This document discusses sulfonamide antibiotics. It provides information on different types of sulfonamides including short, intermediate and long acting agents. It describes their mechanisms of action, antimicrobial spectrum, pharmacokinetics, uses, and side effects. It also discusses fixed dose combinations like cotrimoxazole and its uses for various infections.

1. Dr Chintan Doshi

3.  Sulfonamide: Sulfone + amide
Sulfanilamide [p-aminobenzene sulfonamide]

4. • Sulfadiazine
• Sulfisoxazole (Sulfafurazole)
Short acting
(4-8 hrs)
• Sulfamethoxazole
Intermediate acting
(8-12 hrs)
• Sulfadoxine
• Sulfamethopyrazine
Long acting
(7-8 days)
• Sulfacetamide sodium, Mafenide
• Silver sulfadiazine, Sulfasalazine
Special purpose
sulfonamides

5. Dihydropteroic acid synthetase
Glutamate
Dihydrofolate reductase
Sulfonamide
Trimethoprim
=
=

6.  Bacteriostatic action evidence by:
• PABA antagonizes action of sulfonamides
• Only those microbes which synthesize their own folic
acid are susceptible to sulfonamide
 Human cells directly absorb preformed folic acid,
supplied in diet & not affected by sulfonamides.

7.  Microorganisms that susceptible to sulfonamide:
 Staph. aureus, gonococci, meningococci, E. coli,
Shigella respond, but majority are resistant.
 Anaerobic bacteria not inhibited
Streptococcus pneumoniae
Streptococcus pyogenes
Haemophilus influenzae
Nocardia
Actinomyces
Chlamydia trachomatis

8. • Rapidly absorbed in GIT, reach maximum concentration
within 4-6 hrs
• Widely distributed in body – cross placenta & Blood
brain barrier
• Metabolized in liver by acetylation
• Excreted by kidney through glomerular filtration
(metabolites insoluble in acidic urine - crystalluria)

9. • High plasma protein binding & slow excretion
• Ultra long acting agents (half life → 7-9 days)
• Not suitable for acute pyogenic infection
• Use: in combination with pyrimethamine for treatment of
:malaria
: Pneumocystis jiroveci pneumonia in AIDS patients
: Toxoplasmosis
Sulfadoxine Sulfamethopyrazine

10. • Highly soluble
• Only mild irritating to eye in concentration up to 30%
• Topical - high concentration in anterior segment & aqueous
humour
• Use: ocular infection due to susceptible bacteria & chlamydia
: ophthalmia neonatorum by Ch. oculogenitalis
• S/E: Sensitivity reaction (incidence low but when occur stop drug)
Sulfacetamide sodium

11. • Topically (1% cream)
• Inhibit gram –ve & gram +ve bacteria, against pseudomonas, clostridia
• Active in presence of pus
• Use: burn dressing to prevent infection (not treat already infected case)
• S/E: burning sensation & severe pain on raw surface
: acidosis & hyperventilation
: allergic reaction
• Active against bacteria & fungi, even though resist to other
sulfonamide like pseudomonas
• Slowly release silver ions
• Use: prevent infection of burn surface & chronic ulcers(1% cream)
• S/E: burning sensation & itch
Mafenide
Silver sulfadiazine

12. • Degraded by bacterial flora of colon
Sulfasalazine
5-ASA Sulfapyridine
(5-aminosalicylic acid) ↓
↓ carrier for 5-ASA
antiinflammatory
 USE: Ulcerative colitis & Rheumatoid arthritis
 Dose: 3-4 gm/day (oral)
Sulfasalazine

13. • nausea, vomiting, epigastric pain
• jaundice, hepatic dysfunction, necrosis of liver
• Acetylated metabolites less soluble in acidic urine &
get precipitated in kidney
• Minimized by→ adequate intake of water
→ alkalization of urine(↑ excretion)
GI side effects
Crystalluria & Renal toxicity

14. • 2-5% & after a week of
therapy
• rash, urticaria, drug fever,
Photosensitization
• Serious reaction like
stevens jhonson
syndrome, exfoliative
dermatitis (with long
acting agents)
Hypersensitivity reactions

15. displace bilirubin from protein binding site
↓
free bilirubin pass through BBB
↓
deposited in basal ganglia & subthalamic nuclei
↓
kernicterus (encephalopathy)
 Avoid in neonates & pregnancy
• Acute haemolytic anaemia:
Rare but develop in G6PD deficient patients
• Agranulocytosis & aplastic anaemia extremely rare
Effect on haematopoietic system
Kernicterus in neonates

16. 1) Cotrimoxazole
2) Cotrimazine
3) Sulfadoxine + Pyrimethamine

17. Fixed Dose Combination
Cotrimoxazole
Sulfamethoxazole + Trimethoprim

18. • Diaminopyrimidine related to pyrimethamine
• Selectively inhibit DHFRase (dihydrofolate reductase)
• >1,00,000 times more active against bacterial DHFRase

19. • Same half life (10 hrs)
• Optimal synergy at concentration ratio :
sulfamethoxazole 20 : Trimethoprim 1
• Trimethoprim enters many tissue, ratio obtained in plasma
↓
• Trimethoprim → cross placenta & BBB
→ rapidly absorbed
• Trimethoprim 40% plasma protein bound while Sulfamethoxazole
65% bound
dose ratio 5:1

20.  Additional organism:
 Sulfonamide resistant strain:
 Not against: Pseudomonas, B. fragilis, enterococci
Salmonella typhi
Serratia
Klebsiella
Yersinia enterocolitica
Pneumocystis jiroveci
Staphylococcus aureus
Streptococcus pyogenes
Haemophilus influenzae
E. Coli
Gonococci
meningococci

21. • Sequential blockade, supra additive effect

22. • Individually bacteriostatic, but combination
bacteriocidal
• Reduced development of resistance
• Wide spectrum
• Safe & well tolerated
• Cost effective

23. Trimethoprim (mg) Sulfamethoxazole (mg)
Tablet 80 400
Double strength 160 800
Pediatric tablet 20 100
IV injection/5 ml 80 400

24. Urinary tract infections:
• Acute & uncomplicated cases respond rapidly
• DS tablets BD for 5-10 days
• Acute cystitis – 4 tab of DS formulation (single dose)
Prostitis:
• Acute – one DS tab daily for 3 weeks
• Chronic: 6-12 weeks
 Nocardiosis:
• Drug of choice for pulmonary lesion & abscess

25. Respiratory tract infections:
• Bronchitis, facio maxillary infections, otitis media by
Pneumococcus & H. influenza
• Dose: One DS tab BD
Sexually transmitted diseases:
• 3rd choice drug for Chancroid- 1 DS tab BD for 7-10 days
• also used for Urethritis, lymphogranuloma, gonorrhoea
Pneumonia:
• Pneumocystis jiroveci – in neutropenic & AIDS patient

27. Bacterial diarrhoea & Dysentery:
• Acute gastroenteritis by Shigella & Yersinia enterocolitica,
Traveler’s diarrhoea due to E. coli & Cholera by V. cholera
• Alternative to fluoroquinolones
As alternative drug:
• Typhoid – 1 DS tab BD for 2 weeks
 Intravenous cotrimoxazole – severe infection
 Dose: 80mg Trimethoprim + 400mg sulfamethoxazole
↓
diluted in 125 ml of 5% dextrose(i.v. infusion over 60-90min)

28. • Nausea, vomiting, stomatitis, headache
• Fever, rash, bone marrow hypoplasia (up to 50%)
• Megaloblastic anaemia
• Uremia
• Bone marrow toxicity – elderly
• Blood dyscrasias – rarely

30. • Synthetic AMA having quinolone structure
• Against gram –ve bacteria
• New flourinated compound → (-) gram +ve bacteria
• Mid 1960 – Nalidixic acid
- limited use UTI & GIT infection
• Early 1980 – Fluoroquinolones
• fluorination of quinolone structure at position of 6 and
introduction of piperazine substitution at position 7

31. Nalidixic acid
 Active against:
• Gram –ve bacteria – E.coli, Proteus, Klebsiella, Shigella,
but not Pseudomonas
 Mechanism of action:
• Bactericidal
• Inhibit DNA gyrase
Pharmacokinetic:
• Absorbed orally
• High plasma protein binding & metabolized in liver
• Plasma half life 8 hrs
• Excreted in urine

32.  Adverse effects:
• GI upset & rashes
• Neurological toxicity – headache, drowsiness, vertigo, visual
disturbance, seizure
• Phototoxicity rare
• Haemolysis in G6 PD deficient pt
 Uses:
• As urinary antiseptic
• Diarrhoea
 Dose:
• 0.5-1 gm TDS or QID

34. 1st generation
fluoroquinolones
• Norfloxacin
• Ciprofloxacin
• Ofloxacin
• Pefloxacin
2nd generation
fluoroquinolones
• Levofloxacin
• Lomefloxacin
• Sparfloxacin
• Moxifloxacin
• Gemifloxacin
• Prulifloxacin
• Trovafloxacin
• Alatrofloxacin
• Fleroxacin
1st generation : one flourine substitution
2nd generation: additional fluorine & other substitution
: extended activity to gram +ve cocci & anaerobes
: metabolic stability (long half life)

36.  There is necessary to prevent excessive positive super coiling of
DNA strand, when they separate for replication or transcription
DNA gyrase: in gram –ve bacteria
 FQs bind to A subunit with high affinity interfere with
its function
A subunit – nicking of DNA
B subunit – introduces negative supercoiling
A subunit – reseals the strands

38.  Topoisomerase IV: in gram +ve bacteria
• Nicks & separates daughter DNA strands
• FQs targets Topoisomearse IV with greater affinity & confer
potency against gram +ve bacteria
 Bactericidal action – digestion of DNA by exonuclease
 mammalian cells – topoisomerase II (remove +ve supercoiling)
• Low affinity for FQs → low toxicity to host cells

39. • Salmonella, Pseudomonas, Staphylococci, Gonococci, Pneumococci

40. • Bactericidal activity & high potency
• Long post antibiotic effect
• Low frequency of mutational resistance
• Low propensity to select plasmid type resistant mutant
• Protective intestinal streptococci & anaerobes are spared
• Active against many beta lactam & aminoglycoside resistant
bacteria
• Less active at acidic pH

41. Ciprofloxacin
• Prototype drug
• Most potent 1st generation FQ
• Aerobic gram –ve bacilli
 gram +ve bacteria inhibited at high concentration
 Resistant ones: Bacteroides fragilis, Clostridia,
anaerobic cocci
E. Coli
Klebseila
Salmonella typhi
Shigella
Proteus
N. Gonorrhoea
N. Meningitidis
H. influenzae
Campylobacter jejuni
V. cholerae

42. Pharmacokinetics:
• Rapidly absorbed orally, food delays absorption
• First pass metabolism
• Good tissue penetration- lung, sputum, muscle, prostate, phagocytes,
but low in CSF, bone & aqueous
• Excreted in urine except pefloxacin & moxifloxacin
Adverse effects: (10%)
o GIT: nausea, vomiting, bad taste, anorexia (diarrhoea infrequent)
o CNS: dizziness, headache, restlessness, anxiety, insomnia, impairment
of concentration (caution during driving)
o Skin: rash, pruritus, photosensitivity, urticaria, swelling of lips
o Tendinitis & tendon rupture: higher in those above 60 yr & receiving
steroids

43. Contraindication:
• Pregnancy & children
Interactions:
• ↑concentration of theophylline, caffeine, warfarin
by inhibiting metabolism
• NSAIDs enhance CNS toxicity of FQs
• Antacid, sucralfate, iron salt - ↓absorption of FQs

44. Uses:
 Urinary tract infections:
• High cure rates, even in complicated cases or those with
indwelling catheters/prostitis
• High success rates than cotrimoxazole
 Gonorrhoea:
• Single 500mg dose – 100% curative in non PPNG & PPNG
• Resistance – not 1st line drug
 Chancroid:
• Second line drug – 500mg BD for 3 days
• Alternative to ceftriaxone/ azithromycin

45.  Bacterial gastroenteritis:
• Currently most commonly used
• Reserved for sever cases due to E.choli, Shigella, Salmonella,
Camp. jejuni infection
• ↓ stool volume in cholera
 Bone, soft tissue & wound inection:
• Osteomyelitis & joint pain – prolong treatment with high dose
(750 mg BD for 6-8 weeks)
• Diabetic foot – with clindamycin / metronidazole (cover anaerobes)
 Tuberculosis:
• Second line drug against mutidrug resistant TB

46.  Typhoid:
• First choice of drug
• India – 95% S. typhi were sensitive
• Dose: 750 mg BD for 10 days
: unable to take orally – 200 mg i.v. 12 hrly
: 750 mg BD for 4-8 weeks for carriers
• Advantages: quick defervescene
: early abetment of symptoms
: prevention of carrier state
 Gram –ve septicemia:
• Parenteral ciprofloxacin combined with 3rd generation
cephalosporin or aminoglycoside

47.  Respiratory tract infections:
• Treat Mycoplasma, Legionella, H. influenza infection
• Low susceptibility for pneumococci, streptococci
• 2nd generation FQs – pneumonia & bronchitis
• US FDA approved for inhalational anthrax
 Meningitis:
• Gram –ve bacterial meningitis, specially in
immunocompromised patients or CSF shunt
 Prophylaxis:
• Infection in neutropenic / cancer patients
 Conjuctivitis:
• By gram –ve bacteria , topical therapy

48. Norfloxacin
• Less potent
• Gram +ve & pseudomonas not inhibited
• Low penetration in tissue – non therapeutic level
• Use: urinary & genital infections, bacterial diarrhoea
• Not use for respiratory or other systemic infection
• Dose: 400 mg BD
• methyl derivative of norfloxacin
• More lipid soluble & better penetration in tissue (also in CSF)
• Longer half life – cumulates on repeated dosing
• Use: preferred for meningitis & systemic infection
• Dose: oral - 400 mg BD; i.v. 400 mg
• Dose reduced in liver disease
Pefloxacin

49. Ofloxacin
• Less active against gram –ve bacteria
• Good activity against - gram +ve, anaerobes, chlamydia,
mycoplasma
• More lipid soluble
• Use: mutidrug resistant TB, multidrug therapy for leprosy
: chronic bronchitis & respi. infection, ENT infection
: gonorrhoea, urethritis
• Dose: oral - 200-400 mg BD; i.v. 200 mg

50. Levofloxacin
• Levo isomer of ofloxacin
• Strep. pneumococci & other Gram +ve, gram –ve & anaerobes
• Oral bioavailability 100%
• Single daily dose sufficient – slow elimination
• Theophylline, warfarin, cyclosporine, zidovudine P/K unchanged
during levofloxacin treatment
• Use: community acquired pneumonia
: exacerbation of chronic bronchitis
:sinusitis, pyelonephritis, prostitis, UTI, skin/soft tissue infection
• Dose: oral - 500mg OD, i.v. 500 mg/100ml inj

51. Lomefloxacin
• More active against some gram –ve bacteria, chlamydia
• Long half life – single daily dose
• S/E: phototoxicity, Q-T prolongation
• Dose: 400 mg OD
• Gram +ve, B. fragilis, anaerobes, mycobacteria
• Use: pneumonia
: exacerbation of chronic bronchitis
: sinusitis & other ENT infections
• S/E : phototoxicity, Q-T prolongation
• Dose: 200-400mg OD
 Both Withdrawn in USA available in india
Sparfloxacin

52. • High affinity for bacterial topoisomerase IV
• Used for gram +ve coccal (ENT & respiratory) infections
• S/E: QT prolongation, arrhythmia, phototoxicity,
unpredictable hypoglycemia
• Banned in India March 2011
• Long acting agent
• Gram +ve, beta lactam resistant, anaerobes
• Most potent FQs against M. tuberculosis
• Use: pneumonia, bronchitis, sinusitis, otitis media(not in UTI)
• not give to – predisposed to seizure, receiving pro arrhythmic
drugs; liver disease pt
• Dose: 400 mg OD
Gatifloxacin
Moxifloxacin

53. • Long acting agent
• Gram +ve, beta lactam resistant, anaerobes
• Use: life threatening infections
• S/E: hepatotoxicity
• Dose: 200 mg orally/i.v. OD
• Withdraw from European countries & USA
• Prodrug for Trovafloxacin
Trovafloxacin
Alatrofloxacin

54. • aerobic gram +ve, some anaerobes
• excreted in urine – dose need to be halved
if Cr clearance<40 ml/min
• Use: community acquired pneumonia, chronic bronchitis
• S/E: nausea, diarrhoea, headache, dizziness, skin rashes
: ↑ serum amino transferase & warfarin effect
: QT prolongation
• Dose: 320 mg OD for 5-7 days
Gemifloxacin

55. • Prodrug of ulifloxacin
• Both gram +ve & gram –ve bacteria
• Use: acute exacerbation of chronic bronchitis
: uncomplicated/complicated UTI
• S/E: same as ciprofloxacin, but NO QT prolongation
• Dose: 600mg OD single dose uncomplicated UTI
: up to 10 days for complicated UTI & bronchitis
Prulifloxacin

56. • Broad spectrum(gram –ve & gram +ve methicilin sensitive strain)
• Long acting agent
• Use: UTI, gonorrhoea, respi infection, skin & soft tissue infection,
enteritis
• S/E: GIT, CNS, skin
• Dose: 400 mg OD
Fleroxacin

57. • Under going phase III
• Activity markedly increases at acidic pH
• Very high safety profile
• Widest spectrum
• Long half life
• Clinical option for its trial – UTI, community acquired pneumonia,
bronchitis, COPD, intra abdominal & skin infection
Finafloxacin

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