Respiratory

• Asthma

  1. Triggers include allergens, pollen mould, drugs, food, cold air and stress
  2. Airway lumen becomes narrowed increasing resistance
  3. Recurrent reversible obstruction of airflow due to a stimuli that would not affect a non-asthmatic subject and inflammatory response
  4. We cough tight chest, mucus production and coughing more at night
  5. In flower symptoms include airway academia and goblet cell hyperplasia this is due to hyper responsiveness
  6. Combination of Bronco spasms followed by a later phase of inflammation, which is where eosinophils release mediators adding to bronchoconstruction
• Allergic asthma

  1. Hyperresponsiveness to a specific allergen
  2. On the first exposure, it sensitises individual to antigen by producing T cells and presenting the peptide fragment of allergen on the MHC
  3. Lymphocytes are formed and rise increasing B cell expansion and plasma cells to produce IGE antibodies
  4. On the second exposure, the same allergen is exposed to the antibodies and result in rapid mass degranulation
  5. mass cell degranulation releases spasmogens, including histamine PGD2 and Leukotrienes
  6. Kia static DJ does include TH2 cells and the late phase is inflammatory response
• Bronchodilators B2 agonists

  1. First line treatment for mild to moderate Ing salbutamol which induces dilation and binds to the B2 receptors more stronger than the B1 inhibits media release from cells by increasing mucus secretion
  2. Uses protein cupboard receptors and secondary messengers
  3. Adrenaline or salbutamol binds and activates or two adrenal receptors which activates G protein
  4. Deactivated with diffuse internally comment to contact with Aden cycles which converts ATP into camp camp diffuses an enzyme protein kinase A
  5. this phosphorylates myosin light chain kinase which induces dilation
• Salbutamol

  1. It is a B to Agnes on it as when needed basis given by inhalation to small amounts needed for a side effects to occur
  2. Or dosage is higher and the dosage needed for more distribution and it may bind to a B2 skeletal muscle receptors causing muscle tremors or cardiac B1 which will cause palpitations or tachycardia
  3. Cairo switching occurs so companies can increase patent life by remarketing drugs
  4. produced by fries rearrangement of aspirining Keating undergoes termination Methyl Esther and ketone and replacing bulky tert butyl group with our alkyl substituents
• Muscarinic receptor antagonists


  Drugs that block the action of acetylcholine at muscarinic receptors
• Ipratropium bromide


  • Relaxes constrictions by antagonising M3 receptors, inducing relaxation
  • Given as a nebuliser or facemask to reduce side-effects
  • Main benefits in COPD
  • Not well absorbed in circulation
• At high concentration


  There is no specificity so will antagonise M2 and M1 receptors as well as M3
• M3 antagonism


  Reduced at high dosages
• Tiotropium


  • Longer acting functional selected for M3 but a higher affinity for all muscarinic receptors
  • Longer duration at M3 due to the functional group epoxide which is very strained and reactive with steric hindrance
• Able to cross the bloodline barrier with quaternary nitrogen
• Methylxanthines


  Phosphodiesterase inhibitors
• Inhibition of phosphodiesterase enzymes


  Prevents cAMP degradation
• Inhibition of intercellular phosphodiesterase


  Raises cAMP levels leading to dilation
• Competitive antagonism at adenosine A1 and A2 receptors


  • Adenosine acts as a natural bronchoconstrictor and increases histamine release
  • Antagonising it means relaxation
• Activation of histone acetylase


  Inhibits acetylation of histones required for transcription of inflammatory genes
• Weak diuretic


  • Increases renal blood flow
  • Stimulates heart
  • Constricts vessels
  • Narrow therapeutic window
  • Monitor plasma concentration
• Sustained release preparation or slow IV injection


  1. Metabolised by the P-450 enzymes

  2. Decreases plasma inducing

  3. Increases it inhibition
• leukotriene receptor antagonists

  1. when other inflammation mediators are synthesised and released these are produced by arachidonic acid
  2. NSA inhibit Cox stopping formation of some inflammatory and pain molecules but does not inhibit 5 lipooxygenase so shunted through leukotrienes
  3. administered once a day as third line treatment
• GC anti inflammatory drugs

  1. Increase airway in asthma by reducing inflammatory reactions and prevent progression of chronic asthma
  2. Lipid soluble and Jen and regularly crosses plasma membrane to bind into cellular receptor and interactive DNA to modified transcription
  3. Enhances annexin 1 which suppresses phospholipase A2 reduces prostaglandin formation
  4. decreases formation of TH2 cytokines and recruits eosinophils to promote b clonal expansion
  5. Inhibit gene expression recruit his stone de acid delays to activate genes and reverse the acetylation switch off the jeans
• Beclomethasone

  1. Is a steroid and Cambridge juice ulcers in the stomach
  2. Usually has a prostaglandin which increases mucus and decreases stomach acid meaning it is a protective lining
  3. But if we inhibit Cox, we inhibit the PG and increase by increase an acid and decrease in mucus
• Unwanted GC effects

  1. adrenal suppression and hyperglycaemia
  2. Muscle wasting and red purple stretch marks
  3. Central obesity Buffalo hump and moon face
  4. Osteoporosis due to a decrease in osteoblast and increase in osteoclasts
  5. Stunted growth reduced wounded healing and repair
  6. Excessive GC on HPA may lead to adrenal crisis as sudden withdrawal
  7. Fluid potential peptic ulcers and mood changes
  8. Crushing syndrome increase fat on stomach and chest, but slim arms and legs
  9. Oral thrush fight fungal control
• Guidelines to treat asthma

  1. First line is B2 agonist within inhaled steroids using a spacer and self managed plan of action in education
  2. Severe one or more psychosocial factors relationship about beta blockers and NSAIDs asked
  3. Oxygen actuation and nebulisation
  4. In chronic asthma use intermittent reliever therapy and regular preventer maintenance therapy by using a B2 three times or more
  5. Initial additional controller therapy
  6. Specialist therapy include monoclonal antibodies, immuno suppressants and frequent use of oral corticosteroids
• Salbutamol SE

  1. Tremor headache, muscle cramps, palpitations
  2. Trembling arrhythmia, metabolic changes
• COPD

  1. Emphysema, which is alveoli enlargement due to destruction of walls and loss of elastic recoil and bronchitis for three or more months during two years with or without asthma
  2. Smoking is the main course dust chemical exposures environment and genetics
  3. Amount of female smokers, social economic status, gender and respiratory infections 35 or above
  4. Breathless nurse, chronic cough, regular sputum, production, wheeze, depression, anxiety, more acceptable to infections and worsening of symptoms, pulmonary hypertension
  5. Bronchiolitis through nebuliser oxygen given if appropriate
• Treatments of COPD


  1. Bronco test and nebuliser with oxygen given

  2. aminophylline IV and short course of cortical steroids like prednisone 30 mg daily 7 to 14 days if breathlessness interferes with daily activity

  3. Antibacterial treatment

  4. Chronic COPD use a B2 agonist or a long acting muscarinic antagonist

  5. Smoking cation inhaled corticosteriod vaccine for pneumonia and influenza

  6. Prophylactic antibiotics

  7. Mucic drugs that reduce our sputum viscosity as mucus has large quantities of DNA and increased viscosity so can use dornase alpha which is a human exercise deoxyribonuclease given by inhalation which cleaves DNA short fragments to produce this
• hay fever

  1. allergic inflammation on the lining of the nose which produces symptoms of rhinitis
  2. Nasal obstruction, sneezing and itching with increased grand glandular secretions an allergic response
  3. Aspirin other NSAIDs can cause sensitivity
  4. More common in children or teenagers in boys but men and women equally affected with a family history of allergies, asthma eczema
  5. Frequency, runny or blocked nose, itchy red or watery eyes, itchy throat, mouth and ears cough headache facial pain
• Histamine

  1. Heterocyclic amine as a local hormone for self healing with many physiological defensive immunological roles found on mass cells that secreted in tissue defence mechanisms released by degranulation after activation by direct or physical injury
  2. Four different types of G coupled protein receptors H1 to 4
  3. H1has defensive actions and allergic reactions
  4. H2 gastric acid secretion
  5. H3 cognition and appetite
  6. Four receptors on mass cells
• Antihistamine


  Selectively antagonises at H2 which blocks agonist effects of histamine reducing itching sneezing and nasal obstruction
• Azelastine


  Topical nasal spray with corticosteroids which helps local dilation prolong do you impair the ciliary activity restriction to 7 days max
• Oral leukotriene receptor antagonist


  For asthma
• First generation antihistamines


  • Lipophilic and cross the blood brain barrier
  • Sedative and nonselective with anti-muscarinic effect
  • Chlorphenamine slowly from gut and passes first past metabolism
• Second generation antihistamines


  • Selective and non-sedating
  • More hydrophilic and ionised at physiological pH and do not penetrate blood and barrier
  • Cetrizine unchained by kidneys and elimination
• Third generation antihistamines


  • Active metabolise or optical second generation which are more potent
• Antihistamines do not cure but alleviate symptoms
• Old antihistamines caused drowsiness, which still has purposes if patient has sleep difficulties and can treat motion sickness
• Antihistamines can be administered orally, topically and transnasally
• Different types of pulmonary cells

  1. Ciliated cells waft mucus to the back of the throat and swallow
  2. Goblet produce mucus
  3. serous antimicrobials
  4. Brush form Cilia
  5. Clara produce surfactant
• Pulmonary delivery

  1. Direct access to airways rapid onset of action reduced dose and avoid GI upset
  2. Low efficiency local side effects difficulty in using devices
  3. systemic is non-invasive large surface area less hostile environment but difficulty in using devices correctly as they are complex absorption is limited
• Drug deposition and particle size


  • Influence location of drug
  • Influence mechanism of clinical effectiveness
  • Finer particles deposited further down
  • Larger particles deposited on more central pathways
• Most aerosols are heterodisperse (wide range of sizes)