Tetracyclines
Route of Administration: Oral, intravenous, intratympanic (directly into the ear), ophthalmic, and otic administration.
Ciprofloxacin-Quinolone
is a second generation fluoroquinolone antibiotic that is widely used in the therapy of mild-to-moderate urinary and respiratory tract infections c
Ciprofloxacin-Quinolone
Not active against vaginal lactobacilli
Tinidazole (nitroimidazole)- Nitroheteroaromatic
In 2016 the term FQAD was coined to describe the long term symptoms observed in some patients after taking FQs.
FQ Associated Disability (FQAD)
is a fluoroquinolone antibiotic indicated in the treatment of acute otitis externa (swimmer's ear) caused by the bacteria Pseudomonas aeruginosa and Staphylococcus aureus.
Finafloxacin-Quinolone
Thus far 353 drugs have been linked to liver injury. Many of these drugs were approved before 1999.
Fluoroquinolone
are associated with an increased risk of tendinitis and tendon rupture in all ages.
Fluoroquinolones, including Noroxin
a synthetic 8-methoxyfluoroquinolone with antibacterial activity against a wide range of G+/- microorganisms.
Gatifloxacin-Quinolone
is an antibiotic of the fourth- generation fluoroquinolone family,
Gatifloxacin-Quinolone
acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia.
Gemifloxacin-Quinolone
Contaminated water associated. Diarrheal disease caused by the microscopic parasite Giardia.
Giardiasis
The parasite lives in the intestines and is passed in feces. Many mammals act as hosts.
Giardiasis
bind more effectively than the tetracyclines
Glycylcyclines
exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site.
Tetracycline-Tetracyclines and glycyclines
is a broad spectrum polyketide antibiotic semisynthetically from chlortetracycline, an antibiotic isolated from the Streptomyces genus of Actinobacteria
Tetracycline-Tetracyclines and glycyclines
serious side effects associated with ____________ generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment option
fluoroquinolone antibacterial drugs
Excreted in urine unchanged
fosfomycin- nitroheteroaromatic
Inhibition of cell wall biogenesis by inactivating MurA. This is mediated by the highly reactive epoxide moiety which alkylates Cys 115. This is a unique target to this drug
fosfomycin- nitroheteroaromatic
No interaction with B-lactamases
fosfomycin- nitroheteroaromatic
Nonessential glycerophosphate transporters are mutated (chromosomal and plasmids) leading to resistance.
fosfomycin- nitroheteroaromatic
Primarily used for bladder infections and occasionally prostate infections
fosfomycin- nitroheteroaromatic
chemical structure mimics both glycerol-3-P (G3P) and glucose-6-P (G6P),
fosfomycin- nitroheteroaromatic
Useful laboratory tool to differentiate micrococci and staphylococci (sensitive)
furazolidone
Gemifloxacin-Quinolone side effects
hepatotoxicity
tetracyclines that are most photosensitizing
second generation
used as BOTH an antimalarial drug and food flavoring agent.
quinine
was the important early (1820) metabolite of quinoloneidentified with activity.
quinine
Cinchona tree remains the only active source.
quinolone
a two ringed heterocyclic system
quinolone
it is primarily used to treat Uncomplicated bladder infections and UTIs
Nitrofurantoin- Nitroheteroaromatic Class
nitroheteroaromatic Not to be used with kidney disease or pregnancy
Nitrofurantoin- Nitroheteroaromatic Class
Effective against G+/- and trypanosomiasis.
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Estimated 100 kg for every 100,000 humans on the planet.
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Its use and other nitroheteroaromatics is highly controversial
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Listed under California Prop 65 as both mutagenic and carcinogenic.
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Not well defined but DNA damaging and interacting. Enzymes involved in glucose metabolism.
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Use in Food Animals strictly banned. Have been found in many food products
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class
Extremely abundant drug class.
Nitroheteroaromatic Class
Active against MRSA, MDR Strep pneumoniae, VRE. Well tolerated
Omadacycline (Aminomethylcycline)-Tetracyclines
Overcomes resistance mediated by acquired efflux pumps and/or ribosomal protection. Useful for community-acquired pneumonia
Omadacycline (Aminomethylcycline)-Tetracyclines
Moxifloxacin-Quinolone route of administration
Oral, IV Eye drops
90% eliminated in urine (50% unchanged)
Nitrofurantoin- Nitroheteroaromatic Class
Doxycycline used for rosacea (less photosensitizing then
Minocycline
has little value or activity but forms an important drug class.
Bare quinolone
DNA gyrase and topoisomerase IV. By inhibiting DNA gyrase, DNA replication, transcription, and repair is impaired
Besifloxacin-Quinolone
active against Corynebacterium, Moraxella , Staphylococcus, Streptococcus
Besifloxacin-Quinolone
fourth generation fluoroquinolone-type opthalmic antibiotic for the treatment of bacterial conjunctivitis.
Besifloxacin-Quinolone
Not a drug of choice for Staph and Strep due to resistance (about 50%).
Doxycycline- Tetracyclines and glycyclines
a first generation fluoroquinolone that is typically used to treated urinary tract infections and prostatitis.
Norfloxacin-Quinolone
Treatment of FQAD
1.Antioxidants 2.Mineral replacement 3.Mitochondria repair 4.Restoring cellular energy
FQ Associated Disability (FQAD)The main mechanisms of toxicity appear to involve:
1.Oxidative stress 2.Binding of metals (Magnesium, Calcium, Zinc, Copper, Manganese, Iron, and likely Selenium) 3.Damage to mitochondria 4.Disruption of cellular energy pathways 5.Damage to DNA
FQ Toxicity
1.Tendon Rupture 2.Nervous system disturbances 3.Heart, kidney and liver damage 4.Diabetes
tetracyclines that have a side chain on D ring making it better for drug resistant bacteria
3rd generation
Protein synthesis inhibitors binds to the 30S ribosomal subunit, possibly to the 50S ribosomal subunit as well, thereby blocking the binding of aminoacyl-tRNA to the mRNA-ribosome complex.
Doxycycline- Tetracyclines and glycyclines
This drug is a second-generation tetracycline, exhibiting less toxicity than first-generation tetracyclines.
Doxycycline- Tetracyclines and glycyclines
used for rosacea (less photosensitizing then Minocycline).
Doxycycline- Tetracyclines and glycyclines
Side-effects: Hypersensitivity Reactions. Clostridium difficile-associated diarrhea
Delafloxacin-Quinolone
is used to treat acute bacterial skin and skin structure infections caused by designated susceptible bacteria.
Delafloxacin-Quinolone
inhibitor of arginine vasopressin in the therapy of hyponatremia (H20-electrolyte imbalance) by blocking vasopressin at the kidney and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (when fluid restriction does not work). ADH=Vasopressin=Arginine vasopressin.
Demeclocycline-Tetracyclines and glycyclines
tetracycline that half life ranges between 10 and 16 hours..
Demeclocycline-Tetracyclines and glycyclines
are frequently used for the treatment of Acne vulgaris.
Doxycycline and minocycline - Tetracyclines and glycyclines
are more or less completely absorbed and are 3-5 times more lipophilic than the first-generation tetracyclines
Doxycycline and minocycline - Tetracyclines and glycyclines
Has photosensitivity as a side effect
Doxycycline- Tetracyclines and glycyclines
a broad-spectrum, third-generation fluoroquinolone antibiotic and optically active L-isomer of ofloxacin with antibacterial activity
Levofloxacin, ofloxacin-Quinolone
exerts its antimicrobial activity via the inhibition of two key bacterial enzymes: DNA gyrase and topoisomerase IV.
Levofloxacin, ofloxacin-Quinolone
Poor tissue penetration makes the drug NOT very useful for prostatitis, intra- abdominal infections and pyelonephritis.
Nitrofurantoin- Nitroheteroaromatic Class
is concentrated to up to 200ug/ml in the urine
Nitrofurantoin- Nitroheteroaromatic Class
Its most common applications are dracunculiasis, giardiasis, trichomoniasis and-amebiasis and is used for mild C. diff infections when vancomycin is not available.
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
Suspected tumor promoting agent
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
Used off-label for Crohn's disease, rosacea prevention of preterm births and H. pylori.
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
it is used as an antibiotic and antiprotozoal.
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
was developed at Rhône-Poulenc in theearly to mid-1950s after French scientists described the potent activity of an extract of Streptomycete 6670 on the growth of Trichomoniasis (Trichomonas vaginalis).
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
was the best and quickly was Approved and became standard of care for Trichomoniasis (Trichomonas vaginalis) by 1960.
Metronidazole MET (Nitroimidazole) -Nitroheteroaromatic
Mild-Moderate C. diff colitis is treated with:
Metronidazole, vancomycin, or fidaxomicin orally.
against pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis.
Moxifloxacin-Quinolone
is a fourth generation fluoroquinolone with expanded activity against G+ bacteria as well as atypical pathogens
Moxifloxacin-Quinolone
In the US it is approved for treating bacterial vaginal infections (15-44yrs of age)
Secnidazole (approved 2017)- Nitroheteroaromatic
In vitro studies demonstrates the effectiveness of the drug against Bacteroides fragilis, Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.
Secnidazole (approved 2017)- Nitroheteroaromatic
Food and/or milk reduce GI absorption of oral preparations by 50% or more
Tetracycline-Tetracyclines and glycyclines
May also be used to treat acne.
Tetracycline-Tetracyclines and glycyclines
Metal ion interactions reduce availability and many drug interactions.
Tetracycline-Tetracyclines and glycyclines
Use during pregnancy can harm the fetus and cause permanent discoloration of teeth.
Tetracycline-Tetracyclines and glycyclines
FDA issued a black box warning in September 2010, for tigecycline regarding an increased risk of death compared to other appropriate treatment
Tigecycline-Tetracyclines
It was developed in response to the growing prevalence of antibiotic resistance in bacteria such as Staphylococcus aureus.
Tigecycline-Tetracyclines
Overcomes resistance mediated by acquired efflux pumps and/or ribosomal protection.
Tigecycline-Tetracyclines
glycylcycline (subclass of tetracyclines) antibiotic
Tigecycline-Tetracyclines
increased mortality risk (seen most clearly in people treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia).
Tigecycline-Tetracyclines
Combination therapy to eliminate H pylori.
Tinidazole (nitroimidazole)- Nitroheteroaromatic
antitrichomonal agent effective against Trichomoniasis (Trichomonas vaginalis), Entamoeba histolytica, and Giardia lamblia infections.
Tinidazole (nitroimidazole)- Nitroheteroaromatic
including disulfiram-like reaction if taken with alcohol.
Tinidazole (nitroimidazole)- Nitroheteroaromatic
Finafloxacin-Quinolone route of Administration:
Topical otic administration
60 million cases/year globally. Estimated 3% US population infected.
Trichomoniasis
Most common nonviral STD. >risk of HIV and cancer.
Trichomoniasis
Protozoan STD caused by Trichomonas vaginalis.
Trichomoniasis
Enters cell through OmpF porins coordinated with Mg or other ions
minocycline - Tetracyclines and glycyclines
Increase risk of sunburns (photosensitizing agent).
minocycline - Tetracyclines and glycyclines
Nitrofurazone (Nitrofural)- Nitroheteroaromatic Class route of administration
orally or topically