Pulmonary Flashcards
Pulmonary Arterial Hypertension (PAH or PH):
-Define
-Pathophysiology
Pulmonary HTN (PH): *continuous high BP in pulmonary arteries (mean pulmonary arterial pressure = mPAP > 25mmHg in setting of normal fluid status)
Pathophysiology: imbalance with increased vasoconstrictor (ex. endothelian-1, thromboxane A2) and decreased vasodilator (ex. prostacyclins) substances
-Can have imbalances of cell proliferation and apoptsosi in walls of pulmonary arteries
-Can have increasing amounts of pulmonary artery smooth muscle cells, causing walls to thicken and form scar tissue (vasoproliferation)
Pulmonary Arterial Hypertension (PAH or PH):
-Classifications
-Symptoms
Classifications:
-Primary/idiopathic (Group 1 PAH): no identified cause
-Group 2-5: secondary causes –> focus on treating the underlying cause (ex. Group 2 = pulmonary venous HTN, Group 3 = hypoxia or chronic lung diseases, Group 4 = chronic thromboemoblic PH from PE, Group 5 = conditions that do NOT fit above categories)
Symptoms: fatigue, dyspnea, chest pain, syncope, edema, tachycardia, Raynaud’s syndrome
Drugs that cause pulmonary arterial hypertension (PAH) - less common in general
- Cocaine
- Fenfluramine
- Methamphetamine/amphetamine
- SSRIs during pregnancy (risk in newborn)
- Weight-loss drugs (diethylpropion, phendimetrazine, phentermine)
Pulmonary arterial hypertension (PAH): non-pharmacological therapy
NOT very effective
-Restrict Na-restricted diet (<2.4 grams/day) to manage volume status
-Avoidance of NSAIDs that can increase Na and water
-Routine immunization against influenza and pneumonia
-High altitudes may contribute to hypoxic pulmonary vasoconstriction –> O2 supplementation
Pulmonary arterial hypertension (PAH):
-What is used to confirm diagnosis and drugs?
-What are the next steps to determining therapy?
-Supportive therapy
Confirm diagnosis: right heart catheterization where short-acting vasodilators (ex. inhaled nitric oxide, IV epoprostenol, or IV adenosine) administered for vasoactivity testing
Determining Therapy:
-Reactor to vasodilator: PO CCB - typically long-acting nifedipine, diltiazem, and amlodipine (AVOID verapamil due to more pronounced negative inotropic effects)
-if NOT sustained response in responder, begin 1-2 PAH-approved drugs
-Non-responder to vasodilator: begin therapy w/ 1-2 PAH-approved drugs that are more potent vasodilators (PDE-5is, endothelin receptor antagonists, solubule guanlyate cyclase stimulators, or prostaglandin analogues - PGs for most severe cases)
Supportive Therapy:
-Loop diuretics for volume overload
-Digoxin to improve CO or control HR in Afib
-Warfarin preferred agent if anticoagulant needed (goal INR: 1.5-2.5 - lower goal than typical warfarin use)
-Transplantation
Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-Drugs/Brands
-MOA
-TX
Drugs: epoprostenol (Flolan), treprostinil (Remodulin, Tyvaso, Orenitram), illoprost (Ventavis), selexipag (Uptravi)
MOA: potent vasodilators of both pulmonary and systemic vascular beds and inhibitors of PLT aggregation
TX: pulmonary HTN - non-responder to vasodilator or refractory to CCB
Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-ROA
-Dosing considerations
-Administration considerations
ROA:
-Continuous IV infusion at home: epoprostenol, treprostinil (can be SC)
-IV infusion: selexipag
-Inhalation: illoprost, treprostinil
-PO: treprostinil, selexipag
Dosing: infusions are dosed as NG/kg/min
Administration:
-Parental agents are very potent vasodilators: avoid interruptions and sudden, large dose reductions
-Due to short T1/2 of epoprostenol (6 min) and parenteral treprostinil (4 hours), immediate access to backup pump, infusion sets, and medication is essential
-Epoprostenol: must protect from light before reconstitution and during infusion
-Reconstituted Flolan require ice packs for stability
Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: hypotension, flushing, jaw pain, HA, dizziness, N/V/D, edema, musculoskeletal pain, tachycardia, flu-like syndrome, anxiety, tremor, thrombocytopenia
-SQ/IV infusions: infusion-site pain, especially SC treprostinil
-Inhalations (treprostinil, iloprost): cough, mouth/throat irritation
Warnings:
-Vasodilation rxns (hypotension, flushing, HA, dizziness)
-Rebound PH (w/ interruption or large decreases in dose) which can be fatal
-Increased risk of bleeding
-Chronic IV infusions: sepsis and bloodstream infections (use sterile technique and education pts about infusion site care)
-Treprostinil: oral tablet does NOT dissolve (ghost tablet) and can lodge in diverticulum
CIs:
-Epoprostenil: HF with LVEF
-Treprostinil (PO): severe hepatic impairment (Child-Pugh Class-C)
DDIs:
-Effects of anti-hypertensives, antiplatelets, and anticoagulants can be enhanced
-Treprostinil levels increased by CYP2C8 inhibitors (gemfibrozil) and decreased by inducers (rifampin) –> avoid strong inhibitors w/ selexipag
Endothelin Receptor Antagonists:
-Drugs/Brands
-MOA
-ROA
-TX
Drugs: bosentan (Tracleer), ambrisentan (Letairis), macitentan (Opsumit)
MOA: block endothelin receptors on pulmonary artery smooth muscle cells, which prevents enodethelin exerting its vasoconstrictive effects
ROA: PO
TX: pulmonary hypertension (vasodilator non-responder or refractory to CCBs)
Endothelin Receptor Antagonists:
-AVEs
-Warnings
-CIs
-BBW
-DDIs
AVEs: HA, URTIs (ex. nasal congestion, cough, bronchitis), flushing, hypotension
Warnings: hepatotoxicity, decreased Hgb/Hct, fluid retention (ex. pulmonary edema, peripheral edema), decreased sperm counts, hypersensitivity rxns (bosentan)
CIs: pregnancy, use w/ cyclosporine or glyburide (bosentan), idiopathic pulmonary fibrosis (ambrisentan)
BBWs: teratogenic (negative pregnancy test prior to and monthly thereafter), hepatotoxicity (bosentan)
-Available ONLY through REMS program: pharmacies, patients, and prescribers must enroll (only female patients required)
DDIs:
-Bosentan: substrate and inducer of CYP3A4 and 2C9; can decrease effectiveness of hormonal contraceptives
-Ambrisentan: substrate of CP3A4 (major), 2C19 (minor), and P-gp - limit dose w/ cyclosporine
-Macitenant: substrate of CYP3A4 (major) and 2C19 (minor)
Phosphodiesterase Inhibitors in Pulmonary Arterial Hypertension
-Drugs/Brands
-MOA
-ROA
Drugs: sildenafil (Revatio, Viagra for ED), tadalafil (Adcirca, Cialis for ED/BPH)
MOA: increase cGMP concentrations, leading to pulmonary vasculature relaxation and vasodilation
ROA: PO
Phosphodiesterase Inhibitors in Pulmonary Arterial Hypertension:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: HA, epistaxis, flushing, dyspepsia, extremity or back pain, N/D
Warnings: hearing loss (w/ or w/o tinnitus and dizziness), vision loss (rare, but due to nonarteritic anterior ischemic optic neuropathy = NAION), hypotension, pripaism (seek emergency care if > 4 hours), pulmonary edema
CIs:
-Avoid use w/ nitrates or riociguat
-Revatio: avoid taking w/ PIs
DDIs: major substrates of CYP3A4 (avoid strong inhibitors or inducers)
-do NOT give with other PDE5is for ED
-do NOT use w/ nirtates (hypotension)
-Caution w/ alpha-1 blockers or other antihypertensives (hypotension) –> when tadalafil used, alpha 1-blockers NOT recommended for comorbid BPH
-Alcohol can enhance hypotension
Riociguat:
-Brand
-MOA
-ROA
-TX
Brand: Adempas
MOA: soluble guanylate cyclase (sGC) stimulator - sensitizes sGC to endogenous nitric oxide to increase cGMP for relaxation and antiproliferative effects in pulmonary arterial smooth muscle cells
ROA: PO
TX: pulmonary arterial hypertension (non-responder to vasodilator or refractory to CCBs), chronic thromboembolic pulmonary hypertension (CTEPH)
Riociguat:
-AVEs
-Warnings
-CIs
-BBW
-DDIs
AVEs: HA, dyspepsia, dizziness, N/V/D
Warnings: hypotension, bleeding, pulmonary edema
CIs: pregnancy, use with PDE-5is or nitrates
BBW: teratogenic (negative pregnancy test prior and monthly thereafter) –> available only through REMS program where prescribers, pharmacies, and female pts must enroll
DDIs: Major substrate of CYP3A4, 2C8, and P-gp
-do NOT use with nitrates (hypotension)
-Smoking increases clearance and dose may need to be decreased with smoking cessation
-Separate from antacids by >1 hour
Pulmonary Fibrosis:
1. Scared and damaged lung tissue with most common presentation as ___________.
- Drugs that can cause pulmonary fibrosis
- What two drugs are available for idopathic pulmonary fribrosis?
1. Exertional dsypnea
2. Amiodarone, dronedarone, bleomycin, busulfan, carmustine
- pirfenidone (Esbriet) and nintedanib (Ofev) - slow rate of decline in lung function
-May use PAH drugs ass off-label
Asthma:
-Pathophysiology
-Symptoms
Pathophysiology: chronic airway inflammation and bronchoconstriction, causing expiratory airflow limiation (REVERSIBLE with medications and sometimes spontaneously)
-Activation of inflammatory mediators: histamine, leukotrienes, cytokines
-Increase in inflammatory cells: mast cells, eosinophils
-Genetic predispositions mediated by IgE or seere eosinophilic asthma (require specialized medications beyond routine inhalers)
Symptoms: wheezing, SOB, chest pain, coughing
Asthma: Common Triggers
Environmental: pollution, cigarettes/secondary smoke exposure, cold air/changes in weather, petes, dust/pollen, cockraoches, perfume/cosmetics
Drugs: ASA, NSAIDs, non-selective beta-blockers
Comorbid conditions: infections (colds/viruses), allergic rhinitis, GERD, obesity, obstructive sleep apnea, anxiety, stress, depression
Asthma: Diagnosis
Measure baseline FEV1 w/ spirometry –> give albuterol –> measure post-bronchodilatory FEV1 (an FEV1 increase >12% post-bronchodilator is consistent with asthma)
-Forced expiratory volume in 1 second (FEV1): how much air can be forcefully exhaled in one second
-Forced vital capacity (FVC): maximum volume of air exhaled after taking deep breath
-FEV1/FVC: precentage of total air capacity (“vital capacity”) that can be forcefully exhaled in one seoncd
Other tests: fractional exhaled nitric oxide (FeNO) and peak expiratory flow rate (PEFR)
Asthma: General TX Basics
1. What are the main asthma guidelines?
- What is the long-term goal?
- How can risk factors be controlled
- Global Initiative for Asthma (GINA) and NHLBI’s Expert Panel Report (EPR)
- Reducing impairment (ex. symptoms, frequency of rescue inhaler use, limitations to activity) and risks (ex. exacerbations, hospitalizations)
3. Smoking cessation or avoid tobacco smoke, physical activity should NOT be avoided, identify triggers and avoid if possible, treat comorbid conditions, vaccinations (influenza, COVID, pneumonia), potential desensitizing to allergens
Asthma: General TX Basics
*1. Initial treatment is based on frequency of daytime symptoms and nighttime awakenings. Per frequency of these, state what step patient would be on. *
2. After initial treatment is selected, follow up is done in about 2-6 weeks. What should be assessed then?
- -Step 1: <2x/month daytime, NO nighttime
-Step 2: >/=2x/month, but <4-5 weeks daytime, NO nightime
-Step 3: most days have daytime symptoms, nighttime awakenings: >/=1x/week
-Step 4: daily daytime symptoms, nighttime awakenings: >/=1x/week
- -Adherence, inhaler technique (technique, priming, cleaning)
-Assess control of risk factors, triggers, and comorbid conditions
-Review asthma action plan
-Assess pt control/severity and step up, maintain, or step down treatment (do NOT step up until other factors have been addressed)
Asthma: Rescue drug options and their considerations
Preferred: Low-dose inhaled corticosteroid (ICS) + formoterol combination inhaler
-Formoterol: long-acting, but FAST onset that can reduce risk of exacerbations
-Used intermediately PRN for symptoms
Other options:
1. Inhaled short-acting beta-2 agonist (SABA)s - PRN for symptoms, quickly reverses bronchoconstriction, do NOT treat underlying condition (pt needs an ICS)
- Systemic steroids - injections during exacerbations, PO for exacerbations or severe asthma that is difficult to control with other drug combinations, limit due to adverse events
- Inhaled epinephrine (Primatene Mist) - available OTC for mild asthma only (NOT included in guidelines)
- Inhaled short-acting muscarinic antagonists (SAMAs) - in combo w/ SABAs during exacerbations
Asthma: Maintenance TX options
First-line for ALL patients: inhaled corticosteroids (ICSs)
Other options (add ons):
1. Inhaled long-acting beta-2 agonists (LABAs): should NEVER use alone due to increased risk of serious adverse outcomes, preferred add-on to ICS
- Oral leukotriene receptor antagonists (LTRAs): add-on, most commonly in children
- Theophylline (PO or IV): least desriable add-on due to signifcant AVEs, DDIs, and need to monitor drug concentrations
- Inhaled long-acting muscarinic antagonists (LAMAs): add-on for hx of excarbetaions despite ICS/LABA
- Injectable monoclonal antibodies (SC or IV): add-on in persistent severe asthma
-Omalizumab: severe allergic asthma
-Mepolizumab, reslizumab, benralizumab, and dupilumab for severe eosinophilic asthma
-Tezeplumab: severe asthma regardless of eosinophil counts or biomarkers)
Asthma: GINA TX Algorithm (Step 1-5 therapy options)
Step 1 (Intermittent Asthma): Rescue inhaler: PRN low dose ICS-formoterol OR SABA + low-dose ICS
Step 2 (Mild Persisent Asthma):
-Option 1: PRN low-dose ICS-formoterol
-Option 2: SABA OR ICS-SABA (rescue) + low-dose ICS (maitenance)
Step 3 (Moderate Persisent Asthma):
-Option 1: low-dose ICS-formoterol (rescue) + low-dose ICS-formoterol (maintenance)
-Option 2: SABA OR ICS-SABA (rescue) + low-dose ICS LABA (maintenance)
Step 4 (Severe Persistent Asthma):
-Option 1: low-dose ICS-formoterol (rescue) + medium-dose ICS formoterol (maintenance)
-Option 2: SABA OR ICS-SABA (rescue) + medium-dose ICS LABA (maitenance)
Step 5 (Refer for Assessment):
-Option 1: low-dose ICS-formoterol (rescue) + high-dose ICS formoterol (maintenance)
-Option 2: SABA or ICS-SABA (rescue) + high-dose ICS LABA
Asthma: After a patient has been on inhalers, determine how to maintain, step up, or step down therapy.
Assessment:
1. Daytime asthma symptoms > 2x/week?
2. Any nighttime awakenings from asthma?
3. SABA reliever TX used >2x/week?
4. Activity limited due to asthma?
Well-controlled: no questions answered yes –> maintain current step and step down if controlled for >/= 3 months
Partly controlled: 1-2 questions answered yes –> step up 1 step
Uncontrolled: 3-4 questions answered yes –> step up 1-2 steps and consider short course of oral steroids
Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs)
-Drugs/Brands
-MOA
-ROA
Drugs:
-SABAs: albuterol (ProAir HFA, ProAir RespiClick, Proventil HFA, Ventolin HFA, ProAir Digihaler), levalbuterol (Xopenex, Xopenex HFA), ephrinephrine (Asthmanefin Refill)
-LABAs: salmeterol (Servent Diskus), formoterol (only in combos)
MOA: bind to beta-2 receptors to relax bronchial smooth muscle
ROA: inhalation
Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs)
-Dosing/dosing frequency (albuterol)
-Structure of levalbuterol
-Administration considerations
Albuterol Dose: 90mcg/inhalation - for MDI/DPI 1-2 inhalations Q4-6H PRN (PO NOT recommended)
-SABA use in exercise-induced bronchospasms: use 2 inhalations 5 minutes prior to exercise
Levalbuterol: contains R-isomer of albuterol*
Administration:
-MDIs (HFA products): shake well before use
-Most albuterol inhalers contain 200 inhalations/canister (except: Ventolin HFA which contains either 200 or 60 inhalations/canister)
-Salmeterol: maintenance inhaler only, NOT used for acute bronchospasms
Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs)
-AVEs
-Warnings
-BBW
-Monitoring
AVEs: nervousness, tremor, tachycardia, palpitations, cough, hyperglycemia, decreased K
-AVEs from some hitting of beta receptors on heart especially in overuse or swallowing of inhalation
Warnings: caution in CVD, glaucoma, hyperthyroidism, seizures, diabetes
BBW (salmeterol): increased risk of asthma-related deaths (only in those currently receiving, but NOT adequately controlled on ICS); increased risk of asthma-related hospitalizations in pediatric and adolescents
Monitoring: number of days of SABA use, symptom frequency, peak flow, pulmonary function, BP, HR, BG, K
Inhaled Corticosteroids (ICS):
-Drugs/Brands (alone, NOT in combo with other drugs)
-MOA
-Administration considerations for general drug class
Drugs: beclomethasone (QVAR RediHaler), budesonide (Pulmicort Flexhaler, Pulmicort Respules - neb), fluticasone (Flovent HFA, Flovent Diskus, Arnuity Ellipta), mometasone (Asmanex HFA, Asmanex), ciclesonide (Alvesco)
MOA: inhibit inflammatory response, inhibit late-phase rxn to allergens, and reduce airway hyperresponsiveness
Administration: rinse mouth with water and spit out after each use to prevent thrush (can use spacer with MDI to decrease risk
Inhaled Corticosteroid (ICS): Specific Administration considerations for
-Alvesco
-Budesonide
-Pulmicort Respules
-Qvar RediHaler
-AromAir, AirDuo Digihalers
Alvesco: MDI does NOT need to be shaken
Budesonide: only ICS available as nebulized solution (common in young children), ampules should be used within 2 weeks of opening the aluminum package
Pulmicort Respules: only use with jet nebulizer connected to air compressor (do NOT use ultrasonic neb)
QVAR RediHaler: breath-activated aerosol with characteristics of DPI and MDI; do NOT shake or use with spacer; does NOT need priming or activation
ArmonAir, AirDuo Digihalers: contain built-in electronic module that detects, records, and stores data (when inhaler used and increases inspiratory flow)
Inhaled Corticosteroids (ICSs):
-AVEs
-Warnings
-CIs
-Monitoring
AVEs: dysphonia (difficulty speaking), oral candidiasis (thrush), cough, HA, hoarseness, URTIs, hyperglycemia
Warnings:
-High doses for prolonged periods of time can cause adrenal suppression
-Increased risk of fractures, growth retardation (in children, NOT very clinically significant), and immunosuppression
CIs: primary TX of status asthmaticus or acute episodes of asthma
Monitoring: use of SABA/rescue inhaler, symptom frequency, peak flow, growth in children/adolescents, s/sx of adrenal insufficiency, s/sx of thrush, BMD
Inhaled Corticosteroids (ICSs): catgorizatoin of daily doses for Asthma
-Low daily dose (LDD)
-Medium daily dose (MDD)
-High daily dose (HDD)
**For beclomethasone, budesonide, ciclesonide, fluticasone (MDI and DPI), mometasone (MDI and DPI)
**For NAPLEX may NOT need to know –> more of reference
Becomethasone MDI (40 or 80 mcg/inhalation): 100-200mcg (LDD), >200-400mcg (MDD), >400mcg (HDD)
Budesonide DPI (90 or 180mcg/inhalation): 200-400mcg (LDD), >400-800mcg (MDD), >800mcg (HDD)
Ciclesonide MDI (80 or 160mcg/inhalation): 80-160mcg (LDD), >160-320mcg (MDD), >320mcg (HDD)
Fluticasone MDI (44, 110, or 220mcg/inhalation): 100-250mcg (LDD), >250-500mcg (MDD), >500mcg (HDD)
Fluticasone DPI (50, 100, or 250mcg/inhalation): 100-250mcg (LDD), >250-500mcg (MDD), >500mcg (HDD)
Mometasone MDI (100 or 200mcg/inhalation): 200-400mcg (LDD), 200-400mcg (MDD), >400mcg (HDD)
Mometasone DPI (110 or 220mcg/inhalation): 110-220mcg (LDD), >220-440mcg (MDD), >440mcg (HDD)
Inhaler Combination: Brand Names
1. Budesonide + Formoterol
2. Fluticasone + Salmeterol
3. Fluticasone + Vilanterol
4. Mometasone + Formoterol
5. Umeclidinium + Vilanterol + Fluticasone
- Symbicort, Breyna
- Advair Diskus, Advair HFA
- Breo Ellipta
- Dulera
- Trelegy Ellipta
Inhalers in Asthma Vs. COPD
-ICSs
-LABAs
-LAMAs
ICS: no single product approved for COPD –> ALL asthma
LABA: salmeterol ONLY in asthma –> others in COPD
LAMAs: tiotropium ONLY in asthma –> others in COPD
Inhalers in Asthma Vs. COPD
-ICS/LABAs
-LAMA/LABAs
-LAMA/LABA/ICSs
ICS/LABAs: similar in both (Symbicort, Advair, Breo Ellipta) –> Dulera ONLY in asthma
LAMA/LABAs: no combos approved in asthma
LAMA/LABA/ICSs: Trelegy in asthma and COPD, Breztri in COPD
Differences between MDIs vs. DPIs:
-Brand name identifiers
-Dose delivery
-Propellant
-Spacer
Brand Name:
-MDIs: HFA, Respimat, or no suffix (ex. Symbicort, Dulera)
-DPIs: Diskus, Ellipta, Pressair, HandiHaler, RespiClick, Flexhaler
Dose delivery: aerosolized liquid (MDI), no prepellant - fine powder (DPI)
Propellant: some use a propellant (HFA), no prepellant (DPI)
Spacer: can be used for most in MDI (except QVAR RediHaler or Respimat products), cannot be used in DPIs (powder would fall)
-Helpful in pts incapable of hand-breath coordination and decreases risk of thrush
Differences between MDIs vs. DPIs:
-Shaking prior to use
-Priming
-Breath type
Shaking prior to use: required for all MDIs (except: QVAR RediHaler, Alvesco, Respimat products, and Atrovent HFA); do NOT shake DPIs
Priming: before first use or if NOT used in a certain period (MDIs), no primring for DPIs (except Flexhaler prior to first use)
Breath type: slow and deep (MDI); quick and forceful (DPI - think how its a powder/solid and has NO propellant)
Leukotriene Modifying Agents:
-Drugs/Brands
-MOA
-ROA
-TX
Drugs: montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo)
MOA: reduce airway edema, constriction, and inflammation from leukotrienes
-Montelukast; inibits leukotriene D4 (LTD4)
-Zafirlukast: inhibits both LTD5 and LTE4
-Zileuton: 5-lipoxygenase inhibits luekotriene formation
ROA: PO
-Montelukast: tablet, chewable tablet, packet
TX: asthma (commonly in children)
-Montelukast: allergic rhinitis, exercise-induced bronchoconstriction
Leukotriene Modifying Agents:
-Dosing (montelukast)
-Admin
Dosing (Montelukast):
-Age 1-5 yo: 4mg PO QPM
-Age 6-14 yo: 5mg PO QPM
-Adults: 10mg PO QPM
Administration considerations:
-Montelukast: Take dose in evening. Do NOT take more than one dose in 24 hours. If using daily for an indication, do NOT take another dose to prevent exercise-induced asthma.
-Montelukast granules: can be administered directly into mouth, dissolved in 5mL of breast milk or formula, or mixed with spoonful of applesauce, carrots, rice, or ice cream (do NOT mix with anything else) –> use wihin 15 minutes of opening the packet
-Zafirlukast: protect from light and moisture (store in original container)
Leukotriene Modifying Agents:
-AVEs
-Warnings
-CIs
-BBWs
-Monitoring
-DDIs
AVEs: HA, dizziness, abdominal pain, increased LFTs, URTIs
Warnings: neuropsychiatric events (aggression, hostility, agitation, hallucinations, depression, suicidial thinking), systemic eosinophilia (montelukast and zafirlukast)
CIs: hepatic impairment (zafirlukast, zileuton)
BBW (montelukast): neuropsychiatric events (serious behavior and mood-related changes, including suicidal thoughts or actions)
DDIs:
-Montelukast: minor substrate of CYP3A4 and 2C8/9, weak inhibitor of CYP2C8/9 (gemfibrozil can increase levels of montelukast, Iumacaftor can decrease levels of montelukast)
-Zafirlukast: major substrate of CYP2C9 (can increase levels of theophylline, warfarin)
-Zileuton: minor substrate of CYP1A2, 2C9, and 3A4 and weak inhibitor of CYP1A2 (increases levels of theophylline, propanolol, and warfarin)
Theophylline:
-Brand
-MOA
-ROA
Brand: Theo-24, Elixophyllin
MOA: inhibits phosphodiesterase, increasing cAMP and releasing epinephrine from adrenal medulla –> bronchodilation
-Active metabolite of caffeine and 3-methylxanthine
-Can cause CNS and cardiac stimulation, gastric secretion, and diuresis
ROA: PO
Theophylline:
-Dosing is based on what weight?
-Therapeutic range
-Aminophylline conversion
Dosing based on IBW
Therapeutic range: 5-15mcg/mL (measure peak at ss, 3 days after PO dosing)
Conversion: Aminophylline contains 2:1 theophylline and ethylenediamine (convert aminophylline to theophylline by multiplying by 0.8)
Theophylline:
-AVEs (including toxicity)
-Warnings
-Monitoring
AVEs: N/V, HA, insomnia, increased HR, tremor, nervousness
-Toxicity: persistent vomiting, arrhythmias, seizures
-AVEs: think about effects of caffeine
Warnings: can exacerbate CV arrhythmias, PUD, and seizure disorders
Monitoring: theophylline levels, HR, CNS effects (insomnia, irritability), use of rescue inhaler
Theophylline:
-Kinetics
-Metabolism
-DDIs
-Food/medical condition Interactions
Kinetics: saturable (first-order kinetics followed by zero order): small dose increases can result in large increases in concentrations
Metabolism: Substrate of CYP1A2 (major), 3A4, and 2E1 (minor)
DDIs:
-CYP1A2 inhibitors: increase theophylline levels (ex. cimetidine, ciprofloxacin, fluvoxamine, propranolol, and zileuton)
-CYP3A4 inhibitors: increase theophylline levels (ex. clarithromycin, erythromycin)
-Other drugs that increase theophylline levels: zafirlukast, alcohol, allopurinol, disulfiram, estrogen-containing OCs, methotrexate, pentoxifylline, propafenone, verapamil
-Drugs that decrease theophylline levels: carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, ritonavir, levothyroxine, St. John’s Wort, and tobacco/marijuana smoking
-Can decrease lithium levels and zafirlukast
Food/condition interactions:
-Can increase theophylline levels: CHF, cirrhosis or liver disease, acute pulmonary edema, cor pulmonale, fever, hypothyroidism, shock, and high carbohydrate/low protein diet
-Can decrease theophylline levels: low carbohydrate/high protein diet, daily consumption of charbroiled beef, cystic fibrosis, hyperthyroidism
Omalizumab:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-BBW
Brand: Xolair
MOA: IgG monoclonal antibody - inhibits IgE binding to IgE receptor on mast cells and basophils
ROA: SC
Administration considerations:
-Initiate in healthcare setting under medical supervision (self-administration can be considered after 3 doses if specific criteria met)
-Positive skin test for allergic asthma must be documented before
TX: severe allergic asthma
BBW: anaphylaxis (can occur at any point of TX)
Interleukin Receptor Antagonists:
-Drugs/Brands
-MOA
-ROA
-TX
-Which ones can be administered at home by patient or caregiver?
-BBW
Drugs: mepolizumab (Nucala), reslizumab (Cinqair), benralizumab (Fasenra, Fasrena Pen), dupilumab (Dupixent)
MOA: inhibit interluekins (cytokines responsible for growth, differentiation, recruitment, activation, and survival of eosinophils) to reduce inflammation
-All block interluekin 5 w/ eception of dupilumab that blocks interluekins 4 and 13
ROA: SC
TX: severe eosinophilic asthma
Can be given at home: mepolizumab, dupiumab, Fasenra Pen
BBW (reslizumab): anaphylaxis (patients must be observed after administration)
Tezepelumab:
-Brand
-MOA
-ROA
-TX
-Administration considerations
Brand: Tezspire
MOA: human thymic stromal lymphopoietin blocker - reduces multiple biomarkers of inflammation
ROA: SC
TX: severe asthma of any type
Administration: can be done at home by pt or caregiver
Special Scenarios in Asthma: Exercise-Induced Bronchospasms and Pregnancy
Exercise-induced bronchospasms: SABA or low-dose ICS-formoterol to prevent –> take 5-15 minutes before exercise *
-SABAs: last 2-3 hours
-ICS-formoterol: lasts up to 12 hours
-Salmeterol can be alternative to SABA*, taken 30 minutes before (LABAs should NEVER be used alone for presistent asthma)
-Montelukast: can be taken 2 hours prior to exercise, lasting up to 24 hours
Pregnancy: safer to treat asthma to continue oxygen supply to fetus (down-titration NOT recommended and ICS can be continued and still preferred controller)
Inhalers:
1. In good asthma control, an albuterol inhaler should last about __________.
- If prescribed >1 inhalation of medication at a time, the pt should wait at least _______ between each one.
- If prescribed more than one inhaler, which inhaler should be used first?
- Spacers should be cleaned at least once a ________.
- 12 months (or 3-4 months for smaller ones w/ 60 inhalations)
- 60 seconds
- Bronchodilator to open airways quickly, allowing ICS to travel deeper into lungs
- Week - in warm, soapy water
Peak Flow Meters:
1, What do they measure?
- Peak flow meter care
- Result interpretation
Measure: peak expiratory flow rate (PEFR) - maximum flow rate from a forceful exhalation
-Patient’s best PEFR is called “personal best” (PB) and measured by spirometry
-Measurement takes in account height, gender, and age
Peak Flow Meter Care:
-Use same brand of peak flow meter
-Clean Qweek with warm water and mild soap (clean more if infection occurs)
Results: green >80% PB, yellow 50-80% PB, and red <50% PB
Peak Flow Meters: Technique
-Use meter QAM upon awakening and before use of any asthma medications
-Move indicator to the bottom of numbered scale. Stand up straight. Exhale comfortably.
-Inhale as deeply as possible. Place lips firmly around mouthpiece, creating tight seal.
-Blow out as hard and fast as possible. Write down PEFR.
-Repeat steps two more times with enough rest in between. *Record highest value. *
-Compare peak flow value to personal asthma action plan and follow steps
MDIs: How to administer
Ex: albuterol (Ventolin HFA, ProAir HFA), budesonide/formoterol (Symbicort, Breyna), fluticasone (Flovent HFA), mometasone/formoterol (Dulera)
Step 1:
-Ensure canister is fully inserted if comes seperately. Use actuator that comes with canister.
-Shake inhaler well for 5 seconds immediately before each spray (except: QVAR RediHaler, Atrovent HFA, Respimat products, or Alvesco)
-Remove cap from mouthpiece and check for foreign objects prior to use
Step 2:
-Breathe out fully through mouth, expelling as much air as possible
-Holding the inhaler upright, place mouthpiece into mouth and close lips aorund it
Step 3:
-While breathing in slowly and deeply, press top of canister all the way down with index finger
-Right after spray comes out, take finger off canister
-After inhaling completely, take inhaler out of mouth and close your mouth. Hold breath as long as possible up to 10 seconds then breathe normally.
-If another inhalation needed, wait 1 minute then repeat
-Place cap back on after use
-Rinse mouth with water and spit out for any ICS
MDI: Priming and cleaning specifics in Ventolin HFA/ProAir HFA, Flovent HFA/Dulera, Symbicort/Breyna
Ventolin HFA, ProAir HFA:
-Priming: spray 4 times (3 for ProAir) away from face, shaking between sprays. Prime again if >14 days from last time used or if you drop it
-Cleaning: remove medical canister to not let get wet and rinse mouthpiece only in warm water for 30 seconds then turn upside down and and rinse again for 30 seconds; shake to remove excess water and let air dry. clean weekly
Flovent HFA, Dulera:
-Priming: 4 sprays; prime again with just 1 spray if >7 days since last use (>5 days for Dulera)
-Cleaning: use cotton swab dampened with water to clean small circular opening where medication sprays out, do NOT take canister out of plastic actuator, wipe inside of mouthpiece with damp tissue and let air dry overnight
Symbicort, Breyna:
-Priming: 2 sprays, prime again if >7 days from last use or if you drop it
-Cleaning: wipe inside and outside of mouthpiece with clean, dry cloth; do NOT put into water; clean weekly
Advair Diskus (fluticasone/salmeterol): counseling on inhaler technique / how to clean
Step 1: Hold Diskus in left hand and put thumb of right hand in the thumb grip. Push thumb grip away from you as far as it will go until mouthpiece appears and Diskus snaps into position.
Step 2: Hold Diskus in a level, flat position with the mouthpiece towards you. Slide lever away from mouthpiece until it clicks.
Step 3: Before using, breath out fully while holding the Diskus away from your mouth. Do NOT tilt the Diskus.
Step 4: Put the mouthpiece in your lips. Breathe in quickly and deeply through inhaler. Do NOT breathe in through nose. Remove Diskus from mouth and hold your breathe as long as possilby up to 10 seconds then breathe out slowly.
Step 5: Close the Diskus by putting your thumb in the thrumb grip and sliding as far back towards you as it will go until Diskus clicks shut. Rinse mouth with water and spit out to prevent thrush. Do NOT swallow the water.
To clean: do NOT wash the Diskus. Store in a dry place.
budesonide (Pulmicort Flexhaler): inhaler technique counseling / how to clean
Step 1: Twist off the white cover.
Step 2: Holding the inhaler with one hand, twist the brown base fully in one direction as far as it will go with other hand. Twist it back again in the other direct as far as it will go. You should hear “click” during one of the twisting movements, and the dose is now loaded (no matter how must you twist only one dose loaded, but dose counter will continue to advance).
Step 3: Hold inhaler upright in one hand. Turn your head away from the inhaler and breathe out fully.
Step 4: Place mouthpiece in your mouth and close lips around mouthpiece. Breathe in deeply and forcefully though the inhaler. Remove inhaler from mouth and breathe out.
Step 5: Replace white cover on ihaler and twist shut. Rinse your mouth with water and spit out water to prevent thrush.
To clean: wipe the mouthpiece with dry tissue weekly. do NOT use water or immerse it in water.
albuterol (ProAir, RespiClick), fluticasone/salmeterol (AirDuo RespiClick): inhaler technique counseling / how to clean
Step 1: Make sure cap is closed before each dose. Hold inhaler upright at you open cap, opening all the way back until you hear a “click”. It is now ready to use (Note: opening and closing cap w/o inhaling a dose will waste medication and can damage inhaler).
Step 2: Turn your head away from inhaler to breathe out through your mouth, exhaling as much as you can out of your lungs.
Step 3: Put mouthpiece in your mouth and close lips around it. Breathe in quickly and deeply through mouth until your lungs feel completely full of air. Hold breathe for as long as possible up to 10 seconds. Remove inhaler from mouth.
Step 4: Check dose counter on back to make sure you received dose. Close cap over mouthpiece. For AirDuo Respiclick, rinse mouth with water and spit out to prevent thrush. do NOT swallow water.
To Clean: Keep inhaler dry at all times. do NOT wash or any part of inhaler in water. If mouthpiece needs cleaning, gently wipe with dry cloth or tissue after using.
Chronic Obstructive Pulmonary Disease (COPD):
-Pathophysiology
-Causes
Pathophysiology: obstructed airflow that is NOT FULLY REVERSIBLE with medications
-*Emphysema: destruction of small passages in lungs (alveoli)
-*Bronchitis (or broncholitis): inflammation and narrowing of bronchial tubes and results in mucus production
Causes: tobacco smoke, air pollutants, alpha-1 antitrypsin (AAT) deficiency (AAT protects lungs from inflammation - genetic condition w/ deficiency)
COPD:
-Symptoms
-Diagnosis
-Differences from asthma
Symptoms: chronic and progressive -> dysnpea/SOB, cough, sputum production, wheezing
Diagnosis: spirometry required - a post-bronchodilator FEV1/FVC <0.70 confirms COPD
Differences from asthma:
-Age of onset usually >40 yo (asthma: <40 yo)
-Smoking history
-Sputum production common
-Persistent symptoms (asthma: variable and intermittent)
-Progressive (asthma: stable)
-Bronchodilators are first-line (asthma: ICS first line)
Chronic Obstructive Pulmonary Disease (COPD): Assessment
-GOLD 1-4 categories based on FEV1
-What are the assessments for symptoms?
-Define a COPD exacerbation
-Combined COPD assessment: what are groups A, B, and E?
GOLD: assesses severity of post-bronchodilator airflow limitation
-GOLD 1 (mild): FEV1 >/=80% predicted
-GOLD 2 (moderate): FEV1 50-79% predicted
-GOLD 3 (severe): FEV1 30-49% predicted
-GOLD 4 (very severe): FEV1 <30% predicted
Symptoms:
-Modified British Medical Research Council (mMRC) dyspnea scale: assess breathlessness with scores ranging from 0-4
-COPD Assessment Test (CAT): assess range of symptoms (ex. cough, mucus, energy, chest tightness) with scores ranging from 0-40
COPD exacerbation: increase in respiratory symptoms that worsen over <14 days –> hospitalization is associated with increase risk of death
Combined Assessment:
-Group A: 0-1 moderate exacerbations NOT leading to hospital admission + CAT <10 + mMRC 0-1
-Group B: 0-1 moderate exacerbations NOT leading to hospital admission + CAT >/=10 + mMRC >/=2
-Group E: >2 moderate exacerbations OR >/=1 leading to hospital admission + any CAT or mMRC score
**Moderate exacerbation: was treated with steroids or ABXs
COPD: Non-pharmacological TX
-Tobacco cessation
-Vaccinations to reduce hospitalizations and death (influenza, pneumonia)
-Assessment of inhaler technique and adherence
-Pulmonary rehabilitation program
-Long-term oxygen in severe resting hypoxia
COPD: initial pharmacologic therapy selection
Group A: a bronchodilator (SAMA PRN, SABA PRN, LAMA, or LABA)
Group B: LAMA + LABA
Group E: LAMA + LABA (if blood eosinophils >/=300 cells/uL: consider addition of ICS –> no demonstrated benefit in low counts <100 cells/uL)
COPD: Escalation of Drug TX
Primary problem = dyspnea (SOB): LAMA or LABA –> LAMA + LABA –> switch inahler or check for other causes
Primary problem = exacerbations (flare-ups/acute worsening): LAMA or LABA –> LAMA + LABA (+ICS if eosinophils >/=300) –> consider roflumilast or aztihromycin
**If on LAMA + LABA and need escalation, consider addition of ICS when eosinophils >/=100
COPD Exacerbations TX
SABA w/ or w/o SABA, consider systemic steroids
If ventilated or increased sputum volume: antibiotics should be used
Short-acting muscarinic antagonists (SAMAs) and long-acting muscarinic antagonists (LAMAs) for COPD:
-Drugs/Brands
-DPI or MDI?
-Dosing for SAMAs (including when combined w/ albuterol) and Spiriva HandiHaler/Respimat
-Administration
Drugs/Brands:
-SAMAs: ipratropium bromide (Atrovent HFA)
-LAMAs: tiotropium (Spiriva HandiHaler, Spiriva Respimat), aclidinium (Tudorza Pressair), glycopyrrolate (only in combo products), revefenacin (Yupelri), umeclidinium (Incruse Ellipta)
ROAs:
-DPI: Spiriva HandiHaler (1 capsule QD, but requires 2 puffs), aclidinium, umeclidinium
-MDI: SAMAs, Spiriva Respimat (2 inhalations QD), glycopyrrolate combos
*SAMA Dosing: *
-Atrovent HFA: 2 inhalations Q4-6H PRN
-With albuterol (Combivent Respimat): 1 inhalation Q4-6H PRN
Administration:
-HandiHaler devices: DPIs come w/ capsules placed into device –> do NOT swallow capsules
-Presair devices: DPIs that have an indicator window and turn from green to red if dose inhaled properly
Short-acting muscarinic antagonists (SAMAs) and long-acting muscarinic antagonists (LAMAs) for COPD:
-AVEs
-Warnings
-Monitoring
AVEs: dry mouth, URTIs (nasopharyngitis, sinusitis), cough, bitter taste
Warnings: caution in narrow-angle glaucoma, urinary retention, beningn prostate hyperplasia, or bladder neck obstruction
Monitoring: s/sx of at each visit, smoking status, COPD questionnaires, annual spirometry
Long-acting beta-2 agonists in COPD:
-Drugs/Brands
-ROA: DPI or MDI?
-AVES
-CIs
-Monitoring
Drugs: salmeterol (Serevent Diskus), formoterol (Perforomist), arformoterol (Brovana), olodaterol (Striverdi Respimat), vilanterol (only in combo products)
ROA:
-DPI: Serevent Diskus, Breztri Aerosphere (formoterol/glycopyrrolate/budesonide), vianterol combo products
-MDI: formoterol/budesonide (Symbicort, Breyna), olodaterol
AVEs: nervousness, tremor, tachycardia, hyperglycemia, hypokalemia
CIs: status asthmaticus, acute episodes of asthma or COPD, monotherapy in TX of asthma
Monitoring: s/sx at each visit, smoking status, COPD questionnaires, annual spirometry
Inhaler Combination: Brand Names
1. ipratropium bromide + albuterol = _____________
- glycopyrrolate + formoterol + budesonide = ______________
- Combivent Respimat
- Breztri Aerosphere
Roflumilast:
-Brand
-MOA
-ROA
-TX
Brand: Daliresp
MOA: PDE-4 inhibitor to increase cAMP levels, reducing lung inflammation via smooth muscle relaxation
ROA: PO
TX: in combination with at least one long-acting bronchodilator in severe COPD, chronic bronchitis, and hx of exacerbations
Roflumilast:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: diarrhea, nausea, decreased appetite, insomnia, HA
Warnings: weight loss, psychiatric events
CI: moderate/sever liver impairment
DDIs: substrate of CYP3A4 and 1A2 –> avoid w/ strong inducers, caution with inhibitors
Ipratropium bromide (Atrovent HFA): inhaler technique counseling / how to clean
Step 1: Make sure canister is fully inserted into actuator if it comes seperately. Remove protective dust cap from mouthpiece to check mouthpiece for foreign objects prior to use. You do NOT have to shake before using.
Step 2: Breathe out fully through your mouth. Holding inhaler upright, place mouthpiece into your mouth and close your lips around it. *Keep your eyes closed so no medication will be sprayed into your eyes. *
Step 3: While breathing in slowly and deeply through mouth, press top of canister all the way down with your index finger. Hold your breath as long as possible up to 10 seconds then breathe out slowly. If another inhalation is needed, wait at least 15 econds then repeat. Place cap back on mouthpiece after use.
To Clean: Remove dust cap and metal canister (do NOT let this get wet) and rinse mouthpiece under warm water running for 30 seconds. Shake to remove excess water and let air dry. Clean weekly.
Respimat products: Combivent Respimat, Striverdi Respimat, Stiolto Respimat, Spiriva Respimat - counseling technique / how to clean
TOP: “Turn Open Press”
Step 1: Hold inhaler upright with cap closed. Turn the clear base in the direction of the arrows on the label until it clicks (half a turn)
Step 2: Open the cap until it snaps fully open. Turn head away from the inhaler and breathe out slowly and fully.
Step 3: Close lips around the end of the mouthpiece without cover air vents. While taking a slow, deep breath through your mouth, press the dose release button, and continue to breathe in slowly. Hold your breath as long as possible up to 10 seconds. Close cap when finished.
To clean: Clean mouthpiece including metal part inside mouthpiece with damp cloth or tissue weekly.
Tiotropium (Spiriva HandiHaler): inhaler technique counseling / how to clean
Step 1: Open the HandiHaler device by pressing on the green button and lifting the cap upwards. Open the mouthpiece by pulling the mouthpiece ridge up and away from the base so the cetner chamber is showing.
Step 2: Remove a Spiriva capsule from blister packet and insert it into the chamber (do NOT swallow capsule). Firmly close the mouthpiece against the gray button until you hear a click.
Step 3: Press the green piercing button once until it is flat (flush) against the base then release. do NOT shake the device.
Step 4: *Turn head away from the inhaler and breathe out fully. *
Step 5: aise HandiHaler to your mouth in the horizontal position and close your lips around mouthpiece. Breathe in deeply and fully. You should hear capsule vibrate (rattle). Remove inhaler from your mouth and hold breath for as long as comfortable. Breathe normally. To get full dose, inhaler twice from each capsule. Tip out used capsule into trash can after 2 inhalations and do NOT touch capsule. Close device lid.
To clean: Clean inhaler monthly or PRN. Rinse inhaler under warm water. Make sure any powder build-up is removed. Let air dry (takes about 24 hours)
aclidinium (Tudorza Pressair), aclidinium/formoterol (Duaklir Pressair): inhaler technique counseling / how to clean
Step 1: Remove the protective cap by lightly squeezing on arrows marked on each side of the cap and pulling outwards. Check the mouthpiece for foreign objects.
Step 2: Hold the inhaler wtih mouthpiece facing you and the green button straight above. Before putting into mouth, press the green button all the way down and release. Check control window. *The dose is ready when changed from red to green. *Breathe out completely, away from inhaler.
Step 3: Put lips tightly around mouthpiece. Breathe in quickly and deeply through mouth. Breathe in until you hear a “click” sound and keep breathing in to get the fully dose. do NOT hold down green button while breathing in.
Step 4: Remove the inhaler from your mouth and hold your breath as long as comfortable. Then breathe out slowly away from inhaler. Place protective cap on inhaler. *Check the control window has turned red. *
To clean: routine cleaning NOT required. If needed, wipe outside of mouthpiece with dry tissue or paper towel.
Ellipta products: inhaler techinique counseling / how to clean
Step 1: Open cover of inhaler by sliding the cover down to expose mouthpiece. You should hear a “click”. The counter will count down by 1 number indicating the inahler is ready to use. If you open and close cover w/o inhaling medication, the dose will be lost. It is NOT possible to accidently take a double dose or extra dose in one inhalation.
Step 2: While holding the inhaler way from your mouth, breathe out fully. Do NOT breathe out into the mouthpiece.
Step 3: Put the mouthpiece between your lips and close your lips firmly around it. Take one long, steady, deep breath in through your mouth. Do NOT block the air vent with your fingers. Remove inhaler from mouth and hold your breath for 3-4 seconds or as long as comfortable. Breathe out slowly and gently. Close inhaler.
To clean: routine cleaning NOT required. If needed, clean mouthpiece using dry tissue before closing cover.
Tobacco Cessation: The 5 A’s Model
-A: Ask about tobacco use
-A: Advise to quit
-A: Assess readiness to quit
-A: Assist in quit attempt
-A: Arrange follow up
Tobacco Cessation: general TX and counseling principles:
General TX: most effective strategy is counseling and medication more than one alone
-Options: nicotine replacement therapy (NRT), bupropion, or varenicline
-Electronic cigarretes are NOT recommended for cessation due to health concerns (have some nicotine)
-Counseling = behavioral + social support
-Behavioral counseling is preferred over drugs in: pregnancy, adolescents, smokeless tobacco users (ex. chewing tobacco), “light” smokers (<10 cigarrettes/day)
-Vaccinations: at risk for respiratory conditions –> influenza, pneumonia (19-64 yo)
DDIs with smoking
-Non-nicotine chemicals in tobacco smoke induce CYP1A2 –> smokers who quit may have supratherapeutic levels of caffeine, theophylline, fluvoxamine, olanzapine, clozapine, and R-isomer of warfarin
-Women >35 yo who smoke should NOT take estrogen-containing OCs (increased CV risk)
Nicotine Replacement Therapy (NRT):
-Drugs/Brands
-MOA
-Which ones are OTC vs. Rx?
Drugs: nicotine patch (Nicoderm CQ), nicotine gum (Nicorette), nicotine lozenge (Nicorette Mini), nicotine inhaler (Nicotrol), nicotine nasal spray (Nicotrol NS)
MOA: provide nicotine w/o use of tobacco to help ease withdrawl symptoms –> combination therapy of long-acting and short-acting is more effective than monotherapy
OTC: nicotine patches, gum, and lozenges
Rx: inhaler, nasal spray
Nicotine Replacement Therapy (NRT):
-AVEs
-Warnings
-When to avoid certain formulations?
AVEs: insomnia, HA, dizziness, nervousness, dyspepsia
-Patch: vivid dreams, skin irritation
-Inhaler: mouth and throat irritation, cough, rhinitis
-Nasal spray: nasal irritation, watery eyes, sneezing, transient changes in taste and smell
Warnings:
-Avoid in immediate post-MI period, life-threatening arrhythmias, severe or worsening angina, and pregnancy –> package labeling warnings, but in practice, decision is based on risks of smoking vs. potential risks of NRT
-Inhaler, nasal spray: avoid in asthma/COPD or other chronic respiratory conditions
Avoid:
-Gum: dentures
-Skin conditions: patch
-Asthma, COPD: inhaler, nasasl spray
Nicotine Replacement Therapy (NRT):
1. Which ROA has the fastest delivery, but at highest risk of dependence?
- Which ROA mimics the hand to mouth smoking action, providing a coping mechanism?
- The FDA prohibits the sale of nicotine products to individuals <____ yo. Identification required.
- Which ROA has the highest adherence rate?
- Nasal Spray
- Inhaler
- 21 years old
- Patch
Nicotine Replacement Therapy (NRT): How to determine initial dose on patche, gum, and lozenge.
Patches: initial dose based on number of cigarretes/day (1 pack =20 cigarrettes)
-More than 10 cigarrettes/day: start at 21mg/day x 6 weeks –> 14mg/day x2 weeks –> 7mg/day x2 weeks
-10 or less cigarrettes/day: start at 14mg/day x 6 weeks –> 7mg/day x2 weeks
Gum/Lozenge: starting dose based on timing of first cigarrette
-First cigarrette within 30 minutes of waking: 4mg Q1-2H x 6 weeks (>/=9 pieces/day in 6 weeks) –> 4mg Q2-4H x 3 weeks –> 4mg Q4-8H x 3 weeks
-First cigarrette post 30 minutes of waking: 2mg Q1-2H x 6 weeks (>/=9 pieces/day in 6 weeks) –> 2mg Q2-4H x 3 weeks –> 2mg Q4-8H x 3 weeks
-Max/day: 20 lozenges
**Schedules can be continued indefinitely since NRT is safer than smoking
Nicotine Patch Administration
- At start of each day, remove new patch from pouch and save pouch to throw away used patches.
- Remove backing and apply sticky side of patch to clean, dry, and relatively hairless area of skin (upper arm, inner arm, shoulders). Press patch firmly onto skin for about 10 seconds.
- Wear for 24 hours (especially if cravings begin when waking up). If vivid dreams or trouble sleeping occurs, remove patch prior to bedtime (after about 16 hours) and apply a new one in the morning.
- Discard patch by folding sticky ends together, place it back into pouch, and put in trash with a lid to keep away from children and pets.
- Wash hands after removing and apply a patch.
- Rotate application site: do NOT apply to same site for at least one week. Skin reactions can occur, but generally go away in a few days. Topical hydrocortisone can help with minor irritation.
- Never cut patch or wear more than one patch at a time.
- Remove patches before MRIs.
Nicotine gum administration counseling
- Chew slowly until there is a tingle or peppery flavor in mouth.
- Park it between the cheek and gum.
- When tingle or flavor goes away, begin chewing slowly again until it returns, then park the gum again in different area.
- Repeat until most of flavor or tingle is gone (about 30 minutes).
- Do NOT eat or drink within 15 minutes before or during chewing - acidic beverages/food decrease buccal absorptoin
- 4mg strength can reduce or delay weight gain
Nicotine Lozenge, Inhaler, and Nasal Spray: administration counseling
Lozenge: Do NOT chew or swallow. Allow to dissolve slowly and move from one side of mouth to the other until completely dissolved (about 20-30 minutes).
-May cause warm or tingling sensation
-Do NOT use more than one lozenge at a time or continuously use one after another
-Do NOT eat or drink for 15 minutes before or during use.
Inhaler: Inhale deeply into back of throat or puff in short breaths. Each cartridge provides about 20 minutes of active puffing and only good for one day after opening.
-Clean mouthpiece with soap and water regularly
-Keep at room temp - cold temps reduce amount of nicotine inhaled
Nasal Spray: Tilt head back slightly and spray once in each nostril while breathing through the mouth. Do NOT sniff, swallow, or inhale through nose.
-Can cause sneezing, coughing, watery eyes, runny nose, and hot peppery feeling in back of throat
Varenicline:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
Brand: APO-Varnicline, Chantix (D/C Brand)
MOA: partial neuronal alpha-4-beta-2 nicotinic receptor agonist that results in low-level stimulation of receptors while blocking ability of nicotine to bind to inhibit surges of DA and relieve symptoms
ROA: PO, nasal spray (for dry eyes)
TX: smoking cessation - START 1 week before quit date
AVEs: nausea (30% dose dependent), insomnia, vivid dreams, HA, constipation, vomiting
Warnings: serious neuropsychiatric events (agitation, depression, suicidal thoughts/behaviors), seizures, increased effects of alcohol, somnambulism (sleepwalking), accidental injury (ex. car accident or accidents w/ heavy machinery), CVD risk, hypersensitivity rxns
Varenicline: Administration
-To decrease nausea: take after eating with a full glass of water, can reduce dose if needed
-To decrease insomnia: take 2nd dose earlier than bedtime
-If unable to abruptly quit smoking on day 8, decrease smoking by 50% in first 4 weeks, an additoinal 50% in weeks 5-8, and complete cessation by week 12
-Does NOT need to be tapered when D/C
-Efficacy NOT demonstrated in those <16 yo (NOT recommended)
Bupropion for smoking cessation:
1. What ROA should be used?
- When should bupropion be started?
- What is the dosing and max dose for bupropion in smoking cessation?
- To decrease insomnia AVE, what should be done?
- What is the MOA is targetable for smoking cessation?
- bupropion SR (Zyban) –> do NOT use any other formulations (ex. Wellbutrin SR or XL is for depression)
- Start 1-2 weeks before quit date
-
150mg QAM x3D then 150mg BID (max: 300mg/day)
-In depression: max is 450mg/day - Take first dose upon waking up and second dose 8 hours after first dose
- Increasing DA levels without use of nicotine
