educative

1. DRUGS USED IN THE RESPIRATORY
SYSTEM

2. INTRODUCTION
• Respiratory tract infections are grouped into:
1) Upper respiratory tract infections e.g. Acute
coryza (common cold), acute pharyngitis,
acute tracheobronchitis, influenza, sinusitis
2) Lower respiratory tract infections e.g.
pneumonia, Bronchial Asthma
3) Chronic obstruction pulmonary disease that
include, chronic bronchitis, emphysema
cystic fibrosis

3. Intro cont’
• The respiratory conditions approach of care is:
Symptomatic management e.g. analgesics,
anticoughs (suppressants or decongestants),
hydration, nutrition
Causal management e.g. antibiotics treatment

4. INTRO cont’
OBJECTIVES:
- Anticoughs: modes of action and use
- Histamine, antihistamines and anti allergies
- Respiratory stimulants: their place in therapy
- Drugs used in asthma
- Oxygen therapy
- Antibiotics refer to past discussions

5. COUGH
- Protective reflex used to expel irritants from
the respiratory tract.
- They are 2 sorts of cough; useful and useless.
- Useful cough:- effectively expels secretions or
foreign material from the RT, i.e. when it is
productive. Should be allowed to serve its
purpose and suppressed only when it
exhausts the pt or is dangerous; e.g. after eye
surgery.

6. Cough Cont’
• Useless cough: Unproductive and persistent
cough. Should be stopped.
• Common cause of persistent cough include:
asthma, rhinosinusitis, esophageal reflux,
chronic pulmonary diseases (chronic
bronchitis, TB), drug-induced cough.
• The overall approach to persistent cough must
involve attention to underlying factors.

7. Some Drugs which Induce Cough
- ACE inhibitors
- β-blockers
- Inhaled corticosteroids and disodium
chromoglycate.
- Nebulized acetylcysteine
- Iodides - Amiodarone
- Levodopa - Inhaled ether
- Nitrofurantoin

8. Sites of Action for Treatment of Cough
a) Peripheral sites:
Afferent side of cough reflex - reduce input of
stimuli from throat, larynx, trachea; e.g. a
warm moist environment has a soothing
effect on the pharynx.
Efferent side – Measures to render secretions
more easily removable reduces coughing;
e.g. mucolytics, postural drainage.

9. b) CNS Site
Agents may act on;
- Medullary paths of the cough reflex (e.g.
opioids)
- Cerebral cortex
- Subcortical paths (opioids and sedatives)
NB:The best antitussive of all is the removal of
the cause of cough itself.

10. SYMPTOMATIC MNGT’
can be classified as follows;
a) Pharyngeal demulcents and local sialogogues
e.g. syrups and linctuses, lozenges, cough
drops
b) Expectorants(bronchial secretion enhancers
and mucolytics)
c) Central cough suppressant(antitussives) i.e.
opiods, nonopiods, antihistamins.

11. A . Pharyngeal Demulcents
- Administered generally as lozenges, troches,
cough drops or linctuses.
- Reduce afferent impulses from inflamed
pharyngeal mucosa above epiglottis.
- Act by ↑ing flow of saliva, the best natural
demulcent which produces protective and
soothing effect, hence symptomatic relief.
- Salivary secretion ↑sed by simple methods,
e.g. use of lemon drops.

12. B. Expectorants
- Used to encourage productive cough by
increasing the volume of bronchial secretion.
- Classification:
1) Bronchial Secretion Enhancers:
Guaiaphenesin, Sodium/potassium citrate,
potassium iodide, Ammonium chloride.
2) Mucolytics: Bromhexine, carbocysteine,
acetylcysteine, ambroxol

13. Bronchial secretion enh’
- Expectorants ↑se production of demulcent
respiratory tract fluid that covers and protects
the irritated mucosa.
- Useful in Rx of cough due to irritation of the
resp. mucosa below the epiglottis
- Used in resp. conditions in which secretion is
thick and viscid, needing liquefaction.
- Expectorants can stimulate output of resp.
tract fluid either directly or reflexly.

14. Expectorants: Direct Stimulants
- Certain volatile oils, e.g. eucalyptus oil and
lemon; when admin orally or by inhalation
with steam ↑se resp. secretions by direct
action.
- Guaiaphenesin directly ↑ses resp. secretions
and mucociliary function; used in cough
mixtures….but interferes with hemostasis.

15. Reflex Expectorants
- Act by stimulating reflexes which help to
increase resp. secretions example ammonium
salts are nauseating hence a reflex ↑ing resp
secretions.
- They may cause mild gastric mucosal
irritation, nausea and vomiting.
- Emetic drugs given in subemetic doses are said
to ↑se bronchial secretion producing thin
secretions, easier to expectorate.

16. Examples:
- Potassium salts: Potassium iodide, potassium
citrate.
- Ammonium salts: Ammonium bicarbonate.
- Note ; ALSO CALLED SALINE EXPECTORANTS

17. Mucolytics
- Makes sputum thin and less viscid for easy
expectoration.
- Examples: Acetylcysteine, Carbocysteine and
methylcysteine, bromhexine, ambroxol.
Bromhexine:
• Alkaloid derivative (vasicine)
• Potent mucolytic and mucokinetic
• Induces thin copius bronchial secretions

18. Acetylcysteine
- MOA: Opens disulfide bonds in mucoproteins
present in sputum making it less viscid.
- Given directly to the resp. tract by inhalation
or instillation via tracheotomy tubes.
Carbocysteine: Similar to acetylcysteine but
administered orally. Used more in chronic
bronchitis.S/e include GIT irritation and
rashes.

19. C . Central Cough Suppressants
- They inhibit the cough reflex by suppressing
the coordinating cough centre in the medulla.
- Mainly used in symptomatic relief of dry
irritant cough.
- Not recommended in young children and
should not be administered to those < 1 year.
- They include; opioids, non-opioids and
antihistaminic

20. Cough Center Suppressants ct’
- Opioids: Codeine and pholcodeine
- Nonopioids: Noscapine (nocartine),
Dextromethorphan, Chlorphedianol
- Antihistamines: Chlorpheniramine,
Diphenyhydramine, Promethazine

21. OPIOIDS
CODEINE:
- Opium alkaloid
- Selective for the cough centre suppressing
cough for about 6hours.
- Action blocked by Naloxone
- Side effects: Constipation, respiratory
depression and drowsiness at ↑ doses.
- C/I in asthmatics and pts with ↓ resp reserve.

22. PHOLCODEINE
- Works like codeine for antitussive effects but
its long acting…about 12 hours.
- Has no analgesic or addiction properties.

23. NON-OPIOIDS
DEXTROMETHORPHAN
- Synthetic compound as effective as codeine,
and does not depress the mucociliary function
of the airway mucosa.
- Devoid of constipation and addiction
- Duration of action approx. 6 hours
- Effects not blocked by Naloxone
- Side effects: Dizziness, nausea, drowsy, ataxia.

24. ANTI-HISTAMINES
- Act on the H1 receptor exerting anti-
cholinergic and sedative actions.
- No selectivity for the cough centre.
- No expectorant property, they even may
reduce secretions.
- Used in resp. allergic states.
- Not commonly used in asthma.

25. ADJUVANT ANTITUSSIVES
- Bronchodilators – relieve brochospasm and
bronchoconstriction thereby improving the
effectiveness of cough in clearing secretions.
- ↑ airflow velocity during cough
- Not routinely used; used only when there is
element of bronchoconstriction.
- Examples: Salbutamol, Terbutaline.
- FDC with antitussives unsatisfactory.

26. RESPIRATORY STIMULANTS
• Also called analeptics; e.g. doxapram, progesterone, caffeine,
and theophylline. Doxapram - used in preterm infants who
have apnea, also in pts with sleep apnea and in COPD pts with
acute respiratory failure.
• Cause a significant rise in paO2 by stimulating peripheral
chemoreceptors
• Side effect: convulsions is common due to narrow margin of
safety
Clinical uses
• Apnea in premature infants
• Suffocation in drowning 2o to acute

27. respiratory insufficiency
• Failure of spontaneous respiration after GA
• As an expedient in hypnotic drug poisoning
until mechanical ventilation is instituted

28. ASTHMA
Reversible narrowing of bronchial airways,
marked ↑ in bronchial responsiveness to
inhaled stimuli and inflammation of bronchial
mucosa; characterized by;
- recurrent bouts of coughing
- shortness of breath
- chest tightness
- wheezing

29. DRUGS USED TO TREAT ASTHMA
- Sympathomimetic drugs
- Methylxanthine drugs
- Antimuscarinic agents
- Corticosteroids
- Mast Cell Stabilizers: e.g. Cromolyn &
Nedocromil
- Leukotriene Pathway Inhibitors
- Others (Anti-IGE Monoclonal Antibodies)

30. SYMPATHOMIMETIC DRUGS
MOA: The adrenoceptor agonists;
- relax airway smooth muscle
- inhibit release of bronchoconstricting
mediators from mast cells
- may also inhibit microvascular leakage
- increase mucociliary transport by increasing
ciliary activity

31. Non-Selective Adrenoceptor
Agonists
Examples: Epinephrine, Ephedrine.
Epinephrine:
- effective, rapidly acting bronchodilator when
injected subcutaneously (0.4 mL of 1:1000
solution
- Can also be inhaled as a microaerosol from a
pressurized canister
- Maximal bronchodilation is achieved 15
minutes after inhalation and lasts 60-90
minutes.

32. Epinephrine Cont’
- Epinephrine stimulates α, β1 as well as β2
receptors; therefore side effects
↑…tachycardia, arrhythmias, and worsening
of angina pectoris.
- Used to treat acute vasodilation and shock
and anaphylactic bronchospasm.
- Role in Rx of asthma has been displaced by
more β2- elective agents.

33. Ephedrine
- Used in China for more than 2000 years before
introduction into Western medicine in 1924.
- Compared with epinephrine, has a longer
duration, oral activity, more pronounced
central effects, and much lower potency.
- Used infrequently in Rx asthma due to
development of more β2 -selective agents.

34. Isoproterenol
- Potent bronchodilator; causes maximal
bronchodilation within 5 minutes when
inhaled as a microaerosol from a pressurized
canister.
- 60- to 90-minute duration of action
- Rarely used for asthma due to cardiac
arrhythmias.

35. Beta2-Selective Drugs
- β2 receptors are found in the bronchial
smooth muscle.
- Stimulation relaxes airway smooth muscle,
inhibits mediator release, and causes
tachycardia and skeletal muscle tremor as side
effects.
- Generally adrenoceptor agonists are given by
inhalation: for great local action on airway SM
and less systemic toxicity

36. Beta2-Selective Drugs
- Effective after inhaled or oral administration
and have a long duration of action.
- Albuterol, terbutaline, metaproterenol, and
pirbuterol are available as metered-dose
inhalers.
- These agents produce maximal
bronchodilation within 15-30 minutes and
persists for 3-4 hours.

37. Beta2-Selective Drugs Cont’
- Albuterol (Salbutamol) and terbutaline are
also available in tablet form
- Of β2 selective drugs, only terbutaline is
available for subcutaneous injection (0.25
mg).
- A new generation of long-acting β2-selective
agonists includes salmeterol and formoterol
- They have ↑ lipid solubility and achieve long
duration of action.

38. CORTICOSTEROIDS
MOA: Have broad anti-inflammatory efficacy,
inhibiting production of inflammatory
cytokines
- Do not relax airway SM directly but reduce
bronchial reactivity and frequency of asthma
exacerbations if taken regularly.
- Examples: Prednisolone, beclomethasone,
budesonide, flunisolide, fluticasone,
mometasone, and triamcinolone

39. Clinical Use of Corticosteroids
- effective in improving all indices of asthma
control; e.g.;
- severity of symptoms, reduction of airway
constriction and bronchial reactivity,
frequency of exacerbations, and quality of life.
- Oral and parenteral therapy required for pts
who need urgent Rx.
- Chronic use has severe adverse effects.

40. Clinical Use of Corticosteroids
- Aerosol Rx most effective way to avoid the
systemic adverse effects of corticosteroid
therapy.
- Aerosol risk of systemic complications less
compared to oral or parenteral routes.
- Adrenal suppression related to dose: (secretion
of endogenous Corticosteroids has diurnal
variation)…customary to administer drugs early
in the morning after endogenous ACTH peaks.

41. Corticosteroid Side Effects
- oropharyngeal candidiasis from inhaled drugs;
risk reduction…pts to gargle water and spit
after each inhaled Rx.
- Hoarseness: direct effect on vocal cords.
- Children: inhaled corticosteroids shown to
slow rate of growth.

42. CROMOLYN & NEDOCROMIL
- Cromolyn sodium (disodium cromoglycate)
and nedocromil sodium are stable but
extremely insoluble salts.
- When used as aerosols they effectively inhibit
both antigen- and exercise-induced asthma.
- No effect on SM tone.
- Ineffective in reversing asthmatic
bronchospasm.

43. CROMOLYN & NEDOCROMIL
CONT’
- MOA: alteration in the function of delayed
chloride channels in the cell membrane,
inhibiting cell activation.
- This action on airway nerves causes cough
inhibition, on mast cells causes inhibition of
early response on antigen challenge, on
eosinophils causes inhibition of inflammatory
effect on inhaled allergens.

44. Clinical Use of Cromolyn &
Nedocromil
- Have acute protective effect following single
use: used before exercise, and before
unavoidable exposure to allergens.
- Cromolyn solution is also useful in reducing
symptoms of allergic rhinoconjunctivitis.
- Adverse Effcets: Drugs absorbed poorly; throat
irritation, cough, dry mouth.
- Cromolyn’s lack of toxicity…widely use in
children rapidly growing.

45. LEUKOTRIENE PATHWAY
INHIBITORS
- Leukotrienes result from the action of 5-
lipoxygenase on arachidonic acid
- synthesized by a variety of inflammatory cells
in the airways, including eosinophils, mast
cells, macrophages, and basophils.
- Leukotriene B4 (LTB4) is a potent neutrophil
chemoattractant.

46. Cont’
- LTC4 and LTD4 exert many effects known to
occur in asthma, including bronchoconstriction,
increased bronchial reactivity, mucosal edema,
and mucus.
- 2 approaches to interrupting the leukotriene
pathway pursued: inhibition of 5-
lipoxygenase,(preventing leukotriene synthesis)
and inhibition of the binding of LTD4 to its
receptor on target tissues, (thereby preventing
its action)

47. Leukotriene Inhibitors
- zileuton, a 5-lipoxygenase inhibitor;
- zafirlukast and montelukast, LTD4-receptor
antagonists.
- All these drugs improve asthma control and
reduce the frequency of asthma exacerbations.
- Their effects on airway caliber, bronchial
reactivity and airway inflamm < inhaled
corticosteroids. Principal advantage..taken
orally.

48. METHYLXANTHINE DRUGS
- 3 important methylxanthines are
theophylline, theobromine, and caffeine.
- Their major source is beverages (tea, cocoa,
and coffee, respectively).
- A theophylline preparation commonly used
for therapeutic purposes is aminophylline.

49. METHYLXANTHINE DRUGS: MOA
- Not fully understood.
- May be inhibition of cell surface receptors for
adenosine. Adenosine causes histamine
release from mast cells and associated with
airway SM contraction.
- May inhibit certain members of
phosphodiesterases (PDE hydrolizes cyclic
nucleotides)…results in ↑ conc of Intracellular
cAMP and myriad of cellular effects.

50. Cont’
- Methylxanthines have effects on the CNS,
kidney, and cardiac and skeletal muscle as well
as smooth muscle.
- Of the 3 agents, theophylline is most selective
in its SM effects, whereas caffeine has the most
marked central nervous system effects.
- CNS: methylxanthines especially caffeine cause
mild cortical arousal with increased alertness
and deferral of fatigue .

51. Cont’
- CVS effects: positive chronotropic and inotropic
effects.
- GIT effects: stimulate secretion of both gastric
acid and digestive enzymes.
- Kidney: methylxanthines especially theophylline
are weak diuretics.
- SM effects: bronchodilation, no tolerance.
- Skeletal Muscle: improve contractility and reverse
fatigue of the diaphragm in patients with COPD.

52. Clinical Use of Methylxanthines
- Of the xanthines, theophylline is the most
effective bronchodilator.
Theophylline: relieves airflow obstruction in
acute asthma and the severity of symptoms.
Most preparations are well absorbed from the
GIT. Has a narrow therapeutic window.
Side Effects: Anorexia, nausea, vomiting,
abdominal discomfort, headache, and anxiety
may occur.

53. Theophylline Cont’
- Theophylline is metabolized by the liver, usual
doses may lead to toxic concs of the drug in pts
with liver disease.
- Clearance may be ↑sed thro’ induction of
hepatic enzymes by cigarette smoking or by
changes in diet.
- Theophylline improves long-term control of
asthma, and is inexpensive.
- NB: accidental or intentional overdose can
result in severe toxicity or death.

54. ANTIMUSCARINIC AGENTS
- MOA: Muscarinic antagonists competitively
inhibit the effect of acetylcholine at muscarinic
receptors.
- In the airways, ach released from efferent
endings of the vagus nerves causes SM
bronchospasm.
- Muscarinic antagonists block the contraction
of airway smooth muscle and the ↑se in
secretion of mucus that occurs in response to
vagal activity.

55. Clinical Use of Muscarinic
Antagonists
- effective bronchodilators.
- atropine, the prototypical muscarinic
antagonist, causes bronchodilation at a lower
dose than that needed to cause an increase in
heart rate.
- ipratropium bromide (quaternary ammonium
derivative of atropine) is a more selective and
admini by inhalation.

56. OTHER DRUGS IN THE TREATMENT
OF ASTHMA
Anti-IgE Monoclonal Antibodies
- new approach to the treatment of asthma
exploits advances in molecular biology to
target IgE antibody.
- targeted against the portion of IgE that binds
to its receptors on mast cells and other
inflammatory cells.
- Omalizumab inhibits the binding of IgE to mast
cells preventing mast cells to degranulate.

57. OXYGEN THERAPY
- O2 therapy should be prescribed with the
same care as any drug.
- Absolute indication to supplemental inspired
air is inadequate tissue oxygenation.
- High conc O2 therapy reserved for a state of
low PaO2 in assoc with normal or low PaCO2
e.g. in pulmonary embolism, pneumonia,
pulmonary edema and MI.

58. OXYGEN THERAPY CONT’
- Low conc O2 therapy reserved for a state of
low PaO2 in assoc with a raised PaCO2
typically seen during exacerbations of COPD.
- Continuous long-term domiciliary O2 therapy
is given to pts with severe persistent
hypoxemia and cor pulmonale due to chronic
obstructive pulmonary disease. Pts provided
with O2 concentrator.

59. Referrences
1. B. Katzung; Basic and Clinical
Pharmacology, 11th ed.
2. P. N. Bennett; Clinical Pharmacology, 9th ed.
3. R.S. Satoskar; Pharmacology and
Pharmacotherapeutics, 17th ed.

60. THANK YOU
END