Pulmonary

Question 1

Pulmonary Arterial Hypertension (PAH or PH):
-Define
-Pathophysiology

Answer 1

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)

Question 2

Pulmonary Arterial Hypertension (PAH or PH):
-Classifications
-Symptoms

Answer 2

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

Question 3

Drugs that cause pulmonary arterial hypertension (PAH) - less common in general

Answer 3

1. Cocaine
2. Fenfluramine
3. Methamphetamine/amphetamine
4. SSRIs during pregnancy (risk in newborn)
5. Weight-loss drugs (diethylpropion, phendimetrazine, phentermine)

Question 4

Pulmonary arterial hypertension (PAH): non-pharmacological therapy

Answer 4

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

Question 5

Pulmonary arterial hypertension (PAH):
-What is used to confirm diagnosis and drugs?
-What are the next steps to determining therapy?
-Supportive therapy

Answer 5

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

Question 6

Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-Drugs/Brands
-MOA
-TX

Answer 6

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

Question 7

Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-ROA
-Dosing considerations
-Administration considerations

Answer 7

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

Question 8

Prostacyclin Analogues (“Prostanoids”) and Receptor Agonists:
-AVEs
-Warnings
-CIs
-DDIs

Answer 8

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

Question 9

Endothelin Receptor Antagonists:
-Drugs/Brands
-MOA
-ROA
-TX

Answer 9

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)

Question 10

Endothelin Receptor Antagonists:
-AVEs
-Warnings
-CIs
-BBW
-DDIs

Answer 10

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)

Question 11

Phosphodiesterase Inhibitors in Pulmonary Arterial Hypertension
-Drugs/Brands
-MOA
-ROA

Answer 11

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

Question 12

Phosphodiesterase Inhibitors in Pulmonary Arterial Hypertension:
-AVEs
-Warnings
-CIs
-DDIs

Answer 12

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

Question 13

Riociguat:
-Brand
-MOA
-ROA
-TX

Answer 13

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)

Question 14

Riociguat:
-AVEs
-Warnings
-CIs
-BBW
-DDIs

Answer 14

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

Question 15

Pulmonary Fibrosis:
1. Scared and damaged lung tissue with most common presentation as ___________.

2. Drugs that can cause pulmonary fibrosis
3. What two drugs are available for idopathic pulmonary fribrosis?

Answer 15

1. Exertional dsypnea

2. Amiodarone, dronedarone, bleomycin, busulfan, carmustine

3. pirfenidone (Esbriet) and nintedanib (Ofev) - slow rate of decline in lung function
   -May use PAH drugs ass off-label

Question 16

Asthma:
-Pathophysiology
-Symptoms

Answer 16

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

Question 17

Asthma: Common Triggers

Answer 17

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

Question 18

Asthma: Diagnosis

Answer 18

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)

Question 19

Asthma: General TX Basics
1. What are the main asthma guidelines?

2. What is the long-term goal?
3. How can risk factors be controlled

Answer 19

1. Global Initiative for Asthma (GINA) and NHLBI’s Expert Panel Report (EPR)
2. 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

Question 20

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?

Answer 20

1. -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

2. -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)

Question 21

Asthma: Rescue drug options and their considerations

Answer 21

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)

2. 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
3. Inhaled epinephrine (Primatene Mist) - available OTC for mild asthma only (NOT included in guidelines)
4. Inhaled short-acting muscarinic antagonists (SAMAs) - in combo w/ SABAs during exacerbations

Question 22

Asthma: Maintenance TX options

Answer 22

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

2. Oral leukotriene receptor antagonists (LTRAs): add-on, most commonly in children
3. Theophylline (PO or IV): least desriable add-on due to signifcant AVEs, DDIs, and need to monitor drug concentrations
4. Inhaled long-acting muscarinic antagonists (LAMAs): add-on for hx of excarbetaions despite ICS/LABA
5. 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)

Question 23

Asthma: GINA TX Algorithm (Step 1-5 therapy options)

Answer 23

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

Question 24

Asthma: After a patient has been on inhalers, determine how to maintain, step up, or step down therapy.

Answer 24

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

Question 25

Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs) -Drugs/Brands -MOA -ROA

Answer 25

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

Question 26

*Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs)* -Dosing/dosing frequency (albuterol) -Structure of levalbuterol -Administration considerations

Answer 26

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

Question 27

Beta-2 Agonists (short-acting = SABAs and long-acting= LABAs) -AVEs -Warnings -BBW -Monitoring

Answer 27

*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

Question 28

Inhaled Corticosteroids (ICS): -Drugs/Brands (alone, NOT in combo with other drugs) -MOA -Administration considerations for general drug class

Answer 28

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*

Question 29

Inhaled Corticosteroid (ICS): Specific Administration considerations for -Alvesco -Budesonide -Pulmicort Respules -Qvar RediHaler -AromAir, AirDuo Digihalers

Answer 29

*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)

Question 30

Inhaled Corticosteroids (ICSs): -AVEs -Warnings -CIs -Monitoring

Answer 30

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

Question 31

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

Answer 31

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)

Question 32

*Inhaler Combination: Brand Names* 1. Budesonide + Formoterol 2. Fluticasone + Salmeterol 3. Fluticasone + Vilanterol 4. Mometasone + Formoterol 5. Umeclidinium + Vilanterol + Fluticasone

Answer 32

1. Symbicort, Breyna 2. Advair Diskus, Advair HFA 3. Breo Ellipta 4. Dulera 5. Trelegy Ellipta

Question 33

*Inhalers in Asthma Vs. COPD* -ICSs -LABAs -LAMAs

Answer 33

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

Question 34

*Inhalers in Asthma Vs. COPD* -ICS/LABAs -LAMA/LABAs -LAMA/LABA/ICSs

Answer 34

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

Question 35

*Differences between MDIs vs. DPIs:* -Brand name identifiers -Dose delivery -Propellant -Spacer

Answer 35

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

Question 36

*Differences between MDIs vs. DPIs:* -Shaking prior to use -Priming -Breath type

Answer 36

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)

Question 37

Leukotriene Modifying Agents: -Drugs/Brands -MOA -ROA -TX

Answer 37

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*

Question 38

Leukotriene Modifying Agents: -Dosing (montelukast) -Administration consisderations

Answer 38

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)

Question 39

Leukotriene Modifying Agents: -AVEs -Warnings -CIs -BBWs -Monitoring -DDIs

Answer 39

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)

Question 40

Theophylline: -Brand -MOA -ROA

Answer 40

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

Question 41

*Theophylline:* -Dosing is based on what weight? -Therapeutic range -Aminophylline conversion

Answer 41

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)

Question 42

Theophylline: -AVEs (including toxicity) -Warnings -Monitoring

Answer 42

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

Question 43

Theophylline: -Kinetics -Metabolism -DDIs -Food/medical condition Interactions

Answer 43

*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

Question 44

Omalizumab: -Brand -MOA -ROA -Administration considerations -TX -BBW

Answer 44

*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)*

Question 45

Interleukin Receptor Antagonists: -Drugs/Brands -MOA -ROA -TX -Which ones can be administered at home by patient or caregiver? -BBW

Answer 45

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)*

Question 46

Tezepelumab: -Brand -MOA -ROA -TX -Administration considerations

Answer 46

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

Question 47

Special Scenarios in Asthma: Exercise-Induced Bronchospasms and Pregnancy

Answer 47

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)*

Question 48

*Inhalers:* 1. In good asthma control, an albuterol inhaler should last about __________. 2. If prescribed >1 inhalation of medication at a time, the pt should wait at least _______ between each one. 3. If prescribed more than one inhaler, which inhaler should be used first? 4. Spacers should be cleaned at least once a ________.

Answer 48

1. 12 months (or 3-4 months for smaller ones w/ 60 inhalations) 2. 60 seconds 3. Bronchodilator to open airways quickly, allowing ICS to travel deeper into lungs 4. Week - in warm, soapy water

Question 49

Peak Flow Meters: 1, What do they measure? 2. Peak flow meter care 3. Result interpretation

Answer 49

*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

Question 50

Peak Flow Meters: Technique

Answer 50

-*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

Question 51

*MDIs: How to administer* Ex: albuterol (Ventolin HFA, ProAir HFA), budesonide/formoterol (Symbicort, Breyna), fluticasone (Flovent HFA), mometasone/formoterol (Dulera)

Answer 51

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

Question 52

MDI: Priming and cleaning specifics in Ventolin HFA/ProAir HFA, Flovent HFA/Dulera, Symbicort/Breyna

Answer 52

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

Question 53

Advair Diskus (fluticasone/salmeterol): counseling on inhaler technique / how to clean

Answer 53

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.

Question 54

budesonide (Pulmicort Flexhaler): inhaler technique counseling / how to clean

Answer 54

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.

Question 55

albuterol (ProAir, RespiClick), fluticasone/salmeterol (AirDuo RespiClick): inhaler technique counseling / how to clean

Answer 55

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.

Question 56

Chronic Obstructive Pulmonary Disease (COPD): -Pathophysiology -Causes

Answer 56

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)

Question 57

COPD: -Symptoms -Diagnosis -Differences from asthma

Answer 57

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)*

Question 58

*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?

Answer 58

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

Question 59

COPD: Non-pharmacological TX

Answer 59

-*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

Question 60

*COPD: initial pharmacologic therapy selection*

Answer 60

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)

Question 61

*COPD: Escalation of Drug TX*

Answer 61

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

Question 62

*COPD Exacerbations TX*

Answer 62

SABA w/ or w/o SABA, consider systemic steroids *If ventilated or increased sputum volume: antibiotics should be used*

Question 63

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

Answer 63

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

Question 64

Short-acting muscarinic antagonists (SAMAs) and long-acting muscarinic antagonists (LAMAs) for COPD: -AVEs -Warnings -Monitoring

Answer 64

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*

Question 65

Long-acting beta-2 agonists in COPD: -Drugs/Brands -ROA: DPI or MDI? -AVES -CIs -Monitoring

Answer 65

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*

Question 66

*Inhaler Combination: Brand Names* 1. ipratropium bromide + albuterol = _____________ 2. glycopyrrolate + formoterol + budesonide = ______________

Answer 66

1. Combivent Respimat 2. Breztri Aerosphere

Question 67

Roflumilast: -Brand -MOA -ROA -TX

Answer 67

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*

Question 68

Roflumilast: -AVEs -Warnings -CIs -DDIs

Answer 68

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

Question 69

Ipratropium bromide (Atrovent HFA): inhaler technique counseling / how to clean

Answer 69

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.*

Question 70

Respimat products: Combivent Respimat, Striverdi Respimat, Stiolto Respimat, Spiriva Respimat - counseling technique / how to clean

Answer 70

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.*

Question 71

Tiotropium (Spiriva HandiHaler): inhaler technique counseling / how to clean

Answer 71

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)

Question 72

aclidinium (Tudorza Pressair), aclidinium/formoterol (Duaklir Pressair): inhaler technique counseling / how to clean

Answer 72

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.

Question 73

Ellipta products: inhaler techinique counseling / how to clean

Answer 73

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.

Question 74

Tobacco Cessation: The 5 A's Model

Answer 74

-A: *Ask about tobacco use* -A: Advise to quit -A: Assess readiness to quit -A: Assist in quit attempt -A: *Arrange follow up*

Question 75

Tobacco Cessation: general TX and counseling principles:

Answer 75

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)

Question 76

*DDIs with smoking*

Answer 76

-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)

Question 77

Nicotine Replacement Therapy (NRT): -Drugs/Brands -MOA -Which ones are OTC vs. Rx?

Answer 77

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

Question 78

Nicotine Replacement Therapy (NRT): -AVEs -Warnings -When to avoid certain formulations?

Answer 78

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

Question 79

Nicotine Replacement Therapy (NRT): 1. Which ROA has the fastest delivery, but at highest risk of dependence? 2. Which ROA mimics the hand to mouth smoking action, providing a coping mechanism? 3. The FDA prohibits the sale of nicotine products to individuals <____ yo. Identification required. 4. Which ROA has the highest adherence rate?

Answer 79

1. Nasal Spray 2. Inhaler 3. *21 years old* 4. *Patch*

Question 80

*Nicotine Replacement Therapy (NRT): How to determine initial dose on patche, gum, and lozenge.*

Answer 80

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

Question 81

*Nicotine Patch Administration*

Answer 81

1. At start of each day, remove new patch from pouch and save pouch to throw away used patches. 2. 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. 3. 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. 4. 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. 5. Wash hands after removing and apply a patch. 6. 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. 7. Never cut patch or wear more than one patch at a time. 8. Remove patches before MRIs.

Question 82

*Nicotine gum administration counseling*

Answer 82

1. Chew slowly until there is a tingle or peppery flavor in mouth. 2. Park it between the cheek and gum. 3. When tingle or flavor goes away, begin chewing slowly again until it returns, then park the gum again in different area. 4. Repeat until most of flavor or tingle is gone (about 30 minutes). 5. Do NOT eat or drink within 15 minutes before or during chewing - acidic beverages/food decrease buccal absorptoin 6. 4mg strength can reduce or delay weight gain

Question 83

Nicotine Lozenge, Inhaler, and Nasal Spray: administration counseling

Answer 83

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

Question 84

Varenicline: -Brand -MOA -ROA -TX -AVEs -Warnings

Answer 84

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

Question 85

Varenicline: Administration

Answer 85

-*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)

Question 86

Bupropion for smoking cessation: 1. What ROA should be used? 2. When should bupropion be started? 3. What is the dosing and max dose for bupropion in smoking cessation? 4. To decrease insomnia AVE, what should be done? 5. What is the MOA is targetable for smoking cessation?

Answer 86

1. *bupropion SR (Zyban) --> do NOT use any other formulations (ex. Wellbutrin SR or XL is for depression)* 2. *Start 1-2 weeks before quit date* 3. *150mg QAM x3D then 150mg BID (max: 300mg/day)* -In depression: max is 450mg/day 4. Take first dose upon waking up and second dose *8 hours after first dose* 5. Increasing DA levels without use of nicotine