ANATOMY & PHYSIOLOGY of The respiratory system

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2 ANATOMY & PHYSIOLOGY of The respiratory system 1. Nose and Sinuses 2. Pharynx (Throat) 3. Larynx (Voice Box) 4. Trachea (Windpipe) 5. Bronchi and Bronchioles 6. Lungs

3 Nose First passage for breathing Organ of Smell Contain hairs to filter, and warm incoming air Contains mucus producing goblet cells trap irritants and moisten/lubricate nose Character and resonance to voice and speech Nasal mucosa

4 Sinuses Hollow spaces - Decrease the weight of the Skull Give resonance to voice

5 Pharynx (Throat) Nasopharynx: respiratory function Oropharynx: Respiratory & digestive function Laryngopharynx: Respiratory & vocal function

6 Larynx (Voice Box) Connects pharynx to trachea Epiglottis - covers larynx during swallowing Contains two vocal cords which vibrate together to make voice

7 Trachea and Bronchi Trachea is the wind pipe and it divides into: Right and Left primary bronchus these further divide into Secondary bronchi Cartilage rings Bronchioles : branch 14 times to a final terminal bronchiole

8 Lungs Responsible for gas- exchange

9 Upper & Lower Respiratory System Upper respiratory system refers to nose, pharynx & associated structures (tonsils & sinuses). Lower respiratory system refers to larynx, trachea, bronchi & lungs.

10 Respiratory tract functions mucus cilia Epithelium with goblet cells Bronchial muscle

11 Overview of Cough

12 COUGH A protective and a physiological response Involves rapid expulsion of air from respiratory airway which expel irritants and excessive secretions from respiratory tract Goodman & Gilman (1996), pg 551 Satoskar (1997), pg 318

13 Cough receptors There are two kinds of receptors in the respiratory tract which can initiate cough. The Mechanoceptors Stimulated by stretch impulses as seen in bronchospasm, bronchoconstriction or sudden airflow changes or by non irritating foreign particles. The Chemoreceptors Stimulated by irritant stimuli - dust, pathogens, allergens, chemicals, odors, irritating foreign particles and mucus. These chemoreceptors are also directly stimulated by Histamine which is released from mast cells in upper airway in response to the above irritant stimuli Therefore irritants not only stimulate airway receptors directly but also cause mast cells present in the upper airway to release histamine which further stimulates airway receptors

14 Cough Reflex mechanism Histamine Foreign particles Irritants Airway Chemoceptors Airway Mechanoceptors Cholinergic, vagal pathway Effective cough Patent airway Ciliary action Impulse to Larynx, Intercostal / abdominal muscles Diaphragm Cough Center in Brain stem Stimulation of CNS receptors - cough excitability

15 Dry Cough Needs to be suppressed Cough suppressants have a major role Seen commonly in Upper Respiratory tract infections: Viral colds due to post nasal drip Pharyngitis Tonsillitis Laryngitis Airway Allergies TB Should aggressively be suppressed as: Cause Sleep impairment and fatigue Risk - Hernias, fresh surgeries, etc Irritation and interference in work Useless as no sputum to be expelled Productive cough Should not be suppressed It should be aided - in bringing out mucus by Maintaining bronchodilation Thinning mucus consistency Ensuring ciliary movement Improving expectoration Seen commonly in Lower Respiratory tract infections: Chronic obstructive pulmonary disease (COPD) Acute and Chronic bronchitis Asthmatic Bronchitis Emphysema Pneumonia Bronchiectasis Tuberculosis & Smoking

16 Management of cough Dry cough This should be done by suppressing cough at 2 levels: A) Peripheral To suppress the stimulation of Airway receptors B) Central Suppression of cough center Productive cough This should be done by A) Decreasing mucus viscosity mucolytics B) Improving expectoration of mucus C) Maintaining bronchial patency to expel mucus effectively (bronchodilator)

17 Ideal Dry cough formulation Effective cough suppression peripherally and centrally: CPM DXM Soothing agent To provide soothing action as well as reduce throat pain and soreness Menthol

18 DEXTROMETHORPHAN Acts on cough center: Inhibits incoming cough stimuli Raises threshold of cough and Suppress cough reflex Does not suppress Voluntary cough No dependence, respiratory depression or constipating properties (as seen in Codiene) Efficacy on par with narcotic anti tussive (codiene) Acts within min and action lasts for 4-6 hours. Considered treatment of choice for suppressing dry cough Dose : 10 to 30 mg orally every 4 to 8 hourly (max mg/day)

19 Chlorpheniramine Maleate Inhibits cough by both peripheral and central mechanisms. Peripheral: Decreases histamine induced airway cough receptor stimulation Decreases cholinergic transmission of nerve impulses to the cough reflex. Central: Binds to CNS receptors and controls cough excitability. (Therefore complements central action of Dextromethorphan on cough centre) Dose : 4 mg every 4 to 6 hourly (max, 24 mg/day)

20 20 Menthol: A Soothing Agent Produces cooling, soothing sensation Mild anesthetic action decreases throat pain and soreness and airway cough receptor stimulation

21 MOA Histamine Foreign particles Irritants Cough suppressed CPM Airway Chemoceptors Airway Mechanoceptors Cholinergic, vagal pathway CPM Effective cough Patent airway Ciliary action Impulse to Larynx, Intercostal / abdominal muscles Diaphragm x DX M Cough Center in Brain stem CPM Stimulation of CNS receptors - cough excitability

22 New ZEDEX DC for DXM and CPM ; DC for DUAL CONTROL of Cough!! Each 5ml contains: DXM 10mg and CPM 2mg DCGI approved Dose Adults: 10ml TID Children above 6 years: 5 ml TID 2-6 years : 2.5 ml TID

23 Overview of Common Cold

24 Common cold Most common colds are caused either by Viral infections (Rhinovirus, Coronavirus) or reaction to various substances like dust, pollen etc. Usually resolve spontaneously in 7 to 10 days, with some symptoms possibly lasting for up to 2-3 weeks. Treatment is symptomatic. Average two to four times a year in individual adults and up to 6-12 in individual children. Risk factors Air- conditioned crowded places Constant touching of nose Improper hygiene in sneezing, coughing and hand washing Seasonal change, humidity and pollution Improper diet Low immunity

25 Pathophysiology Mast cells are present on all interfaces with external environment especially upper airway (nose and throat) and skin. They release Histamine when stimulated by pathogens and irritants as in common colds Histamine acts through H1 receptors in nasal mucosa and throat

26 Actions of Histamine Dilation of Blood Vessels Redness Congestion Increase in blood vessel permeability - fluid leakage into mucosa Swelling Congestion Increase in Mucus secretion by stimulation of goblet cells Mucus tickling down throat (post nasal drip) especially at night Running nose Cough, throat irritation/sore throat Stimulation of nasal nerve receptors (free nerve endings) and airway chemoreceptors which cause irritation and itching Sneezing Irritation Itching Irritating Cough

27 Symptoms of common cold Running Nose- Nasal discharge Mucus production by goblet cells stimulated by histamine Mucus maybe watery, or purulent and thick

28 Nasal Congestion and Stuffiness Dilation of blood vessels Fluid leakage into mucosa - swelling Accumulation of mucus Nasal irritation & itching Stimulation of nerve endings by Histamine as well as mucus Common Cold

29 Irritation of Nasal mucosa by foreign particles, irritants or mucus pieces Mast cells release Histamine and stimulate nerve endings in nose Sneezing Signals being sent to the Brain to initiate the sneeze through the 5 th cranial (Trigeminal) nerve The brain relates this initial signal and sends response Activates the facial and throat muscles and creates a large opening of the nasal and oral cavities Powerful release of air and particles (FB and mucus). The powerful sneeze involves numerous organs of the upper body the face, throat, and chest muscles

30 Sinusitis Nasal congestion blocks sinus openings Leads to impaired drainage Nasal and heavy voice Headache and Heaviness of head especially on looking down

31 COLD PATHOLOGY & TREATMENT Pathology Sneezing, running nose, and nasal/throat irritation (due to histamine release from mast cells) Nasal congestion due to dilated blood vessels Decrease viscosity and break down nasal mucus secretions Decrease associated throat pain and fever Soothing and local anesthetic action Treatment Anti histamine CPM Decongestant Phenylephrine Mucolytic Sodium citrate Antipyretic-Analgesic PCM Soother Menthol

32 H1 Antihistaminics 1 st Generation (cross BBB) Highly sedative: Diphenhydramine, Promethazine, Hydroxyzine Moderately sedative: Cinnarazine, Meclizine, Buclizine Mildly sedative: Chlorpheniramine maleate, Triprolidine 2nd Generation: Cetrizine, Terfenidine, Loratidine, Azelastine, Astemazole, and Mizolastine, Olopatidine 3 rd Generation : (active enantiomers or metabolites): Levocetrizine, Desloratidine and Fexofenadine

33 Chlorpheniramine maleate 1 st generation Antihistamine Very effective and most widely accepted Has good oral bioavailability (30-50% compared to 4-5% for triprolidine) Decreases sneezing, running nose and nasal irritation mediated by histamine from mast cells Decreases peripheral airway irritation and cough impulse transmission, and also lowers central cough excitability decreases associated cough with cold especially due to PND

34 Why CPM in cold? 1 st generation Anti-histamines like CPM are preferred over later generation ones like levocetrizine, in cough-cold formulations: In cough and cold patients, the main problem is lack of sleep/rest due to nasal congestion as well as irritating cough due to post nasal discharge when they lie down. CPM is mildly sedative compared to other 1 st generation antihistamines maintains a good balance between inducing sleep at night and maintaining day time activity. 1 st gen AH combine better with decongestants due to similar dosing schedule- A cough-cold syrup is usually meant for multiple (2-3 times) dosing in a day as the soothing action of the syrup base and menthol at regular intervals contributes significantly to relief. Only 1 st generation H1 Antihistamines have central effects like cough suppression and decrease in headache therefore they are preferred in combination cold-cough medicines

35 Decongestants They are vasoconstricting agents and act by counteracting the vasodilation caused by histamine. Antihistaminics prevent further action of histamine but cannot reverse the vasodilation already caused by it for which a vasoconstricting decongestant is required. These dilated nasal vessels are the main cause of nasal stuffiness. Systemic/ Oral agents: Phenylephrine, Pseudoephedrine and Phenylpropanolamine (PPA) Topical agents: Naphazoline, Oxymetazoline, Xylometazoline (can cause rebound congestion) PPA is now not preferred due to the risk of stroke associated with it

36 PHENYLEPHRINE It acts via (Alpha 1) receptors in blood vessels and brings about vasoconstriction It is an effective nasal decongestant (Clin Ther Jun;29(6): ) It also decreases swelling of nasal mucosa and improves sinus drainage It can also decrease mucus production due to reduced blood supply to goblet cells It does not display any cardiac or CNS action at clinical doses. It should be avoided in hypertensives as it can raise BP After congestion or rebound congestion is not a problem as seen with topical agents Long term use of topical decongestants can lead to compromised mucociliary action and mucosal atrophy. This is not seen in oral agents.

37 SODIUM CITRATE It has mucolytic action and helps to break down nasal mucus and reduce its viscosity This helps in easier clearing of mucus

38 PARACETAMOL Cold and URTI in children is frequently associated with fever Paracetamol is the most widely accepted Anti-pyretic in children Post nasal drip is common in children and causes throat irritation, soreness, cough and throat pain. Throat pain and sore throat can lead to discomfort and crying in young children and affect their eating and feeding Paracetamol s analgesic properties helps to reduce throat pain and soreness

39 39 Menthol: A Soothing Agent Produces cooling, soothing sensation Mild anesthetic action further decreases throat pain and soreness and airway cough receptor stimulation

40 New Zedex P For Pediatric cold and cough Each 5 ml contains: CPM 0.5mg Phenylephrine 5mg Sodium Citrate 60mg Paracetamol 125mg Menthol 1mg DCGI approved Dose in children> 2 years = 5ml 6 hourly

41 Dry Cough & Cold Continuum