Respiratory Flashcards
Beta2 Receptor Agonists: Albuterol
(Proair, Ventolin, Proventil)
Selective beta2 agonists with minor beta1 activity
Short-acting
Beta2 Receptor Agonists: Salmeterol
(Serevent)
Long-acting
More selective for beta2 receptors compared with albuterol and have minor beta1 activity
12 hour half life
Beta2 Receptor Agonists: Precautions and Contraindications
- Cardiac arrhythmias
- Diabetes: potential drug-induced hyperglycemia
- Long-acting beta agonists:
- —Black box warning: the risks of salmeterol and formoterol (foradil) outweigh the benefits & should not be used singly in asthma for all ages
- —Twofold increase in catastrophic events (asthma-related intubations & death)
- Terbutaline pregnancy category B (Others category C)
- Children
- —Albuterol safe for children of all ages
- — Salmeterol should not be used in children younger than age 4 years and never singly
Beta Agonsits: ADRs
Usually transient
Tachycardia and palpitations
Some central nervous system (CNS) excitation effects
- Tremors, dizziness, shakiness, nervousness, and restlessness
Headaches
Salmeterol and other long-acting B2RAs increase risk of exacerbation of severe asthma symptoms if patient is deteriorating
Beta Agonists: Drug Interactions
Digitalis glycosides: increased risk of dysrhythmia
Beta adrenergic blocking agents: direct competition for beta sites resulting in mutual inhibition of therapeutic effects
- Including beta blocker eye drops
Tricyclic antidepressants (TCAs) & monoamine oxidase inhibitors (MAOIs) potentiate effects of beta agonist on vascular system
Beta Agonists: Clinical Use
Bronchodilators are used primarily in the treatment of bronchospasm associated with asthma, bronchitis (acute or chronic), and COPD
Albuterol metered dose inhaler (MDI) dose is 2 puffs every 4-6 hours
- Dose via nebulizer is 2.5 mg/dose
- May be repeated twice after 5-10 minutes
- May be combined with ipratropium
Levalbuterol via nebulizer every 4-6 hours
Salmeterol DISKUS: 1 puff twice a day– do not use alone for persistent asthma; combine with an inhaled corticosteroid
Exercise induced bronchospasm (EIB)
- Albuterol 2 puffs 15 minutes before exercise
- Salmeterol 2 puffs 30-60 minutes before exercise— do not use if already on daily dose
- Leukotriene modifiers taken daily may decrease EIB symptoms in 50% of patients but patient will still need to use albuterol before exercise
Beta Agonists: Rational Drug Selection
The Expert Panel 3 says ay short-acting beta agonist can be used in adults
Age
- Only albuterol and metaproterenol are approved for use in children younger than 4 years of age.
- Albuterol is the safest to use in infants
Cost
- Albuterol is the least expensive
Beta Agonists: Patient Education
Metered-dose inhaler (MDI) use
- Demonstrate and have patient do return demonstration
- Check correct inhaler use if patient says the inhaler is not working
- Use a spacer with all patients
Breath-actuated inhalers require inspiratory drive to deliver medication to lungs
Xanthine Derivatives: Theophylline and Caffeine Pharmacodynamics
- Bronchial smooth muscle relaxation
- CNS Stimulation
- Cardiovascular effects
- Increased Gastric acid production
- Stimulation of skeletal muscle
- Increased renal blood flow and glomerular filtration rate
Xanthine Derivatives- Theophylline: Pharmacokinetics
Absorbed rapidly and completely from GI tract
Distributed widely
- Volume of distribution altered in: premature neonates, older patients, cirrhosis, pregnant women (third trimester), and critically ill patients, probably because of altered protein-binding
Metabolized extensively in liver via CYP450 into caffeine
- Disease states and CYP inducers can influence metabolism of theophylline
Eliminated renally
Xanthine Derivatives- Theophylline: Precautions & Contraindications
Monitor patients with HTN, ischemic, heart disease, coronary insufficiency, CHF, or a hx of stroke and cardiac arrhythmias
Monitor for theophylline toxicity
Prolonged clearance and half-life in neonates and older adults
Pregnancy Category C
Xanthine Derivatives- Theophylline: ADRs
- Toxicity with levels greater than 20 mcg/mL
- Some patients have seizures at 15-20 mcg/mL
- CNS effects: irritability, restlessness, seizures, insomnia
- GI effects: reflux, worsening heartburn
- Cardiac effects: palpitations, tachycardia, hypotension, life-threatening arrhythmias
- Toxicity (greater than 20 mcg/mL): N/V, diarrhea, HA, insomnia, & irritability
- Toxicity (greater than 35 mcg/mL): hyperglycemia, hypotension, cardiac arrhythmias, tachycardia, seizures, brain damage, death
Xanthine Derivatives- Caffeine: ADRs
Cardiac arrhythmias Tachycardia Insomnia Agitation Irritability HA N/V Gastric Irritation
Xanthine Derivatives- Theophylline: Drug-Food Interactions
- Many drug interactions are caused by metabolism via CYP450 isoenzyme CYP1A2, CYP2E1, and CYP3A3/4
- Smoking tobacco increases clearance
- Benzodiazepines are antagonized by theophylline
- Beta agonists may cause additive toxicity
- Lithium levels are reduced
- Low-carb/high-protein diet increases clearance
- Charcoal-broiled foods accelerate the hepatic metabolism of theophylline
Xanthine Derivatives- Caffeine: Drug Interactions
Caffeine metabolized via CYP450 isoenzyme CYP1A2, CYP2E1, and CYP3A3/4
Impaired caffeine metabolism: cimetadine, ketoconazole, fluconazole, mexiletine, and phenylpropanolamine
Caffeine elimination may be increased by co-administration of phenobarbitol and phenytoin
Xanthine Derivatives- Theophylline: Clinical Use & Dosing
Second- or third-line drug for asthma and COPD
Adults started on 6 mg/kg/24 hours and dose increased by 25% every 3 days until serum theophylline levels are 10-20 mcg/mL
Maximum dose in adults is 13 mg/kg/day
Children age 5 years or older: 16 mg/kg/day, max 400 mg/day
- 1 to 9 years: max dose 24 mg/kg/day
- 9 to 12 years: max dose 20 mg/kg/day
- 12 to 16 years: max dose 18 mg/kg/day
Apnea of Prematurity: Treatment
Caffeine citrate 10-20 mg/kg
- Maintenance dose of 5 mg/kg per day
Theophylline dose
- Loading dose of 4 mg/kg per dose
- Maintenance dose of 4 mg/kg per day in the premature infant or newborn up to age 6 weeks
Xanthine Derivatives- Theophylline: Rational Drug Selection
Cost and Convenience
Immediate release
- Use at beginning of therapy to determine daily dose
- Once stabilized on immediate release, transition to extended release once the total 24-hour dose has been determined
Timed release
- Taken daily at the same time
Xanthine Derivatives- Theophylline: Monitoring
Monitor for signs of toxicity
Draw frequent levels when dose is being titrated
After steady state, draw levels every 6 to 12 months
Draw levels whenever any new drug is added or deleted from regimen
Xanthine Derivatives- Theophylline: Patient Education
Take medication exactly as prescribed
Discuss signs & symptoms of toxicity
- N/V, insomnia, jitteriness, HA, rash, severe GI pain, restlessness, convulsions, or irregular heartbeat
Avoid large amounts of caffeine containing beverages
Explain that theophylline elimination is influenced by diet
Inhaled Anticholinergics
Ipratropium bromide (Atrovent) - Blocks muscarinic cholinergic receptors
Tiotropium bromide (Spiriva) and Aclidinium bromide (Tudorza Pressair) - Inhibits muscarinic M3 receptors in lungs
All cause bronchial smooth muscle relaxation
Anticholinergics: Precautions and Contraindication
Known hypersensitivity
Not used for acute bronchospasm
Ipratropium bromide is pregnancy category B and tiotropium is pregnancy category C
Not approved for use in children younger than age 12 years
- Expert Panel 3 guidelines state ipratropium may be used in children as an adjunct to beta agonist (albuterol) therapy in acute exacerbations of asthma
Inhaled Anticholinergics: ADRs
Cough is most common
Dry mouth
Mild anticholinergic effects in a few patients
- Constipation
- Urinary retention (less than 2%)
Rare allergic reaction
- Allergy to soybeans, legumes, or soy lecithin appears to be correlated with hypersensitivity to ipratropium bromide
Inhaled Anticholinergics: Clinical Use & Dosing for COPD
- Ipratropium: 2 puffs (36 mcg) 4 times/day (max 12 puffs/day)
- Ipratropium: 1 unit dose via nebulizer 3-4 times/day, may be mixed with albuterol
- Ipratropium-albuterol combination (combivent): 2 puffs 4 times/day
- Tiotropium (spiriva): 2 puffs of a single capsule once/day
- Aclidinium bromide (Tudorza Pressair): 1 puff twice/day
Inhaled Anticholinergics: Clinical Use & Dosing for Asthma
Ipratropium for asthma maintenance is 2-3 puffs 4 times/day for adults
- Children age less than 12 years: 1-2 puffs every 6 hours
Ipratropium-albuterol combination (Combivent) is a second-line quick relief medication in treatment of asthma
Tiotropium and aclidinium are not indicated for the treatment of asthma
Inhaled Anticholinergic: Cost and Patient Education
Cost
- Combined albuterol-ipratropium products are cheaper than the two individual drugs
- —–Generic ipratropium/albuterol nebulizer solution is $32 for a month’s supply
- Tiotropium (Spiriva) costs $415 per month
- Aclidinium bromide (Tudorza Pressair) costs $2360 per month
Patient Education
- Use as prescribed
- Be educated on use of inhaler or handihaler
- Rinse mouth after inhaling medication
Leukotriene Modifiers: Pharmacodynamics
- Induce numerous effects that contribute to inflammatory process
- Smooth muscle contractions
- Leukotriene-Receptor Agonists
- —Zafirlukast & Montelukast
- 5-Lipoxygenase Pathway Inhibitors
- —- Zileuton
Leukotriene Modifiers: Precautions
Do not do the following:
- Use for primary treatment of acute asthma attack
- Abruptly substitute for inhaled or oral steroids
- Prescribe for lactating women
Zafirlukast: patients with hepatic dysfunction