Corticosteroids, Anti-Infectives, Vasodilators & Critical Care Agents

Covers Slides 89–152: Corticosteroids, nonsteroidal anti-asthma agents, anti-infective agents, cold and cough agents, pulmonary vasodilators, neuromuscular blocking agents, diuretics, and fluid resuscitation.

Listen: Corticosteroids, Anti-Infectives, Vasodilators & Critical Care Agents

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Corticosteroids

Corticosteroids produce anti-inflammatory action in the lungs by inhibiting cytokines and pro-inflammatory cells.

Indications: primary maintenance treatment for asthma

Administration: orally, IV, inhalation. Inhalation is the preferred route for respiratory treatment.

Contraindicated for acute exacerbations!

Long lasting. Most are given BID.

Commonly combined with LABAs in a single treatment.


Inhaled Corticosteroids — Reference

Generic NameBrand Name
BeclomethasoneQvar
FlunisolideAerospan MDI
FluticasoneFlovent MDI, Flovent Diskus
BudesonidePulmicort, Pulmicort Respules
MometasoneAsmanex Twisthaler
CiclesonideAlvesco

Inhalation Route

  • First line maintenance and control therapy for chronic asthma and COPD
  • Also prescribed if the patient is using SABA more than a few days per week
  • Given if the patient is also waking up at night with SOB

Side Effects

  • Decrease efficacy of hypertensive and diabetic medications
  • Osteoporosis, cataracts, elevated BP, drug interaction, bleeding risk
  • Potential growth retardation in pre-pubescents

Fungal Infections

  • Candida Albicans — yeast infection (Thrush)
  • Aspergillus Niger

Prevention:

  • Utilize a holding chamber
  • Rinse mouth post treatment

Corticosteroid + LABA Combinations

CombinationBrand Name
Fluticasone + SalmeterolAdvair DPI & MDI
Mometasone + FormoterolDulera MDI
Budesonide + FormoterolSymbicort MDI

Nonsteroidal Anti-Asthma Agents

Primary indication: prophylactic management of mild persistent asthma

Used in conjunction with anti-inflammatory therapy.

Controller medication, not a symptom reliever or for acute exacerbations!


Asthma Inflammation Triggers

Extrinsic or Atopic (Environmental) — allergic hypersensitivity reactions to antigens

  • Examples: pollen, dust, smoke, automobile exhaust, or animal dander

Intrinsic — non-allergic sensitivity; internal factors within the body that can initiate an inflammatory response, even in the absence of external threats like infection or injury.


Inflammatory Trigger Cascade

  1. Extrinsic trigger enters body (allergen sensitivity)
  2. Release of mediators target airway tissue (immune cells that promote inflammation)
  3. Inflammatory cells activated in airways
    • Leukotrienes
    • Histamine
    • Prostaglandins
    • Phosphodiesterase

Mast Cell Stabilizers

Cromolyn Sodium

Action: encapsulates the cell membrane making breach of the membrane more difficult — ultimately neutralizing release of inflammatory mediators (histamine, prostaglandins, leukotrienes).

Result: decreased severity and episodes in asthma and COPD exacerbation.


Anti-Leukotrienes

Zafirlukast (Accolate)

  • Indication: prophylaxis and long-term treatment of asthma in patients 5 years and older
  • Dose: x2 daily with LABA

Montelukast (Singulair)

  • Indication: prophylaxis and long-term treatment of asthma in patients >12 months
  • Dose: x1 daily

Zileuton (Zyflo)

  • Indication: prophylaxis and long-term treatment of asthma in patients 12 years and older
  • Dose: 600 mg tablet QID; two extended-release tablets BID
  • Liver damage susceptibility — liver enzymes checked regularly!

Monoclonal Antibody (Anti-IgE)

Omalizumab (Xolair)

Indications:

  • Moderate or greater perennial allergic asthma
  • Patients >12 years and not controlled with inhaled steroids

Administered: subcutaneous injection q2–4 weeks

Action: prevents IgE (immunoglobulin E) from attaching to mast cells (blocks IgE).


Phosphodiesterase Enzyme (PDE4) Inhibitor

Roflumilast

Indication: inhibit the inflammatory response associated with COPD exacerbations

Action: increases cAMP, produces long-acting inhibition of the PDE4 enzyme. By increasing cAMP, we suppress pro-inflammatory pathways.

Administration: oral


Anti-Infective Agents

Treatments for Pneumonia

Quinolones

Treat Gram+/- bacteria. A more broad-spectrum type of antibiotic.

  1. Ciprofloxacin
  2. Levofloxacin
  3. Moxifloxacin
  4. Gemifloxacin

Macrolides

Treat Gram+ bacteria and limited Gram- bacteria.

  1. Azithromycin
  2. Clarithromycin
  3. Erythromycin

Anti-Infective Inhaled Aerosol — Reference

Generic NameBrand Name
PentamidineNebupent
TobramycinTobi
Gentamicin
AztreonamCayston
Amphotericin B
ZanamivirRelenza
RibavirinVirazole

Pentamidine (Nebupent)

Indication: prophylactic therapy for Pneumocystis Carinii Pneumonia (PCP) common in AIDS infected patients

Negative effects: bronchospasm, shortness of breath, and bronchial irritation

Bronchodilator pre-treatment may reduce symptoms.

Administration: nebulized solution

  • Utilize negative airflow rooms with HEPA filtration
  • Respirgard II nebulizer — protects care environment
  • N-95 mask and full PPE worn by providers

Ribavirin (Virazole)

Indication: infants with severe Respiratory Syncytial Virus (RSV)

Administration: Small Particle Aerosol Generator (SPAG-2)

Precautions:

  • Utilize negative airflow rooms with HEPA filtration
  • Negative side effects — exposure concerns to providers (GI, CNS, hematologic)

Tobramycin (Tobi)

Indication: Chronic Pseudomonas Aeruginosa (common treatment for CF patients) — Gram negative organism

Dose: adults and children >6 yrs — 300 mg in 5 mL, x2 daily

  • Not mixed with other medications
  • Last medication of each therapy visit

Administration: nebulized solution. Use negative airflow rooms with HEPA filtration.

Inhaled negative effects:

  • Teratogenic effects — fetal abnormalities risk during pregnancy
  • Voice alteration and tinnitus
  • Ototoxicity — hearing loss with prolonged use
  • Nephrotoxicity — impaired renal function

Aztreonam (Cayston)

Indication: Chronic Pseudomonas Aeruginosa

Administration:

  • Not recommended for children younger than 7 years of age
  • May cause bronchospasm and decrease in FEV1

Pretreatment with a bronchodilator is recommended.


Gentamicin

Indication: Pseudomonas Aeruginosa (common with CF)


Amphotericin B

Indication: pulmonary fungal infections (transplants)

  • Aspergillosis
  • Candida Albicans

Zanamivir (Relenza)

Indication: influenza in adults and children older than 5 years of age within the first 2 days of infection

Mode: DPI / Diskhaler

Dose: two inhalations — 5 mg each, Q 12 hrs/BID for 5 days

Negative effects:

  • Bronchospasm
  • Not recommended for patients with underlying airway disease

Pneumovax — Pneumococcal Vaccine

Indications:

  • Protects against influenza bacteria
  • Protects against Streptococcus Pneumoniae

Immunization annually: health care providers, children, people with risk of aspiration, school and work communities, individuals predisposed to environmental risk

Contraindications: allergy sensitivity (rare)


Cold and Cough Agents

Antihistamines

Secretion modifiers: medications that inhibit mucus production and/or modify mucus rheology or consistency.

Indication: reduce the volume of secretions associated with upper airway diseases and allergies

Effects: produces strong, long acting, drying effect

Medications:

  • Allegra, Zyrtec and Claritin — non-sedating
  • Benadryl (Diphenhydramine) — sedating effect

Pulmonary Vasodilators

Inhaled Nitric Oxide (INOmax)

Indication:

  • Persistent Pulmonary Hypertension in Neonates (PPHN) >34 wks
  • Decreases need for ECMO

Off label benefits (NOT FDA approved):

  • Acute pulmonary hypertension in adults
  • ARDS — Acute Respiratory Distress Syndrome
  • Post lung transplant perfusion
  • Reduce pulmonary vascular resistance (PVR)
  • Reduce pulmonary artery pressure (PAP)

Treatment: normally for 14 days or less

Delivery modalities:

  • Inline mechanical ventilator life support (primary mode)
  • High flow NC (Vapotherm) — neonates and adults

Recommended dose: less than 20 ppm

Risks

  • Methemoglobin — a ferric (Fe3+) hemoglobin molecule and cannot bind with oxygen
  • Slow weaning — prevent rebound

Prostacyclin

  • Iloprost (Ventavis)
  • Treprostinil (Tyvaso)
  • Epoprostenol Sodium (Flolan)

Skeletal Muscle Relaxants (Neuromuscular Blocking Agents)

NMBAs

Indications:

  • Facilitate intubation (paralyze vocal cords)
  • Surgery — immobilize patients
  • Enhance ventilator synchrony
  • Reduce intracranial pressure (ICP)
  • Reduce O2 consumption

NMBAs work to paralyze and relax skeletal muscles. Affects skeletal muscle only.


Depolarizing Agents

Succinylcholine — only agent in this category

Action: OCCUPIES acetylcholine receptors

  • Paralysis in 60–90 seconds
  • Effect persists for 10–15 minutes
  • Ideal for patients requiring intubation

No reversal agent!

Adverse Effects

  • Dry eyes
  • Tachycardia
  • Hypotension
  • Malignant hyperthermia
  • Muscle pain and muscle weakness
  • Hyperkalemia — efflux of potassium from muscle cells
    • Effects of severe hyperkalemia include arrhythmias and cardiac arrest

Non-Depolarizing Agents

Action: BLOCK acetylcholine receptors

  • Longer duration than depolarizing agent — approximately 30 minutes
  • Preferred for paralysis of mechanically ventilated patients
  • Onset varies — dosage dependent: >5 minutes

Non-depolarizing agents:

  • Rocuronium
  • Vecuronium
  • Pancuronium

Reversal agent: Neostigmine

Adverse Effects

  1. Inadequate ventilation — paralysis of diaphragm and intercostal muscles
  2. Cardiovascular — vagolytic effect triggers tachycardia; increase in mean arterial pressure (MAP). Pancuronium has greatest potential for cardiovascular side effects.
  3. Histamine release — histamine release from mast cells triggers hypotension

Diuretic Agents and Fluid Resuscitation

Urine Output

  • Normal: 30 to 60 mL/hr
  • Anuria: no urine output (sign of renal failure)
  • Oliguria: less than 30 to 60 mL/hr
  • Polyuria: >60 mL/hr

Diuretics

Indications:

  • IV resuscitation fluid overload
  • Congestive Heart Failure
  • Hypertension
  • Pulmonary edema, cerebral edema (TBI), renal dysfunction

Contraindications: hypovolemia, pregnancy and women breast feeding

Diuretic effects:

  • Stimulate urine production
  • Eliminates excess extracellular fluid volume
  • Reduces blood pressure

Side effects: hypovolemia, acid-base abnormalities


Common Diuretics

CategoryMedications
Carbonic Anhydrase InhibitorAcetazolamide, Methazolamide, Dichlorphenamide
OsmoticMannitol, Glycerol, Urea
LoopFurosemide (Lasix) — most commonly used for CHF!
ThiazideChlorothiazide, Hydrochlorothiazide
Potassium SparingAmiloride, Spironolactone

Fluid Resuscitation

Indications:

  • Hypotension
  • Hypovolemia
  • Postural Hypotension
  • Shock

Treatments:

  • Fluids — intravenous and oral rehydration. Give blood products, colloids etc.
  • Chemical — vasopressor agents (norepinephrine, dopamine etc.)
  • Patient placed in Trendelenburg position

Hypotension

Hypotension — blood pressure less than 90/65 mmHg

NOT SYNONYMOUS WITH SHOCK!

Hypotension caused by dehydration (hypovolemia) and is reversed by rehydration.


Hypovolemia

Decreased blood volume.

Causes:

  • Initiation of diuretic treatment or increased dose
  • Reduced dietary sodium intake
  • Diarrhea or excessive sweating
  • Ingesting drugs that impair diuretic administration

Indications: sinus tachycardia; decreased CO and SV; dizziness, extreme thirst, excessive mouth dryness, decrease or dark urine output, constipation


Postural Hypotension

Indication: dizziness upon standing or abruptly sitting up, caused by reduced cerebral blood flow.

  • Healthy individuals with mild hypovolemia
  • Syncope if more serious (fainting)
  • Medication side effects/interactions

Verification method: measure blood pressure in the supine and sitting positions or standing up


Shock

Shock — inadequate delivery of O2 and nutrients to vital organs relative to their metabolic demand.

  • Hypo-dynamic: cardiogenic; hypovolemic
  • Hyper-dynamic: vascular; septic; anaphylactic

Resuscitation Fluids

Colloid — Volume Expanders

Large molecule solution — incapable of crossing the healthy semipermeable capillary membrane owing to the molecular weight/size of the molecules.

  • Human Albumin (4 to 5%) in saline
  • Hydroxyethyl Starch (HES)

Crystalloid — Carrier and Expander

Small molecule solution — flow crosses semipermeable membrane allowing transfer from bloodstream into cells and body tissues.

  • Normal saline (0.9%) — most common