Bronchodilator Drug Therapy of Bronchial Asthma PDF (2024-25)

‫‪Alsalamo Alykom‬‬ ‫‪@urhousehaunted‬‬ ‫املحدد عليه باللون األزرق = كل شي قراه الدكتور‬ ‫اللي باللون الوردي زي كذا = شرح الدكتور‬ ‫والكالم اللي يضيفه للساليد او شرحي انا للجزئية‬...

‫‪Alsalamo Alykom‬‬ ‫‪@urhousehaunted‬‬ ‫املحدد عليه باللون األزرق = كل شي قراه الدكتور‬ ‫اللي باللون الوردي زي كذا = شرح الدكتور‬ ‫والكالم اللي يضيفه للساليد او شرحي انا للجزئية‬ ‫اللي باللون األخضر زي كذا = ملح عليه وقال انه‬ ‫موضع سوال واالكسبلني واي )صيغ االسئله‬ ‫‪Bronchodilator drug therapy of‬‬ ‫اجيبها من كالمه تقريبا والخيارات من عندي(‬ ‫‪bronchial asthma‬‬ ‫‪By Dr Attia Jabr, 2024-25‬‬ ‫‪Qassim university‬‬  Definition & physiology Lectures on you tube: Bronchodilators in asthma 1. https://www.youtube.com/watch?v=0IBXJek8K4w 2. https://www.youtube.com/watch?v=RL5icJH1K5c What is asthma? Asthma is a chronic inflammatory disease of the airways characterized by episodes of acute bronchoconstriction that cause shortness of breath, cough, chest tightness, wheezing, and rapid respiration - ‫عكس‬ ‫عكس‬ [ ‫عكس‬ Not progressive # chronic bronchitis, COPD, bronchiectasis but if untreated► remodeling ▲(severity, excacerbations, death) 1. Physiology; Bronchodilator Bronchoconstriction (Sympathetic B2, Parasympathetic M3, NANC, CAMP, sensory nerves) 2. Predisposing factors; Allergens-irritants-U Resp. T infections-environmental pollution. 3. Non-allergenic causes of asthma: Cold air-smoking-air pollution 4. Drugs & asthma: BBS, NSAIDS--Morphine- Parasympathomimetics Aspirin induced asthma Release histamine Bronchoconstriction = Stimulate m receptor  Pathology & pathogenesis 1. Pathology: Could be severe to the point where it causes & death thats why we give them b agonist Best drug for asthma patients is Cortisone inhalation to reduce side effects (Reversible broncho-constriction + chronic inflammation + T Bronchial hyper-reactivity+ If untreated ► Remodelling ( loss of elastic recoil+ fibrosis+ hyperplasia) ‫لو سألتك عن االسباب‬ 2. What are the causes of airway narrowing? 3 (mucus-edema-muscle) In the past we used to treat asthma patients with anti histamine but its not helpful because there are so many other cytokines in asthma UNLESS the patient has Hyperplasia of goblet cells Duo to inflammation Contraction allergic rhinitis that led to asthma (second generation anti histamines) 3. Many cytokines + chemokines+ GF But in general it is Not used in asthma Especially If its first generation cause it makes sputum more viscous so its hard to release with coughing > 100 (Immediate-minutes-hours) lipid mediators, cytokines, chemokines, and growth factors. A. Immediate phase: Mast cell► (histamine, leukotriensD4, PGD2,) B. Late phase: (TH2 lymphocytes,► IL4, IL 5, 9,13)►eosinophils & B- lymphocytes► Ab 4. What is the difference in pathology between asthma & COPD?  ‫املريض اللي ماياخذ ‪ inti inflammation drugs‬يعتبر ماتعالج‬ ‫الن لو اخذت ‪ bronchodilator‬انت فقط تعالج االعراض وليس السبب‬ ‫‪G‬‬ ‫كل املرضى اللي عايشني على الفنتولني ‪ beta agonist‬عايشني على وهم‬ ‫‪Bronchodilator‬‬ ‫اسباب السبازم كثير زي الروائح والتراب والنباتات والحشائش‬ ‫ولو ماعالجت الربو بيحصل ‪ remodeling‬فيكون قريب لحاله ال‪COPD‬‬ ‫وبشكل عام املورتالتي نادره باالزما دام انه ماصار ‪remodeling‬‬ Asthma Inflammation: Cells and Mediators - Spasm 7 Source: Peter J. Barnes, MD Remodeling Thickness  Types & Goals of TTT 1. Types of asthma; Extrinsic (atopic)-Intrinsic-Brittle -Drug- Exercise, Nocturnal. 2. Pattern of asthma; Intermittent & Persistent 3. Goals of treatment of asthma: ‫ يعتبر ماتعالج‬inti inflammation drugs ‫املريض اللي ماياخذ‬ ‫خصوصا الكرتزون‬ A. To reverse and prevent airway inflammation. B. To decrease the intensity and frequency of asthma symptoms C. Prevent future exacerbations D. Minimize limitations in activity related to asthma symptoms. ‫نحفظها‬ anti inflammatory drug ‫اي مريض ربو الزم ياخذ‬ The Global Initiative for Asthma (GINA) guidelines cortisol ‫( اال اذا معه‬Formoterol ‫ )بالتحديد‬beta agonist ‫وماتعطي فنتولني‬ recommend that all patients with asthma should receive treatment with a long-term controller medication (anti-inflammatory) and a reliever medication 4. General lines of treatment of asthma Avoid irritants-Drugs therapy- Education  Classification of drugs used in treatment of asthma 1. Bronchodilators (Relievers): 1. B2 agonists (▲C.AMP) (Most important) Inhlation 2. AnticholinergicBlock (# M3) 3. Methylxanthines (▲CAMP ,Block # Adenosine) Combination is preferred 4. Mg sulphate (# Ca channels) (Emergency) 2. Anti-inflammatory: (Controllers) 1. Corticosteroids (Most important) Inhalation 2. Antileukotrienes: Zileuton, zafirlukast, montelukast 3. Mast cell stabilizers: Na cromoglycate 4. Methylxanthines; (▲CAMP , #Adenosine) 3. Biological therapy (Monoclonal antibody): Omalizumab (Anti IGE)- Reluximab (Anti IL-5)- Dupilumab ( Il-3-IL4 ) Methods of administration of drugs to the lung ‫للفهم فقط‬ With Asthma patients it is preferred to take the drug by inhalation and not systemic In metered dose inhaler : 1/20 of the systemic dose (less side effects) ‫ مايكرو‬١٠٠ ‫بخه وحده تطلع‬ > ‫عشره اضعاف او اكثر‬ Nebulizer is preferred for children or people who cannot use ihaler - ‫ = خمسه ملي قرام‬inhaler‫ال‬ 11 Methods of administration of drugs to the lung Dry powder inhaler Inhaler Spacer ‫للكبارين او فوق سبعه الن تشفط‬ ‫بسرعه وبقوه فاالطفال مايعرفون له‬ and coordinated with inspiration ‫ الشفط بطيء وعميق‬Inhaler 30% ‫يوصل للشعب‬ 20% ‫يوصل للشعب‬ Dry powder inhaler 12 ‫املريض اصغر من ثالثه اعطيه ماسك مع السبيسر‬ ‫‪ (١‬سهل استعماله‬ ‫‪ (٢‬اضرار الكرتزون انه يترسب بالحلق او يترسب بالحلق ويضعف املناعه او يترسب باالحبال الصوتيه‬ ‫فيعمل ميوباثي فالسبيسر يحميك من ال‪adverse effects‬‬  1. Sympathomimetics (B2-agonists) Types: All inhalations are safe for children and pregnant women 1. Short acting: Salbutamol, terbutaline, metaproterenol (used in acute attack)/4-6h, 2. Long acting: Formoterol (12-24 ug/12 h), Salmeterol 50 mg12h, Bambuterol 10-20 mg ‫احفظوه كويس‬ ‫ بخمس دقايق بينما العالج االخر ياخذ نص ساعه ملا يشتغل‬rapid onset ‫ هو انه اول عالجني‬salmeterol ‫ مع‬formoterol+slabutamol ‫الفرق بني‬ oral - Asthma attack ‫استعمل هذول‬ Mechanism of action: Where? ↑B2- receptors G-protein→ ↑AC → ↑CAMP → ↓ Ca→ relax airway smooth muscle → 1. Broncho-dilatation (physiological antagonist) The best bronchodilator. Why? And Fast· Tolerance 2. ▼Mediators release from mast cells & others ( weak effect due to rapid desensitization) ‫يجي سوال كثير‬ & · 3. Microvascular leakage in the airway (▼edema) after exposure to mediators (e.g., histamine, LTD4, and PGD2 4. ▲Muco-ciliary clearance (water content ) Explain why : Salbutamol is the best bronchodilator? Cause it is a physiologic antagonist 5. ▼Ach release (presynaptic B2) 6. ▲Skeletal muscle stimulation. (Diaphragm-intercostal muscles) Administration: metered dose inhaler dry powder inhaler 1. Inhalation: Is the best. Why; (MDI, DPI, Nebulizer); ► 5 min- 4h 2. Oral??? Dose 20/1: not for the acute -prophylaxis (conventional – or SR) 1h/8 3. Parenteral???: SC, IM, IV infusion, rarely used e.g. in Severe life threatening Asthma Compare between oral and inhalation B2 agonists? Dose-Kinetics, ease of administration- effectiveness-onset of action- systemic side effect.  Molecular mechanism of action of B2 agonists and methylxanthines ‫شاي قهوه‬ = ‫زي البيتا اقونست ايه الن الباثواي واحد وكلهم يعملون‬ tremors hypotension tachycardia Explain why Methylxanthines has the Relaxtaion same side effects as beta 2 agonist? Cause they work on the same pathway (increase cyclic AMP)  Adverse effects of B2 agonists: inhalers‫الجرعه صغيره فقليله االعراض بال‬ Systemic + large dose inhalation only) ( nebulizer ‫بس االعراض املذكوره هنا بالغالب تحصل ملا يكون سستمك او ملا يستعمل‬ ‫او الدكتور جاهل بالجرعات وكاتب له فنتولني بجرعه كببره‬ Why side effects are more in poorly controlled asthma? 2 reasons (▲Dose-hypoxia) All Asthma Inhalations are safe in pregnancy 1.Tremors Why? ▲ Dilate In large doses loss its selectivity in Elderly & COPD (B2) BV = hypotension = reflex tachycardia 10% ‫موجوده بالقلب‬ = 2.Tachycardia & arrhythmias?▲COPD Why? 3 reasons, (B1 & B2) 3.Insomnia & Nervousness? Why? Sympathetic 4.Throbbing headache. Why? > - Down regulation 5.Tolerance Why? With continuous use ►▼Bronchoprotection (▼ Effect ▼Tremors- ▼ insomnia) 6.Hyperglycemia. Why? (With IV or nebulizer) (B2) Beta-2 receptors stimulate glycogenolysis and insulin release, but peripheral glucose production exceeds central utilization, raising blood sugar 7.Hypokalemia? Why? (With IV or nebulizer) B2 + ▲insulin ▲with aminophylline-steroids- diuretics. 8.Weakness? Why?- Hypokalemia- Hypomagnesaemia. Mismatch Transient 9.Hypoxemia: ▼PaO2 tension if lung ventilation/perfusion ratio (V/Q) worsens (Give oxygen). Paradoxical bronchospasm (irritation)‫العنالارلئبهيتاوالتوشعموبجتوودهابالماش اعنفبتوحاالتوفعيينهقالدصماويالهك واسللجيني يفشتوحياووالعاهليجهااالنوعييهاعالطدميوياهملرويفاالضواعيكهستفجتنيح‬ 10.Metabolic‫عليه‬effects: ▲Fatty acid, insulin, glucose, pyruvate, lactate (with large systemic doses) ‫االعتماد املفرط والوحيد‬ 11.?? Death? 3 causes ( Genetic variations of the receptors + Overreliance > 2 canisters/month + Dose ►Arrhythmias) The more the patient needs the inhaler, the less controlled their condition is, and they likely need anti- ↑ with long-acting like salmeterol when used alone in asthma inflammatory treatment—and vice versa  Dosages of B2-agonists & indications A. Short acting: Salbutamol (4444) for TTT of; acute attacks & chronic mild Intermittent Asthma & immediate Prophylaxis (exercise) (Not regular use. Why)? 1. Onset: 4 min by inhalation- 1/2-1h orally 2. Duration: 4 hours inhalation - 8 h orally 3. MDI: 1-2 puffs (100micr) when required…►.up to 4-8 puffs/20 min for 1 h then/1-4 h 4. Nebulizer: 2.5-5 (4) mg/20 min for 1 h then /4h 5. Oral??? : Syrup 2-4 mg/4h (children < 5 years, severe persistent asthma)- SR for adults 6. IM & SC??: 0.4mg/4h (severe life threatening asthma not responsive to inhalers) 7. IV: 4 micrg/kg = 0.25 mg (life threatening cases) ( IV infusion 5-10 micro /min) Rapid onset B. Long acting; Salmeterol-Formoterol. > 12h, Difference? Onset 1. Formoterol dose; 12-24 ug/12 h = Max = 48 ug/day + ICS for long term control & Relief of acute attacks 2. Chronic prophylaxis: Can you use salmeterol alone in chronic prophylaxis of asthma? Why? Should be combined with corticosteroids?▲ X2 3. Immediate prophylaxis: Alone in Immediate prophylaxis of exercise induced asthma & nocturnal asthma 4. Better than short acting in COPD (can used alone). 5. Salmeterol dose 50 ug/12 h by inhalation only= max = 100 ug/day C: Ultralong acting B2 agonists > 24h: 1. Vilanterol + Fluticasone/24h (COPD more effective than salmeterol 2 times/d) 2. Indacaterol (for COPD)  2. Anti-cholinergic drugs (Ipratropium) ‫موسع للشعب لكن البيتا اقوى‬ ‫االسيتايل كولني ماهو املاده الوحيده اللي تسبب ربو فدور العالج هذا ضعيف‬ 1. Generally, are less effective, less adverse effects than B2-agonists. Why? Its in glands and muscles so it Causes Spasm with secretion if not blocked 2. Mechanism : competitively block muscarinic receptors (M1, M2,De M3). Where and what are the actions of them, Which one is important? Present in Larger bronchioles 3. Types of drugs: Ipratropium (short) & Tiotropium (Long) 4. Duration Ipratropium 5- 8h, Tiotropium 24 h ‫يعني اذا عنده اتاك اعطيه بيتا اقونست مو هذا الن هذا‬ ‫متاخر بنص ساعه يمدي يموت فيها‬ 5. Kinetics: Delayed onset of action (15-30 min). Compare with B2 agonists? Water soluble ‫ فصعب يمتصها الجسم فيقعد بالشعب الهوائية بس وتقل االعراض الجانبيه‬ionized version‫العالج هذا مشتق من االتروبني فالسايد افكتس كثيره لالتروبني فعملوا ال‬ · 6. Quaternary amines: given by inhalation only ↳ 7. Could be combined with B2 agonists in acute severe asthma (MDI or nebulizer) (e.g.100 ug salbutamol + 20 ug ipratropium as MDI) or (2.5 mg + 0.5 mg as Nebulizer)  Indications of anticholinergic drugs: 1. Ipratropium is added to B2 agonists in acute severe asthma. 2. Tiotropium is added to LABAs + ICS in TTT of chronic severe persistent asthma ‫للوقايه‬ Long acting b 2 agonist Inhaled corticosteroids with repeated exacerbations 3. Alternative to B2?? Or added to B2 agonists in : ‫اخفف جرعه البيتا اقونست عشان االعراض الجانبيه واضيف العالج هذا‬ 1. Asthmatics unable to tolerate B2 agonists (anxiety, tremors, tachycardia , bronchospasm due to B2 stimulation). > - B2 = arrhythmia 2. Old age (Cardiac, Thyrotoxic) Why? 3. Beta-blockers-induced asthma. Why? 4. Asthma-COPD overlap syndrome (ipratropium-Tiotropium) ►longer duration of action than salbutamol in COPD (▲vagal tone reversible) ‫ واالدويه‬secretions‫ عشان عندهم زياده في ال‬COPD‫ بال‬beta2 agonists ‫ افضل من‬m antagonists‫ال‬ vagal tune‫ عندهم زياده بال‬COPD‫هذي مدتها اطول والسبب الثالث ان مرضى ال‬ A. Why some patients respond good while others not? B. Why increasing the doses above therapeutic level is not more effective? Longer duration C. Why tiotropium is preferred to ipratropium in TTT of COPD? Duration- selective M3 Because tiotropium specific on M3 Ipratropium blocks M2 receptors, which are normally inhibitory and reduce acetylcholine release. Ipratropium M1 M2 M3 = By inhibiting M2, it effectively blocks this inhibition, leading to a reduction in acetylcholine’s effect.  Kinetics and side effects of anticholinergic drugs Kinetics: Delayed onset (15-30 min). Importance? 1. Ipratropium: A. MDI: 1-2-4-8 puffs (20 ug /Puff ) as needed B. Nebulizer: 0.5 mg /20 min for 3 doses, then/ 1-4 h as needed 2. Tiotropium: 18 ug /24H, once daily (prophylaxis in COPD & Chronic asthma) 3. Aclidinium: Prophylaxis 400 mcg/12 h Side effects: Rare (Atropine like) 1. Local: Dry mouth, bitter taste, paradoxical bronchoconstriction (ipratropium) m2. Explain? Ipratropium blocks M2 receptors, which are normally inhibitory and reduce acetylcholine release. By inhibiting M2, it effectively blocks this inhibition, leading to a reduction in acetylcholine’s effect. 2. Systemic: Rare: Urticaria, Nausea, constipation, urinary retention (elderly), tiotropium if its absorbed (rarely) causes urine retention with enlarged prostate, glaucoma (Tiotropium nebulizer with face mask). Pupic dilation  3. Methylxanthines (▼PDE + # adenosine R ) ‫بس مشكلته ضعيف يعني بس يستعمل كعامل مساعد‬ Theophylline, Theobromine, Caffeine, enprophylline (no adenosine antagonist….less side effects) Mechanism of action: Bronchodilator-anti-inflammatory, immunomodulatory 1. Inhibits phosphodiesterase enzyme (PDE 3 ,4,5) → increase ▲cAMP, CGMP (the most important is PDE4) PDE4B (inflammation) 1. ►Broncho-dilatation (compare with B2 agonists) 2. ►Mast cell stabilization→ : inhibit synthesis and secretion of inflammatory mediators (Mast cells, basophils) + # Adenosine receptors in mast cells ► Same effect. mechanism‫لو جاك سوال وش ال‬ 1) Inhibits phosphodiesterase enzyme 2. Block adenosine receptors A1, A2B in the following sites: 2) block adenosine receptors 1. Bronchi: bronchodilatation 3) anti inflammatory 2. CNS; A. ▲ CNS stimulation►▲Dose ►Convulsions. B. ▲Respiration C. Vasocontraction (↓headache) 3. Heart; Tachycardia ►arrhythmias 4. Stomach: ▲acidity - 5. Kidney: diuresis ‫متكسر عند املدخنني‬ 3. Anti-inflammatory effects; 1.▲ Histone deacetylase:► remove acetyl group from histone proteins on DNA making the DNA less accessible to transcription factors▼ inflammatory gene transcription. ▲Effect of Corticosteroids??? In smoking asthmatics 2. ▼PDI►▲IL 10 release (anti-inflammatory) 3. ▲Apoptosis of esinophils, neutrophils, T lymphocytes, by blocking adenosine and PDE. 4. IF serum plasma concentration is > 20 ug/ml ►▲Circulating catecholamines & ↑Release of calcium from sarcoplasmic reticulum especially in cardiac and skeletal muscles, diaphragm ►▲ventilation ▼fatigue but may lead to side effects (arrhythmia) Pharmacological Actions: ‫الدواء غير امن والزم بالفم مافيه منه بخاخات‬ 1. Smooth muscles: Relax smooth muscles (bronchial) no tolerance 2. CNS: A. Caffeine (100-250 mg): 1. Stimulant (alertness, ▲intellectual effort, motor activity ‫ينبه القلب ويرفع الصغط‬ ) ‫اول عالمات التسمم‬ 2. ▲ All, medullary centers, CTZ, VMC, RC (Value?) Vomiting B. ▲Doses ►irritability, nervousness, insomnia, tremors. C. ▲Doses → Confusion,▼ motor tasks, convulsions, death. 3. CVS:. A. Heart: ▲ 1. ▲ Direct (# A1►↑Catecholamines , #PDIII▲CAMP, ▲Ca++. ) 2. Indirect : ▲Sympathetic centrally. B. Blood vessels: 1. Indirect (VC) Hypotension 2. Direct peripheral dilatation (VD). ▲CAMP ‫ لو جرعه كبيره‬arrhythmia ‫ويعمل‬ 3. With large doses the peripheral effects predominate ►VD. Except Cerebral BV? Why? 4. Kidney: Diuretic action: Why? 2 causes. Not important clinically. 5. GIT: ▲Acid and gastric digestive enzymes secretion.+ Direct irritation 6. SKM: +ve skeletal muscles (▲Ventilation, ▼Fatigue of diaphragm,) 7. Others: ▲ BMR, ▲FFA Pharmacokinetics 1. Absorption: Well, Irritant, Food↓, SR, Rectal (unreliable), SR is better. 2. Distribution: Protein bound 50%, Widely distributed Vd (0.5L/kg)► (fetus- milk) ‫اهم ح ا ج ه‬ 3. Metabolism; liver (CYP1A2, 2E1, 3A/3-4): 80-90% (Importance?) A. First order kinetics: t1/2 (8 h)→ ▲Dose► Zero order kinetics ▲to 60 h B. T1/2: Non-Smokers 8h, Smokers 4h, Children 4h, elderly 15 h C. In premature infants; t1/2 up to 50 h D. Therapeutic level: (5-10-15-20 ug/ml). Narrow TI A. Not metabolized to uric acid. (importance?) B. Factors affecting its metabolism: Age, diseases (Liver failure, pneumonia, CHF, pregnancy) & drugs, genetic, environmental (smoking) 4. Excretion: kidney 10% Adverse effects: Narrow safety margin (5-15 mg/l > 15 or (Therapeutic; 10-20 mg/L) 1. CNS: > children Headache (↓PDE4), restlessness, agitation, insomnia, irritability, nervousness, convulsions (# A1 R), Habituation, Behavior disturbances & Learning difficulty and increased activity in children. 2. Behavioral toxicity: ??? Anxiety, fear, panic, dysphoria, depression, hyperactivity. 3. CVS: PD3E, A1, What is the antidote to aminophylline? Esmolol (IV selective beta blocker) 1. Therapeutic doses →Tachycardia + VC→↑BP). So …. ‫في الجرعات العاليه‬ 2. Heart: Tachycardia, arrhythmia > 20 microgm/ml, hypotension. 3. BV: Vasodilatation: Rapid IV of therapeutic doses or large doses → hypotension, arrhythmias, syncope and death. Why?- 4. Kidney: Diuresis ( # Adenosine) 5. GIT: N,V (↓PDE4 in vomiting centre, PU (hematemesis), hyperglycemia, hypokalemia 6. Respiratory: Tachypnea, hyperventilation,.(used in apnea of premature infants) ►▲ dose ►respiratory arrest Drug interactions: I. Pharmacokinetics: A. Drugs inhibit liver metabolism: e.g. Erythromycin, clarithromycin Not azithromycin, Ciprofloxacin, ketoconazole, fluconazole, zafirlukast, OCP, Allopurinol,, diltiazem, heart and hepatic disease, COPD, Viral infections, extremes of age, pregnancy. B. Drugs increase liver metabolism: Rifampicin, antiepileptics, Smoking (↑50-100%)- Charcoal broiled meat, children (1-16 y)- high protein diet-low CHO C. Theophylline inhibits metabolism of other drugs like Warfarin, Sulphonylureas►▲ their effect II. Pharmacodynamics: 1. Theophylline ▲effects of Frusemide, Sympathomimetics, digitalis. 2. Theophylline ▼effect of phenytoin, lithium. Why? Precautions/ Contraindications to methylxanthines: 1. CNS: History of epilepsy & convulsions 2. Hypertension: Caffeine in hypertensives (large, prolonged doses). 3. Heart: Cardiac arrhythmias and IHD, hyperthyroidism. 4. GIT; Peptic ulcer  Indications of methyl xanthines: systemic 1. Asthma & COPD: ‫ليش مايستعمل كثير؟‬ Oral Why it is delayed to3-4thline? Effect-Low TI-monitor-DDI- Side effects How theophylline benefits asthma? peripheral 2 + CNS+ SK M (diaphragm-Intercostal) ‫اخطر شي‬ A. Acute life threatening asthma by IV infusion (only after failure of inhaled B2 agonists in impending respiratory failure) Cause it is a mild anti inflammatory drug B. Chronic asthma Orally; alone (in mild asthma), or added to (Salmeterol + ICS) or Montelukast (in severe asthma) C. COPD (Roflumilast) orally, PDE-4I + ICS Only 2. Apnea in premature infants: (Caffeine or theophylline) monitor serum level. Why? 3. Headache & migraine: (Caffeine) Adenosine causes vasodilation. by blocking? vasoconstriction. Preparations and doses of aminophylline: Dose in acute attack: IV infusion 1. Loading dose = (5 mg /kg/15-30 min) 2. Maintenance dose =0.5 mg( 0.2- 0.8) mg/kg/h Dose in prophylaxis: Orally 1. Adults: 5-10-15-22 mg/kg/day (SR tablets, better, why?) 2. Adults and children > 1 year > 45kg► give 10 mg/Kg to 300-600 mg/day (increased gradually/ 3 days) up to 22 mg/kg = 800 mg/day 3. Children < 45 kg, give 10mg/kg then/ ▲/3 days → give to 16 mg/kg with maximum 400 mg/day 4. Infants dose< 1y old = (0.2 X age in W) +5) = Dose in mg/kg 5. Premature infants; A. < 24 days =1mg/kg/12h B. > 24 d= 1.5 mg/kg/12h 66 + 1 What about the dose in smokers, children, neonates, old age?  ‫لتسمم الحمل‬ ‫لحصوات الكلى نستعمله بعد‬ 4. Magnesium sulphate ‫مانجيب سيرته اال اذا جا يموت والدواء اللي قبله ماكان له فايده‬ Mechanism of action: 1. Blocks calcium channels in smooth cell muscle membrane…→↓calcium influx…→ SM relaxation…→ broncho-dilatation- 2. Decrease acetylcholine release- 3. Reduce histamine induced airway spasm Indications: 1. Acute life-threatening or severe asthma Pharmacokinetics: IV-or nebulizer (isotonic)- Wide distribution-placenta-milk-Kidney- T1/2= 4h, dose in asthma is 1.2- 2gm IV infusion/20 min Unwanted effects: Y 1. Facial flushing, sweating, nausea. 2. Hypotension 3. Hypothermia · 4. Respiratory and CNS depression Drug-Drug interactions: 1. ↑Neuromuscular blocking 2. ↑Calcium Channel blockers effect.Amlodipine Thank you Alsalamo Alykom