Respiratory_Pharm_-_Rudd_Spring_2024_-_Rev_2_-_Presentation_Version_with_Example_True_Learn_Questions_Answers.pdf

Respiratory Pharmacology Understand the pharmacology of and treatment strategies for: The Elephant in the Room I get it: Pharm is Hard. To take care of patients, only knowing a list of things about a medication is not enough. You need to be able to APPLY that knowledge to make the safest & most effe...

Respiratory Pharmacology Understand the pharmacology of and treatment strategies for: The Elephant in the Room I get it: Pharm is Hard. To take care of patients, only knowing a list of things about a medication is not enough. You need to be able to APPLY that knowledge to make the safest & most effective use of medications. Nomenclature Acute vs. Chronic Acute is a new complaint, while chronic is something usually present ‘long’-term You can have acute on chronic (a common presentation) Examples – you can chronically have asthma and have an acute asthma attack you can have chronic Unstable Angina and have acute chest pain Mortality: The risk of Death Increasing mortality = increased risk of death Decreasing mortality = decreased risk of death or improved survival Risk for Toxicity vs. Toxicity Risk for Toxicity are conditions that increase the risk for toxicity developing Toxicity are the negative effects harming the patient, Toxicity may reversible, lead to permeant injury, or cause death (mortality) Generally, toxicity is not interchangeable with adverse effects (side effects) Allergic Rhinitis Common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodeling. Antihistamines (oral) soo hinneistrproble MOA: Reversible inhibition of H1 (histamine) receptors Antagonists: prevent actions of histamine ALREADY released from mast cells Uses: allergic rhinitis, allergic reactions, motion sickness(1G),Vertigo (1G), N&V (1G), insomnia(1G) 1st Generation (not usually 1 line for allergic rhinitis) : diphenhydramine , chlorpheniramine, doxylamine, promethazine st (Benadryl, “PMs”) Side Effects: (N&V) Sedation (highly ability to cross the blood brain barrier vs. 2nd generation – potentiated by alcohol. May cause paradoxical excitation in children.) Antimuscarinic (reduces N&V) Anticholinergic (sedation, dry mouth, urinary retention, thickens bronchial secretions, dizziness, blurred vision, tremors, constipation) ***Diphenhydramine (and most 1G) have a paradoxical effect in children, & ~10% of adults – instead of sedation, you get activation. 2nd Generation (generally 1 line for allergic rhinitis) : loratadine, fexofenadine, desloratadine, cetirizine st Side Effects: Few – well tolerated. Generally, may be used in children 6 months and older. Cetirizine and loratadine preferred. Antihistamines (intranasal & intraocular) MOA: Reversible inhibition of H1 (histamine) receptors Antagonists: prevent actions of histamine ALREADY released from mast cells Uses: Allergic rhinitis - sneezing, itchy, watery nose/eyes (olopatadine for eyes) f Generally, reserved for children > 4 years of age Azelastine & Olopatadine: Side Effects: Sedation Anticholinergic (sedation, dry mouth, urinary retention, thickens bronchial secretions, dizziness, blurred vision, tremors, constipation) epistaxis Allergic Rhinitis Extras: Intranasal Steroids Decongestants Mast Cell Stabilizers Antileukotrienes Intranasal Steroids Examples: Mometasone, fluticasone & triamcinolone MOA: Anti-inflammatory of nasal mucosa Phospholipase A2 inhibition (cytokines) T-cell inhibition Decrease histamine release in mast cells Guidelines: USED FOR Nasal & Ocular SYMPTOMS VERY effective monotherapy including moderate-severe N&O symptoms Generally, reserved for children > 4 years of age Side effects: epistaxis, headache Decongestants Uses: Nasal Congestion Generally, not used in children less than 6 years of age Nasal decongestants (also open auditory tube) Pseudoephedrine (alpha-1/beta 2 agonist; oral) Phenylephrine (alpha-1 agonist; oral & nasal spray) Oxymetazoline (alpha 1 agonist; nasal spray) 19 Side effects (primarily nasal spray): Rebound nasal congestion - primarily if used > 5 days **note – none of these impact histamine so don't use2 Side effects (primarily oral; can occur with nasal spray but infrequent): Hypertension, tachycardia, CNS stimulation, anxiety, urine retention/use cautiously with BPH Less Effective Alternatives Examples: Cromolyn (intranasal & inhaled mast cell stabilizer) montelukast (oral – antileuokotriene) Use: Less effective than everything else Side effects: Cromolyn: Few to none (generally, not used if benefit! Has been studied/used in children > 6 months of age Allergic Rhinitis Therapy Pearls: (knowing only this will not be sufficient to answer the exam/COMLEX questions) Antihistamines & Intranasal Steroids are 1st line for AR symptoms Use 2nd generation antihistamines to avoid ACH side effects of 1st* Know which populations these ACH side effects are most problematic *unless you’re using them for these side effects (sleep, nausea, vertigo) Intranasal & Intraocular – used for local symptom control or for isolated symptoms Decongestants – do not alter histamine, but decrease secretions (know the MOA) Nasal decongestants: think rebound congestion! Vessel constriction stop snoring anything Before Asthma & COPD Prevention & Maintenance Therapy 1. Stop Smoking 2. Get Vaccinated: Flu, COVID, (PCV20 or PCV15 + PCV23,) Tdap, Zoster, and RSV* Physiological Bronchial Tone Regulation (understand these) Acetylcholine (ACh; parasympathetics) Muscarinic Receptors; Stimulation causes BRONCHO-CONSTRICTION e.g. Blocking M Receptors (Antimuscarinic Agents) allow for bronchial relaxation Epinephrine: 2 receptors; Stimulation directly (forces) causes DILATION immediate effect Histamine: Receptor stimulation causes CONSTRICTION Leukotrienes: LTC4, LTD4 and LTE4 Receptor stimulation causes CONSTRICTION & mucus production e.g. Blocking leukotrienes allows for bronchial relaxation Prostaglandins: PGE2 causes DILATION; PGD2 PGF2α causes CONSTRICTION Asthma Asthma Assumptions Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Asthma Assumptions Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting, SABA) Salmeterol, formoterol (long-acting, LABA – NOT FOR ACUTE SOB) Side effects: tremor, arrhythmia Stimulation of Beta-2 adrenergic receptors Sympathomimetics (b2 agonists) on smooth muscle leads to bronchodilation Mechanism: Increased cAMP = relaxation of bronchial smooth muscle Epinephrine: Non-selective (alpha and beta receptors) Use in asthma emergencies to rapidly open airways (systemic) Will cause cardiovascular stimulation via 1 (heart) and 1 (blood vessels) to ↑ HR & BP Asthma Assumptions Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting, SABA) Salmeterol, formoterol (long-acting, LABA – NOT FOR ACUTE SOB) Side effects: tremor, arrhythmia Uncommon to LABAs are not suitable for monotherapy due to increased mortality rate in a subset of patients, possibly due to masking severity of symptoms… But are good for nocturnal asthma & exercise-induced bronchospasm. Seffctiviets Bronchial smooth muscle & sites of action of bronchodilators Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting, SABA) Salmeterol, formoterol, vilanterol (long-acting, LABA) Side effects: tremor, arrhythmia FIRST LINE AGENT (ACUTE - SABA) Inhaled Corticosteroids Cytokine inhibition (via NF-kB protein, Phospholipase A2 & T cell inhibition) Fluticasone, budesonide Side effects: oral thrush FIRST LINE AGENT (maintenance) Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting) weeks inhaled Glucocorticoids Inhaled Corticosteroids Cytokine inhibition (via NF-kB protein, Phospholipase A2 & T cell inhibition) Salmeterol, formoterol, vilanterol (long-acting) Fluticasone, budesonide Side effects: tremor, arrhythmia Side effects: oral thrush ord orIV for ocote dottitify FIRST LINE AGENT (maintenance) I Topes if on chronic therapy (a subset of corticosteroids along with mineralocorticoid properties) Multiple mechanisms of action Decrease inflammation Decrease edema Decrease histamine release Prophylactic (used to prevent exacerbations) Inhaled can take several weeks to show improvement Used SYSTEMICALLY for ACUTE exacerbations Oral has many side effects: GI, neurological, endocrine, adrenal-pituitary axis suppression, growth retardation… a **DO NOT STOP CHRONIC TREATMENT with systemic (oral) steroids ABRUPTLY, WITHOUT TAPERING to avoid pituitary crash (burst therapy, which are oral steroids given for up to 5-7 days, may be discontinued without tapering) 6 Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol Inhaled Corticosteroids (short-acting) Cytokine inhibition (NF-kB) Salmeterol, formoterol, vilanterol (long-acting) Fluticasone, budesonide Side effects: tremor, arrhythmia ways air opel raw to Muscarinic Antagonists COPD so Prevent bronchoconstriction by blocking M3 Side effects: oral thrush FIRST LINE AGENT (maintenance) Tiotropium, ipratropium Side effects: dry mouth, cough *COPD 1st LINE* ↓Efficacy in Asthma Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. if using this MOA poorly understood: inhibits calcium influx & ?? to stabilize membrane Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol Inhaled Corticosteroids (short-acting) Cytokine inhibition (NF-kB) Salmeterol, formoterol, vilanterol (long-acting) Fluticasone, budesonide Side effects: tremor, arrhythmia myosins Muscarinic Antagonists Takes at least 2-4 weeks for effect Does NOT replace ICS +/- exercise-induced bronchospasm Prevent bronchoconstriction by blocking M3 Side effects: oral thrush FIRST LINE AGENT (maintenance) Tiotropium, ipratropium Side effects: dry mouth, cough Mast Cell Stabilizer *COPD 1st LINE* Rarely used in Asthma Cromolyn Prevent mast cell degranulation Side effects: minimal Less efficacious Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Reserved for: VERY SEVERE, DIFFICULT TO CONTROL ASTHMA Anti-IgE Monoclonal mustt Anti-IgE therapy Blocks IgE binding to FcERI (allergic asthma) For asthma resistant to Inhaled Steroids & LABA Omalizumab 10M (only when known IgE-mediated allergies are present) Omalizumab ($10,000-$32,000+/year); injections 1-2x/month ADVERSE effects: headache, injection site reactions, arthralgias, infections Infrequent but severe: major hypersensitivity reaction/anaphylaxis e Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Reserved for: VERY SEVERE, DIFFICULT TO CONTROL ASTHMA Anti-IL5 Monoclonal Severe Eosinophilic Asthma Mepolizumab, reslizumab (directly against IL-5) Benralizumab (IL-5 receptor alpha) Anti-IL-5 therapy (only for severe asthma with frequent exacerbations & elevated eosinophils) Mepolizumab (=/>6 YO; $36,000-$42,000+/yr); SubQ 1X/month Is Reslizumab (=/>18 YO; $1,000+/yr); IV 1X/month Benralizumab (=/> 12 YO$36,000+/yr); SubQ 1X/month for 3 months then 1x/ 3 months ADVERSE effects: headache, injection site reactions Infrequent but severe: major hypersensitivity reaction/anaphylaxis Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Anti-Leukotrienes (+/- Allergic Rhinitis) Allergic Asthma ASA-induced Exercise-induced asthma prevention Nocturnal Asthma montelukast, zafirlukast, zileuton Zileuton: hepatotoxic (IL-5 receptor alpha) Montelukast: Serious neuropsychiatric events Zafirlukast and Montelukast (Singulair) Antagonists at CysLT1 receptors, blocks actions of LTC4, LTD4, and LTE4 Prevents inflammation, edema, bronchoconstriction and formation of thick/viscous mucus Add on therapy for long-term management of mild-moderate asthma Effective alternative for prevention of exercise –induced bronchospasm (montelukast; given ~2 hrs prior to activity; once daily) Also used for nocturnal asthma ***Not For acute asthma, acute exercise-induced bronchospasm, or asthma monotherapy (always need a SABA available) Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Anti-Leukotrienes Allergic Rhinitis & Allergic Asthma ASA-induced & exercise-induced asthma Nocturnal asthma montelukast, zafirlukast, zileuton Zileuton: hepatotoxic (IL-5 receptor alpha) Montelukast: Serious neuropsychiatric events Zafirlukast and Montelukast (Singulair) May take weeks to months to see effect May enhance effects of beta-2 agonists Side Effects: Headache (Z, > 10%) Montelukast: U.S. BLACK BOX WARNING for Serious Neuropsychiatric Events - agitation, aggression, depression, sleep disturbances, suicidal thoughts & behavior, including suicide. MOA not well understood. Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Theophylline ↓ cAMP hydrolysis = ↑ cAMP = Bronchodilation (Note: Blocks adenosine receptors) Narrow therapeutic index Toxicities: Cardio- & Neuro-toxicity Tachycardia, arrhythmias, headache, seizure, vomiting, dry mouth, muscle weakness, numbness & tingling, insomnia & tremors Metabolized by CYP450 know DNS interactions Interacting Medications = CYP450 Inhibitors Diuretics & K+ uptake meds (↑) Fluoroquinolones & Macrolides (↑) Fluconazole(↑) Amiodarone, Verapamil, Diltiazem(↑) Carbamazepine/Phenytoin (↓) Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. First Line Agents Core to treating Asthma Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting) Salmeterol, formoterol, vilanterol (long-acting) SEVERE Asthma Anti-IL5 Monoclonal Severe Eosinophilic Asthma Mepolizumab, reslizumab (directly against IL-5) Benralizumab (IL-5 receptor alpha) Side effects: tremor, arrhythmia Less Efficacious Add-Ons Anti-Leukotrienes Allergic Rhinitis & Allergic Asthma ASA-induced & exercise-induced asthma Nocturnal asthma montelukast, zafirlukast, zileuton Zileuton: hepatotoxic (IL-5 receptor alpha) Montelukast: Serious neuropsychiatric events A maybe… Muscarinic Antagonists Inhaled Corticosteroids Cytokine inhibition (NF-kB) Fluticasone, budesonide Low-medium-high doses available Side effects: oral thrush Anti-IgE Monocolonal Blocks IgE binding to FcERI (allergic asthma) Asthma resistant to Inh Steroids & LABA Omalizumab Mast Cell Stabilizer Prevent mast cell degranulation Cromolyn Side effects: minimal Less efficacious Prevent bronchoconstriction by blocking M3 Tiotropium, ipratropium Aclidinium, umeclidinium Side effects: dry mouth, cough Severe asthma or +/- exercise induced bronchospasm Asthma Assumptions: Bronchoconstriction is mediated by (1) inflammation and (2) parasympathetic tone. Drugs to avoid/be used cautiously with Asthma All Cholinergic Drugs (usually avoid) Muscarinic agonists will result in bronchoconstriction Methacholine (used to irritate airways to diagnose hyper-reactivity) Bethanechol (used for urinary retention or post-operative ileus) Systemic anti-muscarinic drugs (usually avoid) this route of administration causes many adverse effects compared to inhaled drugs NON-SELECTIVE Beta-blockers (cautiously) Histamine-releasing drugs (cautiously) Constriction following: morphine, oxycodone (opioid pain medications) NSAIDS (cautiously) Especially aspirin: block PGE2 & promote PGF2a Causes shift to leukotriene production Remember: an asthma management plan MUST be personalized The above is just an example. Nothing to learn specifically from this that is not covered elsewhere. Pharmacologic strategy for treatment of severe acute asthma status asthmaticus or asthma exacerbation albuterol by nebulizer or metered dose inhalation oxygen as needed to maintain acceptable O2 sat establish IV access IV or oral corticosteroids (methylprednisolone, prednisone, dexamethasone or hydrocortisone) ipratropium by nebulizer or metered dose inhalation IV (IM) epinephrine if life-threatening bronchoconstriction (secure airway) IV magnesium sulfate bolus if life-threatening or no improvement after 1 hour (affects Ca++ handling and can facilitate bronchodilation in a subset of patients) Asthma Pearls: (1st line) All patients should have a SABA for acute use. (LABAs are used for chronic control…and should never be used acutely!!!) (1st line) Outside of asthma with specific triggers (exercise- or cold-induced asthma), ALL PATIENTS with ASTHMA should have an inhaled corticosteroid for chronic control. Patients with very severe asthma are the candidates for monoclonal therapy (usually in addition to inhaled steroids, SABA + LAMA.) Patients with uncontrolled asthma, and an allergic component may benefit from AntiLeukotrienes. **note the black box warnings. Cromolyn and anti-muscarinic agents are rarely used in asthma. Even less rarely theophylline – but watch this – it is used and has big toxicities & druginteractions! COPD COPD Assumptions Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing, mucous) with some airway constriction. COPD Assumptions Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing, mucous) with some airway constriction. Prevention & Maintenance Therapy 1. Stop Smoking 2. Get Vaccinated: Flu, COVID, (PCV20 or PCV15 + PCV23,) Tdap, Zoster, and RSV* 1 if longer live to want stop god smarins stowered https://goldcopd.org/wp-content/uploads/2023/03/POCKET-GUIDE-GOLD-2023-ver-1.2-17Feb2023_WMV.pdf COPD Assumptions Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing & mucous.) COPD Assumptions Muscarinic Antagonists Prevent bronchoconstriction by blocking M3 Tiotropium, ipratropium Aclidinium, umeclidinium Side effects: dry mouth, cough FIRST LINE AGENT (maintenance) Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing, mucous) with some airway constriction. IVM Inhaled β2 Agonist Relaxes bronchial smooth muscle Albuterol, levalbuterol (short-acting) Salmeterol, formoterol, vilanterol (long-acting) Inhaled Corticosteroids Side effects: tremor, arrhythmia Fluticasone, budesonide Cytokine inhibition (NF-kB) Side effects: oral thrush Others Oral Steroids Theophylline Antibiotics (azithromycin/macrolides) PDE-4 Inhibitors roflumilast (↓ inflammation, relaxes airways) COPD Assumptions Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing, mucous) with some airway constriction. with helps Muscarinic Antagonists Prevent bronchoconstriction by blocking M3 Inhaled β2 Agonist Tiotropium, ipratropium Aclidinium, umeclidinium Albuterol, levalbuterol (short-acting) Side effects: dry mouth, cough FIRST LINE AGENT (maintenance) SAMA LAMA ipratropium tiotropium, aclidinium Umeclidinium Improves FEV1 & Symptoms eosinophilia Relaxes bronchial smooth muscle Salmeterol, formoterol, vilanterol (long-acting) Side effects: tremor, arrhythmia a SABA LABA Central to symptom management LAMA + LABA = ↑FEV1, ↓Symptoms & ↓Exacerbations vs. Monotherapy Inhaled Corticosteroids Cytokine inhibition (NF-kB) Fluticasone, budesonide Side effects: oral thrush ICS Decreases hospitalization rates In select patients Increases rates of PNA Most beneficial if eosinophilia Others Oral Steroids Theophylline Antibiotics (azithromycin > doxycycline) PDE-4 Inhibitors roflumilast (↓ inflammation, relaxes airways) COPD Assumptions Airway obstruction related to emphysema (alveoli destruction, small airway collapse on exhale) & chronic bronchitis (inflammation, narrowing, mucous) with some airway constriction. COPD Medications Place in Therapy: GOLD Guidelines Group A Group B Group E Mild symptoms + Low Exacerbation Risk Increased symptoms + No Exacerbations Any symptoms + ≥2 Moderate Exacerbations or 1 Hospitalization in the past year LAMA (maintenance) plus SABA (rescue as needed) LAMA + LABA plus SABA (rescue as needed) LAMA + LABA plus SABA Eosinophilia: + ICS (≥300 cells/uL or ≥100cells/ul + severe exacerbation) Add on, if still having exacerbations: Macrolide Antibiotic Roflumilast Pulmonary Rehab Oxygen Therapy (Pa02 < 55 mmHg) Maybe Theophylline & Chronic Oral Steroids *Exacerbations: Standard meds, plus short acting albuterol & ipratropium (SAMA) via nebulizer or inhaler, oral steroids, oxygen, antibiotic or antiviral (influenza) to target suspected cause. Other Pharm Medications Macrolide Antibiotic: azithromycin As an antibiotic: Inhibits bacterial 50S ribosomal subunit IN COPD: DECREASEs EXACERBATIONS by decreasing neutrophil chemotaxis & infiltration into the respiratory epithelium (decreases respiratory inflammation even when infection is not present) Roflumilast: Selective Phosphodiesterase-4 Inhibitor Improves lung function, decreases exacerbations in SEVERE COPD Side effects: (serious, but fortunately less common) severe psychological events, including suicidality COPD Pearls: (1st line) All patients with COPD should have a LAMA. SAMAs are used during acute exacerbations, usually to supplement the LAMA. (1st line) All patients should have a SABA for acute use. (LABAs are used for chronic control…and should never be used acutely!!!) Group B & E COPD patients generally benefit from LABA. Additional therapies may be employed in Group E patients. Watch compelling indications!!! (eosinophilia= ICS. Multiple ABECB= macrolide. Oxygen only for Pa02 60) QT prolongation Teratogenic!!! Causes cartilage defects – same reason we don’t use in kids ABECB Antimicrobial Therapy Hospitalized: piperacillin + tazobactam: PCN with beta-lactamase inhibitor IV, same idea as amoxicillin + clavulanic acid with ↑ microbial coverage cefepime: 4th generation cephalosporin antibiotic that decreases microbial cell wall synthesis via peptidoglycan cross=linking (like PCN). Has expanded G+/G- coverage vs. others in same class. levofloxacin: Fluoroquinolone alternate: moxifloxacin. Cough Suppressants (antitussives) Codeine and Dextromethorphan (marketed as less addictive than codeine; effectiveness is questionable) To suppress NON-PRODUCTIVE COUGH Centrally-acting in medulla cough center: related to morphine Examples: narcotics (opioids) like codeine & opioid derivatives dextromethorphan In general, avoid in children < 2 years of age. Side effects: constipation (codeine) jitters/irritability (dextromethorphan) – but minimal analgesia/euphoria for prescribed doses Dextromethorphan: High levels are abused as a recreational drug (dexing or robotripping). Expectorants Used for “WET COUGH” to clear MUCOUS from airways May also be called mucolytics or mucoactive agents In general, avoid in children < 2 years of age. Guaifenesin Does NOT suppress cough Irritant that causes ↑ fluid secretions, thinner mucous ↑ ciliary action Decreases mucous viscosity (effectiveness is questionable) Robitussin (Robitussin DM = Guaifenesin + Dextromethorphan) Related Mucolytics N-Acetylcysteine (NAC) – usually used in cystic fibrosis Breaks disulfide bonds in mucous = ↓ mucus viscosity & ↑ cough productivity **Also used for acetaminophen poisoning** Chronic Bronchitis Pearls: ABECB are generally older patients with underlying COPD. Antibiotics may not be indicated, but if they are note what to use and when. Acute bronchitis in adults/children is a different presentation and treatment than ABECB. *note ABECB is an acute bronchitis ON TOP OF chronic bronchitis. They are NOT the same! Antitussives and Expectorants are not the same. Watch their use in children. The Sanford Guide Sanford Guide: ID Update Sanford Guide: English Sanford Guide: Antibacterial Agents: Spectra of Activity (openathens.net) Antimicrobials to Avoid In Pregnancy Pulmonary Hypertension SOB Differential SOB Differential Pulmonary Hypertension Meds Vasoreactive Patients (10-20%): Trial of high dose CCB (amlodipine, diltiazem) Vasoreactive = strong response to vasodilators Usually what is tried first Pulmonary Hypertension Meds Vasoreactive Patients (10-20%) Non-Vasoreactive: Use Endothelin receptor antagonist (ERA) + phosphodiesterase 5 inhibitor Goal: Vasodilation PDE5-I: ↑cAMP Endothelin-1 is a potent vasoconstrictor and smooth muscle mitogen Endogenous endothelin receptors: ETA receptors vasoconstrict; ETB receptors vasodilate. Blocking the ETA receptors leads to vasodilation Medications most commonly used: ambrisentan (ERA, non-selective antagonist – primary effect blocking ET ) + tadalafil or sildenafil (PDE5I) bosentan (ERA, higher ET affinity) + tadalafil or sildenafil A A Pulmonary Hypertension Non-Vasoreactive: Endothelin receptor antagonist (ERA) + phosphodiesterase 5 inhibitor Adverse Effects: ERAs: hepatotoxicity and peripheral edema DO NOT use with concurrent idiopathic pulmonary fibrosis (IPF) DO NOT USE IN PREGNANCY!!!! Likely powerful teratogens. NOT for females unless on multi-faceted birth control; monthly pregnancy test; hormonal birth control may not be as effective. Contraindicated during pregnancy. Restricted access (~$5K+/month) PDE5I: hypotension, priapism Pulmonary Hypertension Pearls: Vasoreactive and Non-vasoreactive PH are treated differently. Vasoreactive: High dose CCB (either type but usually DHP CCB 1st) Non-vasoreactive: ERA PLUS PDE-Inhibitor ERAs have very serious side effects. KNOW THESE. The two ERAs are slightly different in selectivity. PDEi have less side effects– but good to know. And, yes, know their names. VTE: PE PE is treated with anticoagulants for a minimum of 3 months. Pulmonary Embolism is probably underdiagnosed Surprisingly High Prevalence of PE in patients hospitalized with COPD exacerbations Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study - Journal of Thrombosis and Haemostasis (jthjournal.org) Surprisingly High Prevalence of PE in patients with NEW-ONSET exertional dyspnea Prevalence, Risk Factor and Clinical Characteristics of Venous Thrombus Embolism in Patients with Acute Exacerbation of COPD: A Prospective Multicenter Study - PMC (nih.gov) PE Pearls: Pulmonary Emboli are seriously dangerous, this should be in your differential for SOB. I will not be testing on this specific data or medications. This is to be complete in your therapeutic thought process, but tuck it away as you WILL need to know these medications. DrugInduced Pulmonary Diseases Drug Induced Pulmonary Diseases Drug Induced Pulmonary Diseases FYI as you go through your systems: NOT FOR THE EXAM Drug Induced Pulmonary Diseases FYI as you go through your systems: NOT FOR THE EXAM Drug Induced Pulmonary Diseases Drug-Induced Disease Summary: SOME of these are pearls to tuck away as you go through your systems, noting the COMLEX may present you with a patient with pulmonary disease originating from these sources. Anything you have already learned is fair game (and should be easy to identify.) C OM LE X C OM LE X A 10-year-old previously healthy male presents to his pediatrician with complaints of coughing at night. His mother is concerned with his health because he has had continuous episodes of wheezing and shortness of breath, which are most severe when he tries to run around outside, especially when the air is cooler. He has a history of atopic dermatitis, managed by topical corticosteroids, and seasonal allergies. There is no history of second-hand smoke exposure. Vital signs are remarkable for a respiratory rate of 22/min with oxygen saturation of 99% on room air. Physical exam reveals diffuse expiratory wheezing, T4FRRSR, hypertonic paraspinal muscles from T2-T5, hypertonic scalene muscles, and a restricted diaphragm on the right. In addition to a short-acting drug, which of the following will also be appropriate for the chronic management of asthma and allergic symptoms? A. Cromolyn B. Diphenhydramine C. Ipratropium D. Montelukast E. Theophylline A 9-year-old male with a history of eczema and mild intermittent asthma presents with his mother to the urgent care clinic, who complains that her son has a "bad cough". She states that for the past two months, he has had a dry cough which is worse at night. The patient admits that he wakes up about once per week coughing. In addition, he states that he feels "out of breath" with exercise and he needs to use his albuterol inhaler nearly every day. Physical exam reveals scattered end-expiratory wheezes. The first-line treatment to prevent his symptoms from recurring is A. inhaled albuterol B. inhaled beclomethasone C. inhaled ipratropium D. intravenous methylprednisolone E. oral dexamethasone o