Transcript Penicillin - Caangay.com

Case 28
Pharmacology
by
Kongkrapun Pajeenboorawun
sec.c
Casse No. 28
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A 65 y/o male retired government employee
came in ER because of dyspnea, high grad
fever and chills of 2 days duration.
He has productive cough for 1 week with
purulent sputum.
PE done revealed presence of rales on mid to
basal portions.
Gram stain of bronchial secretions showed
gram-positive lancet shaped diplococci in short
chain.
Diagnosis
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High grad fever and chills of 2 days duration due
to infection.
Gram stain of bronchial secretions showed
gram-positive lancet shaped diplococci in short
chain.
This case is infection of Streptococcal
pneumoniae
Streptococcal pneumoniae
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Gram positive diplococci, also
called pneumococci.
Lancet-shaped or arranged in
chains
Polysaccharide capsule.
Positive in the Quellung
Reaction for specific capsular
polysaccharide.
Symptoms include sudden
onset of fever and chills and
sharp pleural pain, feeling
short of breath
Epidemiology
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Pneumococcal pneumonia is most common in elderly,
debilitated, or immunosuppressed individuals.
Most infectious during the course of other infections. Initial
infection will spreads to the lobes of the lungs during
mucous-producing viral infections.
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The disease often sets in after a preceding viral infection
damages the respiratory ciliated epithelium.Incidence
therefore peaks in the winter
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Type 1-8 pneumococci are responsible for about 75% of the
reported adult cases and nearly half of all fatalities
(usually bacterial pneumonia). Usually carriers are adults
(pharyngeal).
Pathological Process
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S. pneumoniae is normal member
of the respiratory tract flora;
invasion results in pneumonia
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Infection causes an outpouring of
fibrinous fluid into the alveoli.
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Portions of the lung may become
consolidated.
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Exudate carries bacteria away
from infected foci.
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Complications include
inflammation of the sinuses and
inner ear
S. pneumoniae
(small dark dots)
under the microscope
Laboratory examination
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Conventional methods for diagnosing pneumonia, primarily using
sputum Gram Stain (blood or cerebrospinal fiuid), are lengthy
Capsular antigen can be detected serologiccally
Streptococcus pneumoniae Test is an in vitro rapid
immunochromatographic assay for the qualitative detection of S.
pneumoniae antigen in the urine of patients with pneumonia and in the
cerebral spinal fluid (CSF) of patients with meningitis. In conjunction
with culture and other methods, it is intended to aid in the diagnosis of
both pneumococcal pneumonia and pneumococcal meningitis.
Streptococcus pneumoniae (Grampositive diplococci are located
outside neutrophils.
TREATMENT
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Penicillin : is the DRUG OF CHOICE (DOC: this term
will be used commonly through out the bacteriology
section).
New penicillin G-resistant pneumococci : have
been reported in the U.S. and elsewhere. These are a
severe management problem in meningitis, (limited
access of alternative antibiotics to the central nervous
system).
Erythromycin : is the secondary DOC for penicilin
allergic
Vancomycin, cephalosporins: for severe infection with
penicillin resistant strains
Penicillin
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Penicillin (sometimes abbreviated
PCN) refers to a group of β-lactam
antibiotics used in the treatment of
bacterial infections caused by
susceptible, usually Gram-positive,
organisms.
The name “penicillin” can also be
used in reference to a specific
member of the penicillin group.
Some penicillins possess the rare
Penam Skeleton, which has the
molecular formula R-C9H11N2O4S,
where R is a variable side chain.
Penicillin
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Absorption vary with the preparation depending on their
acid stability and protein binding
Absorption of most oral penicillins(except amoxicillin)
impaired by food and drugs
Should be given 1-2 hrs before or after meal
Cannot penetrate the blood brain barrier; but 50% of
plasma concentration can pass through in the presence
of imflammation
Metabolized by the liver
Excreted primarily by the kidneys (90% tubular secretion,
10% glomerular filtration)
Penicillin-G
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Penicillin-G where R = an ethyl pheny group, is the most
potent of all penicillin derivatives. It has several
shortcomings and is effective only against gram-positive
bacteria.
It may be broken down in the stomach by gastric acids
and is poorly and irregularly absorbed into the blood
stream.
In addition many disease producing staphylococci are
able to produce an enzyme capable of inactivating
penicillin-G.
Various semisynthetic derivatives have been produced
which overcome these shortcomings.
Machanism of action
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All penicillin derivatives produce their bacteriocidal effects
by inhibition last step in the peptidoglycan synthesis of
bacterial cell wall.
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Specifically, the cross linking of peptides on the
mucosaccharide chains is prevented.
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Inhibition of traspeptidase enzymes and activation of
penicillin binding proteins(PBSs)
Activation of autolysis(murein hydrolases), If cell walls are
improperly made cell walls allow water to flow into the cell
causing it to burst.
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Adverse effects
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Hypersensitivity reaction is most common
Gastrointestinal disturbances after oral administration
Convulsions following rapid IV injection
Chronic use may cause
- hepatitis
- overgrowth of minor/atypical organism following
use broad spectum preparation
Erythromycin
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Prototype
Distributed to total body water
Poor CSF penetration
Food interferes with interaction
Serum half life is 1.5 h normally and 5 hrs in patients
with anuria
Not removed by dialysis
Metabolized in the liver
Transverse the placenta and reaches the fetus
Erythromycin
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Mechanism : Bacteriostatic antibiotic macrolide produced
by Streptomyces erythreus; in sensitive organisms, it
inhibits protein synthesis by binding to 50S ribosomal
subunits; this binding process inhibits peptidyl transferase
activity and interferes with translocation of amino acids
during translation and assembly of proteins.
Adult Dose: 500 mg PO qid or 333 mg PO tid
Hospitalized patients with severe pneumonia: 1 g IV q6h
Alternative: 15-20 mg/kg/d IV divided q6h
Pediatric Dose: 7.5 mg/kg/d PO divided bid
Alternative: 20-40 mg/kg/d IV divided q6h or as constant
infusion; not to exceed 4 g/d
Erythromycin
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Interactions: Coadministration may increase toxicity of
theophylline, digoxin, carbamazepine, and cyclosporine;
may potentiate anticoagulant effects of warfarin;
coadministration with lovastatin and simvastatin
increases risk of rhabdomyolysis
Contraindications: Documented hypersensitivity; hepatic
impairment
Adverse effects: Caution in liver disease; estolate
formulation may cause cholestatic jaundice; GI adverse
effects are common (give doses pc); discontinue use if
nausea, vomiting, malaise, abdominal colic, or fever
occur
Vancomycin
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Poorly absorbed from intestinal tract
99% excreted by glomerular filtration
Half life 6-10 day, not removed by dialysis
Mechanism : Inhibition of cell wall synthesis by mechanism
distinct to that of penicillin (binds to D-Ala-D-Ala moiety of
precursor subunit blocking transpeptidation)
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Adult Dose: 500 mg IV q6h or 1 g IV q12h
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Pediatric Dose: 10 mg/kg IV q6h
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Contraindications: Documented hypersensitivity
Vancomycin
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Interactions: Erythema, histaminelike flushing, and
anaphylactic reactions may occur when administered with
anesthetic agents; with concurrent use, risk of nephrotoxicity
may increase above that associated with aminoglycoside
use alone; neuromuscular blockade may be enhanced when
used concurrently with nondepolarizing muscle relaxants
Advease effects: Caution in renal failure, neutropenia; red
man syndrome is caused by too-rapid IV infusion (dose
given over a few min) but rarely happens when dose given
as 2-h administration or PO or IP; red man syndrome is not
an allergic reaction
Cephalosporins
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Fourth Generation ( Cefepime, Cefpirome)
Fourth generation cephalosporins are extended-spectrum
agents with similar activity against Gram-positive organisms as
first-generation cephalosporins. They also have a greater
resistance to beta-lactamases than the third generation
cephalosporins.
Good activity against most penicillin resistant strain of
streptococci
Penetrates well into CSF
Cleared by kidneys
Half life 2 hrs
Indications : Cephalosporins are indicated for the prophylaxis
and treatment of bacterial infections caused by susceptible
organisms. Good activation against S.pneumoniae, P.
aeruginosa, Enterobacteriaceae, Staph aureus.
Cephalosporins
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Cephalosporins are bactericidal and have the same mode of
action as other beta-lactam antibiotics (such as penicillins).
Mechanism: Cephalosporins disrupt the synthesis of the
peptidoglycan layer of bacterial cell walls. The peptidoglycan
layer is important for cell wall structural integrity, especially
in Gram-positive organisms. The final transpeptidation step
in the synthesis of the peptidoglycan is facilitated by
transpeptidases known as penicillin binding proteins (PBPs).
Contraindicated: in patients with a history of severe of
immediate allergic reactions (urticaria, anaphylaxis,
interstitial nephritis, etc) to penicillins, carbapenems or
cephalosporins
Cephalosporins
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Interactions: Some cephalosporins cause diarrhea.
Certain diarrhea medicines, such as diphenoxylateatropine (Lomotil), may make the problem worse. Check
with a physician before taking any medicine for diarrhea
caused by taking cephalosporins.
Advease effects: diarrhea, nausea, rash, electrolyte
disturbances, and/or pain and inflammation at injection
site. Infrequent ADRs (0.1–1% of patients) include:
vomiting, headache, dizziness, oral and vaginal
candidiasis, pseudomembranous colitis, superinfection,
eosinophilia, and/or fever.
Prevention
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Pneumococcal polysaccharide vaccine
(Pneumovax™ is one brand) gives at least 85% protection
in those under 55 years of age for five years or longer.
Immunization is suggested for those at highest risk of
infection, including those 65 years or older, and generally
should be a single lifetime dose (high risk side effects if
repeated).
The standard 23-valent vaccines are ineffective for
children under two years old.
Prevention
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Vaccines: A multivalent vaccine consisting of 23
types of S. pneumoniae capsules is available.
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Recommended for infants and the elderly who
are at risk of exposure to the organism; also
immunosuppressed or debilitated patients.