission of signals in peripheral nerves

 Uses:
 Strongyloidiasis
 Onchocerciasis
Pyrantel pamoate 26

 Itis a broad spectrum anthelmintic

 Mechanism of action: It is a depolarizing
neuromuscular blocking agent that causes release of
acetylcholine and inhibition of cholinesterase leads
to paralyzes of worms.