This document summarizes drugs acting on the pulmonary system. It discusses first, second, and third generation short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), and long-acting muscarinic antagonists (LAMAs). It provides details on the duration of action, time to onset, and mechanisms of these drug classes. The document also discusses specific drugs, their indications, dosages, side effects, and drug interactions.
This document summarizes drugs acting on the pulmonary system. It discusses first, second, and third generation short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), and long-acting muscarinic antagonists (LAMAs). It provides details on the duration of action, time to onset, and mechanisms of these drug classes. The document also discusses specific drugs, their indications, dosages, side effects, and drug interactions.
This document summarizes drugs acting on the pulmonary system. It discusses first, second, and third generation short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), and long-acting muscarinic antagonists (LAMAs). It provides details on the duration of action, time to onset, and mechanisms of these drug classes. The document also discusses specific drugs, their indications, dosages, side effects, and drug interactions.
hrs duration of action 2nd generation – LABA (12 hrs duration) (salmeterol – starts gradually, formoterol – 1st phase of effect 5-15 min) 3rd generation – LABA (12-24 hrs, start effect about 5-15 min) Selective prolinged beta2agonist (24 hrs) Adenylatcyclaze catalyzing ATP to cyclic AMP transformation Increase of CAMP leads to bronchodilation Action on beta2 receptors 24 times more than beta1 and 20 times more than beta3 FEV elevation for 24 hrs Acts 5 min post inhalation (comparable to salbutamol) Maximal action 2-4 hrs Decreases hyperinflation (increase of volumes at the end of spontaneous expiration) in midsevere and severe COPD Decrease of risk of COPD exacerbations and demand of short time beta2 agonists, ipmrovement of life quality Cmax reached in 15 min post inhalation Bioavailability 43% Systemic exposition due to absorbtion in lungs and intestine increases as dose increase (from 150 to 600 mcg) Excreted with urine – 2% of dose; in oral intake – 90% through intestine T1/2 45,5 - 126 ч. T1/2, basing on the cumulation after repeated use – 40-56 days Prolonged treatment in COPD Contraindication Hypersensitivity, pregnancy, brestfeeding, age < 18 Limitations Cardiovascular diseases, convulsive disorders, thyrothoxicosis, diabetes, QT prolongation (congenital or drug induced), inadequate response to beta mimetics in case history Most – mild degree Nasopharyngitis, upper respiratory infections, ,muscular spasm, sinusitis Hypersensitivity Cough, throat pain, rhinorrhea, rare – paradoxal bronchospasm Rash, itching Dizziness, paresthezy IHD, palpitation, Afib, tachycardia Dry mouth Hyperglycemia/onset of diabetes Peripheral edema, non cardiogenic chest pain With drugs causing QT prolongations – arrhytmias With sympathomimetics –higher risk of systemic actions With drugs causing K decrease – hypokaliemia (incl.with GCS, methylxantines) With beta blockers – decrease of action (accurately selectives can be used) With inhibitors of CYP3A4 and P-glycoprotein – with verapamil and erythromycin Cmax increases 1.2 times After single use of the dose 10 times higher than therapeutic in COPD patients – moderate increase of heart rate, BP, QTc prolongation 150, 300 mcg capsels Onbrez breezhaler 150 once daily usual dose, 300 mcg daily maximal dose High selectivity beta2 mimetic QT prolongation with no influence on the heart rate or rhythm disorders 5 mcg once daily leads to significant improvement of FEV1 during 5 min after first dose Cmax 10–20 min after inhalation Bioavailability 30% CYP2C9 and CYP2C8 of cytochrome Р450 are participating in metabolism T1/2 45hrs No significant changes in aged and concomitant diseases Prolonged treatment of COPD Possibility of use in asthma was not studied Contraindications: age <18 (not studied), individual intolerance Limitations: unstable course of IHD, QT prolongation and rhythm disorders, obstructive CMP, AH, hyperthyrosis, crapms, in patients with recent MI or heart failure decompensation (last year), paroxysmal tachycardia, heart rate > 100/ min Nasopharyngitis, cough Dizziness Hypertension Rash Back pain and arthralgia Pneumonia; lung cancer was observed in 0,7%, 0,3% и 0,2% of patients receiving 10 mcg, 5 mcg and placebo Hyperthermia Diarrhea, constipation Same as Indacaterol Interaction with ketaconazol – increase Cmax 1.7 times 5 mcg once daily (inhalation) Prolonged bronchodilation (12 hrs) Prevents histamine, LT and PGD2 deliberation from mast cells Antiinflammatory properties Asthma, COPD Contraindications Intolerance, age <4 yrs Limitations Thyrotoxicosis, arrhythmia, IHD, uncontrolled hypertension, hypoxial pheochromocytoma, pregnancy, breastfeeding, aged Increase SBP/decrease DPB, rhythm disorders (SVT, PAC, Afib) Diarrhea, abdominal pain, vomiting, viral gastroenteritis, mucosal irritation of throat Dizziness, headache, tremor, anxiety Paradoxal bronchospasm (drug to be cessated), cough Arthralgia, hypokaliemia, allergy rhinitis, laryngitis 2×25 mcg twice daily Maximal dose 4×25 mcg 2 times daily High selective QT prolongation Cmax 5 min T1/2 10 hrs Asthma, COPD Contraindication – intolerance Limitations – coronary insufficiency AH, cramps, thyrotioxicosis, preganncy, breast feeding, age <5yrs Tremor, dizziness, insomnia Pulmonary infections, dyspnoe, tonsillitis, dysphonia Viral infections, chest pain, rash Capsels 12 mcg for inhalation 12–24 mcg 2 times daily 4,5 mcg in one inhalation 1-2 inhalations 1-2 times daily Start of action 5 min Maximal 30–90 min Duration 3–6 hrs T1/2 – for 30% of drug 11 min, for 70% - 120 min 100 mcg Tremor, nervousness, headache, dizziness, accomodation disorder, psychical changes in rare cases Tachycardia, palpitations, rare SBP increase DBP decrease, arrhtytmia Rare cough, pharyngitis, paradoxal bronchospasm Nausea, vomiting Rare rash angioedema urticaria Hypokaliemia, weakness, cramps, urine retention T1/2 — 3,8 hrs, circulation at therapeutic level in blood 2-9 hrs Excreted with urine and bile Maximal effect at 4–5 min, increases to 20 min and reach maximal at 40-60 min, duration 4-5 hrs Maximal effect in 2 doses inhalation 100 mcg 1st generation – SAMA ( 15 min start and 6-8 hrs duration of action 2nd generation – LAMA (24 hrs duration) (Tiotropium bromide) 3rd generation – LAMA (12-24 hrs) Selective M3 receptors longer than M2 (M3 in smooth muscles of bronchi) FEV1 improvement 30 min after 1st dose, maximal 1-3 hrs, lasts more than 12 hrs No influence on QT Cmax 5-15 min (healthy and COPD) T1/2 2-3 hrs COPD Contraindications – individual intolerance, age <18, lactose intolerance Headache Nasopharyngitis Angioedema , rash Dizzinesss Palpitations, tachycardia Dry mucosa Urine retention, worsening of glaucoma No symptoms in healthy after 6000 mcg Asthma – not to be used (no experience) Accurately with recent MI, rhythm disorders, HF III-IV class Dry mouth may lead to caries 322 mcg One inhalation 2 times daily Seebri Breezhaler - 50 mcg (once daily) High selective to M3 Effect is due to local, not systemic action, and lasts 24 hrs Bioavailability (systemic) 19.5% Minimal biotransformation T1/2 5–6 days COPD Contraindications – 1st trimester of pregnancy, <18 Mild dryness in mouth, constipation Cough, local irritation, bronchospas, Tachycardia, urine retention in males with predisposing factors Angioedema Vision disorder, acute glaucoma One capsule inhaled once daily M-blockers Minimally absorbed Bronchodilative effect 5-10 min, lasts 5-6hrs Dilates mostly large and medium bronchi Decreases mucus secretion For tachycardia 500 doses needed 10% reaches bronchiols and alveols Headache, dry mouth Tachycardia, accomodation disorders, decreased perspiration, GI motorics disorder, urine retention Cough, rare paradoxal bronchospasm Rask, urticaria, angioedema, rare anaphylaxia Glaucoma exacerbation 2 doses 2 times daily 0.021 mg in one dose Decreases cells migration and activation Decreases mucus secretion Dilates smooth muscles and normalizes its sensitivity to adrenomimetics Increases number of active beta receptors Effect starts in 4-5 days and reachs maximum for several weeks Hoarse voice Laryngitis, sneezing, cough, paradoxal bronchospasm, eosinophilic pneumonia, candidosis (>400 mcg daily) In dose >1.5 mg daily – systemic effects 50 mcg, 100 mcg, 250 mcg 25% of dose comes to alveoli 90% of dose in GI is destroyed during first passage (bioavailability 10% of all drug passed to intestine) Dysphonia, throat pain, rare – candidosis, nausea, pharyngitis 250 mcg, 500 mcg (suspension for nebulizer)
Pulmicort®Turbuhaler® 100 and 200 mcg
Alvesco Low affinity to receptors Pulmonary esterases transform it to desciclesonide which has proinflammatory activity Less pharyngeal and systemic side effects Active metabolite is metabolized with use of CYP3A4 in liver Asthma Contraindication <6yrs old Accurately in active TB, in pulmpnary infections Diarrhea, dyspepsia Angioedema, paradoxal bronchospasm Oral candidosis – equal to placebo Exema, rash Mild to moderate asthma – 160-640 mcg daily, 640 mcg should be separated to 2 intakes Severe – maximal 1280 mcg In one dose 40, 80, 160 mcg Aclidinium bromide + Formoterol (COPD only) Budesonide + Salbutamol Biasten Budesonide + Formoterol Symbicort Turbuhaler®Foradil Combi Vilanterol + Umeclidinium bromide ANORO ELLIPTA® (22 + 55 mcg /dose – once daily)