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Pharmacology
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GELIANNE ALBA-LOQUEZ, RN 21
ANTI - BACTERIALS II

OUTLINE  1st gen: Norfloxacin

I. FLUOROQUINOLONES  derived from nalidixic acid
a. Classification  has an activity against common
pathogens that cause urinary tract
 1st Generation
infections
 2nd Generation  2nd gen: Ciprofloxacin and Ofloxacin
 3rd Generation  greater activity against gram-negative
b. Pharmacokinetics bacteria
c. Mechanism of action  Also active against: gonococcus, many
d. Resistance gram-positive cocci, myvobacteria,
atypical pneumonia
e. Clinical uses
 3rd gen: Levofloxacin, Gemifloxacin, and
f. Toxicity
Moxifloxacin
II. ANTI - METABOLITE  slightly less active against gram-
a. Sulfonamides negative bacteria (versus 2nd gen)
 Classification  greater activity against grem-positive
 Resistance cocci (S. pneumoniae, some strains of
 Clinical Uses enterococci, and MRSA)
 also known as respiratory
b. Trimethoprim
fluoroquinolones
 Classification and Pharmacokinetics note: you will no that they are part of
 Resistance fluoroquinolons because of the word flo present
 Clinical Uses om each names.
c. Toxicity of Sulfonamides and
Trimethoprim  PHARMACOKINETICS
 all generations have good oral bioavailability
 antacids may interfere
Note: before you administer fluoroquinolones
make sure that they are not also taking antacids
because those anticids would culture the
effectivity of the fluorquinolones
 penetrate most body tissues
 Elimination is through urinary excretion
 can be blocked by probenecid
Note: if you don't want to prolong the antibiotic
inside the patients body then make sure the pt. is
not taking probenecid cause that will block the
urinary excretion of your fluoroquinolones
 dosage production necessary in renal
failure because they are excreted
through the urine except moxifloxacin
which is excreted via biliary excretion.
FLUOROQUINOLONES  its use in urinary tract infection is
 CLASSIFICATION not recommended

 According to "generations"- based on their

antimicrobial spectrum of activity
 per generation it has different spectrum of
activity

BSN 2B TRANSCRIBED BY GROUP 3 1

 MECHANISM OF ACTION
 Interfere with bacterial DNA synthesis by
inhibiting these enzymes:
 Topoisomerase II (DNA gyrase) in gram
negative bacteria
 Topoisomerase IV in gram positive
bacteria
 Similar to aminoglycosides, they also exhibit
post-antibiotic effect
 bactericidal effect continues after drug
levels fall below minimum inhibitory
concentration
note: meaning kahit daw bumaba na sa minimum
inhibitory concentration ang gamot inside the
body of the patient then it will still exhibit
antibiotic effect
 RESISTANCE
 rapid emergence in the case of 2nd
generation fluoroquinolones, especially in:
 campylobacter jejuni
 Gonococci
 MRSA
 Pseudomonas spp
note: ito iyong mga bacteria that are mostly
resistant to your 2nd generation fluoroquinolones
 Bacteria are able to resist due to their ability
to:
 decrease intracellular accumulation of
the drug (by developing efflux pumps)
note: example a bacteria developing pumps to
push the drug outside or away resulting na konti
nalang ang drug na nasa loob ng bacteria. The
concentration of the drug is so small or low that
does not make any effect in the bacteria that is
why nagkakaroon ng resistance ang bacteria
 point mutations in binding regions of
the antibiotics
note: example if your drug is suppose to bind at a
certain receptor of a bacteria. Your bacteria
causes mutation or a change in those binding
sites therefore rendering the binding of the drug
ineffective. Hindi na nakakabind iyong gamot sa
kung saan siya dapat magbind kasi nagmutate or
nagchange na iyong binding site.
 CLINICAL USES
 Effective for treatment of infections in the:
 gastrointestinal tract
 urogenital tract
 Respiratory
 integumentary (and soft tissue)
 Ciprofloxacin and Ofloxacin Clinical Uses
 single oral doses for gonorrhea (as
alternatives to cetriaxone and cefixime)
 still not recommneded to increased
patterns of antimicrobial resistance
BSN 2B TRANSCRIBED BY GROUP 3
 Ofloxacin is possibly used for chlamydia
trachomatis (but requires 7-day course of
treatment)
 Levofloxacin is for community acquired
pneumonia
 Gemofloxacin and Moxifloxacin
 have widest spectrum of activity against:
 gram positive and gram negative
microbes
 Atypical pneumonia agents
 some anaerobic bacteria
 Fluoroquinolones may also be used in cases
of:
 meningicoccal carrier state (carriers
might not exhibit symptoms for
meningicoccal)
 Pulmonary tuberculosis
 Neutropenic patients (prophylaxis)
 TOXICITY
 Gastrointestinal distress mosy common
adverse effect
 Others: rash, headache, abnormal liver
function tests, ptototoxicty, tendinitis, and
tendon rupture
 not recommended for children and the
pregnant due to possible damage to
growing cartilage ( anthropathy)
 not recommended to pregnant women
kasi nagkakaproblema sa growth ng
bata or baby sa loob ng tiyan.
 Opportunistic infections by Candida albicans
and streptococci
 Can prolong QT interval: 3rd generation
fluoroquinolones
 not for patients on medications for
antiarrythmic medications
ANTI - METABOLITE
 Drug that is able to interfere wIth the role of an
endogenous compound in cellular metabolism
note: they interfere with the role of a specific enzyme
or compound that is important for the bacteria to
metabolize or to be able to undergo cellular
metabolism
 Examples are sulfonamides, Trimethoprim, TMP-
SMX
SULFONAMIDES
 weakly acidic compounds that have a common
chemical nucleus resemblung p-aminobezoic
acud (PABA)
note: PABA is important in folic acid synthesis. Folic
acid is very important in DNA and nucleic acid
development or synthesis of the bacteria. PABA is
important to the bacteria to be able to synthesize folic
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acid. Sulfonamides look like PABA, paginiinom ng tao
the drug will in way will trick the bacteria na PABA
iyan iyon pala sulfonamide siya so there is an
alteration of the folic acid synthesis which makes the
folic acid synthesis ineffective for the bacteria
 Members differ mainly in their pharmacokinetic
properties and uses
 modest tissue penetration, hepatic metabolism,
and renal excretion
 CLASSIFICATION:
 short acting (sulfisoxazole)
 Intermediate acting (sulfamethoxazole)
 Long acting (sulfadoxine)
 MECHANISM OF ACTION:
 bacteriostatic inhibitors of folic acid
synthesis
 competitive inhibitors of dihydropteroate
synthase (also acts as subtrates which
produces non functioning forms of folic acid)
note: dihydropteroate synthase triggers your
PABA or lets PABA work so that there will be folic
acid synthesis then sulfonamides targets
dihydropteroate synthase so that there is an
interference in the synthesis of folic acid. So ang
nangyayari when sulfonamides come in there will
be production of non functioning form of folic
acid making the folic acid synthesize by the
bacteria ineffective
 RESISTANCE:
 plasmid-mediated (overproduction of PABA,
folic acid synthesizing enzyme woth low
affinity for sulfonamides, impair
permeability to sulfonamide)
note: di na nagiging effective si sulfonamide kasi
na over power na ng PABA
 decreased intracellular accumulation of the
drug
note: low concentration of drug in the bacteria
for it to take its effect.
 CLINICAL USES:
 Simple UTI (oral; sulfisoxazole)
 Ocular infections (topical; sulfacetamide)
 Burns (topical; silver sukfadiazine, mafenide)
 Ulcerative colitis (oral; sulfasalazine)
 Toxoplasmosis (oral; sulfadiazine)
TRIMETHOPRIM
 CLASSIFICATION AND PHARMACOKINETICS:
 structurally similar to folic acid
 weak acid
BSN 2B TRANSCRIBED BY GROUP 3
 reaches high concentrations in prostatic and
vaginal fluids
 large percentage is excreted unchanged in
the urine
 selective inhibitor of bacterial diydrofolate
reductase (prevents formation of active form
of folic acid)
 bacterial dihydrofolate reductase is 4-5
times more sensitive than the
mammalian version of the enzyme
note: your trimetophrim can easily inhibit
bacterial dihydrofolate reductase because it
is 4-5 times more sensitive than the
mammalian version
 RESISTANCE
 production of dihydrofolate reductase (but
with reduced affinity for the drug)
 note that this is the exact same enzyme
which is targeted by trimethoprim
Note: bacteria is able to produce dihydrofolate
enzyme but not that much affected by the
trimethoprim drug
 CLINICAL USES:
 as TMP-SMX (trimetophrim/
sulfamethoxazole, also known as
Cotrimoxazole)
 UTI, respiratory, ear, and sinud infections (H.
influenza and M. catarrhalis)
 DOC (Drug of Choice) for Pneumocystis
pneumonia (immunocompromised patients)
 Backup drug for cholera, typhoid fever, and
shigellosis
TOXICITY OF SULFONAMIDES AND
TRIMETHOPRIM
 Sulfonamides
 Hyoersensitivity (allergic reactions, fever,
exfoliative dermatitis, and Steven-Johnsons
syndrome)
 GI irritation (nausea, vomiting, and diarrhea)
 Hematoxicity (granulocytopenia,
thrombocytopenia, and apalstic anemia)
 Nephtotoxicity (crystalluria, and hematura)
 Trimethoprim
 Hematoxicity (megaloblastic anemia,
leukopenia, and granulocytopenia)
REFERENCES
“PROF’S PPT ON QUIPPER AND LECTURE”
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