inhibitor of bacterial DNA synthesis.ppt

Contains indication, pharmacokinetics, contraindications of all drugs that inhibits bacteria DNA synthesis in detail

1. INHIBITORS OF BACTERIAL
DNA SYNTHESIS
Dr. NDAYISABA CORNEILLE
CEO of CHG
MBChB,DCM,BCSIT,CCNA
SupportedBY

2. The most common examples of inhibitors of
bacterial DNA synthesis are;
1.Quinolones
2.Fluoroquinolones
Dr Ndayisaba Corneille

3. –Are synthetic antibiotics effective against a
variety of gram-ve & gram +ve bacteria
–These drugs are currently rarely used bcoz they
do not achieve good systemic antibacterial
levels
1. Quinolones
Dr Ndayisaba Corneille

4. Examples of Quinolones (Q) ‘CAPPON’
—Cinoxacin
—Acrosoxacin
—Pepamindic acid
—Piromindic acid
—Oxolinic acid
—Nalidixic acid (most common drug)
Dr Ndayisaba Corneille

5. Mechanism of action
–Inhibits bacterial protein synthesis by inhibiting
DNA gyrase
–This leads to bacterial cell death
Indications
–Useful for Rx of lower UTIs
–Treatment of bacillary dysentery
Dr Ndayisaba Corneille

6. Quinolones: MOA
Dr Ndayisaba Corneille

7. –Are synthetic drugs manufactured by adding
fluorine to quinolones
–This means they are fluorinated analogs of
nalidixic acid
–They are more active against a variety of
gram-ve & gram +ve bacteria when compared
to nalidixic acid
Fluoroquinolones
Dr Ndayisaba Corneille

8. Classifications of fluoroquinolones
1. First generation fluoroquinolones
—Norfloxacin
2. Second generation
—Ciprofloxacin
—Levofloxacin
—Perfloxacin
—Ofloxacin
Dr Ndayisaba Corneille

9. 3. Third Generation
–Sparfloxacin
–Gatifloxacin
4. Fourth generation
–Moxifloxacin
Dr Ndayisaba Corneille

10. Antibacterial activity of fluoroquinolones
oHave excellent activity against gram-ve aerobic
bacteria
oNewer fluoroquinolones hv improved activity
against gram +ve cocci
oAre active against mycoplasma spp &
chlamydia spp
Dr Ndayisaba Corneille

11. oThey are also active against intracellular
pathogens like;
–Legionella spp
–Some mycobacterium like M. tuberculosis &
mycobacterium avium complex
Dr Ndayisaba Corneille

12. Resistance to fluoroquinolones
oDuring therapy, resistant organisms emerge
esp;
–Staphylococci aureus
–Pseudomonas aeruginosa
–Serratia spp
Dr Ndayisaba Corneille

13. Mechanism of action
—Block bacterial DNA synthesis leading to cell
death
—This is by inhibiting bacterial topoisomerase II
(DNA gyrase) & topoisomerase IV
Dr Ndayisaba Corneille

14. —InhibitionofDNAgyrasepreventsuncoilingof
supercoiledDNAthatisrequiredfornormal
transcription&replicationofbacterialDNA
—InhibitionoftopoisomeraseIVinterfereswith
separationofreplicatedchromosomalDNAinto
therespectivedaughtercellsduringcelldivision
Dr Ndayisaba Corneille

15. These drugs are well absorbed from gut
Bioavailability is about 80–95%
They are distributed widely in body fluids & tissues
Serum half-lives ranges frm 3 -10 hours
Long half-lives permit O.D dosing of;
–Levofloxacin -Gemifloxacin
–Gatifloxacin -Moxifloxacin
Pharmacokinetics
Dr Ndayisaba Corneille

16. —Oral absorption of these drugs is impaired by
divalent cations like Ca²+, Mg²+ found in
antacids
—Plasma concentration of IV administered drugs
are similar to those of orally administered drugs
Excretion is by;
–Renal glomerular filtration & tubular secretion
Dr Ndayisaba Corneille

17. Dosages
–Ciprofloxacin;500-750 mg BD
–Levofloxacin;500mg OD
–Norfloxacin; 400BD
–Ofloxacin; 400BD
Dr Ndayisaba Corneille

18. 1.Urinary tract infections
2. Bacterial diarrhoea cozed by;
–Shigella; bacillary dysentery
–Salmonella; typhoid fevers
–Toxigenic E coli ; gastroenteritis
–Campylobacter
Clinical indications of fluoroquinolones
Dr Ndayisaba Corneille

19. 3. Infections like;
–Soft tissues like boils ,cellulitis ,abscesses
–Bones & joint infections
–Intra-abdominal infections
–Respiratory tract infections including those
cozed by MDR-organisms like pseudomonas
–Septic wounds
Dr Ndayisaba Corneille

20. 4. Prophylaxis & tx of anthrax
–Ciprofloxacin is a drug of choice
5. Gonococcal urethritis & cervicitis
–Ciprofloxacin & levofloxacin are effective
6. Chlamydia urethritis or cervicitis
–Ciprofloxacin & levofloxacin are effective
Dr Ndayisaba Corneille

21. 7. Rx of TB & atypical mycobacterial infections
–Ciprofloxacin, levofloxacin, or moxifloxacin
are occasionally used
8.Eradication of meningococcal infection from
carriers
9. Prophylaxis against meningococcal infection in
ISS pts
10. Given prophylactically before surgery
Dr Ndayisaba Corneille

22. 11.Atypicalpneumoniacausedbychlamydia,
mycoplasma&Legionellaspp
12.TreatmentofUpperRTIs&LowerRTIs
Dr Ndayisaba Corneille

23. Adverse effects;
•Fluoroquinolonesareextremelywelltoleratedin
mostpts
1. GI S/Es (the most common S/Es)
–Nausea
–Vomiting
–Dyspepsia
–Diarrhea
Dr Ndayisaba Corneille

24. 2. CNS ;
–Headache
–Dizziness
–Insomnia
–Seizures
–Psychotic reactions
–Acute confusion state
Dr Ndayisaba Corneille

25. 3. Hypersensitivity reactions like
–Skin rash
–Steven Johnson syndrome
–Liver damage /hepatitis
–Photosensitivity
Dr Ndayisaba Corneille

26. 4. MSS
–Damage growing cartilage leading to
irreversible arthropathy
–Tendinitis
–Tendon rupture in adults
–Myalgias & arthralgias
Dr Ndayisaba Corneille

27. CVS
–Heart problems /QT
cprolongation
Metabolic disorders
–Hypokalaemia
–Hyperglycemia in diabetics & hypoglycemia
in pts on oral hypoglycemic agents
Bcoz of this S/Es gatifloxacin was withdrawn
from sales in USA
Dr Ndayisaba Corneille

28. Other uncommon S/Es
–Blood disorders like eosinophilia ,neutropenia
,leucopenia, thrombocytopenia
–Vasculitis
–Hypotension
–Hepatitis with jaundice
–Anorexia
–Disturbances in vision & taste
Dr Ndayisaba Corneille

29. –Sleep disturbances
–Paraesthesias
–Anxiety & depression
Dr Ndayisaba Corneille

30. –Uncorrected hypokalemia
–Pts with h/o hypersensitivity to any
fluoroquinolone
–Inpregnancybcozitcrossesplacentaleading
toariskofabortions&birthdefects
–BFmothersbcozitcrossesblood-milkbarrier
leadingtoinfantmusculoskeletaldamage
Contraindications
Dr Ndayisaba Corneille

31. –Ptswithhxoftendondisordersdueto
quinoloneuse
–Relativelycontraindicatedinchildrendueto
riskofpermanentjointdamage(arthropathy)
–Ptswithepilepsyorotherseizuredisorders
–Pts with severe heart problems /known QT
c
interval prolongation
Dr Ndayisaba Corneille

32. END
BY
DR NDAYISABA CORNEILLE
MBChB,DCM,BCSIT,CCNA,Cyber Security
contact: [email protected] , [email protected]
whatsaps:[phone] /[phone]
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