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

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

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

Sinuses

Pharynx (Throat)

•Nasopharynx:

respiratory function

•Oropharynx:

Respiratory &

digestive function

•Laryngopharynx:

Respiratory &

vocal function

Larynx (Voice Box)

Connects pharynx to trachea Epiglottis - covers larynx during swallowing Contains two vocal cords which vibrate together to make voice

Trachea is the wind pipe and it divides into:

• Right and Left primary bronchus – these further divide into

• Secondary bronchi

Bronchioles :

branch 14 times to a final terminal bronchiole

Trachea and Bronchi Cartilage rings

Responsible for gas- exchange

Lungs

• Upper respiratory system refers to nose, pharynx & associated structures (tonsils & sinuses).

• Lower respiratory system refers to larynx, trachea, bronchi & lungs.

Upper & Lower Respiratory System

Respiratory tract – functions

Bronchial muscle

cilia

mucus

Epithelium with goblet cells

Overview of Cough

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

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

Histamine

Airway Mechanoceptors

Cholinergic, vagal

pathway

Cough Center in

Brain stem

Impulse to Larynx, Intercostal / abdominal

muscles Diaphragm

Airway Chemoceptors

Foreign particles Irritants

Ciliary action

Effective cough

Patent airway

Stimulation

of CNS receptors -

cough excitability

Cough Reflex mechanism

Dry Cough Productive 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

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

Management of cough

Dry cough Productive 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

• This should be done by

• A) Decreasing mucus viscosity – mucolytics

• B) Improving expectoration of mucus

• C) Maintaining bronchial patency to expel mucus effectively (bronchodilator)

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

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 15-20 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 90-120mg/day)

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

Produces cooling, soothing

sensation

Mild anesthetic action –

decreases throat pain and

soreness and airway cough

receptor stimulation

Menthol: A Soothing Agent

Histamine

Airway Mechanoceptors

Cholinergic, vagal

pathway

Cough

Center in Brain stem

Impulse to Larynx, Intercostal / abdominal

muscles Diaphragm

Airway Chemoceptors

MOA

Foreign particles Irritants

Ciliary action

Effective cough

Patent airway

CPM

CPM

DXM x

Stimulation of CNS

receptors -cough

excitability

CPM

Cough suppressed

New ZEDEX

• DC for DXM and CPM ;

• DC for DUAL CONTROL of Cough!!

Each 5ml contains:

• DXM 10mg and CPM 2mg

Dose

• Adults: 10ml TID

• Children above 6 years: 5 ml TID

• 2-6 years : 2.5 ml TID

DCGI approved

Overview of Common Cold

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

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

Actions of Histamine

• Dilation of Blood Vessels

• Increase in blood vessel permeability

- fluid leakage into mucosa

• Increase in Mucus secretion by stimulation of goblet cells

• Mucus tickling down throat (post nasal drip) especially at night

• Stimulation of nasal nerve receptors (free nerve endings) and airway chemoreceptors which cause irritation and itching

• Redness

• Congestion

• Swelling

• Congestion

• Running nose

• Cough, throat irritation/sore throat

• Sneezing

• Irritation

• Itching

• Irritating Cough

Symptoms of common cold

Running Nose- Nasal discharge

• Mucus production by goblet cells stimulated by histamine

• Mucus maybe watery, or purulent and thick

Nasal Congestion and Stuffiness

Nasal irritation & itching

• Dilation of blood vessels

• Fluid leakage into mucosa - swelling

• Accumulation of mucus

• Stimulation of nerve endings by Histamine as well as mucus

Common Cold

• Irritation of Nasal mucosa by foreign particles, irritants or mucus pieces

• Mast cells release Histamine and stimulate nerve endings in nose

• Signals being sent to the Brain to initiate the sneeze through the 5th 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

Sneezing

• Nasal congestion blocks sinus openings

• Leads to impaired drainage

• Nasal and heavy voice

• Headache and Heaviness of head especially on looking down

Sinusitis

COLD PATHOLOGY & TREATMENT

Pathology Treatment

Sneezing, running nose, and

nasal/throat irritation (due to

histamine release from mast cells)

Anti histamine

Nasal congestion due to dilated

blood vessels

Decongestant

Decrease viscosity and break

down nasal mucus secretions

Mucolytic

Decrease associated throat pain

and fever

Antipyretic-Analgesic

Soothing and local anesthetic

action

Soother

CPM

Phenylephrine

Sodium citrate

PCM

Menthol

H1 Antihistaminics

• 1st 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

• 3rd Generation : (active enantiomers or metabolites): Levocetrizine, Desloratidine and Fexofenadine

Chlorpheniramine maleate

• 1st 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

Why CPM in cold?

• 1st 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 1st generation antihistamines – maintains a good balance between inducing sleep at night and maintaining day time activity.

• 1st 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 1st generation H1 Antihistamines have central effects like cough suppression and decrease in headache therefore they are preferred in combination cold-cough medicines

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

PHENYLEPHRINE

• It acts via (Alpha 1) receptors in blood vessels and brings about vasoconstriction

• It is an effective nasal decongestant (Clin Ther. 2007 Jun;29(6):1057-70)

• 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.

SODIUM CITRATE

It has mucolytic action and helps to break down nasal mucus and reduce its viscosity

This helps in easier clearing of mucus

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

Produces cooling, soothing

sensation

Mild anesthetic action –

further decreases throat pain

and soreness and airway

cough receptor stimulation

Menthol: A Soothing Agent

New Zedex P

• For Pediatric cold and cough

Each 5 ml contains:

• CPM 0.5mg

• Phenylephrine 5mg

• Sodium Citrate 60mg

• Paracetamol 125mg

• Menthol 1mg

• Dose in children> 2 years = 5ml 6 hourly

DCGI approved

Dry Cough & Cold Continuum