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Pharma Conference Difficulty in breathing •Known case of bronchial asthma since September 2009 •via salbutamol challenge test •Salbutamol nebulization as needed •No maintenance •No regular follow up done 6 weeks PTA • occasional dry cough • night awakenings due to cough ( 2-3 / week) • give Salbutamol neb every 4 hours •Improved by having a good sleep after • no consult was done 2 weeks PTA • Still persistent dry cough •Night awakenings due to cough (3-4 x/ week) consulted consulted at local health clinic > had chest X ray showed pneumonitis w/ lymphadenopathies * given with * loratidine ( loraped) once daily * cefaclor 5mL for 7 days * asked to come back after 3 days 10 days PTA • according to mother after 3 days • noted decrease frequency of dry cough •Decrease night awakening • At follow up • Loratidine was replaced with Citirizine 2.5 mL every 4 hours •Cafaclor was continued for another 4 days 1 day PTA •Still there was cough •Fever ( highest temp 38.2C) •Watery nasal discharge •Post-tussive vomiting of previously ingested milk •Mother gave •5mL paracetamol (125mg/5ml) for every 4 hrs •Salbutamol nebulization (1/2 nebule + 1cc NSS) every 4 hours • there was improvement after nebulization however the symptoms re occur after several hours which prompt consult at UST - ERCD Gen: no weight loss, no decrease in appetite HEENT: no headache, no eye discharge, no epistaxis, no sore throat Cardiovascular: no bruises, no syncope GI: no diarrhea, no melena, no hematocheiza GU: no difficulty in urination Endocrine: no tremors, Musculoskeletal: no bone pain, no muscle pain, no limitation in range of motion Nervous System: no seizure, convulsions, weakness Feeding history • Breast fed until 1 week of life and fed after with milk formula • Started complimentary feeding at 6 months • Now, the patient was fed with mixed diet with Nido with 1:1 dilution, 8 ounce 3/day 24 food recall Food CHO (g) CHON (g) FATS (g) Calories Breakfast Lunch 1 cup soy milk Pancit Canton Beef nilaga with 2 pc meat ½ cup rice Merienda 4 pcs wafer 1 juice tetrapack Dinner Beef nilaga with 2 pc meat 1/4cup rice Midnight snack French fries Milk 3 ounces 1.5 23 2 2 21.5 100 2 23 16 2 82 100 11.5 6 1 8 50 1 41 11.5 1 50 23 18 2 12 100 253 15 ACI % 919.5 (86%) RENI 1070 Developmental History • Gross Motor: Run well with out support, can jump • Fine Motor: feeds self with spoon • Language: produces 2 words sentences, can point what he wants • Social: plays with other kids Immunization • Patient completed the EPI program in our OPD-CD however cant recall the exact dates • BCG 1 - dose • Hep B – 3 doses • DTP – 3 doses • OPV – 3 doses • Measles – 1 dose • Hib – 1 dose Admtted last December 2009 for pneumonia No skin allergies, No surgeries, no blood transfusion (+) Asthma (father, uncle maternal side) (+) hypertension (grandfather – maternal side) (+) heart problem ( grandmother – paternal side) (-) DM, skin allergy , anemia, leukemia, renal disease, seizures Name Age Relation AS 46 LS 52 KR 27 Grand father Grand mother Father CR 25 Mother LS 33 Aunt RS 21 Uncle Educational Attainment Occupation Health Graduate Technician (+)HPN Vocational Healthy High School Housewife graduate College Technician (+) asthma graduate Healthy Graduate Housewife Vocational Graduate None Healthy vocational Highschool None Healthy graduate lives with his parents, maternal grandparents, uncle and aunt 2 storey building made of cement Well lit, well ventilated with 2 bedrooms and 1 comfort room Drinking water is brought from a refill station Garbage not segregated but collected daily No nearby factories, no pets in the house, no second hand smoke exposure There was planted flowers in front of their house which they noted the patient to cough every time he passes by HR: 120bpm RR: 38/min Wt: 14kg (Z score O) Ht: 86.6 (Z score 0) HC: 48 cm (above 0) Temp: 37.1 C Awake, good activity and crying Skin: Warm, moist skin, no active dermatoses, no jaundice, good skin turgor HEENT: closed fontanels, Pink palpebral conjunctivae, anicteric sclerae, no opacities, normal direct pupillary light reflex, pupils 2-3mm ERTL; nonhyperemic EAC and intact tympanic membrane, AU, no aural discharge; no alar flaring, septum in midline, congested turbinates, (+) whitish nasal discharge; hyperemic posterior pharyngeal wall w/ no exudates, uvula midline, tonsils not enlarged Neck: Supple neck, (-) palpable cervical lymph node Lungs: Symmetrical chest expansion, no lagging, (+) suprasternal, intercostal, subcostal retractions, (+) wheezes on both lung fieds, (+) coarse crackles on both lung fields Heart: Adynamic precordium, apex beat at 4th LICS MCL, no thrills, heaves, lifts, murmurs Abdomen: globular soft abdomen, NABS, no palpable masses, no tenderness upon palapation Extremities: Full and equal pulses on all extremities, no edema, no cyanosis, no limitation in movement Genitourinary: bilaterally descended testes, no discharge, no masses Alert, awake, crying and irritable CN I-XII were intact Motor: all extremities moves spontaneously Sensory: No sensory deficits Reflexes: All DTR +2, (-) babinski (-) nuchal rigidity, kernig’s and brudzinski * * * * * 2years old/ male (+) family history of asthma known bronchial asthma dry cough, noucturnal awakenings noted coughing when the pastient passes by infront of the house where there are flowers * good response to salbutamol neb * RR 38/min , (+) suprasternal, intercostal, subcostal retractions, (+) wheezes on both lung fieds, (+) coarse crackles on both lung fields Approach to diagnosis Look for a symptom, sign, or laboratory finding found in the least number of diseases Shortness of breath Cough Wheeze •Asthma exacerbation •Acute bronchitis •Vocal cord dysfunction •Foreign body aspiration •Gastroesophageal reflux Asthma common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, airflow obstruction, and bronchospasm. Asthma is caused by environmental and genetic factors. These factors influence how severe asthma is and how well it responds to medication. Asthma Asthma predominantly occurs in boys in childhood, with a male-to-female ratio of 2:1 until puberty, when the male-to-female ratio becomes 1:1. Asthma prevalence is increased in very young persons and very old persons . Asthma symptoms may include the following: • Cough, worse particularly at night • Wheezing • Shortness of breath • Chest tightness • Sputum production • Decreased exercise tolerance Asthma General asthma physical findings • Evidence of respiratory distress manifests as increased respiratory rate, increased heart rate, diaphoresis, and use of accessory muscles of respiration. • Marked weight loss or severe wasting may indicate severe emphysema. Pulsus paradoxus Depressed sensorium Chest examination • End-expiratory wheezing or a prolonged expiratory phase is found most commonly, although inspiratory wheezing can be heard. • Diminished breath sounds and chest hyperinflation Acute Bronchitis clinical syndrome produced by inflammation of the trachea, bronchi, and bronchioles usually occurs in association with viral respiratory tract infection Characteristic symptoms include productive cough, shortness of breath and wheezing. clinical course of acute bronchitis is selflimited, with complete healing and full return to function typically seen within 10-14 days following symptom onset. Acute Bronchitis The incidence is equal in males and females occurs most commonly in children younger than 2 years, with another peak seen in children aged 9-15 years. begins as a respiratory tract infection that manifests as the common cold. Acute Bronchitis Symptoms often include coryza, malaise, chills, low grade fever, sore throat, and back and muscle pain. The cough in these children is usually accompanied by an initial watery nasal discharge. Crackles, rhonchi, or large airway wheezing, if any, tends to be scattered and bilateral **There is no specific therapy. The disease is self-limited Vocal Cord Dysfunction abnormal adduction of the vocal cords during the respiratory cycle (especially during the inspiratory phase) that produces airflow obstruction at the level of the larynx. Presents with wheezing, cough, and dyspnea This condition is predominantly observed in females This condition predominates in people aged 20-40 years, but it can occur in people aged 6-83 years Vocal Cord Dysfucntion History Wheezing Cough A feeling of tightness in the throat Hoarseness and voice change Stridor Shortness of breath Dyspnea on exertion Inspiratory difficulty Unresponsiveness to bronchodilators and corticosteroids Physical Exam Laryngeal auscultation may reveal harsh stridulous sounds during symptoms. Wheezing may be heard in the chest (transmitted from the upper airway). Foreign Body Aspiration The male-to-female ratio is 2:1 Children, especially those aged 1-3 years Choking or coughing is present in 95% of patients Approximately 50% of children have inspiratory stridor or expiratory wheezing, with prolongation of the expiratory phase, and medium-to-coarse rhonchi. Foreign Body Aspiration Tachypnea; nasal flaring; intercostal, subcostal, and suprasternal retractions; and differences in percussion between hemithoraces also are common findings Fever and central cyanosis are less common consider the possibility of foreign body aspiration, particularly with unilateral wheezing Gastroesophageal reflux Immaturity of lower esophageal sphincter (LES) function, manifested by frequent transient lower esophageal relaxations (tLESRs) that results in retrograde flow of gastric contents into the esophagus. Gastroesophageal reflux has been associated with significant respiratory symptoms in infants and children Gastroesophageal reflux Signs andsymptoms of gastroesophageal reflux in infants and young children • Typical or atypical crying and/or irritability • Apnea and/or bradycardia • Poor appetite • Vomiting • Wheezing • Abdominal and/or chest pain • Stridor • Weight loss or poor growth (failure to thrive) • Recurrent pneumonitis • Sore throat • Chronic cough • Hoarseness and/or laryngitis Signs and symptoms in older children - All of the above, plus heartburn and history of vomiting, regurgitation, unhealthy teeth, and halitosis CLINICAL DIAGNOSIS Bronchial asthma, mildly persistent, in moderate exacerbation Course in The Ward (1st HD) Please admit the patient under the service of Dr. Moral-Valencia at bed 320G Diet for age with strict aspiration precaution Hold feeding of RR > 40cpm Medications given were salbutamol nebulization, 1 neb every 1 hour, hydrocortisone 60mg/SIVP now then every 6 hours, paracetamol 125 mg/5ml, 6 ml every 4 hrs for fever >38.5C, 0.65% NaCl drip Patient was given O2/cannula at 1-2 lpm as needed. IVF D5IMB 500ml to run at 37-38 ml/hr Course in The Ward (2nd HD) Salbutamol + ipratropium bromide was started, alternating with salbutamol nebulization every 6 hours Course in the Ward (3rd HD) Salmeterol + fluticasone propionate (seretide inhaler) 1 puff BID Prednisolone 20mg/5ml 4.5ml SANE Criteria Safety Affordability Need Efficacy Problems in the Patient Pharmacologic therapy to address • Bronchial asthma, mildly persistent, in moderate exacerbation Drugs for Acute Asthma Bronchodilators • Anticholinergics • Methylxanthines • Sympathomimetics Catecholamines – epinephrine B2 agonists SABA Anti-inflammatory • Corticosteroids Systemic Inhaled Relievers Quickly reverse bronchoconstriction during acute exacerbation or breakthrough symptoms; taken prn Bronchodilators • SABA, epinephrine, methylxanthines Anti-inflammatory • Systemic steroids agents Controllers Have to be taken continuously on a maintenance basis to control asthma Bronchodilators • LABA Anti-inflammatory • Inhaled • Systemic • LT antagonists • Mast cell stabilizers agents Bronchodilators MOA: activation of B receptors -> activation of Gs coupling proteins -> cAMP -> phosphorylation of target enzymes -> relaxation of bronchial muscles Epinephrine B2 agonists Epinephrine For anaphylaxis Not effective in oral intake Rapidly conjugated and oxidized in GIT and liver a1= a2 ; B1=B2 Triggers sympathetic response, fear, anxiety, tenseness, restlessness, cardiac arrythmias Not used in acute asthma, unless not responsive to B2 agonist or asthma is caused by anaphylaxis SABA Terbutaline Salbutamol After oral inhalation, 10% deposited in bronchial airway where absorption takes place -> systemic circulation. No substantial effect on inflammation B2 Agonists SABA • Oral Peak effect 2 hrs Duration of action 4-8 hrs • Inhaled Peak effect 30-90 mins, 75% of maximum bronchodilation by 5 mins >4 hrs Adverse Effects of B2 agonists Skeletal muscle tremors tachycardia, arrthymias increased bronchial hyperreactivity and deterioration of disease control Anticholinergic Drugs Ipratropium bromide: treatment for asthma Binds M2 and M3 receptors with equal affinity, competitive antagonist to acetylcholine at M3 receptors on smooth muscles -> blocking bronchospasm -> decrease mucus secretion In combination with SABA, provides quick relief for acute asthma attack Combivent contains a microcrystalline suspension of ipratropium bromide and salbutamol in a pressurized metered-dose aerosol unit for oral inhalation administration. The 200 inhalation unit has a net weight of 14.7 grams. Anticholinergic bronchodilator Each actuation meters 21 mcg of ipratropium bromide and 120 mcg of salbutamol from the valve and delivers 18 mcg of ipratropium bromide and 103 mcg of salbutamol from the mouthpiece. Dosage 2 inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. Safety and efficacy of additional doses of COMBIVENT Inhalation Aerosol beyond 12 puffs/24 hours have not been studied. All Adverse Events (in percentages), from Two Large Double-blind, Parallel, 12-Week Studies of Patients with COPD Methylxanthines Theophylline – both bronchodilator and anti-inflammatory actions inhibits PDE -> increases cAMP ->smooth muscle relaxation High level of toxicity; narrow therapeutic index AE: nausea, vomiting, GIT disturbances, headache, Corticosteroids Anti-inflammatory effects due to inhibition of production of proinflammatory cytokines -> decreased trafficking of lymphocytes, eosinophils -> decreased bronchial hyperreactivity Potentiates B2 agonist effect by increasing synthesis of B2 receptors Decrease mucus production Corticosteroids Systemic steroids • Oral: prednisone, prednisolone, methylprednisolone • Parenteral: hydrocortisone, methylprednisolone Inhaled steroids • Budesonide, fluticasone Indications of CS Systemic steroids • For relief of acute asthma exacerbations • Control of severe persistent asthma Inhaled steroids • As maintenance therapy for all levels of persistent asthma Adverse Effects of CS Inhaled CS adverse effects: hoarseness/dysphonia, oral candidiasis, throat irritation and cough Systemic CS adverse effects: truncal obesity, moon facies, buffalo hump, osteoporosis Anti-Asthma Drugs Safety Affordability Need Efficacy Combivent nebulizer (salbutamol + ipratropium bromide) ++++ ++++ P33.25 ++++ ++++ Theophylline 300mg/tab ++ +++++ P1.50 ++ ++++ Epinephrine HCl 1ml +++ P40.00 ++ ++ Prednisone 20mg/5ml, 3ml ++ P6.25 ++ ++ Methylprednisolone 500mg/IV ++ + P3509.75 ++++ ++++ Salmeterol + fluticasone propionate +++ ++++ ++++ Hydrocortisone 100mg/IV +++ ++++ +++ +++ P40.75 Pre Post Pre Post Pre Post Time 7:30AM 8AM 815AM 842AM 9AM 920AM Spot O2 96 96 94 93 96 96 RR 38 34 34 32 32 40 CR 120 128 128 130 148 140 Temp 37.1 37.5 38 38 38.1 37.8 Air entry Fair Fair Fair Fair Fair Fair to good Retractions -suprasternal + + + - + + -intercostal + + + + + + -subcostal + + + + + + -supraclavicular + + + + + + Alar flaring - - - - - - Wheezes + + + + + + Crackles + + + + + + Rhonchi + + + + + +