COUGH

Cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes.

COLD
The common cold is a viral infectious disease of the upper respiratory tract which affects primarily the nose. Symptoms include coughing, sore throat, runny nose, sneezing, and fever which usually resolve in seven to ten days, with some symptoms lasting up to three weeks.

FLU
Usually referred to as the flu or influenza is a highly infectious respiratory disease. The disease is caused by certain strains of the influenza virus. When the virus is inhaled, it attacks cells in the upper respiratory tract, causing typical flu symptoms such as fatigue, fever and chills, a hacking cough, and body aches.

BRONCHOCONSTRICTION
Bronchoconstriction is defined as the narrowing of the airways in the lungs (bronchi and bronchioles). Air flow in air passages can get restricted due to 3 factors:

A spasmodic state of the smooth muscles in bronchi and bronchioles An inflammation of the airways Excessive production of mucus due to an allergic reaction or irritation caused by mechanical friction of air (due to shear stress), overcooling or drying of airways.

TRIGGERING AGENTS:
INFLAMMATORY FACTORS: Allergens, respiratory infections(flu ,cold), work IRRITANTS: cold air, sudden temperature changes, stress exercise strong odor. OTHERS: smoking, medications like ACE inhibitors, food additives, gastric reflux, pollutants . Fumes. ( epoxy resins, plastic,)Organic and chemical dust. (Woodworkers, cotton , platinum)Gases( like toluene, nitrous oxide),Food processing, Chemical processing, Textile, plastics and rubber manufacture

PATHOPHYSIOLOGICAL FEATURES:
Airway hyperresponsiveness (contract too much , too easily spontaneously, in response to exogenous and endogenous stimuli) Air flow obstruction Inflammation Mucous hypersecretion Airway remodeling ( in some patients

PATHOPHYSIOLOGY OF COUGH:MEDIA

MEDIATORS RELEASED:
MEDIATORS 1) Leukotrines EFFECTS Bronchoconstriction Increased vascular permeability Increased mucous secretion Aggregation of platelets Release of histamine Bronchoconstriction Increased mucous secretion

1) Platelet activating factor 1) Histamine ( is not consider important mediator as anti histamine do no provide benefit ) 1) Prostaglandin D2

Bronchoconstriction Increased vascular permeability

TREATMENT OF COUGH COLD AND FLU:

TREATMENT STRATEGY: Decrease mucous secretion Bronchodilation Decrease inflammation

ALLOPATHIC TREATMENT:
Mucokinetics are a class of drugs which aid in the clearance of mucus from the airways, lungs, bronchi, and trachea. Such drugs can be further categorized by their mechanism of action. expectorants mucolytic agents An expectorant (from the Latin expectorate, to expel from the chest) works by signaling the body to increase the amount or hydration of secretions, resulting in more yet clearer secretions and as a byproduct lubricating the irritated respiratory tract. One expectorant guaifenesin is commonly available in many cough syrups. ADRs: nausea, vomiting, dizziness,itching,kidney stones by guaifenesin

ALLOPATHIC TREATMENT: (CONT)

A mucolytic agent : Acetylcystein,tyloxapol is an agent which dissolves thick mucus and is usually used to help relieve respiratory difficulties. It does so by dissolving various chemical bonds within secretions, which in turn can lower the viscosity by altering the mucin-containing components. Acetylcystein reduces disulfide linkage of mucoproteins. Expectorant increases bronchial secretions and mucolytics help loosen thick bronchial secretions. Expectorants reduce the thickness or viscosity of bronchial secretions thus increasing mucus flow that can be removed more easily through coughing, Mucolytics break down the chemical structure of mucus molecules. The mucus becomes thinner and can be removed more easily through coughing.

ANTI-TUSSIVE DRUGS:

BRANDS AVAILABLE: Delsym (dextromethorphan) , Tessalon (benzonatate ) , Robitussin DM ( dextromethorphan/guaifenesin) Centrally acting: Codeine phosphate, morphine, dextromethorphane ,antihistamines like diphenhydramine. ACTIONS: Depression of modularly centres or associated higher centres and Increased threshold of cough centre. Peripherally acting: Tincture benzoin and menthol ACTIONS: Interruption of tussle impulses from respiratory tract, having soothing effect. ADRs: Headache, Dizziness, Pruritis, Nasal Congestion ,burning of eyes & tightness in chest.

SYMPATHOMIMETIC DRUGS :
BETA 2 AGONISTS: salbutamo/albuterol,terbutaline salmeterol, formeterol AVAILABLE BRANDS: ventoli(salbutamol), aerolin(salbutamol) ACTIONS: Inhaled beta2-agonists are bronchodilator medications by increasing level of c AMP in and around the tightened airways so that the airways reopen. Used in acute excerbations for relieving symptoms of coughing and wheezing. ADRs: in high dose also act on beta-1 & gives palpitation, muscle tremors, tachysardia , Restlessness Headache.

CORTICOSTEROIDS(GLUCOCORTICOIDS):
AVAILABLE BRANDS: Oral: prednisolone(deltacotril) , Dexamethasone (decadron) IV: Hydrocortisone(cortef 100mg) Inhaler: Betamethasone , Beclomethasone (bekson , betatec) ACTIONS: anti-inflammatory action by decreasing the release of mediators ,mucus production, permeability of vessels so, relieve smooth muscles spasm (bronchospasm). ADRs: oral thrush, stomach irritation ,nausea, insomnia, muscle weakness, tachycardia, high B.P.

MAST CELL STABALIZERS: CROMOLYN ,

NEDOCROMOLYN AVAILABLE BRANDS: cromolin(sodium cromoglycate),cromogol(sodium cromoglycate) ACTIONS: Inhibit degranulation of mast cells & inhibit release of mediators e.g:histamine , cytokine etc. ,causing inflammation. Pre-treatment block allergen or exercise induced bronchoconstriction. ADRs.: cough , throat irritation,bitter taste

METHYLXANTHINES:
AVAILABLE BRANDS theophylline (quibron), aminophyline(amphyll) ACTIONS: It block the Phosphodiesterase enzyme that convert cAMP to 5-AMP, so increase cAMP and gives bronchodilation. It is less recommended to use because of NTI(naarrow therpeutic index) ADRs :Insomnia Upset stomach,Gastroesophadeal reflux symptoms

LEUKOTRINES ANTAGONISTS:
AVAILABLE BRANDS : montelukast (myteka), zafrilukast ACTIONS: By selectively block csyteinyl leukotriene receptor so, relax airway smooth muscles. ADRs: GI upsets, headache,

ANTICHOLINERGICS:
AVAILABLE BRANDS Ipratropium(atem), tiotropium(spiriva), atropine ACTIONS :It block M3 muscarinic receptors located on smooth muscle cells and submucosal glands leading to a reduction in smooth muscle contraction and mucus secretion, thus producing a bronchodilatory effect. ADRs: Dry mouth and throat irritation, sedation, blurred vision.

ANTI IG E MAB (OMALIZUMAB)

ACTIONS:A recombinant DNA derived from monoclonal Ab bind to IgE Ab leads to decrease binding of IgE to receptors on basophil & mast cells, ADRs:wheezing, tightness in your chest, trouble breathing;hives or skin rash;feeling anxious or light-headed, fainting;

CUFFIX AS A TREATMENT OF COUGH COLD AND FLU:

DISCRIPTION: Cuffix cough syrup is a brownish yellow viscous liquid with palatable taste. COMPOSITION:

constituent Ephedra gerardiana Adhatoda vasica Glycyrrhiza Glabra Hyssopus officinalis Papaver somniferous Zizyphus vulgaris Quantity in each 5ml 66.6mg 83.3mg 83.3mg 83.3mg 83.3mg 83.3mg

Hyoscyamus niger

83.3mg

INDICATIONS: Cuffis syrup is indicated in the treatment of Cough Cold Flu Sore throat Chest congestion Stuffed nose SPECIFICATIONS: Established safety and efficacy Fast onset of action Long duration of action Non drowsy formula helps you to actively fight against the symptoms of cold and flu. Natural and effective broad spectrum coverage So safe that Cuffix can b given to children with no side effects.

CLINICAL PHARMACOLOGY:

Cuffix syrup completely relief the symptoms of cough , cold and flu by multiple mode of actions. ADHATODA VASICA: it contain vasicin inhibit 5HT receptors thus inhibiting histamine induced bronchoconstriction as well as act a mucolytic when it act on mucous formative stage on the glands within the mucus secreting cell depolymerasing and hydrolyzing fiber of mucopolysaccharides resulting in the decreased viscosity and elasticity of tracheal mucus. EPHEDRA GIARDIANA: it contains ephedrine which causes indirect stimulation of adrenergic receptors to increase the activity of norepinephrine at post syneptic beta 2 receptors and they cause bronchodilaion and relaxation of smooth muscles of airways. GLYCYRRHIZA GLABRA: it contains glycyrrhizin which inhibit phospholipase A2 inhibiting the inflammatory process and also act as antileukotrienic agent. PAPAVER SOMNIFERRUM: it contain codein and morphine which are opiod receptor agonists suppress cough reflex by direct action on cough center. HYOCYAMUS NIGER: it contains hyocyamine and scopolamine which are potent ACH inhibitor and inhibit the ACH induced bronchoconstriction and mast cells degradation which release histamine.

PHARMACOKINETICS:

Cuffix cough syrup is 75% absorbed orally and plasma half life is 3-11 hours.