Pharm Ch 13 Antiifective agents

Clinical Indications for Pentamidine

• Aerosolized pentamidine is indicated for preventing Pneumocystis pneumonia (PCP) in HIV-infected patients
• It is prescribed to patients with a history of one or more PCP episodes
• It is also prescribed for patients with a peripheral CD4+ (T4 helper cell) lymphocyte count of 200/mm³ or less
• NebuPent is a brand name version

Rationale for Aerosol Administration

• Allows for local targeted lung delivery
• Fewer or less severe side effects compared with systemic administration

Description of PCP

• Mammals usually get infected when they are young
• The disease occurs with suppression of the immune system, commonly AIDS
• It is also known as Pneumocystis jiroveci

Dosage of Pentamidine

• Administer 300 mg via inhalation once every 4 weeks
• Dosing may be altered by the treating physician
• The drug is a dry powder
• Each vial contains 300 mg
• Reconstitute with 6 mL of sterile water
• Do not reconstitute with saline, as it can cause precipitation

Administration of Pentamidine

• Use a Respirgard II nebulizer
• Power the nebulizer with a flow rate of 5-7 L/min from a 50-psi gas source
• Filter any escaped particles to limit healthcare worker exposure
• Nebulizer performance is a mass median diameter (MMD) of 1-2 μm

Respirgard II Nebulizer System

• It uses one-way valves and an expiratory filter to scavenge exhaust aerosol

Side Effects of Pentamidine (Aerosol Administration)

• Cough and bronchial irritation affects 36% of patients in one study
• Shortness of breath
• Bitter or burning taste from aerosol impacting in the oropharynx
• Bronchospasm and wheezing affect 11% of patients
• Spontaneous pneumothoraces
• Conjunctivitis
• Rash
• Neutropenia
• Pancreatitis
• Renal insufficiency
• Dysglycemia (hypoglycemia and diabetes)
• Digital necrosis in both feet
• Appearance of extrapulmonary P. jiroveci infection

Environmental Contamination of Pentamidine

• Environmental contamination is caused by nebulized pentamidine
• There is exposure to the drug itself from exhaust aerosol
• There is a risk of infection with tuberculosis
• It is not known to be teratogenic or mutagenic
• Possible carcinogenic effects are minimal

Clinical Indications for Ribavirin

• Aerosolized ribavirin is indicated for treating hospitalized infants with severe lower respiratory tract infection caused by respiratory syncytial virus (RSV)
• Ribavirin is classified as an antiviral drug that is active against RSV, influenza viruses, and herpes simplex virus
• It is a nucleoside analog that resembles guanosine and inosine
• Ribavirin is virostatic, not virucidal
• It inhibits both DNA and RNA (retrovirus) viruses

Nature of Viral Infection

• Process:
  • Adsorbs to cell
  • Penetrates cell
  • Uncoats itself
  • Recodes cell DNA
  • Assembles itself
  • Sheds from cell
• It is an obligate intracellular parasite
• Diagnosis is usually based on clinical signs
• Diagnosis requires isolating the virus or demonstrating antibody titer increase

Dosage of Ribavirin

• Administer as a 20-mg/mL solution using SPAG-2
• Treatments last 12 to 18 hours per day for a minimum of 3 days and no more than 7 days
• It is supplied as 6 g of powder in a 100-mL vial
• Concentration is 6 g/300 mL

SPAG Unit

• A small particle aerosol generator (SPAG) unit is used for nebulizing ribavirin

Side Effects of Ribavirin

• Pulmonary Deterioration of pulmonary function and worsening of asthma or chronic obstructive disease; pneumothorax, apnea, and bacterial pneumonia
• Cardiovascular: Cardiovascular instability, including hypotension, cardiac arrest, and digitalis toxicity
• Hematological: Effects on blood cells have been reported with oral or parenteral administration but not with aerosol use
• Reticulocytosis (excess of young erythrocytes in circulation) has been reported with aerosol use
• Dermatological/topical: Rash, eyelid erythema, and conjunctivitis

Environmental Contamination Ribavirin

• Potential for mutagenic and carcinogenic effects
• Effect on fertility is uncertain
• Caused testicular lesions in rats
• Effect on pregnancy is of particular concern
• Can be teratogenic or embryocidal in animal species

RSV Infection—Other Agents: Palivizumab

• Palivizumab (Synagis) is prescribed for the prevention of serious lower respiratory tract disease caused by RSV in children and infants at high risk
• Safety and efficacy established for infants with BPD
• It is administered to premature infants (<35 weeks) and children with congenital heart disease
• Dosage is 15 mg/kg, given IM monthly in RSV season
• Mechanism of action includes Monoclonal antibodies that provide neutralizing and fusion-inhibiting activity, and prevents viral replication

Clinical Indications for Tobramycin

• Aerosolized tobramycin is indicated for the management of chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF)
• It is clinically used for pulmonary infections in CF
• It treats or prevents early colonization with P. aeruginosa
• It also maintains present lung function or reduces the rate of deterioration

Aerosolized Tobramycin

• Dosage and administration include 300 mg BID
• 28 days consecutively/following 28 days off
• 300 mg in 5-mL ampule and Administered with PARI LC Plus
• Its mechanism of action Binds irreversibly to 30S subunit of bacterial ribosomes
• Blocks protein synthesis in bacteria and causes cellular death, a bactericidal

General Considerations: Tobramycin

• General considerations in aerosolizing antibiotics include:
  • May affect nebulizer performance
  • Environmental contamination
  • Incompatibility with other drugs

Clinical Indications for Aztreonam

• Aerosolized aztreonam is indicated to improve symptoms in CF patients with P. aeruginosa infection
• The clinical use includes pulmonary infections (CF)
• It improves pulmonary symptoms in CF patients colonized with P. aeruginosa
• It is not indicated for patients <7 years old
• Only studied in patients having an FEV₁ about 25% or below 75% of predicted

Aerosolized Aztreonam

• Dosage and administration includes that it must be reconstituted
• 2-mL single use glass vials contain 75 mg of lyophilized aztreonam
• It must be mixed with provided 1 mL of sterile diluent (0.17% sodium chloride)
• Comes in 28-day kit Delivered by itself using Altera Nebulizer System

Clinical Indications for Zanamivir

• Inhaled zanamivir is indicated for influenza in adults and children 5 years and over who have been symptomatic for no more than 2 days
• It has off-labeled use for treatment and prophylaxis of H1N1 influenza A (swine flu)
• Dosage and administration includes DPI (Diskhaler) that is 5 mg/blister
• Adults and children 5 years and older take two inhalations (two blisters, for a total of 10 mg) that should be taken twice a day, approximately 12 hours apart, for 5 days

Inhaled Zanamivir

• Bronchospasm and deterioration of lung function
• It is not indicated with patients with underlying asthma or COPD
• Other adverse effects include: undertreatment of bacterial infection, allergic reactions, gastrointestinal, respiratory, and dizziness/headache

Inhaled Zanamivir

• Treatment with 10 mg of zanamivir twice daily resulted in approx. 1 day less to median time to improvement in symptoms compared with placebo
• Treatment with zanamivir 30 hours or less after onset of symptoms resulted in 3 days or less to median time to alleviation of symptoms
• Not generally recommended for patients with underlying airway disease and Not approved for prophylaxis

Respiratory Care Assessment: Before Treatment

• Asses the patient for the presence of a disease in which use of the agent is indicated for:
  • Pentamidine: risk of PCP
  • Ribavirin: presence of severe RSV infection
  • Tobramycin: chronic P. aeruginosa infection in CF patient
  • Aztreonam: chronic P. aeruginosa infection in CF patient
  • Zanamivir: acute influenza infection within two days of onset
• Assess equipment
• Initial patient assessment

General Contraindications

• Bronchospasm and cough
• Ribavirin, should be avoided during exposure by pregnant caregiver
• Tobramycin: Drug resistance
• Aztreonam: Drug resistance
• Zanamivir: Caution in patients with preexisting airway disease