quinolones, folic acid ant urinary antiseptics Flashcards
what kind of microbial activity does fluroquinolones have
broad spectrum
what is bad about fluroquinolone
tied to clostridium difficile infection and spread of antimicrobial resistance in many organisms
what does DNA gyrase do?
introduce negative supercoils into the DNA, to prevent excessive supercoiling, allows DNA to replicate
what does topoisomerase IV do
promotes seperation of chromosomal DNA into daughter cells
What does fluoroquinolones target
targets DNA gyrase primarily in gram negative bacteria
targets topoisomerase IV in gram positive bacteria to inhibit DNA replication
what are the types of fluoroquinolones
ciprofloxacin
levofloxacin
moxifloxacin
What kind of administration are there for fluoroquinolones
oral, IV, ophthalmic
What can you say about the absorption of fluoroquinolones
generally well absorbed after oral but should take on empty stomach as if ingested with calcium or other divalent cations, like aluminium or magnesium containing antacids, or dietary supplements that has iron or zinc can reduce absorption
how is the distribution of fluoroquinolones
high in bones , urine ( except moxifloxacin), kidney, prostatic tissues and concentration in lungs exceed those in serum
what is the primary route of clearance of quinolones
renal. Thus dose adjustment necessary for patients with renal failure
Where is moxifloxacin metabolised, when will dose adjustment be needed?
mainly in liver, when patients have hepatic failure
what is ciprofloxacin most active against
gram negative strains and enteric coliform
highly active against P. aeruginosa
Travellers diarrhoea caused by ecoli. food poisoning caused by enterobacteriaceae and campylobacter jejuni
typhoid fever caused by salmonella typhi
used as anthrax caused by bacillus anthracis
prostatitis
What has increased resistance against fluoroquinolones
UTI
which infection should you avoid using ciprofloxacin? why?
MRSA infections, associated with high incidence of staphylococcal resistance. Ineffective against anaerobes
what type of fluoroquinolones have better coverage against gram positive organisms and anaerobes?
third gen- levo and moxifloxacin
what is levo and moxifloxacin used for
prostatitis due to E coli
CAP, nosocomial pneumonia
Excellent activity against S. pneumoniae, and mycobacterium tuberculosis
What are some adverse effects of quinolones
○ GI related most common: nausea, vomiting and diarrhoea
○ Risk of dysglycaemia especially in diabetic patients
○ Aortic dissections or ruptures of an aortic aneurysm. Rare but serious events of ruptures or tears in aorta
§ Can lead to dangerous bleeding or even death
○ Increased risk of C. diff colitis as they clear the bowel flora, especially with ciprofloxacin
○ Headache and dizziness or light headedness. Patients with CNS like epilepsy should be treated cautiously
○ Fluroquinolones can cause phototoxicity. Avoid excess exposure to sunlight, use sunscreen
○ May have an increased risk of tendinitis or tendon rupture
○ May cause joint problems in young animals, not recommended for infants or children below 18 years of age
○ Fluoroquinolones may prolong the QTc interval (cardiac)
§ Thus should not be used in patients predisposed to arrhythmias or other medications that can cause QT prolongation
Peripheral neuropathy with systemic use
should fluoroquinolone be used as a first line drug?
No, because it can cause potentially many side effects
What are some contraindications of using fluoroquinolones
during breast feeding should not use ciprofloxacin
avoid in patients with myasthenia gravis as it may exacerbate muscle weakness
avoid in patients with g6pd deficiency
what are some drug interactions of quinolones
may raise serum levels of warfarin and cyclosporine
what does folic acid do
is a B vitamin, helps body make red blood cells
what are some examples of folic acid inhibitors
trimethoprim, sulfonamides, cotrimoxazole
how does sulfonamides work
competitive inhibitors of dihydropteroate synthase
what does dihydropteroate synthase do
resposible for the incorporation of para-aminobenzoic acid into dihydropteroic acid, the immediate precursor of folic acid
how is sulfonamides administered
oral administration
how is sulfonamides distributed
sulfa drugs bound to serum albumin, penetrates well into CSF even without inflammation. Can pass placenta barrier to enter fetal tissue
distributes well in bodily fluids
How is sulfonamides metabolised
acetylated and conjugated primarily in liver
has potential to precipitate at acidic or neutral pH
what adverse effect can sulfonamide cause?
crystallruia due to precipitation of acetylated product at neutral or acidic pH that can cause potential damage to kidney
hypersensitivity like rashes or SJ syndrome
Hematopoietic disturbance
- hemolytic anemia in patients with G6PD deficiency, can also cause thrombocytopenia
Kernicterus which can occur in newborns when sulfa drugs taken in late pregnancy can displace billirubin from binding sites on serum albumin. Bilirubin then can pass into the CNS as BBB is not fully developed
can have drug potentiation, anti coagulant effect of warfarin results from the displacement from binding sites on serum albumin in patients receiving sulfamethoxazole and warfarin
How are sulfa drugs eliminated, and do they need dose adjustments
by glomerular filtration and secretion, and require dose adjustments for renal dysfunctions
What are the contraindications of sulfonamides
avoid in newborn and infants less than 2 months of age and pregnant women in term
What is trimethoprim function
inhibits bacterial dihydrofolate reductase Decreases availability of tetrahydrofolate cofactors required for purine, pyrimidine and a.a synthesis
what are the clinical uses of trimethoprim
anti bacterial spectrum similar to sulfamethoxazole
may be used laone to treat UTI and bacterial prostatitis
What bacteria is resistant to trimethoprim and why
gram negative bacteria, because there exists altered dihydrofolate reductase that has a lower affinity for trimethoprim
How is the absorption of trimethoprim
orally, rapidly absorbed
High concentrations are achieved in relatively aciic prostatic and vaginal fluids, due to it being a weak base
Hows the distribution of trimethoprim
widely distributed into CSF and tissues and fluids
how is trimethoprim excreted
60-80% excreted renally, unchanged
what are some adverse effects of using trimethoprim
can produce the effects of folic acid deficiency
- megaloblastic anemia
- leukopenia
- granulocytopenia
What category of pregnancy is trimethoprim
Cat C
How to manage folic acid deficiency with trimethoprim
simultaneous administration of folinic acid which interconverts to tetrahydrofolic acid
What is cotrimoxazole comprised of
trimethoprime compounded with sulfamethoxazole 1:5 ratio
What is the mechanism of action of cotrimoxazole
synergistic antimicrobial activity from
- sulfamethoxazole inhibits incorporation of PABA into dihydrofolic acid precursors
- trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate
How is cotrimoxazole administered
orally with water
IV may be used in patient with severe pneumonia, UTI if patient cannot take orally
what are the clinical indications of sulfonamide drugs
pneumocystis carinii
for drug resistant malaria and for toxoplasmosis
In IBD
for infected burns
for STI like chlamydia
how is the distribution of cotrimoxazole
concentrates in relatively acidic milieu of prostatic fluids, can treat prostatitis.
Has good CSF penetration, can readily cross BBB
How is cotrimoxazole excreted
in urine
What are the clinical uses of cotrimoxazole
treat UTI, E coli
Respiratory tract infection by haemophilus, klebsiella pneumonia
MRSA and community acquired skin and soft tissue infections
Pneumocystis pneumonia caused by pneumocystis jiroveci
What are some adverse effect of cotrimoxazole
rashes
photosensitivity
nausea vomitting
stomatitis, glossitis
hemolytic anemia in patients with g6pd deficiency
megaloblastic anemia, leukopenia, thrombocytopenia ( can be reversed with concurrent administration of folinic acid)
What is nitrofurantoin used for
treatment and prevention of lower UTI
How does nitrofurantoin act
nitrofurantoin sensitive bacteria reduce drug to highly active intermediate that inhibits various enzymes disrupts the syntehsis
what is the antimicrobial effect of nitrofurantoin
against many strains of e.coli and enterococci
what is resistant against nitrofurantoin
most species of proteus and pseudomonas and many species of klebsiella and enterobacteria are resistant
how is administration of nitrofurantoin
oral
what form of nitrofurantoin is absorbed and excreted slower
macrocrystalline form
How is nitrofurantoin distributed
achieves high urinary concentration while limiting systemic exposure due to rapid clearance
how is nitrofurantoin eliminated
40% excreted unchanged into urine
colours urine brown
adverse effects of nitrofurantoin
nausea, vomiting, diarrhea
hypersensitivity reactions
hemolytic anemia with g6pd deficiency as nitrofurantoin produces a lot of freee radicals
hepatocellular damage, cholestatic jaundice
peripheral neuropathy in patients renally impaired or on long treatment
Contraindications of nitrofurantoin
indiv with impaired renal function
pregnant women (38-42 weeks gestation )or when labor is imminent
infants <1 month of age
