Pharmacology
1. Pharmacology: The study of the interaction of drugs with the organism.
2. Drug: Any chemical compound that may be administered to or used in an individual to aid in the diagnosis, treatment, or prevention of disease, to relieve pain, or to control or improve any physiologic disorder or pathologic condition.
3. LD50: The dosage of a drug that would be lethal to 50% of a test population.
4. ED50: The dosage of a drug that would have therapeutic effects for 50% of a test population.
5. Therapeutic index (TI): The numerical ratio of the LD50 to the ED50 (LD50/ED50). This ratio shows how close the lethal and therapeutic doses of a drug are for a test population. Low indices mean the therapeutic and lethal doses are similar and the drug has a high potential for overdose or toxic side effects (Figure 17-1).
6. Side effect: Any physiologic response other than that for which the drug was administered.
1. Chemical name: Name illustrative of chemical structural formula of the drug.
2. Code name: An investigational designation, usually alphanumeric.
3. Generic name: An assigned name given for clinical investigation of a promising chemical.
4. Official name: Usually the generic name after the drug is accepted for general use.
5. Trade, brand, or proprietary name: The name under which a particular manufacturer markets the drug.
C Principles of drug action: There are three phases of drug action from initial dosing to pharmacologic effect. Each phase includes aspects of the pharmacology of the drug.
1. Pharmaceutical phase: Administering the drug.
a. Dosage forms: Tablet, capsule, liquid, powder, or ointment
b. Route of administration (listed in order of speed in obtaining blood levels)
2. Pharmacokinetic phase: The drug movement phase, including entry into or elimination from the body. This phase generally includes absorption, distribution, metabolism, and elimination of a drug. These factors determine onset of action, peak plasma drug level, and duration of drug action.
a. Absorption: Rate of absorption is determined by the specific physical and chemical characteristics of a drug.
(1) The lung mucosa provides an excellent surface for absorption of inhaled drugs.
(2) A substantial portion of an inhaled drug may be absorbed systemically in the mouth or proximal airways, thereby reducing its ability to affect the distal airways.
(3) Only particles <3 μm in diameter are carried to the distal airways.
b. Distribution: Movement of the drug to an area of desired pharmacologic activity.
(1) The primary mechanism for distribution is the circulatory system.
(2) Topical administration for effect on skin or mucous membrane decreases the likelihood of further undesired distribution.
c. Metabolism: Inactivation of the drug by the body.
(1) The primary organ for detoxification is the liver.
(2) Secondary organs for detoxification are the kidneys and gastrointestinal (GI) tract.
(3) The body’s cells or plasma proteins may inactivate many drugs.
d. Excretion or clearance: Mechanism for elimination of the drug from the body.
3. Pharmacodynamic phase: Drug-receptor interaction
a. Drugs usually create their effect by stimulating or blocking a receptor.
b. Drug-receptor types (Figure 17-2)
(1) Ligand-gated channel receptors: These transmembrane receptors traverse the cell membrane, acting as a high-speed conduit for transfer of specific chemicals, often ions, into and out of the cell.
(2) Tyrosine kinase linked receptor: Also a transmembrane receptor; binding of a drug to its extracellular receptor site enzymatically activates its intracellular end, acting as a tyrosine kinase. In this example, a phosphate group is added to (phosphorylates) the amino acid tyrosine in proteins that this receptor contacts, changing the protein to produce the clinical effect.
(3) G protein-coupled receptors: Transmembrane receptors that act through an intermediary, the G protein, located within the cell membrane, bound to a molecule of guanosine diphosphate. In this example a drug-receptor binding stimulates the G protein to exchange a guanosine diphosphate molecule for a guanosine triphosphate molecule. Once phosphorylated, the G protein migrates to a separate protein target to create the end drug effect.
(4) Steroid-receptor complex: Lipophilic steroid molecules readily pass through cell membranes and bind to receptors in the cell cytoplasm. Translocation of the steroid-receptor complex into the nucleus allows the complex to affect DNA transcription. The end effect of the drug occurs only after translation of new proteins from the affected DNA, making this a slow process.
(1) Affinity: Tendency of a drug to combine with a matching receptor.
(2) Potency: The activity of a drug per unit weight. A potent drug has a large biologic activity at a small unit dose (Figure 17-3).
(3) Efficacy: The maximum effect produced by a drug regardless of dose (Figure 17-4).
(4) Cumulation: A gradual increase in the body’s total drug level that occurs when the administration rate of the drug is greater than the body’s rate of removal.
(5) Tolerance: The body’s ability to increase its metabolism of a drug. Increasing amounts of the drug are required to produce the same effect.
1. Additive: Two drugs, when given together, produce an effect equal to the sum of their individual effects.
2. Potentiation: Potentiation occurs when a drug active at a specific receptor site is given with a drug inactive at that receptor site, and the resulting effect is greater than that of the active drug alone (1 + 0 = 3).
3. Synergism: Two drugs active at a receptor site, when given together, cause an effect greater than the sum of their individual effects (1 + 2 = 6).
4. Antagonist: This is a drug with affinity but no efficacy (i.e., it blocks an effect).
a. Competitive: An antagonist whose effects are directly related to dosage. A competitive antagonist decreases potency but does not affect efficacy of the other drug.
b. Noncompetitive: An antagonist whose effects are not dose related. Potency and efficacy of the other drug are decreased.
5. Agonist: This is a drug with affinity and efficacy (i.e., causes an effect).
E The prescription: This is the written order for a drug composed of:
1. The patient’s name, address, and the date.
2. Rx: “Take thou”; take and prepare the medication.
3. Inscription: Name and quantity of the drug.
4. Subscription: Directions (when applicable) to the pharmacist for compounding the drug.
5. Sig: Transcription, “write”; instructions to the patient for taking the drug.
II Administering Aerosolized Drugs (see Chapter 35)
1. Ultrasonic nebulizers (not recommended for bronchodilators)
2. Gas-powered small volume nebulizers
3. Metered dose inhaler (MDI), with or without extension (spacer) device
B Particle size and deposition
C Basic protocol of administration
1. Gas-powered small reservoir nebulizers
b. Nebulizing flow: 6 to 8 L/min (viscous antibiotics, 12 L/min)
a. Assemble, shake canister, and charge with one actuation.
b. Hold 4 cm in front of open mouth or rest on mandibular teeth of open mouth.
d. Begin slow deep breath, and activate MDI.
e. Inspire to total lung capacity, and hold breath at least 3 to 5 seconds.
3. General notes regarding administration
a. Bronchodilators: Wait at least 1 minute, and then take a second puff.
b. Corticosteroids: Take after bronchodilators, hyperextending the neck while inhaling; use a spacer; rinse mouth and throat after dosing.
c. Dry powder inhalers: These require rapid inspiration with high flow rates (60 to 120 L/min) for dispersion.
d. Spacers or extensions with MDIs reduce the need for coordination and oropharyngeal impaction.
III Wetting Agents and Diluents
A Isotonic solution: A solution equivalent to a 0.9% weight/volume (w/v) solution of NaCl. Isotonic solutions are used in respiratory therapy primarily in small-volume nebulizers to increase aerosol volume during drug delivery.
B Hypertonic solution: A solution with a concentration >0.9% w/v solution of NaCl. Hypertonic solutions are used in respiratory therapy primarily for sputum induction.
C Hypotonic solution: A solution with a concentration <0.9% w/v solution of NaCl. Hypotonic solutions are most commonly used in respiratory therapy in large-volume aerosol generators and seem to have less effect on increasing airway resistance than normal saline or water.
D Distilled water: Used in respiratory therapy in all types of humidifiers.
1. Replace and replenish a deficient endogenous surfactant pool in neonatal respiratory distress syndrome (RDS).
2. Endogenous surfactant is normally recycled by reentering the type II alveolar cell as small vesicles. Exogenously administered surfactant can restore a depleted endogenous pool of surfactant, relieving RDS.
B Composition of pulmonary surfactant
1. Surfactant, a complex mixture of lipids and proteins produced by type II alveolar cells, regulates the surface tension forces of the lipid alveolar lining (see Chapter 5).
a. A film of liquid exists at the alveolar-air interface.
b. As the alveolus is compressed during expiration, surfactant decreases surface tension, requiring less pressure and effort to reexpand the alveolus during the next inspiration.
2. Surfactant is composed of lipids (85% to 90%) and proteins (10% to 15%)
(1) 85% to 90% of surfactant by weight.
(2) 90% of lipids are phospholipids.
(3) Phosphatidylcholine comprises 75% to 80% of the phospholipids.
(4) Depalmitoylphosphatidylcholine (DPPC or lecithin) is the component predominantly responsible for decreasing alveolar surface tension.
(1) 10% of surfactant by weight.
(2) Only 20% of the proteins are surfactant-specific proteins; 80% are serum proteins.
(3) The four surfactant-specific proteins are SP-A, SP-B, SP-C, and SP-D.
c. The alveolar type II cell synthesizes all surfactant components.
C Exogenous surfactant preparations
1. Colfosceril palmitate (Exosurf Neonatal)
a. A protein-free, synthetic lyophilized powder reconstituted with 8 ml of preservative-free sterile water to form a milky white suspension.
b. Colfosceril palmitate is depalmitoylphosphatidylcholine.
(1) Prophylactic therapy for infants with birth weight <1350 g.
(2) Prophylactic therapy for infants with birth weight >1350 g and evidence of pulmonary immaturity and risk for RDS.
(1) The first dose is 5 ml/kg, given as two divided doses.
(2) A single vial of reconstituted Exosurf has a volume of 8 ml and can treat infants with birth weight up to 1600 g.
(3) A second dose of 5 ml/kg is given 12 hours after the first.
(4) A third dose, if necessary, is given 12 hours after the second dose.
(1) Instilled directly into the endotracheal tube (ETT) through a side-port adaptor that is Luer-Lok fitted to the ETT.
(2) With the infant in the midline position, the first half dose is sequentially instilled in synchrony with the inspiratory phase of the ventilator.
(3) The infant is then rotated to one side and ventilated for 30 seconds.
(4) Repositioned to midline, the infant is given the second half dose, then rotated to the opposite side, and ventilated for 30 seconds.
a. A natural bovine lung extract mixed with colfosceril palmitate (DPPC), palmitic acid, and tripalmitin.
b. Contains surfactant proteins SP-B and SP-C but not SP-A.
(1) Used prophylactically for premature infants with birth weight <1250 g.
(2) Used for infants with evidence of surfactant deficiency and risk of RDS.
d. As Survanta, this surfactant preparation comes in an 8-ml solution suspended in 0.9% sodium chloride, having a concentration of 25 mg/ml. Thus one vial has 200 mg.
(1) To gently warm the refrigerated suspension, it should be set out at room temperature for 20 minutes.
(2) Settling of the suspension should be countered by gentle agitation of the vial. The container should not be vigorously shaken.
(3) The dose is given in four aliquots, instilled directly into the trachea through a 5-French catheter.
(4) After each of the aliquots, the catheter is withdrawn, and the infant is ventilated and stabilized for at least 30 seconds.
a. An organic solvent extract of calf lung obtained by bronchoalveolar lavage.
b. This surfactant preparation is a suspension containing SP-B and SP-C.
(1) Used prophylactically in infants <29 weeks gestational age.
(2) Used for rescue of intubated premature infants aged <3 days who develop RDS.
(2) Repeat doses can be given 12 hours apart or as early as 6 hours for infants in continued distress.
(3) Each 6-ml vial contains 210 mg phospholipids, enough to treat a 2-kg infant.
a. A natural surfactant extracted from porcine lung, consisting of 99% phospholipids and 1% surfactant proteins SP-B and SP-C.
(1) Rescue or treatment of premature infants with RDS.
(2) Used off-label for prophylaxis in RDS, acute respiratory distress syndrome (ARDS) from viral pneumonia, HIV-infected infants with Pneumocystis carinii pneumonia, and management of ARDS after near drowning. Efficacy in all of these settings is controversial.
(2) Two subsequent doses of 1.25 ml/kg birth weight can be given in 12-hour intervals for continued distress.
(1) Two equal aliquots are given through a 5-French catheter whose tip is positioned at the tip of the ETT.
(2) Each aliquot is given to an alternate side, positioned dependently, stabilizing the infant by mechanically ventilating with 100% oxygen for at least 1 minute between doses.
(3) Airway suctioning should be avoided for 1 hour after treatment, provided significant airway obstruction does not occur.
2. Generic name: Acetylcysteine (N-acetyl-L-cysteine)
3. Mechanism of action: Lyses disulfide bonds holding mucoproteins together, thus increasing fluidity of mucoid sputum.
4. Concentration: 10% or 20% w/v solution
a. Standard dosage: 4 ml of 10% w/v or 2 ml 20% w/v solution with 2 ml water or normal saline solution
6. Indications: Thick, retained mucoid or mucopurulent secretions
7. Contraindications: Hypersensitivity
a. Questionable efficacy when aerosolized.
(1) Mucolytic activity well documented in vitro.
(2) No data clearly demonstrate the clinical efficacy of aerosolized Mucomyst.
(3) May be useful for direct bronchial instillation during bronchoscopy.
b. Highly recommended that drug is administered in conjunction with bronchodilator.
c. Should be refrigerated after opening.
e. Should be administered in glass, plastic, or nontarnishable metal containers because it reacts with rubber, some plastics, and iron.
f. Ineffective on predominantly purulent secretions.
g. Supplied in 4-, 10-, and 30-ml vials.
h. Should be administered after pretreatment with a bronchodilator.
2. Generic name: Dornase alfa—originally rhDNase (recombinant human DNase)
3. Mechanism of action: A genetically engineered clone of human pancreatic DNase enzyme, it is a peptide proteolytic enzyme that can break down extracellular DNA and F-actin polymers from neutrophils found in purulent secretions.
4. Indication: Cystic fibrosis management to manage purulent mucoid secretions; more effective than Mucomyst in reducing the viscosity of sputum in cystic fibrosis.
a. 2.5 mg/ampule, 1 ampule daily via recommended nebulizer system (e.g., Hudson T Updraft II, Marquest II, or PARI LC Jet Plus).
b. 3 to 5 ml of 5% to 10% w/v solution in 0.45% or 0.9% saline solution.
6. Contraindication: Hypersensitivity to dornase or other components of the drug preparation.
a. Unlike the earlier animal pancreatic dornase (Dornavac), dornase alfa does not cause antibody-mediated allergic reactions, such as bronchospasm.
b. Pharyngitis and vocal alterations
g. Less commonly a variety of respiratory symptoms (e.g., cough, dyspnea, rhinitis, and sinusitis), GI obstruction, hypoxia, and weight loss.
VI Mast Cell Stabilizers (Table 17-1)
TABLE 17-1
| Drug | Brand Name | Formulation and Dosage |
| Cromolyn sodium | Intal | MDI: 800 μg/actuation |
| Adults and children ≥5 yr: 2 inhalations QID | ||
| SVN: 20 mg/ampule or 20 mg/vial | ||
| Nasalcrom | Spray: 40 mg/ml (4%) | |
| Adults and children ≥6 yr: 1 spray each nostril 3-6 times daily every 4-6 hr | ||
| Nedocromil sodium | Tilade | MDI: 1.75 mg/actuation |
| Adults and children ≥12 yr: 2 inhalations QID |
MDI, Metered dose inhaler; QID, four times daily; SVN, small-volume nebulizer.
From Wilkins RL, et al: Egan’s Fundamentals of Respiratory Care, ed 8. St. Louis, Mosby, 2003.
1. Generic name: Cromolyn sodium
a. Inhibits release of histamine and leukotrienes during allergic, immunoglobulin (Ig) E-mediated responses of pulmonary mast cells.
b. Suppresses response of mast cell to antigen-antibody reaction.
3. Concentration: 20-mg capsules (powder) or 20 mg/2 ml H2O ampules (liquid).
4. Standard dosage: 20 mg three or four times daily.
6. Primary indications: Prophylactic maintenance for patients with severe bronchial asthma exercise-induced bronchospasm.
7. Secondary indications: Result of the effect of cromolyn sodium on all mast cells.
8. Contraindications: Hypersensitivity
1. Generic name: Nedocromil sodium
a. Inhibits most cell cytokine release
b. Modulates the synthesis and release of proinflammatory cytokines
3. Concentration: 1.75 mg per MDI actuation (only preparation)
4. Standard dosage: Two inhalations four times per day
6. Primary indication: Prophylactic therapy for the management of mild to moderate asthma.
VII Leukotriene Inhibitors (Antileukotrienes) (Table 17-2)
TABLE 17-2
| Drug | Brand Name | Formulation and Dosage |
| Zafirlukast | Accolate | Tablets: 10 mg, 20 mg |
| Adults and children >12 yr: 20 mg (1 tablet) BID, without food | ||
| Children 5-11 yr: 10 mg BID | ||
| Montelukast | Singulair | Tablets: 10 mg, 5 mg, and 4 mg (cherry-flavored chewable) |
| Adults and children >15 yr: 1 10-mg tablet each evening | ||
| Children 6-14 yr: 1 5-mg chewable tablet each evening | ||
| Children 2-5 yr: 1 4-mg chewable tablet each evening | ||
| Children 12-23 mo: 4 mg oral granules each evening | ||
| Zileuton | Zyflo | Tablets: 600 mg |
| Adults and children ≥12 yr: 1 600-mg tablet QID |
BID, Twice daily; QID, four times daily.
From Wilkins RL, et al: Egan’s Fundamentals of Respiratory Care, ed 8. St. Louis, Mosby, 2003.
1. Originally isolated from leukocytes, leukotrienes have a carbon chain skeleton with three double bonds in series, a triene.
2. Chemically they are lipid mediators of inflammation synthesized from arachidonic acid (AA).
3. Potent bronchoconstrictors, they stimulate airway edema, mucus secretion, and recruitment of other inflammatory cells.
4. They are particularly effective in controlling exercise-induced, aspirin-induced, and, less effectively, allergen-induced asthma.
B Leukotriene production (Figure 17-5)
1. In cell cytoplasm, phospholipase A2 (PLA2) moves to the cell nuclear membrane, where it hydrolyzes phospholipids to form free AA. AA binds to 5-lipoxygenase (5-LO)-activating protein (FLAP; AA-FLAP). 5-LO moves to the nuclear membrane and oxygenates AA of the AA-FLAP complex, resulting in 5-hydroperoxyeicosatetraenoic acid (HPETE). HPETE is converted to leukotriene A4 (LTA4), an unstable intermediate that is the source of all leukotrienes. LTA4 is converted into leukotriene B4 (LTB4) or leukotriene C4 (LTC4), both of which move to the extracellular space. LTC4, which structurally contains the amino acid cysteine, can be converted to leukotrienes D4 and E4 (LTD4 and LTE4). These three are known as the cysteinyl leukotrienes (CysLTs). The three CysLTs (LTC4, LTD4, and LTE4) are the components previously known as slow reacting substance of anaphylaxis (SRS-A).
1. Leukotrienes bind to leukotriene receptors to exert inflammatory effects.
a. Increased bronchial hyperresponsiveness to other irritants such as histamine.
c. Increased vascular permeability causing airway wall edema.
d. Plasma exudation into airway lumen.
e. Cumulative effect is increased secretion viscosity and possible airway occlusion often seen in asthma.
2. The CysLT1 receptor, located on smooth muscle cells in the airway, mediates the proasthmatic action of the CysLTs.
a. Stimulation of the CysLT1 receptor causes bronchoconstriction.
b. The CysLTs are more potent airway constrictors than histamine.
a. The CysLTs are produced by eosinophils, mast cells, and macrophages, all of which are seen in the airways of persons with asthma.
b. The CysLT2 receptor subtype mediates constriction of vascular smooth muscle.
c. Drugs that block the binding of leukotrienes to CysLT1 have the generic suffix –leukast.
a. Approved for use in early 1997.
b. Orally active inhibitor of 5-LO, preventing catalysis of leukotrienes from AA.
c. Indicated for prophylactic and long-term management of asthma in adults and children aged >12 years.
a. Available as a single tablet of 600 mg.
b. One 600-mg tablet four times daily for total daily dose of 2400 mg.
4. Precautions: Patients should be monitored for liver injury.
a. Hepatic transaminase enzymes should be evaluated before initiation of treatment, monthly for the first 3 months, and every 2 to 3 months thereafter for the first year of treatment.
b. With clinical signs of liver injury (e.g., right upper quadrant pain, nausea, fatigue, lethargy, pruritus, jaundice, or flulike symptoms), discontinue use.
a. Headache, abdominal pain, loss of strength, and dyspepsia.
b. Elevated liver function test values.
(1) Hepatic transaminase enzymes should be monitored before and during treatment.
(2) Liver function test values may return to normal either during or after treatment.
c. Contraindicated in patients with acute liver disease or transaminase levels greater than three times normal.
a. Approved for use in the United States in 1996 as Accolate.
b. Indicated for prophylaxis and long-term management of asthma in adults or children aged ≥12 years.
a. Leukotriene receptor antagonist that blocks inflammatory effects of leukotrienes.
b. Binds to the CysLT1 receptors.
c. Competitively inhibits leukotrienes LTC4, LTD4, and LTE4, blocking inflammation.
a. Rapidly absorbed orally, reaching peak plasma levels in 3 hours.
b. Half-life approximately 10 hours.
d. 10% excreted in urine, remainder in feces.
e. Administration of zafirlukast with food reduces mean bioavailability by 40%.
a. Headache, infection (primarily respiratory), nausea, diarrhea, and generalized and abdominal pain.
b. Liver disease will increase drug plasma levels.
c. Doses >40 mg daily can cause elevations in serum liver enzymes.
d. Instances of hepatitis and hyperbilirubinemia reported in patients receiving 40 mg/day for 100 days.
a. Approved for use in February 1998.
b. Orally active leukotriene receptor antagonist.
c. Indicated for prophylaxis and long-term management of asthma.
(1) Has no bronchodilatory effect in short-term asthma treatment.
(2) Approved for use in pediatric patients (children aged ≥2 years).
(3) Efficacious in management of mild to moderate asthma and exercise-induced bronchial constriction.
(4) Exhibits improved asthma control in children aged 6 to 14 years and in adults and adolescents aged >15 years.
a. Supplied in 10-mg oral tablet or 4-mg and 5-mg chewable cherry-flavored tablets.
b. Adults and adolescents aged >15 years: one 10-mg tablet daily, taken in the evening.
c. Pediatric patients aged 6 to 14 years: one 5-mg chewable tablet daily, taken in the evening.
d. Pediatric patients aged 2 to 5 years: one 4-mg chewable tablet daily, taken in the evening.
a. Competitive antagonist for the CysLTs LTC4, LTD4, and LTE4.
b. Binds to the CysLT1 receptor subtype, preventing leukotriene receptor stimulation in airway smooth muscle and secretory gland cells.
c. Shown to inhibit early- and late-phase asthmatic bronchoconstriction.
(1) A 10-mg dose reaches peak plasma concentration in 3 to 4 hours.
(2) A 10-mg dose has mean bioavailability of 64%, not influenced by intake of food.
b. A 5-mg fasting dose had slightly higher concentrations than when taken with food.
c. A 4-mg tablet reached peak plasma concentrations in 2 hours.
d. Mean plasma life in adults: 2.7 to 5.5 hours.
e. Metabolized in liver and excreted via bile.
f. Mild to moderate liver disease will increase plasma levels.
VIII Aerosolized Antimicrobial Agents
1. Aerosolized delivery achieves high drug concentration in lung tissue.
2. Antibiotics effective against particular organisms, such as Pseudomonas; have poor lung bioavailability when taken orally.
1. Nebulization of antibiotics should occur in contained rooms to prevent escape of the drug and possible development of resistant organisms within the local environment.
2. Caregivers should be protected to prevent development of sensitivity reactions or resistance to antibiotics.
3. Antibiotic solutions vary in viscosity from the aqueous solutions for which disposable nebulizers were designed.
a. An aminoglycoside used for management of Pseudomonas aeruginosa, a pathogen often associated with chronic infection of cystic fibrosis patients.
b. Tobramycin solution for inhalation (TOBI) is a preservative-free preparation that may reduce the risk of adverse effects.
c. TOBI should be administered in the PARI LC Plus nebulizer to ensure adequate drug output and particle size.
3. Contraindicated in patients with hypersensitivity to aminoglycosides.
4. Dose: 300 mg twice daily in repeated cycles of 28 days on drug, followed by 28 days off drug.
D Colistimethate (Coly-Mycin, Colistin)
a. A polypeptide antibiotic used in aerosol form for management of Pseudomonas pneumonia.
b. Most often used for immunocompromised patients or patients with cystic fibrosis.
2. Contraindicated in patients with known hypersensitivity to the drug.
1. Characteristics: An antifungal agent given prophylactically to prevent fungal pneumonia in immunocompromised patients.
2. Contraindicated in patients with known hypersensitivity to the drug.
a. Usual dose: 10 mg twice daily.
b. A vial with 50 mg powder is reconstituted in 10 ml sterile water for inhalation, creating a concentration of 5 mg/ml.
a. Extubated patients: Via Pari nebulizer.
(1) Using a small-volume nebulizer, dilute the 2-ml dose (5 mg/ml) with 2 ml water for a final solution of 4 ml.
(2) Use additional ventilator expiratory limb filter to prevent drug interference with exhalation valve or flow sensor.
c. Amphotericin B, incompatible with most drugs, should not be mixed with other drugs in the nebulizer.
a. An antiprotozoal agent used for prophylaxis of P. carinii pneumonia, often seen in immunocompromised patients.
b. Has been replaced by trimethoprim-sulfamethoxazole (TMP/SMX) for treatment (IV) and prophylaxis (nebulized) in patients allergic to sulfa drugs.
I Table 17-3 lists commonly used antibacterial agents with their mechanisms of action, spectra of activity, and toxicities.
TABLE 17-3
Common Antibacterial Antibiotics, Mechanisms, Spectra of Activity, and Toxicities
| Class | Examples | Mechanism of Action | Spectrum of Activity | Toxicity |
| Penicillins | Penicillin, amoxicillin, amoxicillin-clavulanate (Augmentin), piperacillin, ticarcillin | Cleave bonds contained in peptidoglycan cell wall, disrupting bacterial structural integrity | G+/G−, and anaerobic activities increasing with successive generations | Hypersensitivity, GI intolerance, hepatitis with prolonged use |
| Cephalosporins | Cefazolin (Ancef), cephalexin (Keflex), ceftriaxone (Rocephin), ceftazidime | Same as penicillins | Same as penicillins | Rare cytopenias |
| Carbapenems | Imipenem | Same as penicillins | Broad G+, G−, anaerobic coverage | Seizure, GI intolerance, occasional cytopenias |
| Monobactams | Aztreonam | Same as penicillins | Broad G+, G−, anaerobic coverage | Similar to penicillins |
| Aminoglycosides | Gentamicin, tobramycin (TOBI) | Antiribosomal: interfere with translation of proteins from mRNA by binding the bacterial ribosome 30S subunit, bacteriocidal | G− | Nephrotoxicity, ototoxicity, rare paralysis; levels requiring monitoring |
| Tetracyclines | Tetracycline, doxycycline, minocycline | Antiribosomal; bind the 30S subunit; bacteriocidal at high concentrations | G+, atypicals |
