chemotherapy...my notes & lippincott

1. Paul ehrlich??????

2. MIC
 MBC is the lowest concentration of antibiotic that
kills 99.9 percent of bacteria
Superinfection
 Tetracycline>chloramphenicol>ampicillin>amoxy
cillin

3. Classification
 Broad spectrum
tetracycline
chloramphenicol
• Narrow spectrum
pencillin
streptomycin
erythromycin

4. Based on source
 Fungi
eg: pencillin ,cephalosporin, griesofulvin,streptomycin
 Bacteria
eg:polymyxin B,collistin,bacitracin,tryothrin
 Actinomyces
eg:aminoglycosides,macrolides,tetracycline,chloramp
henicol,

5. Mode of action
 Bacteriostatic
eg:sulphonamides,tetracycline, chloramphenicol,etha
mbutol,erythromycin
 Bacteriocidal
eg:clotrimoxazole,ciprofloxacin,pencillin,cephalospori
n,aminoglycoside,rifampicin,vancomycin

6. Mechanisms of action of
antimicrobial agents
 1. Inhibition of cell wall
 1.Penicillins, cephalosporins, bac






synthesis :
2. leakage of the cytoplasmic
membrane :
3. Inhibition of protein synthesis
&impairment of function of
ribosomes
4. Interference in
transcription/translation of
genetic:
5. Antimetabolite actions :
6. Binding to viral enzymes
essential for DNA synthesis
itracin,vancomycin,cycloserine




2.Polymixin, collistin, polyene, a
ntifungal antibiotics
3.Aminoglycosides,tetracycline,
chloramphenicol,Macrolide
antibiotics, and clindamycin
4.Quinolones, metronidazole
5.Sulfonamides, trimethoprim
6.Vidarabine and acyclovir

7. Superinfection
 New infection occurring during antimicrobial treatment
for another infection.
 Assoc c broad /extended spectrum antibiotics such as
tetracycline ,chloramphenicol,ampicillin ,newer
cephalosporins
 Eg:
1. Pt on CS therapy
2. AIDS pt
3. SLE & DLE
4. Leukemia & other malignancies
5. Autoimmune disorders (MM,MG)
6. Diabetes

8. Eg:
 Clostridium difficile treatment result in





pseduomembraneous colitis due to treatment with
clotrimoxazole,clindamycin,ampicillin,aminoglycoside
,tetracycline.
Resistant Staph enteritis due to treatment c cloxacillin
& its congeners.
Candida albicans result in oral thrush.
Pseudomonas
Proteus treatment result in UTI
Diarrhoea due to treatment c tetracycline

9. Combined use of drugs





To prevent drug resistance
To obtain synergism
To dec adverse effects
To broaden spectrum of activity
Eg:
1.2 static drusgs combined – additive effect
sulfamethoxazole+trimethoprim=clotrimoxazole
(septran)
2.2 cidal drugs combined – additive only if bact sensitive to both
3.Cidal + static =??
If bact sensitive to static drug =synergism
If bact sensitive to cidal drug =antagonism

10. Adverse effects
 Local toxicity – thrombophebitis
 Systemic –c high therapeutic index
eg:eythromycin,pencillin,cephalosporin
-c low therapeutic index (not safe)
eg: aminoglycoside,tetracycline,
chloramphenicol
- c very low
eg: polymyxin,vancomycin,amphotericin B
Hypersensitivity reaxn-pen,ceph,sterp

11. Qn
 Which one of the following patients is least likely to
require antimicrobial treatment tailored to the
individual’s condition?
A. Patient undergoing cancer chemotherapy.
B. Patient with kidney disease.
C. Elderly patient.
D. Patient with hypertension.
E. Patient with liver disease.

12. Qn
 In which one of the following clinical situations is the
prophylactic use of antibiotics not warranted?
A. Prevention of meningitis among individuals in close
contact with infected patients.
B. Patient with a hip prosthesis who is having a tooth
removed.
C. Presurgical treatment for implantation of a hip
prosthesis.
D. Patient who complains of frequent respiratory illness.
E. Presurgical treatment in gastrointestinal procedures.

13. Qn
 Which one of the following is the best route of
administration and dosing schedule for treatment with
aminoglycosides based on the drug’s
concentrationdependent killing property?
A. Oral every 8 hours.
B. Oral every 24 hours.
C. Parenterally by continuous intravenous infusion.
D. Parenterally every 8 hours.
E. Parenterally every 24 hours.

14. Qn
 A 57-year-old man complains of
fever, headache,confusion, aversion to light, and neck
rigidity. A presumptive diagnosis of bacterial meningitis is
made.Antimicrobial therapy should be initiated after
which one of the following occurrences?
A. Fever is reduced with antipyretic drugs.
B. Sample of blood and cerebrospinal fluid have been taken.
C. A Gram stain has been performed.
D. The results of antibacterial drug susceptibilitytests are
available.
E. Infecting organism(s) have been identified by the
microbiology laboratory

15. Sulfonamides
 First antibiotic to treat pyogenic infections .These agents are bacteristatic; and
get inactivated by presence of pus. Also called sulfa drugs.
Classification
1.Short Acting Sulfonamide:4-6hr
a. Sulfadiazine /orally given
b.Sulfisoxazole
2.Intermediate Acting Sulfonamide:8-12hr
a. Sulfamethoxazole
3.Long Acting Sulfonamide:7 days
a. Sulfadoxine
4. Special sulfonamides
for local application:
a. Mafenide-used in burns
b. Silver sulfadiazine –used in burns
c. Sulacetamide- ophthalmic use
for GIT disturbance:
a. Phthalyl sulfathiazole
b. Sulfasalazine-antidiarrhoeal/poorly absorbed from gut

16. uses
 Used rarely alone ;in combi c trimethprim
P.carnii,granuloma ingunale,chancroid
(STD)Earlier used in treatment of typhoid.
 Ocular sulfacetamide sodium –bact ocular infn
inclding chlamydia
 Sulfamethopyrazine&Sulfadoxine used c
pyrimethamine for chloroquine intolerant malaria.

17. MOA
Folic acid is donor for DNA synthesis,This reaction takes place in
bacteria & humans
 PABA
inhibitFolate synthetase (blocked by
sulfamethazole)
 DHFA
Folate reducatse (blocked by trimethoprim)
 THFA

18. Adverse reactions
1.Urinary Tract Disturbances
 Sulfonamides may precipitate in urine producing crystalluria, hematuria or
even obstruction.(acetylated metabolites )/mcq
Crystalluria is treated by administration of sodium bicarbonate to alkalinize the
urine.
2. Hematopoietic Disturbances
 Sulfonamides can cause hemolytic or aplastic anemia (Blood dyscrasias).
 May provoke hemolytic reactions in patients whose red cells are deficient in
glucose-6-phosphate dehydrogenase/mcq
3.Hepatitis
4.Contact dematitis
5.Bm toxicity in elderly pt
6.Kernicterus in newborns. (trimethoprim)displace bilirubin from protein
binding,free bilirubin deposit in basal ganglia & thalamus /mcq

19. uses
 Nocardial infection
 Leprosy ,dapsone ( sulfone)
 Toxoplasmosis /Sulfadiazine
 Ulcerative colitis/Sulfasalazine

20. Fluoroquinolones
 Naladixic acid is the predecessor to all
fluoroquinolones.
 fluorinated quinolones (FQs) represent a major
therapeutic advance:
 Quinolones are rapidly bactericidal drugs
«Broad spectrum of activity
«Improved PK properties – excellent
bioavailability, tissue penetration, prolonged half-lives
«Overall safety
 Disadvantages: resistance, expensive

21. Classification

22. MOA
 Inhibiting bacterial topoisomerase (DNA gyrase) and
topoisomerase IV, block bacterial DNA synthesis and
put bacteria to death.

23. Mechanisms of Resistance
 Altered target sites – chromosomal mutations in genes
that code for DNA gyrase or topoisomerase IV
«most important and most common
 Altered cell wall permeability –decreased porin
expression
 Expression of active efflux – transfers FQs out of cell
 Cross-resistance occurs between FQs

24. Pharmacokinetics
 Ofloxacin, enoxacin and lomefloxacin are almost
completely absorbed orally; norfloxacin is 35-45%;
ciprofloxacin is 67% orally absorbed.
 The FQs are widely distributed in body fluids and
tissues , The concentrations in
prostate,kidney, neutrophils, and macrophages exceed
serum concentrations, but in the cerebrospinal fluid
are low.
 Most FQs are elimiated by renal mechanisms;therefore
the dosage must be adjusted according to renal fn

25.  Norfloxacin is the least active of FQs against both gram-





negative and gram-positive organisms.
Ciprofloxacin is the most active agent against gramnegatives, P.aeruginosa in particular.
Levofloxacin, the L-isomer of ofloxacin and twice as
potent, has superior activity against gram-positive
organisms, including S. pneumoniae.
Methicillin-susceptible strains of S. aureus are generally
susceptible to FQs, but methicillin-resistant strains of
staphylococci are often resistant.
Pneumococci and streptococci of group are resistant to
enoxacin.
In general, Penicillins and cephalosporins are more active
than FQs against streptococci and staphylococci

26. USES
 Urinary tract infections:FQs are effective for





uncomplicated and complicated UTI even when caused by
multidrug-resistant bacteria.
Ciprofloxacin and ofloxacin are effective forgonococcal
infection;
Ofloxacin is effective for chlamydial urethritis or cervicitis.
Intestinal tract infections:
effective for intraabdominal infections and bacterial
diarrhea caused by shigella, salmonella, E. coli, or
campylobacter.
prostatitis

27. USES
 Respiratory tract infections:Not been routinely
recommended for treatment of pneumonia and other
upper respiratory tract infections.These
infections, predominantly caused by pneumococci and
streptococci, are usually well treated with betalactams or
macrolides.
 However, levofloxacin, sparfloxacin, and newer FQs with
enhanced G+ activity and activity against
atypicalpneumonia pathogens (e.g.
chlamydia, mycoplasma, and legionella) are likely to be
effective and used increasingly for treatment of upper and
lower respiratory tract infections

28.  Infections of the bones, joints, skin and soft
tissues:Including those caused by multidrug-resistant
organisms such as pseudomonas and enterobacter.
 6. Others: Ciprofloxacin or ofloxacin is occasionally
used for treatment of tuberculosis and atypical
mycobacterial infections.
 Ciprofloxacin is also a second-line agent for
legionellosis.

29. Adverse effects
 1.Gastrointestinal upsets (the most
 common)Nausea, vomiting, diarrhea, dyspepsia
2.Allergy and anaphylaxis
3.Central Nervous System (1~7%)
 Headache, agitation, insomnia, dizziness, rarely,
 hallucinations and seizures (rarely)
4.Possibly damage to growing cartilage: NOT recommended
for patients younger than 14 years old, pregnant or nursing
women.
5.Concomitant administration of theophylline and
quinolones can lead to elevated levels of theophylline with
the risk of toxic effect, especially seizure.

30. Qn
 A 30-year-old male is diagnosed to be human
immunodeficiency virus (HIV) positive. His CD4+ count is
200 cells/mm3 and his viral load is 10,000 copies/mL. In
addition to receiving antiviral therapy, which of the
following is indicated to protect him against pneumonia
due to Pneumocystis jiroveci?
A. Trimethoprim.
B. Ciprofloxacin.
C. Cotrimoxazole.
D. Clindamycin.
E. Sulfamethoxazole.

31. Qn
 A 26-year-old young man presents with the symptoms
of gonorrhea. Because this condition is often
associated with an infection due to Chlamydia
trachomatis,which of the following quinolones would
be the best choice for treating him?
A. Ciprofloxacin.
B. Nalidixic acid.
C. Norfloxacin.
D. Levofloxacin.
E. Moxifloxacin.

32. Qn
 In which one of the following infections is
ciprofloxacin ineffective?
A. Urinary tract infections due to a β-lactamase
producing strain of Klebsiella.
B. Pneumonia due to Streptococcus pneumoniae.
C. Exacerbation of chronic bronchitis due to Moraxella
catarrhalis.
D. Urinary tract infection due to Escherichia coli.
E. Urinary tract infection due to Pseudomonas
aeruginosa.

33. Qn
Sulfonamides increase the risk of neonatal
kernicterus,because they:
A. Diminish the production of plasma albumin.
B. Increase the turnover of red blood cells.
C. Inhibit the metabolism of bilirubin.
D. Compete for bilirubin-binding sites on plasma
albumin.
E. Depress the bone marrow.

34. β Lactum antibiotics
Classification
1.Natural –pencillin G/benzathine (longest duration of action)
2.Semisynthetic pencillin
a) acid resistant –phenoxy methyl penicillin(pencillin V)
phenoxy ethyl penicillin
b)pencillinase resistant – methicillin (not acid resistant)
DOC in staphy infn
Cloxacillin, oral(acid resistant)
c)Extended spectrum-amino -ampicillin,amoxycillin
carboxy -carbenicillin,ticarcillin
ureido -mezlocillin,azlocillin,piperacillin
3.β lactamase inhibitors-clavulenic acid ,sulbactum

35. Pencillin G or benzyl pencillin









Bactericidal
Mold Penicillium chrysogenum.
Narrow spectrum
Acid labile
Food interfere c absorbtion,get destroyed by gastric acid
,oral route not given
IV/IM given
Anaphylaxsis seen SCRATCH test
Jarisch – Hexeimer reaction – seen in syphilis
pt,spirochetes release lytic products react c pencillin
Fever ,myalgia,rashes,angioedema noted

36. Routes/mcq
 Type of pencillin
 Routes
Procaine pencillin
2. Benzathine pencillin
3. Crystalline pencillin
4. Pencillin V
 Deep im
1.
 Deep im
 Im/iv
 oral

37. uses
Gram +ve cocci
 Streptococcus pneumoniae*
 Streptococcus pyogenes
 Streptococcus viridans group/SABE
Gram+bacilli
 Bacillus anthracis
 Corynebacterium diphtheriae
Gram –ve cocci
 Neisseria gonorrhoeae
 Neisseria meningitidis
Anaerobic
 Clostridium perfringens/gas gangene
Spirochetes
 Treponema pallidum (syphilis)
 Treponema pertenue (yaws

38. Ampicillin
 Prodrug is becampicillian ,well absorbed orally
 Act by inhibiting transpeptidase ..(mcq)
 Incomplete oral absorbtion, food interferes; so interfere c




metabolism of other drugs
eg:OCpills,Hydrocortisone & pencillin not mixed in same
syringe as hydrocortisone inhibit action of pencillin,
allupurinol INC rashes by ampicillin,
prebenecin retards excretion by competing cfor tubular
secretion
Superinfection common,frequent diarrhoea after oral.

39. Amoxycillin
 Lesser incidence of skin rashes & diarrhoea
compared to ampicillin
Pencillin DOC in
1. Syphilis
2. Gonorrhoea
3. Actinomycosis
4. St infn
5. Abscess
6. cellulitis

40. β lactamase inhibitor
Clavulenic acid
 Progressive inhibitor
 After binding to βlactamase get inactivated called
SUICIDE inhibitor
 Combi c amoxycillin called coamoxiclav
Sulbactum
 Progressive, after binding to βlactamase get
inactivated.
 Combi c ampicillian called Sulficillin

42. Generation Effective against Ineffective
against
Examples
1
Gram +ve
PEcK-Proteus,E
coli,Klebsiella
Cefadroxil.
Cephalexin.
Cephalothin
Cefazolin.
2
Gram +ve & -ve
Pseudomonas Cefaclor,Cefoxitin,Cefprozil,
HEN PEcKS
Cefuroxime
H influenza
,Enterobacter
aerogenes,Neisser
ia ,Serratia
marcescens
3.
Broad gram –ve
&Some gram +ve
4
Similar to gen 3
MRS
but more effective
Gram -ve
Gram +cocci
Cefdinir,Cefixime,Cefpodoxime.
Ceftibuten,Ceftriaxone,Cefotaxime.
Cefepime,cefipirome

43.  Cephalosporium C
 same mode of action as penicillins
 tend to be more resistant than the penicillins to
certain β-lactamases.
 Addition of side chain to position 7 of βlactum ring
alter spectrum of activity
 Addition of side chain to position 3 of dihydrothiazine
ring alter pharmacokinetics

44. Adverse effects
 Diarrhoea & maculopapular rash-most common
 Nephrotoxicity (highest c Cephaloridine)
 Bleeding due to hypoprothrombinaemia (seen in
Cefoperaozone,Ceftriazone)
 Neutropenia& thrombocytopenia –Ceftazimide
 Disulfiram like reaction c alcohol–
Cefoperazone,cefotetan

45. Other βlactamases
 Carabapenems
 Monobactum

46. Carbapenem
 Carbapenems are synthetic β-lactam antibiotics that
differ in structure from the penicillins
 Broad spectrum activity
 Used in combi c Cilastatin , which prevents its rapid
hydrlysis at renal tubular cells

47. Monobactum
 Azotreonam- βlactam in which other ring s missing
 lacks cross sensitivity so promising in pt c pencillin
allergy

48. Qn
 An elderly diabetic patient is admitted to the hospital with
pneumonia. The sputum culture stains for a gram-negative
rod. The patient is started on IV ampicillin.Two days
later, the patient is not improving, and the microbiology
laboratory reports the organism to be a β-lactamase
producing H. influenzae.
What course of treatment is indicated?
A. Continue with the IV ampicillin.
B. Switch to IV cefotaxime.
C. Switch to oral vancomycin.
D. Add gentamicin to the ampicillin therapy

49. Qn
A 70-year-old alcoholic male with poor dental hygiene is to
have his remaining teeth extracted for subsequent
dentures. He has mitral valve stenosis with mild cardiac
insufficiency and is being treatedwith
captopril, digoxin, and furosemide. The dentist decides
that his medical history warrants prophylactic antibiotic
therapy prior to the procedure and prescribes which of the
following drugs?
A. Vancomycin.
B. Amoxicillin.
C. Tetracycline.
D. Cotrimoxazole.
E. Imipenem.

50. Qn
A patient with degenerative joint disease is to undergo
insertion of a hip prosthesis. To avoid complications due to
postoperative infection, the surgeon will pretreat this
patient with an antibiotic. This hospital has a significant
problem with MRSA. Which of the following antibiotics
should the surgeon select?
A. Ampicillin.
B. Imipenem/cilastatin.
C. Gentamicin/piperacillin.
D. Vancomycin.
E. Cefazolin.

51. Qn
 A 25-year-old male returns home from a holiday in the
Far East and complains of 3 days of dysuria and a
purulent urethral discharge. You diagnose this to be a
case of gonorrhea. Which of the following is
appropriate treatment?
A. Ceftriaxone IM.
B. Penicillin G IM.
C. Gentamicin IM.
D. Piperacillin/tazobactam IV.
E. Vancomycin IV.

52. Broad spectrum
TETRACYCLINE
Bacteriostatic
Classification
Group1-chlortetracycline ,oxytetracycline,tetracycline
Group2-Demeclocycline,Lymecycline
Group3-Doxycycline,Methocycline
Gp1&2 not absorbed orally(1/2-2hrbefore food) ,food
interferesbut gp3 are well absorbed orally & widely
distributed

53.  MOA-act by inhibiting protein synthesis by binding to 30S







ribosome
Absorbed better in empty stomach
Conc in liver spleen & bind to CT including bone
Intracellularly bind to mitochondria
Primarily excreted in urine( dose reduced in renal disease
except doxycycline )
Form insoluble complex c milk ,metal ion ,antacid , fe
prepn & cause toxicity forming CHELATE
Minocycline conc in fat
CI in pregnant & lactating mother.sec in breast milk

54. Adverse effects
 Esophageal ulceration if material from doxycycline is






released in esophagus
Liver damage –acute hepatic necrosis in pregnant
Renal failure/FANCONI’s SYNDROME –produced by use
of oudated tetracycline resulting renal tubular necrosis;
acidosis result so bicarbonate given to neutralize it.
Phototoxicity/highest c demeclo&doxycycline
Vestibular toxicity – minocycline(ataxia,vertigo,nystgmus)
Superinfection – pseudomembraneous colitis
Brownish dicolouration of teeth- if midpregn&5mt EU
cycle,3 mo – 5 yr affect premanent ant teeth,late pregnancy
& childhood –supress bone growh

55.  Conc in gingival crevice 2-10 times that in serum,widely
used in treatment of periodontal disease
 It potentiates anticoagulant action of coumarin drugs
 Avoided in infants & children upto 12 yr of age
Dose
tetracycline-250 mg qid
Minocycline-100 mg bid
Doxycycline -100mg od
Local drug delivery in PD pocket
Eg:ACTISITE-25%tetracycline
ATRIDOX-10%doxycycline

56. Uses
 first choice of drug in LGV,
 Granuloma ingunale,
 cholera,
 PLAQUE,
 atypical pneumonia,
 rickketssial infn-Q fever/rocky mountain spotted
fever,
 brucellsis

57. Chloramphenicol
 Obtained from st venezulae
 Act by binding to 50s ribosome
 Broad spectrum & bacteriostatic
 Most common cause of BM depression causing aplastic
anemia,agranulocytosis,thrombocytopenia
 GRAY BABY SYNDROME-when given to neonates esp
premature infants .
 Metabolised by glucoronide conjugation ;def results

59.  Pneumonic tularemia results from infection by the





respiratory route or by bacteremic seeding of lungs.
Gentamicin is effective in treating this rare lymphoid
disease
Not ototoxic –netilmycin
used as anti TB drug???
Topical ???neo/gentamycin
Most resistant to bact inactivating enzymeAMIKACIN

60. Macrolides
 Macrolides are a class of antibiotics, the basis of the
chemical structure of which is macrocyclic lactone
ring
 Depending on the number of carbon atoms in the ring
14-membered
(erythromycin,roxithromycin,clarithromycin)
15-membered (azithromycin)
16-membered (midecamycin, spiramycin, josamycin).
Mechanism of action
 Inhibit protein synthesis by binding to the 50 s subunit

61. Pharmacokinetics
 Low conc bacteriostatic,high concentration




bactericidal
Absorption incomplete but adequate from intestine
Inactivated by gastric HCL, hence given as :
Enteric coated tablets or ester (stearate, ethyl succinate )
Food delays absorption
Not metabolized and actively secreted in bile ( major
route of excretion
Widely distributed into most tissues, except the brain and
CSF ; Cross the placental barrier

62. Indications
 Narrow antibacterial spectrum
 Used as alternative to pencillin/allergic pts
(Staph.Aureus,S. pyogens, S.pneumoniae,T.pallidum)
 Diphtheria & whooping cough – drug of choice

Legionnaires disease- drug of choice
 Pneumoniae ( M. pneumoniae ) – children

Chlamydia trachomatis

63. Azithromycin
 Extended spectrum
 Acid stable
 Rapid oral absorbtion
 Marked tissue distribution
 Intracellular penetration
Advantage over erythromycin & clarithromycin
Once daily dosing
No inhibition of cytochrome P- 450

64. Clindamycin
 Major problem –pseudomembraneous /c.difficle
 Drug for treatment –metronidazole or vancomycin

65. Antitubercular drugs

66.  Drugs Used in Tuberculosis
First-line drugs :
1. Rifampin,
2. Isoniazid (INH),
3. Pyrazinamide,
4. Ethambutol, and
5. Streptomycin
Mnemonics  RIPES

67. drug
Action
adverse effect
INH
CIDAL
Peripheral neuritis
Hepatotoxicity
Neurotoxicity
Rifampicin
CIDAL
Hepatotoxicity
Imparts orange colour to urine,tears
Inc hepatic microsomal enzyme causing INC
metabolism of drugs
Streptomycin
CIDAL
Neurotoxicity
Ototoxicity
Ethambutal
STATIC
Optic neuritis
Peripheral neuritis
Pyrazinamide
CIDAL
HYPERURICEMIA

69. Leprosy
. DAPSONE & OTHER SULFONES:
 used effectively in the long-term treatment of leprosy.
Mechanism of action :
 Dapsone like the sulfonamides, inhibits folate
synthesis (PABA antagonist).
 bacteriostatic
Clinical uses :
1.
2.
Tuberculoid leprosy: with rifampin
Lempromatous leprosy: with rifampin and clofazimine

70. Qn
 Desfuroxamide???????
 Granestron????