What is the goal for acute antibiotic treatment? prophylactic?

Acute - bacterial eradication

Prophylactic - reduced progression

1. reducing/eradicating inflammation (decreases cellular and tissue alterations)

2. reducing bacterial burden on pulmonary tree (decrease acute exacerbations and alter disease course)

gene on the long arm of chromosome 7 that encodes for the cystic fibrosis transmembrane regulator (CFTR) protein

delta-F508 allele (3 base-pair deletion = absence of phenylalanine)

1. defective protein production

2. defective protein processing

3. defective channel regulation

4. defective channel conductance

GI:

Pancreas - digestive enzyme & insulin deficiency

Intestines - viscous secretions (obstruction)

Liver - biliary cirrhosis/fatty infiltration (portal HTN/esophageal varices)

Pulmonary - viscous secretions, infection

Sweat glands - failure to reabsorb sodium (hypoNa)

Reproductive - obstruction of epididymis, vas deferens, and seminal vesicles (aspermia) or viscous cervical mucus (decreased fertility)

Hematologic - anemia

Bone and Joint - arthritis, osteopenia

loss of functional CFTR →

defective 3-5-monophosphate stim Cl transport→

decreased Cl secretion and increased Na absorption

trypsin

chymotrypsin

carboxypeptidase

amylase

lipase

Fat soluble (ADEK) - from lipase deficiency

Vitamin B12 + Zinc - pancreatic enzyme def

low insulin concentrations &

enhanced peripheral sensitivity 

without islet cell or antiinsulin antibodies

not usually associated with ketosis

hepatic isoenzymes:

gamma-glutamyltranspeptidase (GGP)

alanine aminotransferase (ALT)

aspartate aminotransferase (AST)

alkaline phosphatase (ALP)

1. exaggerated inflammatory response

2. bactericidal activity

3. altered mucus clearance

1. airway infection

2. inflammation

3. obstruction

What is the result of defective anion-mediated fluid secretion in mucus glands?

hyposecretion or hyperabsorption

1. Staphylococcus aureus

2. Pseudomonas aeruginosa

3. Haemophilus influenzae

P. aeruginosa - predominates throughout life

1. asymptomatic colonization

2. chronic deterioration with fever/weight loss

3. rapid, usually fatal deterioration

P. aeruginosa produces:

    extracellular toxins

    proteases

    hemolysins

    exopolysaccharides

that may be associated with what 3 problems?

1. direct airway damage

2. increased mucin production by epithelium

3. production of immune complexes (immunoglobins G and M)

1. granulocyte elastase

2. TNF-alpha

3. IL-1

4. IL-2

5. neutrophil elastase

Which inflammatory mediator clearly contributes to pulmonary patho?

How?

neutrophil elastase

1. overwhelms and neutralizes native antiproteases (a1-antitrypsin and secretory leukocyte protease inh)

2. destroys structural fibers

3. inh complement-mediated phagocytosis and antipseudomonal antibodies

they are having to use accessory muscles to move the air through the obstructed muscles

increased anterior-posterior chest diameter

1. relative exercise intolerance

2. increased resting energy expenditure

3. hemoptysis

4. gastroesophageal reflux

5. pneumothorax (collapsed lung)

6. right-sided heart failure (cor pulmonale) secondary to pulmonary hypertension

7. digital clubbing (related to chronic hypoxia)

defective chloride absorption across the water-impermeable sweat duct epithelium

the levels are normal in the gland lumen because chloride is secreted through other channels too, but as the sweat progresses through the duct towards the skin's surface, absorption is reduced

1. epidydymis

2. vas deferens

3. seminal vesicles

1. iron availability (decreased GI absorption)

2. erythropoietin regulation (nl to low levels)

1. Arthritis - usually nondestructive and episodic from immune complexes secondary to chronic pulmonary infections

2. Hypertrophic osetoarthropathy - occurs in association with pulmonary diseases

3. Osteopenia/osteoporosis - from bone demineralization

1. vitD malabsorption

2. decreased vitD conversion (via sunlight)

3. deayed puberty and endocrine development

4. poor nutrition

5. limited physical activity 

6. chronic acidosis

foul odorous

bulky

greasy

more frequent in #

steatorrhea

cyclical

relative well-being to acute pulmonary deterioration

Sweat test:

1. how many samples do you need?

2. how are they collected?

3. what level is diagnostic?

1. 2 samples

2. collected using pilocarpine iontophoresis 

3. chloride concentrations >60mEq/L

FEV1 <30% predicted

PaO2 <50mmHg

PCO2 >55mmHg

What is the chief variable in enzyme replacement products?

What are the ingredients?

lipase content

lipase/protease/amylase

Perianal irritation resembling diaper rash (excess powder)

Hyperuricosuria - high purine content of products

Proximal colonic stricture (fibrosing colonopathy) if dose >24000u/kg/day

enemas with isoosmolar contrast

often surgery is required

Ursodeoxycholic acid (a bile acid with choleretic properties) at doses of 15-20mg/kg/day

sometimes used in combo with taurine supplementation

1. antiobstructive

2. antiinflammatory

3. antiinfective

percussion and postural drainage (1-2x/day healthy, ~6x/day in exacerbation)

Flutter devices - produces vibrations in airways when exhaled through

Nebulizer therapy - sterile water of 0.9% sodium chloride, might use bronchodialators and mucolytics too (N-acetylcysteine, Mucomyst)

RhDNAse - inhalation QD-BID

hypertonic saline inhalation - 7% solution generally (must be compounded) - do not mix with other nebulizer solutions

systemic bronchodilators (theophylline + B-ag)

Theophylline clearance and BA may be decreased so use larger dose (2nd line)

1. yearly influenza (amantadine prophylaxisis or treatment if indicated)

2. pneumococcal

3. H. influenzae

corticosteroid therapy - but problems with glucose and growth

ibuprofen - beneficial but therapeutic drug monitoring is required

1. finding known pathogens at high density in airways

2. increased cough

3. increased sputum production (thicker, darker)

4. decrease in lung function

5. loss of appetite

6. reduced exercise tolerance

trimethoprim-sulfamethoxazole

amoxicillin-clavulanic acid

any of the oral cephalosporins

ceftazidime

aztreonam

ciprofloxacin

trimethoprim-sulfamethoxazole

chloramphenicol

ceftazidime

trimethoprim-sulfamethoxazole

chloramphenicol

doxycycline

piperacillin

1. increased total body clearence for many ABs (AG, some BL, TPM/SMZ)

2. variations in hepatic metabolic activity 

increased

fleroxacin is decreased

dicloxacillin, ticarcillin, tmp-smz are not affected

methicillin, cloxacillin, dicloxacillin, ticarcillin, aztreonam, ceftazidime, tmp, amikacin

theophylline is increased too

fleroxacin is decreased

Table 32-4:Oral AB

1. what AB are listed?

2. which oral ABs can be used BID?

3. which oral ABs have an adult max dose? 

4. what is the adult max dose?

1. Amoxicillin, Amox/Clav, Cipro, Cephalexin, Dicloxacillin, TMP/SMZ

2. Ciprofloxacin and TMP/SMZ

3/4.  TMP/SMZ - 0.64g/day (of TMP)

 Cipro - 1.5g/day

Cephalexin - 6g/day

Dicloxacillin - 6g/day

T32-4: Parenteral ABs

1. which drugs are listed?

2. which drugs can be given q8h?

3. q6-8?

4. q6?

5. q4-6?

6. which have adult max doses? what are the doses

1. tobramycin, gentamicin, netilmicin, amikacin, azlocillin, aztreonam, ceftazidime, colistin, imipenem, nafcillin, ticarcillin, ticarcillin/clav, piperacillin

2. tobra, gent, netilmicin, amikacin, ceftazidime

3. colistin

4. aztreonam, imipenem

5. azlocillin, nafcillin, ticarcillin, ticarcillin/clav, piperacillin

6.     imipenem - 4g/day

ceftazidime - 6g/day

nafcillin - 6g/day

aztreonam - 8g/day

ticarcillin - 18g/day

piperacillin - 18g/day

azlocillin - 24g/day

quinolones (altered DNAgyrase target site)

B-lactams (prod.of Bush group 1 B-lactamase)

AG (dec. permeability and modifying enzymes)

carbapenems (decreased permeability)

extended-spectrum PCNs

ticarcillin, azlocillin, piperacillin (dose of at least 350mg/kg/day divided into 4-6doses)

they have synergy and prevent emergence of resistance

FEV1 at the end of 1 week of treatment

recovered >40% = 2 weeks of therapy

1. growth hormone

2. protease inh - for inflammation

(a1-antitrypsin aerosol, secretory leukocyte PInh)

3. pentoxifylline - inh TNF-a and stim PMN

4. amiloride - diuretic may block Na reabsorption

5. adenosine and uridine triphosphate - increase chloride excretion in epithelial cells

6. phenylbutyrate - increases amt of functional protein that reactes the cell surface

7. 8-cyclopentyl-1,3-dipropylxanthine (CPX)

8. milrinone (PDEI)

9. genistein (tyrosine-kinase inh)

- all activate mutant CFTR

10. gentamicin - suppresses certain premature stop mutations in CFTR

Tobramycin

1. Brand?

2. BBW?

3. Dosing?

4. Age minimum?

5. Admin?

6. Storage

7. prego?

8. serum levels

1. TOBI (R)

2. nephrotoxicity/neurotoxicity

3. 300mg q12h (NOT<6h apart), 28d on/28d off

4. 6yo

5. inh ~15m using PARI-LC PLUS hh neb

6. refrigerate, at RT in foil pouch for 28d

7. pregD, AG cause fetal harm, breast milk +

8. ~1mcg/mL 1h post 300mg dose

bronchodilator

hypertonic saline

pulmozyme

airway clearance technique (vest, flutter, chest pt, ipv)

antibiotics

steroids

What is tobramycin's

1. drug class?

2. MOA?

3. spectrum

4. ADE

1. aminoglycoside

2. binds to 30S and 50S ribosomal subunits

3. gram-negative bacilli (including Pseudomonas aeruginosa), Burkholderia cepacia

4. can cause voice alterations

Aztreonam:

1. Brand

2. Dosing

3. Min age

4. Admin

5. Storage

1. Cayston (inh), Azactam (IM/IV)

2. inhalation - 75mg TID (at least 4h apart) for 28 days, do not repeat for 28 days

3. >7 years old

4. only use Altera(R) neb system, admin over 2-3min, doses > 4h apart; if used with a SA bronchodilator use 15m-4h before, LA use 30m-12h before)

5. refrigerate, store aztreonam and diluent at room temp for up to 28days

Aztreonam:

1. class

2. MOA

3. spectrum

4. prego

5. ADEs

1. synthetic monocyclic beta-lactam AB

2. binds to PBPs to inh trspep in pep-gly synth

3.pseudomonas aeruginosa, acinetobacter, alcaligenes, klebsiella, serratia (almost pure aerobic g- activity)

4. PregB, milk+

5. fever, cough, congestion, pharyngeal p, wheezing

Colistimethate

1. Brand

2. Dosing

3. Storage

4. ADEs

5. Prego

1. Coly-Mycin M

2. 50-75mg in NS via neb 2-3x/day 

3. intact vials at RM temp, reconstit 24rt or frige

4. paresthesia, slurred speech, renal toxicity, respiratory arrest, superinfection

5. pregC, unknown if in milk

Colistimethate/Coly-Mycin(R) M

1. Class

2. MOA

3. Spectrum

4. DDI

1. Misc, polymixin B

2. PRODRUG: hydrolyzed to colistin that acts as a cationic detergent damaging the bacterial cytoplasmic membrane = leakage

3. pseudomonas aeruginosa, gram-neg bacilli resistant to other AB

4. AG, AmphB, Capreomycin, Polymyxin B, Typhoid Vaccin, Vanc, NMBlk

Dornase Alfa

1. Brand

2. Min Age

3. Dosing

4. Storage

5. Prego

6. ADE

1. Pulmozyme

2. > 3mo (Pari-Baby nebulizer)

3. 2.5mg once daily for pt with FVC>40%

4. Refrigerate and protect from light

5. PregB, unknown lactation

6. chest p, fever, rash, pharyngitis, rhinitis, voice

Dornase alfa is a DNAenzyme that selectively cleaves DNA to reduce viscosity of lung secretions

Aztreonam (Cayston)

pancreatic elastase test: 

what is it?

what do your results mean?

fecal test

severe <100

nl >200 (200-500)

What are Hi-Vegi-LipTablets?

pancreatin

gluten, lactose, and sugar free

4800/60,000/60,000 L/P/A

OTC

Pancreaze

Zenpep

Creon

Tri-Pase

4200/10,000/17,500

10,500/25,000/43,750

enteric-coated microtablets

6,000/19,000/30,000

12,000/38,000/60,000

24,000/76,000/120,000

enteric-coated spheres

5,000/17,000/27,000

10,000/34,000/55,000

15,000/51,000/82,000

20,000/68,000/109,000

enteric-coated beads

Tri-Pase 8: 8t/30t/30t

Tri-Pase 16: 12t/60t/60t

What is Mucomyst?

MOA:

ADE:

N-acetylcysteine

mucolytic agent

unpleasant taste and odor, may cause bronchospasm

Amikacin and Kanamycin

Therapeutic peaks: 16-32, 15-40

Toxic P/T: >35, >10

Dose mg/kg/d: 15

Gentamicin and Tobramycin

Therapeutic peaks: 4-8mcg/mL

Toxic P/T: >12, >2

Dose: 3-5mg/kg/day

What is the relative OTOXICITY of AGs?

vestibular toxicity?

auditory?

kana=strepto>amikacin=gent=tobra

vestibular: streptomycin and gentamicin

auditory: kanamycin and amikacin

Which of the following statements best describes the pathophysiology of diarrhea in CF pts?

A. GI system is unabe to absorb water in foods consumed

B. bowel bc fibrotic + unable to absorb nutr.

C. liver promotes enh metabolism of nut.

D. pancreas doesn't produce enough enzymes for digestion

E. stomach doesn't produce enough acid to digest food

Suppressive antibiotic therapy is aimed at which of the following?

A. bacterial proliferation

B. normalizing pulmonary fx tests

C. reducing sputum viscosity

D. suppressing airway inflammation

E. increasing biofilm production

Which of the following best describes the abnormality observed by the sweat test?

A. increased Na, decreased Cl

B. increased Na, normal Cl

C. normal Na, decreased Cl

D. decreased Na, increased Cl

E. increased Na, increased Cl

Ursodeoxycholic acid can be use if the pt is experiencing which of the following situations?

A. serum liver function enzymes increased

B. pulmonary exacerbation with P. aeruginosa

C. frequent, watery, foul-smelling stools

D dehydration from sweat loss

E. hospitalization for any pulm or pancreatic reason