DR. MARWA SHAALAN PHARM-D

 Basic functions of the respiratory system  Breathing (Pulmonary Ventilation) – movement of air in and out of the lungs Inhalation (inspiration) draws gases into the lungs. Exhalation (expiration) forces gases out of the lungs.  Gas Conditioning – as gases pass through the nasal cavity and paransal sinuses, inhaled air becomes turbulent. The gases in the air are warmed to body temperature humidified cleaned of particulate matter  Gas Exchange - respiration Supplies body with oxygen Disposes of carbon dioxide  Produces Sounds  Protects respiratory surfaces  Site for olfactory sensation

 Respiration – four distinct processes must happen  Pulmonary ventilation – moving air into and out of the lungs  External respiration – gas exchange between the lungs and the blood  Transport – transport of oxygen and carbon dioxide between the lungs and tissues  Internal respiration – gas exchange between systemic blood vessels and tissues

 Respiratory organs  Nose, nasal cavity, and paranasal sinuses  Pharynx, larynx, and trachea  Bronchi and smaller branches  Lungs and alveoli

Figure 21.1

 Consists of  Respiratory muscles – diaphragm and other muscles that promote ventilation  Respiratory zone – site of external respiration – respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli.

 Alveoli cell types  Type I cells site of gas exchangeand  Type II cells - secrete surfactant  Macrophages Figure 21.10b

RESPIRATORY DISORDERS

TRIALS

-If it necessary – hospitalization with i/v infusion of glucocorticosteroids and euphyllin

 Cough is a useful physiological mechanism that serves to clear the respiratory passages of foreign material and excess secretions.  It should not be suppressed indiscriminately.  There are, however, many situations in which cough does not serve any useful purpose but may, instead only annoy the patient or prevent rest and sleep.

 Chronic cough can contribribute to fatigue, especially in elderly patients, in such situations the physicians should use a drug that will reduce the frequency or intensity شده of the coughing.  Cough reflex is complex, involving the central and peripheral nervous systems as well as the smooth muscle of the bronchial tree.

 It has been suggested that irritation of the bronchial mucosa causes bronchoconstriction, which in turn, stimulates cough receptors( which probably represent a specialized type of stretch receptor) located in the tracheobronchial passages.

 Afferent conduction from these receptors is via fibers in the vagus nerve; central components of the reflex probably involve several mechanisms or centres that are distinct from the mechanisms involved in the regulation of respiration.

 The drugs that directly or indirectly can affect this complex mechanism are diverse. -For example, cough may be the first or only symptom in bronchial asthma or allergy, and in such cases bronchodilators(e.g.,  2 – adrenergic receptor agonists have been shown to reduce cough ) without having any significant central effects, other drugs act primarily on the central or the peripheral nervous system components of the cough reflex.

Forceful release of air from lungs Sudden, often involuntary (protective) reflex and major defensive mechanism Cont…..

 Expulsion of respiratory secretion or foreign particles or irritant or excessive mucus from air passages  Symptom an underlying respiratory and/or cardiovascular pathology Causes of cough :

A) Acute cough =lasting<3 weeks B) Chronic cough =lasing >8 weeks Cough may be i) Un productive (dry) cough OR ii) Productive cough (sputum) cont.

 Common cold,  Upper/lower respiratory tract infection  Allergic rhinitis  Smoking  Chronic bronchitis  Pulmonary tuberculosis  Asthma  Gastroesophageal reflux  Pneumonia  Congestive heart failure  Bronchiectasis  Use of drugs (e.g., Angiotensin-converting enzyme inhibitors)

1) Antitussives (cough centre suppressants) 2) Expectorants (Mucokinetics) 3) Mucolytics 4) Antihistamines 5) Bronchodilators 6) Pharyngeal Demulcents

Drugs suppress cough & produces symptomatic relief MOA Mainly suppress cough centre in medulla (both central & peripheral effects) E.g., Opoid drugs (codeine, pholcodeine, noscapine, dextromethorphan) Opioid = most effective for cough

 Codeine= prodrug  metabolized to morphine  It is an alkaloid found in Opium poppy plant  Has less addiction  resp. centre depressant ↓  Has useful antitussive action at low doses (<15 mg)  Produce drowsiness, thickening of sputum & constipation

 Related to papaverine  Do not have addictive, analgesic & constipating properties  Do not interfere with mucocilliary movement  Noscapine (15 mg) & pholcodeine (10 mg)=syrup

Available in syrup, tablets, spray forms MOA NMDA receptor antagonist Uses Cough suppressant, temporary relief of cough caused by minor throat & bronchial irritation (accompanies with flu & cold), pain relief Ad Effects= Nausea, vomiting, drowsiness, dizziness, blurred vision

 Act peripherally  Increase bronchial secretion OR  Decrease its viscosity  facilitates its removal by coughing  Loose cough ►less tiring & more productive Cont….

Classified into b) Directly acting E.g., Guaifenesin (glyceryl guaiacolate), Na+ & K+ citrate or acetate, b) Reflexly acting E.g., Ammonium salt

 They act directly Actions: ▲ Bronchial secretion by salt action ii) Guaifenesin  Expectorant drug usually taken by mouth  Available as single & also in combination MOA=Increase the volume & reduce the viscosity of secretion in trachea & bronchi

Ammonium salts Gastric irritants  reflexly  bronchial secretions + sweating

Help in expectoration by liquefy the viscous tracheobronchial secretions E.g., Bromhexine, Acetyl cysteine, i) Bromhexine Synthetic derivative of vasicine (alkaloid= Adhatoda vasica) Cont….

MOA of Bromhexine a) Thinning & fragmentation of mucopolysaccaride fibers b) ↑ volume & ↓ viscosity of sputum ii) Acetylcysteine Given directly into respiratory tract cont.

Opens disulfide bond in mucoproteins of sputum = ↓ viscosity Uses Cystic fibrosis (to  viscosity of sputum) Onset of action quick---used 2-8 hourly Adverse effects Nausea, vomiting, bronchospasm in bronchial asthma

 Added to antitussives/expectorant formulation  Due to sedative ا & anticholinergic actions produce relief in cough but lack selectivity for cough centre  No expectorant action = ▼ secretions (anticholinergic effect)  Suitable for allergic cough (not for asthma) E.g., Chlorpheniramine, diphenhydramine, promethazine

 Bronchospasm or stimulation of pulmonary receptors = induce or aggravate زياده cough + bronchoconstriction  e.g. β 2 -agonist (salbutamol, terbutaline) MOA of bronchodilators in cough  ▲ surface velocity of air flow during cough → Clear secretions of airway  مهمه Not used routinely for every type of cough but only when bronchoconstriction is present

 Soother the throat (directly & also by promoting salivation)  ▼ afferent impulses from inflamed/irritated pharyngeal mucosa  Provide symptomatic relief in dry cough arising from throat E.g. lozenges, cough drops, glycerine, liquorice, honey

Etiology of coughTreatment 1) Upper/lower respiratoryAppropriateantibiotics tract infections 2) Smoking/chronic bronchitis Cessation of smoking 3) Pulmonary tuberculosisAntibiotics 4) Asthmatic coughInhaled β2-agonists/iprat- ropium/corticosteroid 5) Postnasal drip (sinusitis)Antibiotics, nasal decon- gestants, antihistamines

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