Pharm Week 6 Objectives: Drugs for Asthma and COPD PDF

Pharm Week 6 Objectives: Drugs for Asthma and COPD Describe the therapeutic actions, indications, pharmacokinetics, contraindications, most common adverse reactions and important drug-to-drug interaction associated with: 1. **BRONCHODILATORS** a. **Adrenergic Bronchodilators:** - **Albut...

Pharm Week 6 Objectives: Drugs for Asthma and COPD Describe the therapeutic actions, indications, pharmacokinetics, contraindications, most common adverse reactions and important drug-to-drug interaction associated with: 1. **BRONCHODILATORS** a. **Adrenergic Bronchodilators:** - **Albuterol (Proventil)** - **Therapeutic Action**: BRONCHODILATION - Sympathomimetic drug: ↑ the amount of cyclic adenosine monophosphate (cAMP) in bronchial tissue cells leading to bronchodilation and relieving bronchospasms - stimulate beta-2 adrenergic receptors in the smooth muscles of the airways, causing these muscles to relax - ↓airway resistance and facilitating airflow to the lungs - beta2 agonists have a limited role in suppressing histamine release in the lung and increasing ciliary motility - **Indications:** - Short-Acting Bronchodilator (SABA) - "Rescue Inhaler" - Selective beta2 agonist - 1^st^ line therapy used PRN for SOB associated with COPD - Used for the quick relief of acute bronchospasm in conditions like asthma and COPD - Use of a SAB more than 2-3X week means asthma is not well controlled and adjustments to baseline therapy need to be made - **Pharmacokinetics:** - INH: rapid onset (1-15 min), peak in 30-60 min, duration is 3-6 hours - PO: onset 15-30 min, peak 2-3 hours, duration 4-6 hours or more - Absorption: PO administration is well absorbed in GI tract and rapidly enters blood steam; when inhaled- systemic concentration is low - Distribution: distributed widely in the body tissues; small amounts appear in breast milk - Metabolism: extensively metabolized by the liver - Excretion: primarily in the urine as metabolites (\~75%) and feces (\~10%) - **Contraindications:** - Hypersensitivity to adrenergic amines - Use cautiously: Cardiac disease, HTN, hyperthyroidism, diabetes, glaucoma, seizure disorders - Excess inhaler use may lead to tolerance and paradoxical bronchospasm - OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk - Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant - Pedi: Children \ - **Adverse Reactions:** - High doses may cause some degree of beta1 responses - Reactions occur more often when given PO - Side effects may diminish after a week or longer - PARADOXICAL BRONCHOSPASM (excessive use of inhalers; wheezing) - CNS: nervousness, tremors, insomnia, hyperactivity (children), headache - CVS: tachycardia, heart palpitations (high doses), ↑BP, angina, arrythmias, chest pain - GI: nausea/vomiting - Hyperglycemia - Hypokalemia - **Drug-to-drug Interactions:** - Concurrent use with other adrenergic agents will have ↑ adrenergic side effects. - Use with MAO inhibitors may lead to hypertensive crisis - Use with beta blockers may negate therapeutic effect - May ↓ serum digoxin levels (hypokalemia ↑ this risk) - Use with Tricyclic antidepressants may potentiate cardiovascular effects - Use of potassium-losing diuretics ↑ risk of hypokalemia - Drug-Natural Products: Use with caffeine-containing herbs (cola nut, guarana, tea, coffee) ↑ stimulant effect. - **Salmeterol (Serevent Diskus)**: - **Therapeutic Action**: BRONCHODILATION - MOA similar to SABA: produces accumulation of cAMP at beta2-adrenergic receptors - **Indications:** - Long-Acting Bronchodilator (LABA) - Used for long-term maintenance and prevention of bronchospasm in conditions like asthma, COPD, and exercise induced asthma - Concomitant in patients who are currently taking but are inadequately controlled on an inhaled corticosteroid - Typically a LABA and inhaled corticosteroid is used in combination to control asthma symptoms - Not suitable for the relief of acute symptoms - **Pharmacokinetics:** - INH ONLY: onset 10-25 min, peak 3-4 hours, duration 12 hours (9 in adolescents) - Half-life: 3-4 hrs - Absorption: Slow absorption when inhaled, minimal systemic absorption - Distribution: action is primarily local - Metabolism: Metabolized in the liver via the CYP3A4 isoenzyme - Excretion: 60% excreted in feces, 25% excreted in urine - **Contraindications:** - Not suitable for relief of acute symptoms (PRN) - Should not be used more than BID - [BLACK BOX WARNING]: LABA are not indicated for abortive therapy for bronchospasm. If taken they could result in unrelieved bronchospasm. As LABA are associated with increased risk of asthma related death, intubation or hospitalization it is no longer recommended as monotherapy for asthma - [Contraindicated in:] Hypersensitivity to salmeterol or milk proteins, acute attack of asthma (onset of action is delayed), Patients whose asthma is currently controlled on low- or medium-dose inhaled corticosteroid therapy - Patients not receiving a inhaled corticosteroid (↑ risk of asthma-related death) - [Use Cautiously in]: cardiovascular disease (including angina and hypertension), seizure disorders, Diabetes, Glaucoma, Hyperthyroidism, Pheochromocytoma - OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; may inhibit contractions during labor - Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant - Pedi: Children \ - **Drug-to-drug Interactions:** - Beta blockers may ↓ therapeutic effects - MAO inhibitors and tricyclic antidepressants may potentiate cardiovascular effects - Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, ritonavir, atazanavir, clarithromycin, nefazodone, or nelfinavir, may ↑ levels and the risk of toxicity; concurrent use not recommended. - Drug-Natural Products: Use with caffeine-containing herbs (cola nut, guarana, mate, tea, coffee) ↑ stimulant effect b. **Methylxanthines (Theophylline):** - **Therapeutic Action:** BRONCHODILATION - ↑cAMP which relaxes the smooth muscles of the airways and pulmonary vessel and suppresses the response of the airways to stimuli - ↑ force of contraction of diaphragmatic muscles, enhancing respiratory function - IV theophylline has been employed in emergencies - Have impact on most body systems including: Powerful CNS stimulants, CVS effects -- dilate coronary vessels, diuretic effect - **Indications:** - Treatment option for COPD but not very frequently used in COPD and asthma - Use only if beta2 agonists and anticholinergics are unavailable or if the patient cannot afford long-term therapy with other drugs - Often used in combination with other medications for better control of symptoms - Used to treat apnea of prematurity (AOP) d/t effect on CNS stimulation and effect on diaphragmatic contraction - **Pharmacokinetics:** - Onset 30 min (for SR caps: 1-2 hours), duration for SR 8-25 hours (6 hrs for IV or Oral theophylline) - Large volumes of fluid and high-protein meals may increase the rate of absorption - Absorption: Rapid and complete absorption in GI tract after oral administration; ER tablets are affected by gastric pH and food - Distribution: distributes freely into fat-free tissues but poorly into body fat. Its volume of distribution may increase in certain conditions like prematurity, hepatic cirrhosis, and acidemia; crosses BBB and placenta - Metabolism: Extensively metabolized in the liver by CYP450 enzymes (CYP 1A2, CYP 2E1, and CYP 3A4); Meds that induce CYP450 can increase clearance of theophylline; It forms active metabolites such as caffeine and 3-methylxanthine. - Tobacco smoking increases metabolism of theophylline drugs, thereby decreasing the half-life of the drug - Excretion: Excreted mainly in the urine, with about 50% excreted unchanged in neonates and about 10% in older children and adults - **Contraindications:** - Patients with cardiac d/t its stimulatory effects - Patients with renal or hepatic dysfunction - **Adverse Reactions:** - Nausea/vomiting, gastric pain (due to increased gastric acid secretion) - Tachycardia - Irritability - Seizures - Cardiorespiratory collapse - Theophylline toxicity (NO ANTIDOTE) - **Drug-to-drug Interactions:** - Beta-blockers & erythromycin: ↓liver metabolism of theophylline-thereby increasing the half-life and adverse effects of theophylline - Barbiturates: induce CP450, stimulating theophylline metabolism which can result in subtherapeutic levels of theophylline - Macrolide antibiotics: inhibits metabolism of theophylline & ↑ renal clearance of erythromycin - Digoxin: ↑ risk of digoxin toxicity - Lithium: theophylline decreases the effects of lithium - SMOKING: ↓ theophylline levels. Some patients who smoke may require an increase in theophylline dosage of up to 50%\*\*\*\* - Caffeine: the effects of theophylline can be ↑ by foods containing caffeine (also remember that many OTC preparations frequently contain caffeine. Remember that theophylline in a prodrug and is converted to caffeine) - **Monitoring:** - Serum theophylline levels - Toxicity likely to occur when level exceeds 20 mcg/ml - When levels exceed 30 mcg/ml: hyperglycemia; hypotension, seizures, brain damage and death can occur - If serum levels of theophylline have not been stabilized, screen the client's diet, other drugs being taken (including OTC drugs, smoking habits and adherence to prescribed regimen\*\*\*) - TOXICITY TREATMENT: - Charcoal, emesis, gastric lavage to ↓ absorption of the oral medication - Lidocaine: to treat dysrhythmias - Diazepam: to control seizures c. **Anticholinergics** - **Ipratropium (Atrovent)** - **Therapeutic Action:** BRONCHODILATION - antagonizes the action of acetylcholine by blocking receptors - by block muscarinic acetylcholine receptors in the airways, leads to bronchodilation and reduced bronchospasm - ↓ contractility of smooth muscle thereby reducing bronchospasm - An atropine derivative - Can be administered by oral inhalation or intranasal spray - Inhalation: Inhibits cholinergic receptors in bronchial smooth muscle, resulting in decreased concentrations of cyclic guanosine monophosphate (cGMP). ↓ levels of cGMP produce local bronchodilation - **Indications:** - Long-acting muscarinic antagonist (LAMA) - Inhaled anticholinergic drugs are considered 1^st^ treatment for COPD whose symptoms have become persistent - Inhalation: bronchodilation without systemic anticholinergic effects - Intranasal: Local application inhibits secretions from glands lining the nasal mucosa, ↓rhinorrhea - Helps to relieve symptoms such as wheezing, coughing, chest tightness, and SOB - Primarily used to manage and prevent symptoms of COPD, including chronic bronchitis and emphysema. - It is also used in combination with other medications for severe asthma exacerbations - Used off-label for asthma and is included in current evidence-based guidelines for asthma management - The combination of ipratopium with albuterol (Combivent) is used to treat chronic bronchitis - The combination is more effective & has longer duration of action than if either agent is used alone - The combination is more effective in increasing FEV1 (which is the parameter used to evaluate asthmatics and obstructive lung disease & response to the bronchodilators) - **Pharmacokinetics:** - Inhalation: onset 1-3 min, peak 1-2 hrs, duration 4-6 hrs - Intranasal: onset 15 min, peak unknown, duration 6-12 hrs - Absorption: When inhaled, ipratropium is absorbed slowly and has minimal systemic absorption (1-2% for inhalation solution; 20% for inhalation aerosol; \ - **Adverse Reactions:** - PARADOXIC BRONCHOSPASM with aerosol ipratropium (especially with 1^st^ inhalation in newly opened MDI) - Dry mouth and irritation of the pharynx - CV: hypotension, palpitations - Derm: rash - EENT: blurred vision, sore throat; nasal only: epistaxis, nasal dryness/irritation - GI: GI irritation, nausea - Neuro: dizziness, headache, nervousness - Resp: bronchospasm, cough. - Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis) - **Drug-to-drug Interactions:** - ↑ anticholinergic effects with other drugs having anticholinergic properties (antihistamines, phenothiazines, and disopyramide) - **Teaching:** - Beta-agonist inhalant should administer it 5 min before using ipratropium - When using the anticholinergic agent in conjunction with an inhaled glucocorticoid or cromolyn, the ipratropium should be used 5 minutes before the steroid or cromolyn - This causes the bronchioles to dilate so the steroid or cromolyn can be deposited in the bronchioles - \*\*ipratropium aerosols can produce a paradoxic acute bronchospasm that can be life-threatening - Usually is seen with the first inhalation from a newly opened MDI - New MDI should be primed with 2 sprays before use 2. **INHALED GLUCOCORTICOID STEROIDS (ICS)** - **Flunisolide (AeroBid)** - **Therapeutics Action:** ANTIINFLAMMATORY - Synthetic corticosteroid - Functions by ↓ airway inflammation - Used to PREVENT (not treat) an acute bronchoconstriction attack - They inhibit the production of leukotrienes and prostaglandins through interference with arachidonic acid metabolism - Reduce the migration & activity of the inflammatory cells - Exerts its effects by binding to glucocorticoid receptors, leading to the suppression of inflammatory cytokines and mediators - ↑ the \# and responsiveness of beta receptors in airway smooth muscles - diminishes airway inflammation, bronchial hyperresponsiveness, and mucus production, which are characteristic of asthma - **Indications:** - 1^st^ line treatment for persistent asthma - Maintenance treatment of asthma as a prophylactic therapy in adults and pediatric patients \6 years and older - Reduction or elimination of the need for oral corticosteroids in asthma patients requiring oral corticosteroid therapy - Treatment of allergic rhinitis - **Pharmacokinetics:** - Inhalation: onset 5-10 min, peak 30-60 min, duration 12-24 hours, half-life 1.3-1.7 hours - Absorption: absorbed through the lungs into bloodstream with minimal systemic absorption (↓ systemic side effects) - Distribution: extensively distributed throughout the body reaching various tissues and exert its anti-inflammatory effects throughout the body - Metabolism: metabolized by the liver - Excretion: primarily in the urine - **Contraindications:** - Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required - Use in children younger than 6 years of age - Patients with known hypersensitivity to flunisolide or any component of the formulation - **Adverse Reactions:** - During inhalation (especially when a spacer is not used) flunisolide is deposited in the mouth and pharynx where some of the drug is swallowed. Some systemic absorption may occur - Sore throat (pharyngitis) - Hoarseness - Coughing (typically mild and transient) - Dry mouth - Runny nose (rhinitis) - Sinusitis - Oral fungal infections (candidiasis/thrush of mouth and pharynx) - Paradoxical bronchospasms immediately after dosing - Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is possible with long term daily use, but this effect is very rare. \*\*\* - Patients transitioning from oral to inhaled steroids have an ↑ risk of adrenal insufficiency if they experience trauma, surgery, or infections (especially gastroenteritis) - **Drug-to-drug Interactions:** - Desmopressin: can ↑ risk of hyponatremia - Systemic corticoids: When transitioning from systemic corticosteroids to flunisolide, taper the systemic corticosteroids slowly to avoid adrenal insufficiency - Immune suppressing medications: can exacerbate infections 3. **LEUKOTRIENE RECEPTOR ANTAGONISTS** - **Zafirlukast (Accolate)** - **Therapeutic Actions:** PREVENT BRONCHOCONSTRICTION AND VASODILATION - Leukotriene receptor antagonist (LTRA) that works by blocking the action of leukotrienes, which are inflammatory chemicals the body releases in response to allergens - helps ↓ inflammation, bronchoconstriction, and mucus production in the airways, making it effective in managing asthma symptoms - ↓ airway edema, smooth muscle constriction, and mucus production, thereby alleviating asthma symptoms - **Indications:** - Primarily for the prophylaxis and chronic treatment of asthma in adults and children aged 5 years and older - Used as a long-term control medication to prevent asthma attacks and improve lung function - Off-label uses include the management of chronic urticaria, prevention of exercise-induced bronchospasm, and treatment of allergic rhinitis - Can be used as an alternative to inhaled corticosteroids but are less effective - **Pharmacokinetics:** - PO: Onset 1-2 hours, peak 3 hours, duration 24 hours, half-life 10 hours - Absorption: rapidly absorbed after oral administration - Distribution: highly protein bound in plasma (\99%, primarily to albumin) with moderate volume of distribution - Metabolism: extensively metabolized by the liver, primarily by CYP2C9 - Excretion: mainly in the feces - Can take up to 2 weeks to really see the effects - The bioavailability of zafirlukast is ↓ by approximately 40% when taken with high-fat or high-protein meals. To optimize absorption, it should be taken on an empty stomach, either 1 hour before or 2 hours after meals - **Contraindications:** - Use with patients with known hypersensitivity to the drug - Should not be used to control acute asthma/asthma attack - Severe liver disease (including cirrhosis) or with ↑ transaminases - Should not be used in children \5 years old (powerpoint says 12) - Should not be used during an acute asthmatic attack - Churg-Strauss syndrome (a rare blood condition)---Use with caution. May make this condition worse. - **Adverse Reactions:** - Headache - GI: nausea, diarrhea, anorexia, abdominal pain - Upper respiratory tract infections - Cold symptoms - Elevated liver enzymes - Less common: unusual changes in mood/behavior such as agitation, aggression, restlessness, irritability, anxiety, depression, confusion, problems with memory/attention, stuttering, tremors, uncontrolled muscle movements, suicidal thoughts, hallucinations, sleep problems, vivid dreams, sleep-walking, compulsive or repetitive behaviors - Drug-to-drug Interactions: - CYP3A4 Inhibitors: Drugs like erythromycin and ketoconazole can ↑ Zafirlukast levels. - CYP2C9 Inhibitors**:** Drugs like fluconazole and valproic acid can also ↑ Zafirlukast levels. - Drugs Metabolized by CYP3A4: Zafirlukast can ↑ the levels of drugs like warfarin, leading to an ↑ risk of bleeding - There is increased warfarin elimination and anticoagulant dosages should be adjusted - Theophylline levels may increase while on Zafirlukast so need to monitor serum theophylline levels - Aspirin increases the plasma concentration of Zafirlukast by 45% 4. **MAST CELL STABILIZERS** - **Cromolyn (Intal)** - **Therapeutic Action:** ANTIINFLAMMATORY - Functions by inhibiting the release histamine and other inflammatory mediators of Type-I allergic reactions from mast cells, thereby preventing allergic reactions - Works at the surface of the mast cell to inhibit its rupture and degranulation after contact with an antigen - Suppress bronchial inflammation - ↓ inflammatory cells such as eosinophils and macrophages - **Indications:** - Asthma**:** Prophylaxis of allergic and exercise-induced asthma - Alternative to inhaled glucocorticoids - Allergic Rhinitis: Symptomatic treatment of perennial allergic rhinitis - Conjunctivitis**:** Treatment of vernal keratoconjunctivitis and vernal conjunctivitis - Mastocytosis: Symptomatic treatment of systemic mastocytosis - Food Allergy**:** Adjunct therapy in the treatment of food allergies - **Pharmacokinetics:** - To be administered via nebulizer - Onset 15 min, peak 30-60 min, duration 8-12 hours, half-life 80-90 min - Maximal effects may take weeks to develop - Absorption: absorbed through the lungs into the bloodstream; Approx 8% of the inhaled dose is absorbed systemically - Distribution: minimally distributed throughout the body due to its poor systemic absorption; remains largely within the respiratory tract - Metabolism: not extensively metabolized in the body; most of the drug is excreted unchanged. - Excretion: majority of the drug is excreted unchanged in the feces, with a small amount excreted in the urine - **Contraindications:** - SHOULD NOT BE USED DURING ACUTE ASTHMA ATTACK: may worsen symptoms - Should not be used in patients who are allergic to cromolyn or any of its components - Patients with severe renal or hepatic impairment - Antiinflammatory effects are less than with glucocorticoids; therefore cromolyn is not a preferred drug for asthma therapy - Cromolyn may be prescribed as alternative therapy when glucocorticoids create problems - **Adverse Reactions:** - Adverse effects occur in \< 1 of every 10,000 patients. - GI: Nausea, vomiting, diarrhea, abdominal pain, bitter taste - CNS: Headache, dizziness, difficulty speaking - Derm: Rash and itching. - Respiratory: Cough and throat irritation, bronchospasm - **Drug-to-Drug Interactions:** - ↓ potential for drug interactions due to minimal systemic absorption - **Patient Education:** - Effective use requires regular administration - Helps PREVENT but will not STOP an attack in progress - Effects may not be apparent until used regularly for at least 1 month - If used to prevent exercise-induced bronchospasm: use 15-20 minutes prior to activity - While these medications are used infrequently, it is important to remember that it is not a bronchodilator. It is contraindicated for treating acute bronchospasm - - **Differentiate between the drug classes that are used for COPD and asthma and the desired effects of each:** A screenshot of a black screen Description automatically generated **Key Differences in COPD vs. Asthma Treatment:** - **COPD management** focuses on long-term control, symptom relief, and reducing exacerbations, primarily using bronchodilators and corticosteroids. - **Asthma management** is more focused on preventing inflammation, controlling acute exacerbations, and minimizing airway hyperresponsiveness, often using a combination of ICS, beta-agonists, and leukotriene modifiers. - **Describe the side effects of beta2-adrenergic agonists:** - Beta₂-adrenergic agonists, commonly used as bronchodilators for conditions like asthma and COPD, can have several side effects due to their stimulation of beta₂-adrenergic receptors - Side effects of beta2-agonists may diminish after a week or longer - The bronchodilating effects may ↓ with continued use - Adverse effects occur more frequently when the drug is administered orally than when it is inhaled - **Inhaled Preparations: Short Acting (SABAs)** - **Tremors:** Due to stimulation of beta₂ receptors in skeletal muscles - **Palpitations & Tachycardia:** Caused by some spillover stimulation of beta₁ receptors in the heart - **Angina** - **Inhaled Preparations: Long Acting (LABAs):** - **↑ risk for severe asthma and asthma-related death when used as monotherapy for long-term control** - Use only in patients taking a recommended medication for long-term control and only if that medication has been inadequate by itself - LABAs should never be used as first-line therapy for prolonged control - LABAs should never be used alone - **Oral Prparations:** - likely to produce some activation of beta1 receptors in the heart - **Angina pectoris and tachydysrhythmias:** seen with use of large doses due to activation of beta1 receptors - **Chest pain** - **Tremors:** due to activation of beta2 receptors in skeletal muscle (can be reduced by ↓ dosage; with continued use tremor declines spontaneously) - **Describe the side effects and important drug-to-drug interactions associated with methylxanthines (Theophylline):** - Due to the narrow therapeutic even modest alterations in metabolism (caused by other medications) can lead to subtherapeutic effects or toxic side effects - **Side effects:** - **Central Nervous System Stimulation:** - **Insomnia, Nervousness, and Anxiety:** Often due to overstimulation - **Tremors:** Fine tremors can be a common complaint - **Seizures:** Occur at toxic levels - **Gastrointestinal Disturbances:** - **Nausea, Vomiting, and Abdominal Discomfort:** Frequently reported, especially with higher doses - **Cardiovascular Effects:** - **Tachycardia and Palpitations:** Can occur even at therapeutic levels - **Arrhythmias:** More likely if levels become toxic or in patients with underlying heart conditions - **Diuresis:** - **Increased Urination:** mild diuretic effect. - **Drug-to-Drug Interactions:** - Because methylxanthines are primarily metabolized by cytochrome P450 enzymes (especially CYP1A2), several drugs can alter their metabolism: - **CYP450 Inhibitors (↑ Methylxanthine Levels):** - These meds can ↑ plasma levels of theophylline primarily by inhibiting hepatic metabolism: - **Cimetidine:** An H2 receptor antagonist that can ↓ metabolism - **Erythromycin and Certain Fluoroquinolones (ie: Ciprofloxacin):** These antibiotics can inhibit CYP1A2, leading to ↑ methylxanthine concentrations and i↑ risk of toxicity - **Other Medications:** Some antifungals and antivirals may also inhibit the relevant CYP enzymes. - To avoid theophylline toxicity, the dosage of theophylline should be ↓ when the drug is combined with these agents - **CYP450 Inducers (↓ Methylxanthine Levels):** - These meds can ↓ theophylline levels by inducing hepatic drug-metabolizing enzymes: - **Phenytoin, Phenobarbital, and Carbamazepine:** These anticonvulsants can accelerate the metabolism of methylxanthines ↓ their efficacy - **Rifampin:** An antibiotic known to induce CYP enzymes, potentially↓ methylxanthine levels - **Other Considerations:** - **Food Interactions:** While not a drug interaction per se, dietary components (especially high-fiber meals) can affect the absorption of methylxanthines - **Caffeine:** Caffeine is also a methylxanthines and can intensify the adverse effects of theophylline on the CNS and heart - - - - - - if a smoking patient stops smoking but the dose of theophylline is not ↓, the patient is at risk for theophylline toxicity over time - - **Differentiate between the therapeutic and toxic level of theophylline:** - Theophylline has a narrow therapeutic index (range between an effective dose and a toxic dose is small). Max dose typically 600mg/day (if insufficient, dosing may be ↑ based on serum theophylline concentration) - **Therapeutic Levels:** - **Target Serum Concentration:** maintained between 10--20 mcg/mL (many patients are therapeutics @ 5mcg/mL and there is little benefits to ↑ levels above 15mcg/mL) - **Clinical Effects:** At these levels, theophylline provides effective bronchodilation with minimal side effects. - **Toxic Levels:** - **Mild-Moderate Toxicity:** - **Serum Levels:** Approx 20--25 mcg/mL - **Symptoms:** Nausea, vomiting, diarrhe, insomnia restlessness - **Severe Toxicity:** - **Serum Levels:** \>30 mcg/mL - **Symptoms:** severe dysrhythmias (ie: V-fib) and convulsions that can be highly resistant to treatment. - Death may result from cardiorespiratory collapse. - **Key Points to Remember:** - Monitoring is Critical: Due to the narrow therapeutic range, regular monitoring of serum levels is important, especially when starting therapy or adjusting doses. - Individual Variability: Factors such as age, smoking status, concurrent medications (especially CYP450 inhibitors or inducers), and liver function can significantly affect theophylline metabolism and serum concentrations - **Describe the client teaching related to drugs commonly used for COPD and asthma:** **1. Inhaled Bronchodilators** - **Short-Acting Beta₂-Agonists (SABAs) -- e.g., Albuterol (Ventolin, ProAir):** - **Purpose:** Used for rapid relief of acute bronchospasm - **Technique:** Demonstrate correct inhaler or nebulizer use; stress the importance of shaking the inhaler and using a spacer if recommended - **Side Effects:** May include tremors, tachycardia, and nervousness - **When to Use:** Instruct clients to use SABAs as rescue medications and not as a substitute for controller medications - Carry it at all times - Overuse can indicate poor asthma control and may require review of treatment plan - **Long-Acting Beta₂-Agonists (LABAs) -- e.g., Salmeterol, Formoterol:** - **Purpose:** Provide long-term bronchodilation as part of a maintenance regimen - **Usage:** Emphasize that these are not for acute symptom relief. - **Safety:** Often combined with inhaled corticosteroids to reduce asthma-related risks - NOT for acute symptom relief - Use as prescribed, usually BID - **Anticholinergics -- e.g., Ipratropium, Tiotropium:** - **Purpose:** Help to open airways by blocking acetylcholine (muscarinic receptors) useful in both COPD and sometimes asthma. - **Technique:** Proper inhaler technique is critical; demonstrate usage and emphasize cleaning the device regularly - **Side Effects:** Dry mouth and possible throat irritation, stay hydrated - Use regularly for maintenance - NOT for quick relief **2. Inhaled Corticosteroids (ICS) -- e.g., Fluticasone (Flovent), Budesonide (Pulmicort)** - **Purpose:** Reduce airway inflammation and prevent exacerbations - **Usage Tips:** - **Proper Technique:** Show how to use the inhaler correctly; the use of a spacer can improve medication delivery. - **Rinsing Mouth:** Advise rinsing the mouth after use to prevent oral thrush. - **Adherence:** Stress the importance of daily use, even when symptoms are controlled - It may take a few weeks to see full benefits **3. Combination Therapies** - **ICS+LABA Combinations -- e.g., Fluticasone/Salmeterol (Advair), Budesonide/Formoterol (Symbicort):** - **Purpose:** Provide both anti-inflammatory effects and sustained bronchodilation - **Usage:** Emphasize that these medications are for maintenance and not for immediate symptom relief. - **Monitoring:** Advise clients to note any changes in symptoms and to report concerns to their healthcare provider - DO NOT use for immediate relief - Rinse mouth after use **4. Oral Medications** - **Methylxanthines (e.g., Theophylline):** - **Monitoring:** Inform clients about the need for regular blood tests due to the narrow therapeutic index - **Side Effects:** Teach them to recognize early signs of toxicity (nausea, tremors, arrhythmias) - **Leukotriene Modifiers (e.g., Montelukast):** - **Purpose:** Help reduce inflammation and bronchoconstriction, especially in allergic asthma. - **Usage:** Typically taken once daily (usually in the evening); stress adherence for long-term control. - **Side Effects:** May include headache or mood changes; advise reporting unusual symptoms or mood changes - **Oral Corticosteroids (e.g., Prednisone)** - **Purpose:** reduce severe inflammation - **Usage:** short-term exacerbations - **Monitoring:** side effects like weight gain, mood changes - Follow the tapering schedule to avoid withdrawal **5. General Client Teaching Points** - **Medication Adherence:** - **Consistency:** Emphasize the importance of taking medications exactly as prescribed, even when feeling well. - **Daily Routine:** Encourage integrating medication routines into daily life. - **Proper Technique**: Ensure correct inhaler technique to maximize drug delivery to the lungs. - **Spacer Use**: Use a spacer with metered-dose inhalers (MDIs) to improve medication delivery. - **Recognizing Symptoms:** - **Exacerbations:** Teach clients how to recognize early signs of an exacerbation and when to seek medical help. - **Action Plans:** Provide a written asthma or COPD action plan that details steps to take during worsening symptoms. - **Lifestyle and Environmental Factors:** - **Triggers:** Educate about identifying and avoiding triggers (e.g., allergens, smoke, pollution). - **Smoking Cessation:** For COPD patients, stress the importance of quitting smoking and offer resources or referrals. - **Follow-Up and Communication:** - **Regular Monitoring:** Remind clients of the importance of follow-up visits to monitor lung function and adjust therapy. - **Side Effect Reporting:** Instruct them to report any unusual or severe side effects immediately. - **Proper Storage and Maintenance:** - **Storage:** Explain how to store medications properly (e.g., away from extreme temperatures). - **Device Maintenance:** Review how and when to clean inhalers or nebulizers to ensure proper function. - **Review the "GOLD" standards in COPD:** **1. Diagnosis** - **Spirometric Confirmation:** - COPD is confirmed when the post-bronchodilator Forced Expiratory Volume in 1 second (FEV₁)/Forced Vital Capacity (FVC) ratio is \< 0.70. - This objective measure distinguishes COPD from other respiratory conditions - **History and Symptoms:** - A thorough patient history, including smoking exposure and environmental factors, occupational exposures, genetic factors is essential - Symptoms: chronic cough, sputum production, and dyspnea are evaluated **2. Assessment and Classification** - **Spirometric Staging (GOLD 1--4) based on FEV1 as a % of predicted value:** - **GOLD 1 (Mild):** FEV₁ ≥ 80% predicted - **GOLD 2 (Moderate):** 50% ≤ FEV₁ \< 80% predicted - **GOLD 3 (Severe):** 30% ≤ FEV₁ \< 50% predicted - **GOLD 4 (Very Severe):** FEV₁ \< 30% predicted - **Symptom and Exacerbation Risk Assessment (ABCD Groups):** - **Group A:** Low symptom burden, low exacerbation risk - **Group B:** More symptoms, but still low exacerbation risk - **Group C:** Fewer symptoms, but high risk of exacerbations - **Group D:** High symptom burden and high exacerbation risk - **Tools such as the Modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT) help determine the symptom severity.** **3. Management Strategies** - **Non-Pharmacologic Interventions:** - **Smoking Cessation:** The most critical intervention for all COPD patients - **Pulmonary Rehabilitation:** Improves exercise tolerance and quality of life - **Vaccinations:** Annual influenza and pneumococcal vaccinations are recommended - **Oxygen Therapy:** For patients with severe resting hypoxemia, long-term oxygen therapy can improve survival - **Pharmacologic Treatment:** - **Bronchodilators:** - **Short-Acting Beta₂-Agonists (SABAs):** For immediate relief of symptoms - **Long-Acting Beta₂-Agonists (LABAs) and Long-Acting Muscarinic Antagonists (LAMAs):** Mainstay for maintenance therapy - **Inhaled Corticosteroids (ICS):** - Often used in combination with LABAs for patients with frequent exacerbations or evidence of eosinophilic inflammation - **Combination Therapies:** - **LABA/ICS or LABA/LAMA (long-acting muscarinic antagonists** - Tailored based on the patient's ABCD group, balancing symptom control and exacerbation prevention - **Other Agents:** - **Phosphodiesterase-4 inhibitors:** For severe cases with chronic bronchitis - **Theophylline may be considered in select cases** **4. Exacerbation Management** - **Recognition:** - Educate patients to identify worsening symptoms and seek timely medical intervention - **Treatment:** - Often involves short-acting bronchodilators, short-term systemic corticosteroids and antibiotics when bacterial infections are suspected - **Prevention:** - Ongoing pharmacologic and non-pharmacologic strategies are aimed at reducing the frequency and severity of exacerbations **5. Monitoring and Follow-Up** - **Regular Assessments:** - Monitoring lung function, symptom progression, and treatment adherence is crucial. - **Individualized Care:** - Treatment plans should be adjusted based on the patient's response, exacerbation frequency, and any side effects from medications - **Patient Education**: Importance of adherence, inhaler technique, and recognizing exacerbation signs. **6. Updates and Guidelines** - **Evidence-Based Revisions:** - GOLD guidelines are updated regularly to reflect new research, ensuring that management strategies remain current - **Patient-Centered Approach:** - Emphasizes shared decision-making and individualized treatment planning - **Identify the therapeutic uses of antihistamines:** - Antihistamines are commonly used to treat a variety of conditions due to their ability to block the effects of histamine, a substance in the body that causes allergic symptoms. Here are some of the primary therapeutic uses of antihistamines: 1. **Allergic Reactions** - **Allergic Rhinitis (Hay Fever)**: Relieves symptoms like sneezing, runny nose, and itchy eyes - **Allergic Conjunctivitis**: Reduces redness, itching, and tearing of the eyes - **Urticaria (Hives)**: Alleviates itching and swelling of the skin - **Food Allergies**: Helps manage mild allergic reactions to certain foods **2. Respiratory Conditions** - **Common Cold**: Eases symptoms such as runny nose and sneezing - **Bronchitis**: Provides relief from cough and congestion **3. Skin Conditions** - **Atopic Dermatitis**: Reduces itching and inflammation - **Angioedema**: Manages swelling under the skin, often associated with allergic reactions. **4. Motion Sickness and Nausea** - **Motion Sickness**: Prevents and treats nausea, vomiting, and dizziness. - **Nausea and Vomiting**: Used in some cases to control these symptoms, especially in combination with other medications **5. Sleep Disorders** - **Insomnia**: Some first-generation antihistamines are used off-label to induce sleep due to their sedative effects **6. Anxiety** - **Mild Anxiety**: Certain antihistamines can be used to reduce anxiety symptoms **7. Other Uses** - **Parkinson's Disease**: In some cases, used to manage symptoms when traditional medications are not tolerated - **Differentiate between first generation and 2nd generation antihistamines (& receptor sites affected):** - **Both Classes Target H1 Receptors:** Both diphenhydramine and fexofenadine block histamine H1 receptors to relieve allergy symptoms such as itching, sneezing, and runny nose - **Histamine:** locally acting compound - Dilates small blood vessels - ↑capillary permeability - Present in just about all tissues - Stored in mast cells and basophils - Release is caused by allergic and nonallergic mechanisms - **H1 stimulation:** - Vasodilation - ↑ capillary permeability - Bronchoconstriction - Itching and pain - **H2 stimulation:** - Secretion of gastric juice - **H1 antagonist:** - Preventing action of H1 - Can cause excitation and depression of CNS - Useful in treating allergic disorders: - Mild allergy - Severe allergy - Motion sickness - Insomnia - Side effects: sedation, dizziness, nausea, vomiting, drying of mucous membranes - **1st generation H1 Antagonists (Non-Selective): diphenhydramine, promethazine, chlorpheniramine:** - Also interacts with muscarinic receptors, which contributes to anticholinergic effects (dry mouth, blurred vision, urinary retention) - May affect alpha-adrenergic receptors, contributing to orthostatic hypotension - Can interact with serotonin receptors to some extent - **Highly Lipophilic:** Easily crosses the blood-brain barrier - **Sedation:** Commonly causes drowsiness and sedation due to central nervous system (CNS) effects. - **Advantages:** - Effective in relieving acute allergic symptoms - Sometimes used as a sleep aid due to its sedative properties - **Disadvantages:** - Causes sedation, impaired coordination, and anticholinergic side effects - Not ideal for use during daytime activities or when alertness is required  - **2nd generation H1 Antagonists (Selective): fexofenadine** - Primarily targets the peripheral H1 receptors with minimal or no action on muscarinic, alpha-adrenergic, or serotonin receptors - **OTC**: cetirizine, fenofexadine, loratadine - **Rx:** Levocetirizine, Desloratadine - **Low Lipophilicity:** Limited penetration across the blood-brain barrier - **Less Sedation:** Designed to minimize drowsiness and other CNS side effects - **Advantages:** - Effective for seasonal allergic rhinitis and chronic urticaria with a lower risk of sedation - Better suited for daytime use - **Disadvatages:** - May be less potent in very acute allergic situations, but overall provides a favorable side-effect profile for long-term management **Summary of 1^st^ vs 2^nd^ Generation Antihistamines:** - **1^st^ Generation**: Blocks H1 receptors but is non-selective, affecting additional receptor sites (muscarinic, alpha-adrenergic, etc.), which results in significant sedation and anticholinergic side effects - **2^nd^ Generation:** Selectively targets peripheral H1 receptors with minimal CNS penetration, leading to effective allergy relief with fewer sedative and anticholinergic effects **Top of Form** **Bottom of Form**