PBL CASE 4: FACULTY LEARNING OBJECTIVES
(1) What are the most probable causes of hemoptysis? Describe the mechanism
behind each cause
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Hemoptysis is a productive cough that is either pure blood or mixed with
sputum and is usually of vascular origin (rarely massive)
According to research the four most common causes of hemoptysis are:
o bronchitis/bronchiectasis (26%)
o lung cancer (23%)
o pneumonia (10%)
o tuberculosis (8%).
Pathophysiology
o The lungs have a dual blood supply
o Pulmonary arterial circulation: a high-compliance, low-pressure
system that terminates in the pulmonary capillary bed and is
responsible for gas exchange.
o Bronchial artery circulation: branches of the aorta that bring nutrients
to the lung parenchyma and major airways.
 high-pressure system and most causes of hemoptysis result
from disruption of branches of the bronchial arterial tree.
Bronchitis and bronchiectasis
o Bronchitis usually causes mild hemoptysis.
o Inflammation of the airways leads to mucosal hyperemia, and
disruption of small mucosal vessels produces blood-streaked sputum.
o Conditions such as bronchiectasis are associated with chronic
inflammation of the lung, with local bronchial arterial proliferation and
increased blood flow.
o Inflammation leading to erosion of these bronchial vessels can result in
severe hemorrhage.
Lung cancer
o Hemoptysis due to lung cancer is usually mild, resulting in bloodstreaked sputum.
o Mechanism: there is a small erosion of mucosal vessels in airways
involved by tumor.
o Massive hemoptysis in patients with lung cancer is typically caused by
malignant invasion of central pulmonary vessels by large central
tumors.
Pneumonia
o Pneumonia is a lung infection caused by a number of different
microorganisms and in people with weakened immune systems the
microbes settle in the lungs, where they grow and multiply.
o As the lung tissue tries to protect itself, inflammation of the tissue
occurs and disruption and of the small vessels in the lung produces a
bloody sputum.
Tuberculosis
o Hemoptysis in patients with tuberculosis can result from several
mechanisms.
 Endobronchial tuberculosis may cause local airway bleeding.
 Calcified tuberculous lymph nodes can compress and erode
lobar and mainstem bronchi, causing local bleeding and
coughing of calcified debris in the sputum.
 Large cavitary lesions in patients with advanced tuberculosis
often do not fully close despite antituberculosis treatment and
these lesions sometimes are colonized by Aspergillus.
 Bronchial arterial bleeding from inflammation in the
walls of cavities may result in bleeding
(1)
Hemoptysis Differential
Diagnosis
Infectious:
 Chronic bronchitis
 Bronchiectasis
 Tuberculosis
 Nontuberculous mycobacteria
 Lung abscess
 Necrotizing pneumonia
Cystic fibrosis
Cardiovascular:
 Left ventricular heart failure
 Mitral stenosis
 Pulmonary embolism or
infarction
 Aortic aneurysm
 bronchovascular fistula
Neoplastic:
 Lung cancer
 Bronchial adenoma
 Metastatic disease
Vasculitic:
 Wegener's granulomatosis
 Systemic lupus erythematosus
Miscellaneous:
 Idiopathic pulmonary
 Hemosiderosis
 Aspirated foreign body
 Pulmonary contusion or trauma
 Posttransthoracic needle biopsy
PBL CASE 4: FACULTY LEARNING OBJECTIVES
(2) How would you go about evaluating a patient that you think has Chronic
Obstructive Pulmonary Disease? What is the importance of a reversible
component?
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Chronic Obstructive Pulmonary Disease
o May be associated with bronchitis, asthma, or emphysema
o Obstructive Pulmonary Disease
 Disease state characterized by airflow limitation that is not
fully reversible.
 Progressive and associated with an abnormal inflammatory
response of the lungs to noxious particles or gases.”
o Chronic bronchitis
 Chronic productive cough for 3+ months in two successive
years
o Emphysema
 Enlargement of airspaces with destruction of bronchiole walls
o Asthma
 inflammatory disease of airways with significantly reversible
narrowing
Clinical:
o Patients are usual 20+ pack/yr. smokers
o Usually starts with a chronic cough but dyspnea may not occur until
10-20 years later
o As COPD progresses, chronic clear sputum production
o Weight loss
o Morning headache
o Hypercapnia with hypoxemia
Physical Examination:
o Prolonged expiration
o Hyperinflation – Increased A-P diameter
o Hyperresonent to percussion
o Depressed diaphragm
o Decreased breath sounds
o Wheezes – airflow obstruction
o End-stage – accessory muscles, pursed lips, cyanosis, enlarged liver,
asterixis
Diagnosis
o Chest x-ray
o Chest CT
o Pulmonary function tests
 Decreased FEV-1
 Decreased FEV-1/FVC
 Increased total lung capacity
 Absence of bronchodialator response  irreversible
(3) What is your approach to the diagnosis and treatment of pneumonia?
DIAGNOSIS
 The classic clinical presentation of pneumonia is at least two symptoms of
acute infection, along with evidence of acute infiltrate on chest radiograph,
and auscultatory findings of pneumonia (altered breath sounds and/or rales)
o Rales are heard on auscultation of the chest over the involved lobe or
segment
o If consolidation is present, an increase in tactile fremitus and bronchial
breathing may be present
(2)
PBL CASE 4: FACULTY LEARNING OBJECTIVES
(3)
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Symptoms
o Fever or hypothermia
o Rigors
o Sweats
o New cough, with or without sputum production or, in those with a
chronic cough, change in color of respiratory secretions
o Chest discomfort
o Dyspnea
TREATMENT
 Outpatient Treatment
o Community acquired pneumonia is most commonly caused by
Streptococcus pneumoniae (among many others)
o With patient of mild to moderate illness, no co-morbidities and,
younger than 60 years old:
 Oral macrolide
 Doxycycline
 fluoroquinolone
o With patient of mild to moderate illness, co-morbidities, and/or over 60
years old:
 Fluoroquinolone
 Inpatient Treatment
o Hospital acquired pneumonia is often caused by a gram negative bacilli
(Klebsiella or Enterbacteria)
 Pending culture results, start with Cefotaxime or ceftriaxone
 Add a macrolide to cover Legionella, Mycoplasma, and
Chlamydia
 or a fluoroquinolone with good activity against S.
pneumoniae may substitute for the Beta lactam +
macrolide
(4) Outline your use and evaluation of the more common pulmonary function tests
in differentiating between obstructive and restrictive disease.
PULMONARY FUNCTION TESTING
 In disease two general patterns can be distinguished
o Restrictive (pulmonary fibrosis): both the FEV and FVC are
reduced but the FEV1.0/FVC% is normal or increases
o Obstructive (asthma): the FEV is reduced more that the FVC
resulting in a reduced FEV1.0/FVC%
 Forced Expiratory Flow Rate (FEF25-75%): the average flow rate measured
over the middle half of the expiration
o Restrictive Diseases: maximum flow rate is reduced as is the total
volume exhaled
 The flow rate is often abnormally high during the latter part
of expiration because of increased lung recoil
 Inspiration is limited by reduced compliance of the lung or
chest wall or is limited by weakness of the inspiration muscles
o Obstructive Diseases:
 flow rate is very low in relation to lung volume, and a
“scooped out” appearance is often seen on the curve
 Total lung capacity is abnormally large but expiration ends
prematurely due to early airway closure from increases
smooth muscle tone of the bronchi (asthma) or from loss of
radial traction (emphysema)
o The FEV1.0 is reduced by an increases in airway resistance or a
reduction in elastic recoil of the lung
Normal ventilation: FEV1.0/FVC%
should be near 80%.
Restrictive (pulmonary fibrosis): both
the FEV and FVC are reduced but the
FEV1.0/FVC% is normal or increases.
Obstructive (asthma): the FEV is
reduced more that the FVC resulting in
a reduced FEV1.0/FVC%
PBL CASE 4: FACULTY LEARNING OBJECTIVES
(4)
ANALYSIS OF PULMONARY FUNCTION
 Obstructive lung disease – easy to fill lungs, hard to empty
o TLC is normal
o FRC, RV are increased
o VC, FEV1, FEV1/VC% are decreased
 Restrictive lung disease – lungs are less compliant than normal
o TLC, IC, VC are decreased
o RV is normal
o FEV1/VC% is normal or even increased
(5) How do you pharmacologically treat patients with COPD?
 COPD Treatment
o Treat the Asthma
 β-2 agonist bronchodialators
 Metered dose inhaler
o Anticholinergic Agents
 Inhaled ipratropium – first line therapy
 Additive effects of anticholinergics and beta-agonists
o Theophylline
 Use is controversial; watch for toxicity
o Corticosteroids
 Inhaled –may slow rate of decline of FEV-1
 Oral – up to 20% of patients may benefit
 Consider short term use for exacerbations
 Long term use only if all other meds are at maximal
therapy
o Supplemental Oxygen
 If O2 saturation < 88% on room air or < 85% with exertion
(6) How does chronic alcoholism influence drug and treatment choice
 Alcohol can influence the effectiveness of a drug by altering its availability
 Alcohol (acutely) may inhibit a drug's metabolism by competing with the drug
for the same set of metabolizing enzymes.
o This interaction prolongs and enhances the drug's availability,
potentially increasing the patient's risk of experiencing harmful side
effects from the drug.
 Alcohol ingestion (chronic) may activate cytochrome P450 enzymes, thus
decreasing the drug's availability and diminishing its effects.
o After these enzymes have been activated, they remain so even in the
absence of alcohol, affecting the metabolism of certain drugs for
several weeks after cessation of drinking.
o Chronic drinkers may need higher doses of medications than those
required by nondrinkers to achieve therapeutic levels of certain drugs.
 Activated cytochrome P450 enzyme may transform some drugs into toxic
chemicals that can damage the liver or other organs.
 Alcohol can magnify the inhibitory effects of sedative and narcotic drugs at their
sites of action in the brain
 As a result, any antibiotic/medication prescribed that has hepatic metabolism via
P450 enzymes or has any risks of heptatotoxicity should be monitored.
The drug names you need to know related to treatment of COPD:
Methylxanthines: aminophylline, theophylline, caffeine, epinephrine, ephedrine, metaproterenol, terbutaline, albuterol=salbutamol,
salmeterol, ipratropium, methylprednisoline, prednisone, triamcinolone, beclamethasone, flunisolide, budesonide
 PBL #3 LEARNING ISSUES
PBL CASE 4: FACULTY LEARNING OBJECTIVES
(5)
Antibiotics Overview
CELL WALL SYNTHESIS INHIBITORS
 Vancomycin
o Mechanism: binds with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor and prevent
peptidoglycan synthesis
 Steric hindrance for peptidoglycan synthetase
o Most potent antibiotic against staphylococci
o Indicated for severe staph infections, particularly in pencillin-hypersensitive patients
o Distribution
 Very poorly absorbed orally
 Enters CSF when meninges are inflamed
 Excreted by kidney (dosage adjusted in renal insufficiency)
o Acquired resistance increasing
o Toxicity
 Hypersensitivy reactions
 Ototoxicity can occur with large/continued doses
 Nephrotoxicity
 Beta-lactams (Penicillins, Cephalosporins, ect…)
o Mechanism: Bind to the penicillin binding proteins (transpeptidases) that catalyze terminal reactions in bacterial
cell wall synthesis
 Inhibits cross-linking of peptidoglycan by transpeptidasE
o Resistance: bacteria produce a beta-lactamase or penicillinase which cleaves the beta lactam ring so it cannot bind
to the transpeptidase
o Penicillin G
 Highly active against gram positive cocci
 Acid labile  approximate 1/3 or oral dose absorbed from GI tract
 Better absorbed in newborns and people over 60 (decreases gastric acid)
 PCN G/Benzathine  given IM
 Achieves low/persistant concentrations
 Concentration are only good against certain organisms
 Effective against group A beta-hemolytic strep or syphilis
 Rapidly excreted by kidney so dose must be adjust to kidney functioning
o Penicillin V
 Highly active against gram positive cocci
 Orally available
o Penicillinase Resistant Penicillins (methicillin, cloxacilin, dicloxacilin, oxacilin, nafcillin)
 Less potent antimicrobial activity against bacteria sensitive to PCN G
 S. aureus treatment
o Aminopenicillins (Amoxicillin, Ampiciliin)
 Extended spectrum of penicillins to include gram negatives
o Anti-pseudomonal penicillins (Ticarcillin, Pipercillin)
 Broad activity against G-bacilli including pseudomonas
o Penicillin + Beta Lactam Inhibitors (Amoxicillin/Clavulanic Acid and Ticarcillin/Clavulanic Acid)
 Clavulanic Acid  non competitive inhibitor of many beta-lactamases
o Cephalosporin  extended or broad spectrum beta lactam antibiotics (same mechanism as penicillins)
 First Generation (Cephalexin, Cefadroxil, Cefazolin)
 DO NOT penetrate the CNS
 Very active against gram positive cocci
 Second Generation (Cefaclor, Cefoxitin, Cefuroxime)
 Increased resistance to beta-lactamase
 Increase in Gram negative activity; decrease in Gram positive
 Third Generation (Cefotaxime, Ceftriaxone, Ceftaxidine)
 Penetration of CNS
 Little activity against Gram positive, but broad Gram negative activity
 Variable activity against Pseudomonas
 Fourth Generation (Cefepime)
 Comparable to third generation but more resistant to some beta lactamases
 More G positive activity than third generation
PBL CASE 4: FACULTY LEARNING OBJECTIVES
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Elimination
 primarily excreted by kidney (alter dose with renal insufficiency)
 Toxicity:
 Hypersensitivity  8% cross sensitivity with penicillin
 Thromophlebitis with IV use and pain at injection site
 Nephrotixicity potential
 Nausea, vomiting, hiarrhea
 Bleeding
Beta-lactamase/penicillinase inhibitors (Clavulanic Acid, sulbactam, tazobactam)
o Beta-lactamase  bacterial enzymes that cleave the beta lactam ring
o `Four classes exist (A, B, C, D)
 Clavulanic acid inhibts classes A and D beta lactamases
 Clavulanic acid is the prototype drug which inhibits the bacterial enzyme and the ring remains intact and is
available to inhibit the cross linking of peptidoglycan strands
INHIBIITORS OF PROTEIN SYNTHESIS
 Aminoglycosides
o Mechanism: bactericidal inhibitor of protein synthesis; extended spectrum antibiotics which act on the 30 S
ribosome to inhibit bacterial protein synthesis.
o Selective toxicity  Bacterial ribosomal subunits are different (size, etc.) than our ribosomal subunits
o Amikacin, gentamicin and tobramycin have good activity against Pseudomonas (Anti-pseudomonal
aminoglycosides)
o Extended spectrum antibiotics which act on the 30 S ribosome to inhibit bacterial protein synthesis.
o Primarily used for serious gram negative infection
o Absorption
 High polar cations
 Poorly absorbed from GI tract (given IV)
o Distribution
 Aminoglycosides are largely excluded from our cells, CSF, and eye (for meningitis  given intrathecally)
 To get into the bacterial cell, they are taken up by an active process which is linked to oxidative
phosphorylation.
 Strict anaerobes will not take it up, nor will bacteria in anaerobic conditions.
o Elimination
 Not metabolized to any significant extent
 Almost entirely dependent on kidney for elimination
 Dosage may have to be adjusted with impaired renal function
 Usually moniter plasma concentrations during therapy
o Toxicity
 Ototoxicity
 Repeated courses can result in hearing loss over time
 Contraindicated late in pregnancies
 Nephrotoxicity
 Acute tubular necrosis (reversible)
 Accumulated and retention of aminoglycosides in the renal cortex by proximal tubular cells (can
be detected 10-20 after dose is stopped)
 Neuromuscular Blockade
o Resistance
 Most commonly via inactivation by microbial enzymes
 The bacterial enzymes modify the drug by adding various groups to it.
 Amikacin is most resistant to bacterial modification and the development of resistance.
o Streptomycin
 Mechanism of Action  freezes protein synthesis at the initiation complex stage (formed but cannot form
proteins)
 Streptomycin’s target for inhibition is the 30S ribosome (specific parted called S12)
 This binding results in accumulation of abnormal initiated complexes and blockage of further
translation\
 Used generally in combination with other antimicrobial agents
 Used for TB
o Neomycin
 Has little or no indication for parenteral administration
PBL CASE 4: FACULTY LEARNING OBJECTIVES
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 If given parenterally, causes renal damage and loss of hearing
 Used in combination with erythromycin after bowel surgery
o Amikacin
 More resistant to aminoglycoside inactivating enzymes
 BROADEST spectrum of aminoglycosides
 Usage restricted to serious infections by gram negative oraganisms
o Gentamicin
 Used in combination with a penicillin for some serious infections
o Tobramycin
 Similar pharmacological properties as Gentamicin
Tetracyclines (BROAD spectrum)
o Mechanism: bind to 30S and prvent aminoacyl-transfer RNA attachment to 70S; bacteriostatic inhibitor of
protein syntheis
o Effective against some obligate intracellular parasites
o Primarly excreted in urine (glomerular filtration) and also via enterohepatic circulation
o Distribution
 Form stable chelates with metal ions and can decrease absorption of drug (don’t give with diary)
o Elimination
 Primarly excreted in urine (glomerular filtration) and also via enterohepatic circulation
o Toxicity
 GI irritation including nausea, vomiting and discomfort (fewer GI side effects with doxycycline)
 Phototoxicity  abnormal sunburns (mainly doxycycline)
 Causes brown discoloration of teeth (newly forming teeth so don’t give to children under age of 12)
 Hepatic  pregnant women and renal function impairment susceptible
 Renal  don’t administer with other nephrotoxic drugs
 PRECAUTIONS  not for pregnant women, children under 12 and patients with renal insufficienty
o Resistance
 Drug does not reach its target via decreased intracellular accumulation by bacteria (caused by impaired
influx or increase efflux)
 Altered target  production of proteins that interfere with tetracycline binding to ribosome
 Enzymatic inactivation
o Doxycycline  safest for renal failure
o Mincycline  metabolized mainly by liver
o Tetracycline/Oxytetracycline  incompletely absorbed
o Doxycycline/Minocycline  well absorbed (not affected by diary)
Chloramphenicol (BROAD SPECTRUM but toxic)
o Mechanism: inhibits elongation by inhibiting elongation
 Binds to 50S ribosome subunit and prevents attachment of the AA end of the aminoacyl-tRNA to the A
site
 Also inhibits mitochondrial synthesis on mammalian cells
o Alternative drug for treatment of typhoid fever, meningitis
o Causes serious and fatal blood dyscrasias
o Absorption
 Well absorbed from GI tracts and goes into CSF
o Elimination
 Almost totally metabolized in liver (90% glucuronidated)
 Dosage reduction may be needed with decreased hepatic fuction
 Not toxic with renal failure
o Toxicities
 bone marrow suppression
 Aplastic anemia during therapy; dose related; recovery complete after cesseation of treatement
 Purpura and hemorrhage after therapy; not dose related; usually fatal
 Gray baby syndrome  abdominal distension, loose green stool, cyanosis
 the newborn lever unable to glucuronidate
 reduced kidney function and inadequant excretion of unconjugated drug
o Resistance
 Inactivation of drug by an acetyltransferase (drug cannot bind to 50S)
 Bacteria can shut down influx mechanism
PBL CASE 4: FACULTY LEARNING OBJECTIVES
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Macrolides (Erythromycin, Azithromycin, Clarithromycin)
o Mechanism: interacts with the 50S ribsome and inhibits translocation step
o Absorption
 Acid labile and absorption better when stomach empty
 Have coating that allows them to get to small intestine
o Elimination
 concentrated in liver and excreted unchanged in the bile
o Toxicity
 Irritative effects (epigastric pain, nausea, diarrhea)
 Pyloric stenosis
 Cholestatic hepatitis
o Resistance
 Efflux of drug by active transport
 Modified 50S subunit preventing binding
 Production of bacterial methyltranferases that modify the ribosomal target
 Cross resistance to clindamycin and chlorampheicol
o Clarithromycin
 Similar spectrum of action to erythromycin
 Fewer side effects
 Improved acid stability
 More expensive
 High doses teratogenic
o Azithromycin
 Less side effects
i. More active against some bacteria
ii. Fewer drug interactions
o Clindamycin (anaerobic infections outside CNS)
 Abosorption:
 Completely absorbed after oral administration
 Elimination:
 Eliminated by hepatic mechanisms
 Half life slightly longer with impaired renal function
 Toxicity
 Use is limited only to where is it clearly superior to other drugs
 Diarrhea, skin rashes, psedumembranous colitis (superinfection)Resistance
 Resistance
 mutation of ribosomal receptor
 Methylation of ribosomal RNA
 Enzymatic inactivation
NUCLEIC ACID SYNTHESIS INHIBITORS
 Rifampin
o Mechanism: inhibition of RNA synthesis by interacting with DNA dependent RNA polymerase
 interacts with enzyme from sensitive bacteria but not resistant strains
 Mammalian RNA polymerase NOT affected
o Absorption
 Red-orange color
 Absorbed from GI tract and distributed throughout body
o Elimination
 Rapidly eliminated in bile and undergoes eneterohepatic circulation
 Excreted primarily in feces and secondly in urine
 Induces most cytochrome P450 isotypes (many interactions)
o Toxicities
 Hepatotoxicity rare
 Rash, fever, nausea, vomiting most common
o Resistance
 Develops rapidly and due to alteration of polymerase (reduced binding of drug to target enzyme)
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PBL CASE 4: FACULTY LEARNING OBJECTIVES
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Flurorinated Quinolones (Norfloxacin, Ciprofloxacin, Gatifloxicin, Moxifloxacin, Levofloxacin)
o Mechanism: Inhibits DNA gyrase by prevent relaxation of supercoilded DNA needed for normal transcription
 Mammlians only affected at high concentrations
 Gram positive – Topoisomerase IV main target
 Gram negative – DNA gyrase main target
o Absorption
 Absorbed after oral administration
 Distributed widely in the body (NOT norfloxacin)
o Elimination
 Primarily excreted by kidney (NOT moxifloxacin)
o Toxicities
 Nausea, abdominal discomfort, headache, dizziness
 Hyperglycemia or hypoclycemia
 NOT recommended for patients under age of 18 or pregnant women
 Tendon rupture is complication in adults
 Prolonged QT interval, so use with caution in patients with known QT interval prolongation
o Resistance
 Point mutation which alter target DNA gyrase
 Active efflux of drug
o Norfloxacin: limited use b/c doesn’t reach necessary systemic concentrations to be effective
o Ciprofloxacin is a broad agent used for many indications including urinary tract infections and bone and soft tissue
infections.
o Ciprofloxacin/Levofloxacin  excellent gram negative active (some gram positive)
o Gatifloxacin/Moxifloxacin  anaerobic activity, improves against gram positive
Folate Metabolism Inhibitors (Indirect Nucleic Acid Inhibition)
o Inhibitors of Dihydropteroate Synthetase
 Sulfonamides (Sulfamethoxazole and Sulfisoxazole)
 Absorption
 Rapidly absorbed from the GI tracts
 Distributed throughout all tissues of body (CSF and fetus)
 Elimination
 Acetylated in liver (no activity but still toxic)
 Eliminated by kidneys
 Toxicity
 Anorexia, nausea, vomiting
 Urinary Tract  need high fluid intake, crystalluria
 Resistance
 Altered dihydropteroate synthetase
 Reduced drug uptake/increased efflux
 Increased production of substrate of dihydropteroate synthetase
o Inhibitors of Dihydrofolate Reductase
 Trimethoprim (bacterial hydrofolate reductase) and Pyrimethamine (malrial dihydrofolate reductase)
 Mechanism: Competitive inhibitor of dihydrofolate reductase
 Combination of Trimethoprim/Sulfamethoxazole  sequential blockage of one patheway and synergistic
 Absorption
 Drug plasma concentration  20 parts sulfamethoxazole and 1 part trimethoprim
 Toxicity
 All undesirable effects of sulfonamides
 More dermatological effects
 Potential teratogen
 Resistance to Trimethoprim
 Altered dihydrofolate reductase
 Increased amounts of dihydrofolate reductase
PBL CASE 4: FACULTY LEARNING OBJECTIVES
( 10 )
Properties of Penicillins
Pencillin G/V
Penicillinase Resistant
Penicillins
Aminopenicillins
Antipseudomonal
Penicillins
Name
Penicillin G
Penicillin V
Oxacillin
Cloxacillin
Dicloxacillin
Nafcillin
Ampicillin
Amoxicilin
Ticarcillin
Piperacillin
Oral Absorption
Variable/Poor
Good
Good
Good
Good
Variable
Good
Excellent
Poor
Poor
Resistant to penicillinase
NO
NO
YES
YES
YES
YES
NO
NO
NO
NO
Antimicrobial Spectrum
Streptococcus, Neisseria,
spirochetes, anaerobes
S. aureus
Extend to include Haemophlius, E.
coli (more gram neg)
Extend to include Pseudomonas,
Enterbacteria
Cephalosporin Generations
Cephalexin (oral)
Name
Cefadroxil (oral)
Cefazolin (IV)
Antimicrobial Spectrum
Very active against (+) cocci;
modest against (-)
Increased (-) activity; less (+)
activity
Increase betalactamase resistance
Cefaclor
Cefuroxime (oral)
Cefoxitin (IV)
Ceftriaxone (csf)
Cefotaxime (csf)
Ceftazidine (pseudo)
FIRST GENERATION
SECOND GENERATION
THIRD GENERATION
Antipseudomonal
Penicillins
Cefepime (csf)
Little (+) activity, broad (-) activity,
penetrates CNS
More resistant to beta lactamases
and more (+) activity
Aminglycoside
Streptomycin
Neomycin
Amakacin
Gentamicin
Tobramycin
Tetracyclines
Tetracycilne
Doxycycine
Minocycline
Oxytetracycline
Macrolides
Erythromcyin
Azithromycin
Clarithromycin
Others
Clindamycin
Chloramphen,
Linezolid
Quniopristan
Dalfopristin
DNA Inhibitor
Rifampin
Quinolones
Flouroquinolones
Gatifloxacin
Moxifloxacin
Ciprofloxacin
Levofloxacin
CIDAL / 30 S
STATIC / 30 S
STATIC / 50 S
STATIC / 50 S
RNA Pol
Pol IV /gyrase
Folate Inhibit
Sulfonamides
Trimethoprim
Indirect
Metrodinzaole
Anaerobes