Pulmonary Flashcards
Family HX (age of onsent) Asthma and COPD
Asthma: < 30
-Family Hx: usually
COPD: > 40
-Family Hx: uncommon
Prominent cough (age of onsent) Asthma and COPD
Asthma: < 30
- Prominent cough: Nocturnal, post excercise
COPD: > 40
- Prominent cough: early in the morning
Hx of Atopy (age of onsent) Asthma and COPD
Asthma: < 30
- Hx of Atopy: often
COPD: > 40
- Hx of Atopy: uncommon
Bronchodilator Reversibility (age of onsent) Asthma and COPD
Asthma: < 30
- Bronchodilator reversibility: highly to completely
COPD: > 40
- Bronchodilator reversibility: partial
Steroid responsiveness (age of onsent) Asthma and COPD
Asthma: < 30
- steroid responsiveness: strong
COPD: > 40
- steroid responsiveness: weak usually
Progressive deterioration (age of onsent) Asthma and COPD
Asthma: < 30
- Progressive deterioration: uncommon
COPD: > 40
- Progressive deterioration: typical
Anticholinergic responsivity (age of onsent) Asthma and COPD
Asthma < 30
- Anticholinergic Deterioration: B agonist better
COPD > 40
- Anticholinergic Deterioration: Best first line treatment
Beta agonist responisivity (age of onsent) Asthma and COPD
Asthma < 30
Beta Agonist Responisvity:
Excellent
COPD > 40
Beta agonist responisivity: Anticholinergic better
Purulent sputum (age of onsent) Asthma and COPD
Athma < 30
Purulent sputum: uncommon
COPD > 40
Purulent Sputum: Typical
Smoking hx (age of onsent) Asthma and COPD
Asthma > 30
Smoking hx:
Variable
COPD > 40
Smoking hx:
Usually present
Pulmonary - Parental route:
- Will result in high plasma concentrations
- High ratio of side effects to desired effects
- Only used for severely ill patients who cannot be administered drugs via any other means
Pulmonary - Oral Route:
- Theophylline( ineffective if given via inhaled route)
- Corticosteroids when needed for interstitial disease
- β 2 Agonist and Corticosteroids only if the patient is too young or physically unable to administer the drugs via inhaler
- Dose will have to be about 20:1 greater if given via oral route
80% of the drug delivered via inhalation will be swallowed, absorbed and enter the systemic circulation after first pass metabolism and some drug will also enter the systemic circulation after it reaches the lungs.
T/F
TRUE
What is the optimum particle size for inhaled medications?
2-5 um mass medium aerodynamic diameter (MMAD)
Delivery to smaller airways in cases of COPD and severe asthma will need 1um using hydrofluoroalkane propellant.
T/F
TRUE
The lack of a spacer will reduce the amount swallowed and absorbed and therefore will decrease systemic effects.
T/F
FALSE
Pressurized Metered-Dose Inhalers (pMDI)
- Patients frequently fail to use these appropriately
- Must be coordinated with inspiration
- Usually will contain up to 400 doses of medication (100-400 range)
What to know about Spacer Chambers
- Device that is placed between the pMDI and the patient
- Decreases the velocity of the drug and the amount of the drug deposited on the oropharynx = more drug to pulmonary tissue
- Useful in small children
Requires less coordinated effort - Decreases side effects of drugs (less systemic absorption
Dry Powder Inhalers
More difficult for children less than 7 years of age as they cannot generate enough respiratory flow
Nebulizers
- Jet: Stream of air or oxygen
- Ultrasonic: vibrating piezo-electrical crystal
- Delivers much higher dose of drug
- Used for acute exacerbations of asthma or COPD
- Infants and children who cannot use inhaler
Commonly used bronchodilators
- β 2 Adrenergic Agonist
- Theophylline
- Anticholinergic Agents (muscarinic receptor antagonists) – primarily parasympathetic muscarinic receptors in lungs
What role do B2 agonists play in the role of bronchodilation?
Decrease:
- plasma exudation
- cholinergic neuro-transmission
- neutrophil function
- bacterial adherence
Increases –> mucociliary clearance
Which class and medications are indicated to treat:
- Acute asthma attack
- Not for prophylaxis
- Duration of Action 2-4 hrs
B2 Agonist - Short acting bronchodilator
- Albuterol
- Metaproterenol
- Terbutaline
Oral and Parenteral also
Which class and medications are indicated to treat:
- Asthma Prophylaxis not for acute attacks
- Duration of Action 12-24 hrs
- Bronchoconstriction prevention > 12 hours
- Always used with inhaled corticosteroid as they do not reduce chronic inflammation
B2 Agonist Long action (LABA)
- Salmeterol,
- Formoterol,
- Indacaterol
- Vilanterol
What is the recommended dose of epinephrine given SQ)
- Adults in doses of 0.3 to 0.5 mg subcutaneously. -Epinephrine injection is associated with some pain at the injection site; potential side effects include: -headache
-tremor - palpitations
-GI upset
Injections may be repeated every 20 to 30 minutes for a total of 1 mg.
What is the recommended dose of terbulatine given SQ?
1 dose of 0.5 mg or in 2 doses of 0.25 mg 30 minutes apart.
What are side effects of B2 agonists?
- Muscle tremor
- Tachycardia
- Hypokalemia
- Restlessness
- Hypoxemia
LABAs should typically be used as an independent therapy.
T/F
FALSE
- ALWAYS USE IN COMBINATION OR ALONG WITH ICS.
COMBINED USE OBVIATES THE ISSUE WITH LABAS AND INCREASED MORTALITY.
Increased morbidity and mortality are associated with which two classes of medications used to treat pulmonary ailments?
Found with both short-acting β2 Agonist and LABA
Possibly related to Up regulation of PLC (phospholipase C) which can lead to an increased broncho-constrictor response to cholinergic activation
If the use of short acting inhaled β2 agonist for short term symptom control are needed more than 3 X a week, which adjunct therapy is recommended?
ICS is also required for control of asthma at this point
Describe the effects of Mehtylxanthines
THEOPHYLLINE:
- Phosphodiesterase Inhibition and Adenosine Receptor Antagonist
- Decreases Eosinophil Count
- Acts on T-Lymphocytes to decrease cytokines
- Acts on Mast cells to decrease mediators of inflammation
- Acts on Macrophages to decrease circulating cytokines
- RESULTLING IN BRONCHODILATION
- INCREASED STRENGTH IN MUSCLES OF RESPIRATION
- DECREASE LEAK IN ENDOTHELIAL CELLS
What are the administration requirements for theophylline?
Nocturnal Asthma: - Slow Release Pill - Duration: 12 hours IV for Acute Asthma: - 6mg/kg over 20-30 minutes - Maintenance Dose = 0.5mg/kg/hour - Beta agonist are preferred over this choice and theophylline is used in addition to the beta agonist in a patient with severe asthma.
What are the side effects of theophylline?
PDE4 Inhibition: - Nausea and Vomiting A1 Receptor antagonism: - Diuresis and Epileptic seizures PDE3 Inhibition and A1 Receptor antagonism: - Cardiac arrhythmias
What is a muscarinic antagonist?
- An agent that have high binding affinity for the muscarinic receptor but have no intrinsic activity.
What do muscarinic antagonists compete with occupy muscarinic receptors?
- Acteylcholine
- They are competitive (reversible) antagonists of acetylcholine
- Their pharmacological actions are opposite to that of the muscarinic agonists.
Anticholinergic medications effectively inhibit the bronchoconstriction mediated via vagal nerve activation AS WELL AS bronchoconstriction caused by inflammatory such as histamine or leukotrienes. T/F
FALSE
They do NOT inhibit bronchoconstriction caused by inflammatory such as histamine or leukotrienes
Muscarinic cholinergic antagonists in asthma are more effective against asthma exacerbated by cold air and emotional triggers?
T/F
TRUE
Muscarinic cholinegic antagonists in asthma are less effective in older asthmatic patients if there is fixed airway obstruction.
T/F
FALSE
Muscarinic Cholinergic Antagonists in Asthma May have an additive effect in acute asthma attacks when combined with a β2 Agonist.
T/F
TRUE
Muscarinic Cholinergic Antagonist in COPD May be as effective or even better than β2 Agonist. T/F
TRUE
- Inhibits the vagal tone which may be one of the few reversible elements in this population
- Reduces air trapping
- Improve exercise tolerance in this population
Tiotropium Bromide: Spiriva
- Long acting for once daily dosing
- More effective in COPD patients than Ipratropium multi-dosing
- Improved lung function and reduces exacerbations and mortality in COPD population
Ipratropium Bromide: Atrovent
- Slow onset with maximum effect 30-60 minutes after administration
- LOA = 6-8 hours so given 3-4 X a day
- May be used as a combination with B2 agonist albuterol Combivent for patient with COPD to decrease side effects of increase B2 dose
Adverse effects of Spriva and atrovent (which are muscarnic cholinergic antagonists) are…
- Rebound effect after stopping
- Little systemic absorption so few systemic side effects.
- May cause glaucoma in elderly due to drug coming in contact with the eye: use a mouth piece.
- Urinary retention and dry mouth are possible.
Are corticosteroids the most effective controller therapy available for asthma?
YES
What disease processes are corticosteroids primary used for?
- Asthma
- Sarcoidosis
- Interstitial lung disease
- Pulmonary eosinophilic syndromes.
Glucocorticoids in asthma are involved in Transcription of anti-inflammatory genes and suppression of other genes responsible for inflammation.
T/F
TRUE
Glucocorticoids in asthma may increase the inflammatory cells in the epithelium and sub-mucosal layers in pulmonary tissue.
T/F
FALSE
Glucocorticoids in asthma may completely resolve issues in patients with mild asthma pathology.
T/F
TRUE
Glucocorticoids in asthma inhibit the formation of cytokines and secretions of T-lymphocytes, macrophages and mast cells and the formation of mucus. T/F
TRUE
Glucocorticoids in Asthma ARE effective in early response but very effective in later response (within a few hours) but most effective in decreasing the hyper-responsive nature of the asthmatic pulmonary airway.
T/F
FALSE
are NOT effective in the early response
It is true that when Glucocorticoids in Asthma are withdrawn the airway eventually returns to the original state
T/F
TRUE
ICS do not potentiate the effect of the B2 agonist. T/F
FALSE
Increase the transcription of the β2 receptor in pulmonary mucosa and stabilize the messenger RNA
β2 agonist potentiate the effect of ICS.
T/F
TRUE
Increase nuclear translocation of GR receptors and enhance the binding of the Glucocorticoid receptor to the DNA in the nucleus of the cell
The use of a reduces the systemic absorption of ICS reducing side effects.
T/F
TRUE
Beclomethasone and Ciclesonide are pro-drugs which are only active after the ester group has not NOT been removed by esterases in the lung.
T/F
FALSE
Budesonide and fluticasone propionate undergo more extensive first pass metabolism and therefore result in less systemic side effects.
T/F
TRUE
ICSs are recommended for patients who are using a β2 Agonist inhaler more than twice a week to control their asthma.
T/F
TRUE
Initial recommendations may be to use an oral steroid or ICS up to 4 times a day until the initial asthma exacerbation is controlled.
T/F
TRUE
ICS is recommended for use three times daily (to improve compliance) after asthma has been brought under control.
T/F
FALSE
Only two times daily
In regards to ICS, the dose should be minimal required to control the asthma.
T/F
TRUE
- < 400 υg per day up to 2000ug per day in resistant individuals
- > 800 ug per day? USE A SPACER to decrease systemic effects
- Children < 400 ug/day showed no growth suppression.
- Young children can utilize a nebulizer for delivery
ICS have a place in the treatment of COPD unless there is also a component of asthma.
T/F
FALSE
ICS have no effect on slowing the progression of COPD.
T/F
TRUE
Predisolone and prednisone oral steroids: clinical improvement takes several weeks.
T/F
FALSE
several days, not several weeks.
- 30-40 mg daily to achieve maximal effect
- Then 10 =15 mg day
- Dose may be increased to 30-40 mg a day for two weeks and then tapered.
- Usually given in the morning
If lung function is < 30% or show no response to β2 agonist then IV steroids are not indicated.
T/F
FALSE
They are indicated.
-Hydrocortisone: 4mg/kg for initial dose then 3mg/kg every 6 hours; effective in 5-6 hours
Adverse effects of systemic steroids?
- Dysphonia
- Oropharyngeal candidiasis
- Cough
- Adrenal suppression and insufficiency
- Growth suppression
- Bruising
- Osteoporosis
- Cataracts
- Glaucoma
- Psychiatric disturbances
- Pneumonia
- Abnormalities in glucose, insulin and triglyceride levels
As mediator antagonists, newer Antihistamines (such as cetirizine and azelastine) may have some beneficial effects.
T/F
TRUE
Anti-leukotrienes used in the prophylaxis of asthma. MOA block the leukotriene pathways.
T/F
TRUE
Anti-Leukotrienes have been found in clinical trials to inhibit bronchoconstriction related to allergens, exercise, cold air in asthmatics. Because they are orally administered this increases compliance.
T/F
TRUE
Anti-Leukotrienes have been found to not help in the following symptoms:
- Reduce need for rescue inhalers
- Improve lung function in patients with mild to moderate asthma
- Less improvement in patients with severe asthma
- Effective in blocking exercise induced asthma.
T/F
FALSE
They do help!
Anti-Leukotrienes: meds
- Zileuton: (Zyflo): Reduces synthesis of leukotrienes
- Montelukast (Singulair): Antagonist at leukotriene receptor
- Zafirlukast: (Allocate): Antagonist at leukotriene receptor
Adverse effects of Anti- Leukotrienes
RARE:
- Hepatic dysfunction
- Churg Strauss syndrome
Immunotherapy/Antibodies/Others
Mepolizumab: interleukin-5 antagonist for patients 12 or over with severe asthma:
- Injection 100 mg every 4 weeks
- Eosinophilic phenotypes (only for those with eosinophilic phenotype; NOT for all asthma types)
Omalizumab: IGE antibody is bond on mast cells:
- Prophylaxis of asthma
- Given by injection
- Fevipiprant is an orally available antagonist of the prostaglandin D2 receptor.
Appears to prevent eosinophils from collecting in the lungs. Just cleared Phase III trials.
- Fevipiprant is an orally available antagonist of the prostaglandin D2 receptor.
Pharmacologic Control of Asthma/Bronchospasm After Induction of Anesthesia
1) Deepen level of anesthesia with your volatile anesthetic agent. Consider ketamine, propofol, lidocaine.
2) Administer 100% oxygen
3) Administer a β2 Agonist
4) Consider epinephrine IV or sq
5) IV corticosteroids
Hydrocortisone IV: 4mg/kg bolus; infusion 0.5mg/kg/hr
Methylprednisolone IV: 0.8 mg/kg bolus; infusion: 0.1mg/kg/hr
Albuterol
*Metaproterenol and Terbutaline are similar
Subclass:
Short-acting agonists
MOA:
Beta2-selective agonist
• bronchodilation
Use:
Asthma acute attack relief drug of choice (not for prophylaxis)
P-Kinetics:
Inhalation (aerosol) Duration: 2–4 h
S.E.
Tremor, tachycardia
Salmeterol and Formoterol
Sublass:
Long-acting agonist
MOA:
Beta2-selective agonists; bronchodilation; potentiation of corticosteroid action
Use: Asthma prophylaxis (not for acute relief) • indacaterol and vilanterol for COPD
P-Kinetics:
Inhalation (aerosol) Duration: 12–24 h
S.E.:
Tremor, tachycardia, cardiovascular events
Epinephrine & Isoproterenol
Subclass:
Nonselective Sympathomimetics
MOA:
Nonselective β activation • epinephrine also an α agonist
Use:
Asthma (obsolete)
P-Kinetics:
Inhalation (aerosol, nebulizer) Duration: 1–2 h
S.E.:
Excess sympathomimetic effect (Chapter
Theophylline
Subclass:
Methylxanthines
MOA:
Phosphodiesterase inhibition, adenosine receptor antagonist • other effects poorly understood
Use:
Asthma, especially prophylaxis against nocturnal attacks
P-Kinetics:
Oral slow-release Duration: 12 h
S.E.:
Insomnia, tremor, anorexia, seizures, arrhythmias
Ipratropium
Subclass:
Antimuscarinic
MOA:
Competitive pharmacologic muscarinic antagonists
Use:
Asthma and chronic obstructive pulmonary disease
P-Kinetics:
Inhalation (aerosol) Duration: several hours
S.E.:
Dry mouth, cough
Montelukast
Subclass:
Leukotriene antagonists
MOA:
Pharmacologic antagonists at LTD4 receptors
Use:
Prophylaxis of asthma
P-Kinetics:
Oral Duration: 12–24 h
S.E.:
Minimal
Zileuton
Subclass:
Leukotriene antagonists
MOA:
Inhibitor of lipoxygenase • reduces synthesis of leukotrienes
Use:
Prophylaxis of asthma
P-Kinetics:
Oral Duration: 12 h
S.E.:
Elevation of liver enzymes
Beclamethasone
Subclass: Corticosteroids - Inhaled
MOA:
Inhibition of phospholipase A2 • reduces expression of cyclooxygenase
Use:
Prophylaxis of asthma: drugs of choice
P-Kinetics:
Inhalation Duration: 10–12 h
S.E.:
Pharyngeal candidiasis • minimal systemic steroid toxicity (eg, adrenal suppression)
Prednisone
Subcalss:
Corticosteroids - Systemic
MOA:
Like inhaled corticosteroids
Use:
Treatment of severe refractory chronic asthma
P-Kinetics:
Oral Duration: 12–24 h
S.E.:
See Chapter 39
Omalizumab & Mepolizumab
Subclass: Antibodies
MOA:
Binds IgE antibodies on mast cells; reduces reaction to inhaled antigen
Use:
Prophylaxis of severe, refractory asthma not responsive to all other drugs
P-Kinetics:
Parenteral • administered as several courses of injections
S.E.:
Extremely expensive • long-term toxicity not yet well documented
Bronchodilators
Relax constricted airway smooth muscle in vitro and cause immediate reversal of airway obstruction in asthma in vivo. Alos prevent bronchoconstriction.
Meds:
- Β2 Adrenergic Agonist
- Theophyllline
- Anticholinergic agents (muscarinic receptor antagonists)
Β2 Adrenergic Agonist
Bronchodilator tx of choice for asthma, most effective, with minimal side effects.
Systemic, short acting, long acting, nonselective and inhaled.
Methylxanthines
Similar to caffeine. Used since 1930s. Heavily used in developing countries d/t low cost. Frequency of side effects and relatively low efficacy has diminished its use.
Drug: Theophylline
Inhaled Corticosteroids
First line therapy for patients with asthma.
Should be started in any patient who needs a B2 agonist inhaler more than twice a week.
Use two daily.
Utilized in mild, moderate and severe asthma.
Anti-cholinergic agents (muscarinic receptor antagonists)
Anagonists of ACh at muscarinic receptors for lung relief.
Competitive binding at muscarinic receptors of ACh, resulting in inhibition of bronchoconstriction.
Play a role in the parasympathetic nervous systems ability to regulate bronchomotor tone.
Mediator Antagonists
Antihistamine (H1) and anti-leukotrienes.
Many mediators have been noted in both asthma and COPD; in theory, suppression of these receptors have shown to be minimally effective in controlling inflammation in airways. Overall, intermittent efficacy.
Immunomodulators
Methotrexate, cyclosporin A, gold intravenous immunoglobulin
Immunosupressive therapy, utilized in asthma when oral steroids have been proven to be ineffective. Many side effects and more difficult to regulate therapeutic levels.
Antitussives
Viral infx of the upper respiratory tract are common causes.
cough is a defensive mechanism; inhibiting it w/ bacterial infx is ill advised.
meds used to suppress:
- narcotics
- dextromethorphan
- benzonatate (tessalon pearls)
-
