1. LINCOLN UNIVERSITY COLLEGE
DRUGS ACTING ON THE
RESPIRATORY SYSTEM
BHOLE NATH, Lecturer
Dept. of Pharmacy
LINCOLN UNIVERSITY COLLEGE
MALAYSIA

2. MAIN FUNCTIONS OF
RESPIRATORY SYSTEM
1. Deliver oxygen to the cells 2.To eliminate carbon dioxide from the body 3.To regulate the pH of the blood

4. COMPONENTS OF LUNG FUNCTION
VENTILATION Movement of air to and from the lungs
DISTRIBUTION Air entering lungs are distributed to all parts including
the alveoli
DIFFUSION Oxygen from the inspired air diffuses through the
walls of the alveoli to the blood capillaries surrounding
the alveoli-similarly carbon dioxide diffuses in opposite
direction
PERFUSION Blood with high concentrations of carbon dioxide and
low in oxygen is pumped to the pulmonary arteries by
the right ventricle and after diffusion, the arterial blood
is returned to the left atrium by the pulmonary veins

5. VENTILATION PASSAGE OF OXYGEN AND CARBON DIOXIDE
SOURCE OF OXYGEN – INSPIRED AIR
SOURCE OF CARBON DIOXIDE-ALVEOLI-
Following diffusion from the blood due to metabolism in the body.
PATHWAY FOR THE GASES:
PHARYNX
LARYNX-TRACHEA
BRONCHI
BRONCHIOLES
ALVEOLI

6. atmosphere o
oxygen c
Carbon dioxide
Right heart-arteries
Left heart-arteries
Systemic circulation

7. COMMON SIGNS AND SYMPTOMS
RESPIRATORY DISEASES
COMMON SIGNS AND SYMPTOMS
COUGH
WHEEZING
SHORTNESS OF BREATH-DYSPNOEA
CYANOSIS
5. PAIN AROUND CHEST

8. MAY BE VOLUNTARY OR INVOLUNTARY
COUGH – FORCED EXPIRATION AGAINST A CLOSED GLOTTIS WHICH SUDDENLY OPENS TO EXPEL AIR AND UNWANTED MATERIAL FROM THE RESPIRATORY TRACT
MAY BE VOLUNTARY OR INVOLUNTARY
Mucosal surface lining respiratory tract
Impulses relayed via vagus
Cough centre in brain
Efferent's
diaphragm glottis muscles of chest and abdomen

9. Mucokinetics are a class of drugs which aid in the clearance of mucous from the airways, lungs, bronchi, and trachea. Such drugs can be further categorized by their mechanism of action.
expectorants
mucolytic agents
In general, clearance ability is hampered by bonding to surfaces (stickiness) and by the viscosity (thickness) of mucous secretions in the lungs. In turn, the viscosity is dependent upon the concentration of mucoprotein in the secretions.

10. Expectorants and mucolytic agents are different types of medication, yet both intend to promote drainage of mucus from the lungs.
An expectorant (from the Latin expectorare, 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. Sometimes the term "expectorant" is incorrectly extended to any cough medicine, since it is a universal component.
A mucolytic agent 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.e.g ,Bromohexine, Acetyl Cysteine

11. ANTITUSSIVE/ COUGH SUPPRESSANTS
A cough medicine (or linctus, when in syrup form) is a medicinal drug used in an attempt to treat coughing and related conditions. For dry coughs, treatment with cough suppressants (antitussives) may be attempted to suppress the body's urge to cough. However, in productive coughs (coughs that produce phlegm), treatment is instead attempted with expectorants (typically guaifenesin, in most commercial medications) in an attempt to loosen mucus from the respiratory tract.
These are the drugs that act in the CNS to the threshold of cough center or act peripherally in the respiratory tract to reduce tussal impulses.
NOTE: It is only for dry unproductive coughs

12. ANTITUSSIVE/ COUGH SUPPRESSANTS
Unproductive distressing cough- central cough depressants
e.g. pholcodine, dextromethorphan
Productive cough-do not use cough suppressants
Use expectorants and mucolytics
Expectorants-act by increasing the volume of secretions in respiratory tract so that they may be more easily removed by ciliary action and coughing
e.g.ammonium salts, guaphenesin, ipecacuanha
Mucolytics- considered to affect sputum viscosity
e.g.acetylcysteine, bromhexine, carbocisteijne, methyl cysteine

13. DEXTROMETHORPHAN The principal non-opioid antitussive
Dextromethorphan-has a central action on the cough centre.
Morphine and related opioids depress the cough reflex , at least in part by a
direct effect on the cough centre in the medulla. Suppression of cough by such
agents appear to involve receptors in the medulla that are less sensitive to
naloxone than are those responsible for analgesia.
Structurally related to morphine but little or no analgesic properties,
And minimal (little) sedative activity.
Antitussive effects may persist for up to 5 hours.
Dextromethorphan should not be administered to patients with or at risk of
Developing respiratory failure.
Do not administer to patients on monoamine oxidase inhibitors-
risk of severe reactions-hyperpyrexia, fatalities
PHOLCODINE
CENTRALLY ACTING COUGH SUPPRESSANT
UNLIKE CODEINE, THERE IS LITTLE OR NO METABOLISM
TO MORPHINE
LONGER HALF-LIFE THAN CODEINE- DOSES MAY BE GIVEN ONCE
OR TWICE A DAY

14. Reduction in cholinergic transmission
ANTIHISTAMINES E.G. DIPHENHYDRAMINE
OFTEN USED AS ANTI-TUSSIVES
MODE OF ACTION – Due to sedative and ant cholinergic actions.
SUGGESTIONS-
Reduction in cholinergic transmission
Suppression of cough because of sedative action
Reduces nasal secretions and therefore the post-nasal drip that causes cough
Should not be used to treat productive cough as it increases the viscosity of the mucus

15. MUCOLYTICS
The viscosity of pulmonary mucus secretions depends on the concentrations of mucoproteins
and deoxyribonucleic acid (DNA).
While mucoprotein is the main determinant of viscosity in normal mucus, in purulent
inflammation the mucoid concentration of DNA increases (due to increased cellular debris)
and so does its contribution to mucoid viscosity.
Some patients with respiratory tract disease, the bronchial inflammation
will be associated with the presence of large amounts of relatively viscous, inflammatory exudate
and mucus which is firmly attached to the lining of bronchioles and bronchi.
This would in practical terms increase bronchial wall thickness.
Adverse effects of increased mucus accumulation are
Increase the "lumen narrowing" effects of bronchial constriction
2. Enhance the overall inflammatory process
Potentiate persistent coughing.

16. Mucolytics would be useful in facilitating recovery/relief of symptoms
The two most frequently prescribed mucolytics
bromhexine hydrochloride
Acetylcysteine-probably reduces viscosity by splitting the disulphide bonds in mucoproteins
Other forms:
Normal saline, directly administered to the airways by effective nebulisation therapy-extremely effective mucolytic and expectorant
Acetylcysteine:

17. DORNOSA ALFA
ACTS AS A MUCOLYTIC
BY HYDROLYSING DNA THAT HAS ACCUMULATED IN THE SPUTUM FROM DECAYING NEUTROPHILS
USED AS A NEBULIZING SOLUTION IN PATIENTS WITH CYSTIC FIBROSIS

18. BRONCHODILATION ACHIEVED
via anticholinergic agents- ipratropium bromide 0.5 mg nebulised repeat every six hours (including beta 2 agonists),
beta 2 adrenergic receptor agonists –nebulised salbutamol ( mg every two to six hours, terbutaline
agents such as the methylxanthines which produce
bronchodilation at least in part due to increased intracellular
cAMP levels in bronchial smooth muscle.
Inhaled anti-inflammatory agents- corticosteroids-
beclomethasone or budenoside micrograms twice daily
Oral corticosteroids mg once daily
Intravenous hydrocortisone- 200 mg every six hours

19. Adrenergic agonists
All adrenergic agonists have variable alpha and beta receptor affinity.
Due to the distribution of alpha and beta receptors-
non-selective beta receptor agonists such as isoprenaline or
mixed alpha and beta receptor agonists such as adrenaline
are more likely to produce cardiovascular side effects than similarly administered selective beta agonists.
Therefore drugs with preferential affinity for beta 2 receptors provide more effective bronchodilation with fewer side effects.
A possible exception may be with the treatment of acute allergic bronchospasm.
The M-2 receptor-mediated inhibition of cholinergic bronchospasm may be helpful.
For this reason, the use of an adrenergic agent with both alpha 2 and beta 2 agonist activity may be
beneficial in the peracute management of allergic bronchospasm.
Due to risks associated with administering systemic non-selective adrenergic agonists to a hypoxic and
already tachycardic patient, it is preferable for them to be administered by inhalation.
Selective beta 2 agonists- lead to rapid and effective pulmonary beta 2 receptor activation with low
systemic drug concentrations by inhalation of small doses of the drug in aerosol form.

20. Methylxanthines POSSIBLE ACTIONS
Relaxation of smooth muscle, particularly bronchial smooth muscle
Stimulate the central nervous system
Weakly positive chronotropes and inotropes
Mild diuretics.
Naturally occurring methylated xanthines
Caffeine, theophylline and theobromine - relatively insoluble. Solubility enhanced by the
formation of complexes with a wide variety of compounds e.g. aminophylline which is the
ethylenediamine
complex of theophylline with differing quantities of water of hydration.
When dissolved in water, aminophylline readily dissociates to its parent compounds.
Theophylline has a low therapeutic index- Therefore dose rates should be determined on lean
body mass.
The dose rate of theophylline varies depending on the preparation used.

21. Widely available at present- codeine phosphate and hydrocodone.
Codeine has a high oral-parenteral potency with oral administration providing around 60% of its parenteral efficacy. Once absorbed, codeine is metabolized by the liver . Inactive metabolites
excreted predominantly in the urine. In man approximately 10% of administered codeine is demethylated to form morphine -and both free and conjugated forms of morphine can be
found in the urine of patients receiving therapeutic doses of codeine.
In man, codeine's plasma half-life is around 2 to 4 hours.
Codeine phosphate is contained in numerous "over the counter" analgesic preparations as well
as in 30 and 60mg tablets which have restricted scheduling.
Hydrocodone is generally marketed in combination with homatropine as both an elixir and tablet formulations. The addition of homatropine is designed to enhance any reduction in respiratory secretions, which may come about as a result of the administration of hydrocodone.
BENZONATATE
Cough suppressant believed to act both centrally and peripherally.
Related to amethocaine ( a local anaesthetic) and therefore has a local anaesthetic action on
the mucosa. .
OPIOID ANTITUSSIVES

22. LEUKOTRIENE RECEPTOR ANTAGONISTS
Inflammation of the respiratory tract is frequently characterised by the classical markers of inflammation;
accumulations of inflammatory cells
exudate.
associated with varying degrees of bronchoconstriction
and, or, bronchospasm.
Additionally "airway hyper reactivity" may become a standard response of sensitised patients to various inhaled compounds.
Although glucocorticoids remain the "gold standard" in controlling this inflammatory-induced bronchoconstriction, the leukotriene receptor antagonists represent a new class of drugs which may facilitate management of these various forms of bronchoconstriction.

23. DEMULCENTS
INDIRECTLY ACTING COUGH SUPPRESSANTS
? MODE OF ACTION
POSSIBLY BY PROVIDING A PROTECTIVE COATING OVER THE SENSORY RECEPTORS IN THE PHARYNX
EXAMPLES- GLYCEROL, HONEY, LIQUORICE AND SUCROSE SYRUPS

24. HYDRATION
LIQUEFYING MUCUS
DEMULCENT EFFECT
METHODS
DRINK PLENTY OF FLUIDS
STEAM INHALATION
INHALATION OF AEROSOLS CONTAINING
WATER, SODIUM BICARBONATE, SODIUM CHLORIDE,
SURFACTANTS E.G. TYLOXAPAL
PROTEOLYTIC ENZYMES E.G. CHYMOTRYPSIN, TRYPSIN

25. BTS GUIDELINES FOR MANAGEMENT OF ASTHMA
INHALED SHORT-ACTING BETA-2 AGONIST AS REQUIRED
ADD INHALED STEROID MICROGRMS/DAY
ADD INHALED LONG-ATINGBETA 2 AGONIST- CONSIDER INCREASING STEROID INHALED DOSE
CONSIDER USING LEUKOTRIENE RECEPTOR ANTAGONIST OR THEOPHYLLINE
ADAPTED FROM THORAX 2008;63 (suppl 4): )

26. ACUTE BRONCHITIS
TREATMENT USUALLY NOT REQUIRED IN PREVIOUSLY HEALTHY PATIENTS BELOW AGE 60
EXACCERBATION OF COPD-START WITH DOXYCYCLINE 200MG OD -SECOND LINE-AMOXICILIIN (OR CO-AMOXICLAV)
BRONCHIECTASIS-CO-AMOXICLAV 1.2 G TDS IV OR IF AVAILABLE PIPERICILLIN + TAZOBACTAM 4.5 G TDS
CYSTIC FIBROSIS- CIPROFLOXACIN 500MG BD ORALLY OR 400MG BD IV IF PSEUDOMONAS IS SUSPECTED
Adapted from Pocket Prescriber

27. ADVERSE EFFECTS OF INHALED CORTICOSTEROIDS EXAMPLE BECLOMETASONE
ORAL CANDIDIASIS ( decreased by rinsing mouth with water after use)
HOARSE VOICE-
RARELY GLAUCOMA
INCREASING DOSES MAY CAUSE ADRENO-CORTICAL SUPPRESSION, CUSHING’S
DECREASE IN DENSITY OF BONES
DECREASE IN GROWTH HORMONE ?
Very rarely-paradoxical bronchospasm
Adapted from Pocket Prescriber

28. SALBUTAMOL
BETA 2 AGONIST- SHORT ACTING
ACTIONS:
1. DILATES BRONCHIAL SMOOTH MUSCLE
2. RELAXES UTERINE SMOOTH MUSCLE
3.INHIBITS MAST-CELL MEDIATOR RELEASE
BEWARE USE -IN CARDIO-VASCULAR DISEASE Esp. arrhythmias-susceptibility to
increased QTc
- DIABETES MELLITUS- MAY INCREASE RISK OF DIABETIC
KETO-ACIDOSIS
- MAY INCREAE THYROXINE LEVELS
SIDE EFFECTS- FINE TREMOR, HEADACHE, NERVOUSNESS
INCREASE IN HEART RATE, PALPITATIONS, ARRHYTHMIAS
DECREASE IN SERUM POTASSIUM
MUSCLE CRAMPS
Prolonged treatment -? Increased risk of glaucoma

29. THEOPHYLLINE
METHYLXANTHINE BRONCHODILATOR- Additive effects with beta 2 agonists but increases risk of hypokalaemia
Beware – caution in patients with
Cardiac disease especially risk of arrhythmias,
Epilepsy
Peptic ulcer
Hypertensive heart disease
Fever
Porphyria
In acute febrile illness
Glaucoma
Diabetes mellitus

30. THEOPHYLLINE
SIDE EFFECTS-
ARRHYTHMIAS
SEIZURES
GASTRO-INTESTINAL UPSET- NAUSEA
RESTLESSNESS, INSOMNIA
HEADACHE
LOWERS SERUM POTASSIUM
MONITOR- SERUM POTASSIUM, BLOOD LEVELS 6 HR AFTER ADMINISTRATION
TOXIC EFFECTS MAY OCCUR EVEN WITH NORMAL BLOOD LEVELS E.G MG/L

31. MONTELUKAST
LEUKOTRIENE RECEPTOR ANTAGONIST
CAUTION
ACUTE ASTHMA
CHURG-STRAUSS SYNDROME (asthma with + or – rhinitis, sinusitis with sytemic vasculitis and increased eosinophil counts

32. MONTELUKAST
SIDE EFFECTS
HEADACHE
GASTRO-INTESTINAL UPSET
MYALGIA
DRY MOUTH/THIRST
MONITOR
FULL BLOOD COUNT
WATCH FOR VASCULITIS
PERIPHERAL NEUROPATHY
INCREASED CARDIAC AND RESPIRATORY SYMPTOMS