RESPIRATORY CONDITIONS

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1 RESPIRATORY CONDITIONS 1

2 RESPIRATORY STRUCTURES & FUNCTIONS

3 THE RESPIRATORY TRACT Mouth UPPER Respiratory Tract LOWER Respiratory Tract Nose Pharynx (Larynx) Larynx Trachea Bronchi/Bronchioles Alveoli/Lungs

4 UPPER RESPIRATORY TRACT The Sinuses Maxillary Ethmoid Frontal Sphenoid

5 RESPIRATION Inspiration Normal Forced Only diaphragm contracts External intercostals contract Expiration Normal Forced Diaphragm relaxes Abdominal/internal intercostals contract

6 MECHANICS OF RESPIRATION

7 RESPIRATION / LUNG CAPACITIES Inspiratory Reserve Volume Vital Capacity (FEV1) Tidal Volume Expiratory Reserve Volume Residual volume

8 ALVEOLUS

9 GAS EXCHANGE (PO 2 /PCO 2 ) Alveolus PO 2 = 105 Capillary PO 2 = 40 PCO 2 = 45 PCO 2 = 40

10 RESPIRATORY EPITHELIUM 10

11 MUCOUS MEMBRANE Mucous glands Goblet cells Cilia Mucus-producing cells Mucociliary escalator (5-10mm/minute)

12 MUCOCILIARY CLEARANCE Clearance rate Optimum range Watery mucus Viscous mucus

13 MUCOUS Glycoprotein Matrix Mucous Glycoprotein Disulfide cross-bridges

14 MUCOUS Glycoprotein Matrix Mucous Glycoprotein Disulfide cross-bridges Mucolytic

15 ASTHMA

16 RESPIRATORY CONDITIONS

17 UPPER RESPIRATORY CONDITIONS Common Cold Otitis Media Pharyngitis Sinusitis Allergic Rhinitis Influenza Tonsillitis Laryngitis

18 LOWER RESPIRATORY CONDITIONS Otitis Media Pertussis Coughing Bronchi -ectasis Tuberculosis CAP Asthma

19 UPPER RESPIRATORY CONDITIONS The Common Cold Viral, airborne, contagious Nasal, sinuses, ears, bronchi Children at greater risk Treatments: analgesics, decongestants, antihistamines, cough remedies, rest, increased fluids Influenza ( Flu ) Mutating viral attacks Nose, throat, lungs, malaise, dry cough Children, elderly Secondary infections (sinusitis, OM, bronchitis, CAP) Treatments: analgesics, decongestants, antihistamines, cough remedies, antibacterials, bed rest, increased fluids

20 UPPER RESPIRATORY CONDITIONS Allergic Rhinitis / Hayfever 1 in 7 people, QoL, starts < 20 yrs Seasonal (Pollens, spores) Itching (throat, ears, eyes), sneezing, stuffy/runny nose Perennial (Dust, fur, feathers, fungi) Symptoms similar to SAR, less intense, longer-lasting Combination Sinusitis Acute - purulent discharge, pain, swelling & tenderness Chronic - mild discharge, often asymptomatic

21 UPPER RESPIRATORY CONDITIONS Cough Productive ( Wet [phlegm]) cough Non-productive ( Dry ) cough Productive cough Viscosity of phlegm Force of coughing Cough therapy Treat the cause Suppress the cough reflex Suppress a wet cough?

22 LOWER RESPIRATORY CONDITIONS Asthma (Gk: panting ) Two Types Extrinsic ( Atopic ) allergens (dust, stress, exertion, weather changes) Intrinsic ( Non-atopic ) no allergen (EIA) Not COPD Emphysema, Chronic Bronchitis (AECB), Bronchiectasis Treatment: bronchodilator

23 LOWER RESPIRATORY CONDITIONS Chronic Bronchitis Dyspnoea after cough/phlegm Obese Blue face Normal chest Harsh breathing Enlarged heart Airways obstruction reversible Normal, slightly TLC Copious, green phlegm Low O 2, raised CO 2 R heart failure common, fatal COPD Emphysema Dyspnoea before cough/phlegm Skinny Pink face Inflated chest Quiet breath sounds Long, thin heart Airways blockage permanent TLC Moderate, white phlegm Low O 2, low CO 2 R heart failure rare

24 RESPIRATORY TRACT INFECTIONS Commensals Symbiosis Opportunistic pathogens Gram Positive Streptococcus pneumoniae Staphylococcus aureus Gram Negative Moraxella catarrhalis Haemophilus influenzae Atypical Mycoplasma pneumoniae Mycobacterium tuberculosis Klebsiella pneumoniae Chlamydia pneumoniae Antibiotics perform two types of actions: Bacterio-static (inhibits growth) Bacteri-cidal (destroys)

25 TREATMENT FOR RESPIRATORY CONDITIONS

26 TREATMENTS FOR COUGH/COLDS Antihistamines Antitussives Decongestants Treatment for Coughs & Colds Analgesics Bronchodilators Expectorants

27 TREATMENTS FOR COUGH/COLDS Antihistamines (Des)loratadine Phenyltoloxamine Doxylamine Diphenhydramine Promethazone Chlorpheniramine Brompheniramine Triprolidine

28 ANTIHISTAMINES Histamine Inflammatory mediator (allergen-driven) Sneezing, coughing, runny / blocked nose Antihistamines - 2 classes: Older first generation, sedating antihistamines Newer second generation, non-sedating antihistamines

29 ALLERGIC RHINITIS Pharmacological management Antihistamines Decongestants Intranasal cromolyn Anticholinergics Corticosteroids Immunotherapy

30 (DES)LORATADINE A 3 rd generation antihistamine acts within 30mins 10 times more potent than loratadine in vivo More potent antagonist at H 1 receptors Less sedation (no BBB), no cardiac AEs (QT) Has significant anti-inflammatory effects Has significant decongestant effects

31 (DES)LORATADINE Food does not affect its absorption No clinically relevant drug-drug interaction No potentiation of adverse psychomotor effects of alcohol Protects against allergen challenges for up to 24 hours

32 (DES)LORATADINE Early Phase allergic response The primary effect is the release of histamine Symptoms are mainly impacting the nose and eyes running, watery Sufferers called SNEEZERS and RUNNERS (usually Seasonal AR) 32

33 (DES)LORATADINE Early Phase allergic response The primary effect is the release of histamine Symptoms are mainly impacting the nose and eyes running, watery Sufferers called SNEEZERS and RUNNERS (usually Seasonal AR) Late Phase allergic response Immune response (white blood cells) kicks in, characterised by inflammation Symptoms are congestion and stuffiness Sufferers called BLOCKERS (usually Perennial AR) 33

34 (DES)LORATADINE Early Phase allergic response The primary effect is the release of histamine Symptoms are mainly impacting the nose and eyes running, watery Sufferers called SNEEZERS and RUNNERS (usually Seasonal AR) Late Phase allergic response Immune response (white blood cells) kicks in, characterised by inflammation Symptoms are congestion and stuffiness Sufferers called BLOCKERS (usually Perennial AR) Desloratadine works in both Early and Late phase AR (2 nd generation antihistamines work only in the early phase) While not as potent as intranasal steroids (INS), DES nevertheless reduces inflammation (blocked nose, stuffiness) Studies show that DES significantly reduces the need for INS or decongestants 34

35 (DES)LORATADINE Why should I use antihistamine tablets over a nasal spray? Answer: Although there is a place for nasal sprays in the treatment of allergic rhinitis, you can t use them for long periods of time as you may end up with rebound. Nasal sprays also lead to nasal ulcerations, nose and throat irritation, sneezing and changes in taste. Desloratadine is proven to reduce nasal congestion and inflammation, so when using it for your allergic rhinitis patients you do not even have to worry about using a nasal spray or the side effects it comes with, not to mention adding to the cost of treatment. 35

36 TREATMENTS FOR COUGH/COLDS Antitussives Dextromethorphan Codeine Noscapine Pholcodine

37 COUGH SUPPRESSANTS Coughing - protective mechanism Type of cough determines Tx Symptom of an underlying disorder Cough drugs target the cough reflex CNS-acting drugs raise cough threshold (CNS Cough Centre) Peripherally-acting drugs decrease RT receptor sensitivity Indirect effects Alter mucociliary factors Local analgesic or anaesthetic action on receptors Protecting the receptors from irritant stimuli

38 COUGH SUPPRESSANTS Non-productive often from viral infections Treat underlying disorders (eg. asthma, chronic bronchitis, heart failure/pulmonary congestion, lung cancer, oesophageal reflux, post nasal drip, etc) Provide patient relief from non-productive cough, particularly if administered at night

39 TREATMENTS FOR COUGH/COLDS Decongestants Phenylephrine Phenylpropanolamine L-/pseudo-Ephedrine

40 DECONGESTANTS Reduce the volume of nasal mucosa Contraction/shrinking of arterioles supplying the nasal mucosa Opens airways = alpha-adrenergic agonists Common decongestants: Pseudoephedrine (new Dimetapp, Colcaps, Demazin, Flusin, Nurofen C&F, Sinuclear, Sinumax, Degoran) Phenylpropanolamine / PPA (old Dimetapp, old Degoran, Colcaps caps, Rinex, Sinuclear, Sinustat, Sinutab selected) Phenylephrine (Colcaps, Corenza, Demazin, Grippon, Rinex) Available orally (tabs, caps, syrup) & topically (gels, sprays, drops)

41 TREATMENTS FOR COUGH/COLDS Aminophylline Orciprenaline Terbutaline Bronchodilators

42 TREATMENTS FOR COUGH/COLDS Expectorants Ammonium Chloride Guaiphenesin Mucolytics Carbocysteine Bromhexine Expectorants

43 TREATMENTS FOR COUGH/COLDS Mucolytic Expectorants Ammonium Chloride Guaiphenesin Mucolytics Carbocysteine Bromhexine Expectorants

44 TREATMENTS FOR COUGH/COLDS Aspirin Paracetamol Acetominophen Phenacetin Codeine Analgesics

45 ANALGESICS NSAID s (non-steroidal anti-inflammatory drug): Ibuprofen (Advil, Nurofen), aspirin (Anadin, GrandPa, Disprin), & naproxen (Alleve) Effective in relieving inflammation, pain & fever Paracetamol: Panado, Calpol, Paramed Effective in relieving pain & fever Caution with unintentional overdose, as many cold preparations already contain Paracetamol (Sinumax, Colcaps, Sinuclear) Particular caution with children

46 TREATMENTS FOR COUGH/COLDS Antihistamines Decongestants Analgesics Mucolytics Phenyltoloxamine Doxylamine Diphenhydramine Promethazone Triprolidine Pseudoephedrine L-ephedrine Phenylpropanolamine Phenylephrine Paracetamol Phenacetin Aspirin Codeine Acetaminophen Carbocysteine Bromhexine Bronchodilators Expectorants Antitussives Orciprenaline Guaifenesin Codeine Aminophylline Ammonium chloride Dextromethorphan Terbutaline Pholcodine Noscapine

47 DISCLAIMER This presentation contains forward-looking statements about the company s operations and financial conditions. They are based on Litha Healthcare Group Limited s best estimates and information at the time of writing. They are nonetheless subject to significant uncertainties and contingencies many of which are beyond the control of the company. Unanticipated events will occur and actual future events may differ materially from current expectations due to new business opportunities, changes in priorities by the company as well as other factors. Any of these factors may materially affect the company s future business activities and its ongoing financial results. 47

Drugs Used to Treat Chronic Obstructive Pulmonary Disease (COPD)

Drugs Used to Treat Chronic Obstructive Pulmonary Disease (COPD) COPD COPD is a chronic, irreversible obstruction of airflow that is usually progressive. Symptoms include cough, excess mucus production,