Debre Markos University

Drugs affecting the respiratory

system

By Wubetu Yihunie (B.Pharm, MSc. In Pharmacology)

1 4/1/2025
Introduction

 Regulation of Respiratory System

 By spontaneous rhythmic discharges from the

respiratory centre (in the medulla) which is
modulated by input from
Vagal afferents from the lungs

Higher CNS centres (Medulla oblongata, pons, etc )

2 4/1/2025
 Autonomic pathways innervate the airways

oParasympathetic innervations
M3 Rbronchial smooth muscle and glands
 mediate bronchoconstriction and
mucus secretions
Stimulation of the vagus causes
bronchoconstriction

3 4/1/2025
 Cont’d
o Sympathetic
 Β2 -adrenoceptors are abundantly expressed on human
airway smooth muscle

 Β2-agonists relax bronchial smooth muscle

 The common Respiratory disorders

Asthma

Cough

rhinitis

4 4/1/2025
 BRONCHIAL ASTHMA

 A chronic reversible airway obstruction characterized:

 Clinically:-
By recurrent episode of cough, shortness of breath,
chest tightness, wheezing and rapid respiration
particularly at night/early morning.

 Physiologically;
By reversible narrowing of the airway, which
increases resistance to airflow and consequently
reduces the efficiency of movement of air to and
from the alveoli.
In addition to airway obstruction, cardinal features of asthma
include inflammation and hyper-reactivity of the airway

5 4/1/2025
 Factors contribute to airway obstruction in asthma

Contraction of the smooth muscle that

surrounds the airways

Excessive secretion of mucus and in some,

secretion of thick, tenacious mucus that

adheres to the walls of the airways

Edema of the respiratory mucosa.

6 4/1/2025
Pathophysiolgy of Asthma

 Antigens sensitize individuals by eliciting the production of

antibodies of the IgE type.

 These antibodies attach themselves to the surface of mast

cells and basophils.

 If the individual is re-exposed to the same antigen, results

in release of histamine and the cysteinyl leukotrienes from

mast cells Produce bronchoconstriction,
Mucus secretion
Pulmonary edema.
7 4/1/2025
 Mast cells also release a variety of chemotactic

mediators leukotriene B 4 and cytokines.

Recruit and activate additional

inflammatory cells like;

Eosinophils and alveolar macrophages, both

of which are also rich sources of leukotrienes
and cytokines.

8 4/1/2025
9 4/1/2025
 Chronic inflammation leads to marked bronchial hyper

reactivity to various substances, including

antigens

histamine

muscarinic agonists, and

 irritants such as SO2 and cold air

 This reactivity is partially mediated by vagal reflexes

10 4/1/2025
11 4/1/2025
 Ultimately, repeated exposure to antigen

establishes a chronic inflammatory state in the

asthmatic airway.

Mediators of Bronchial Asthma

histamine, peptides (kinins)

arachidonic acid derivatives (prostaglandins),

leukotriens and platelet activating factors

12 4/1/2025
 TREATMENT STRATEGY

Objectives:
 to return lung function to as near normal as possible and

to prevent acute exacerbations of the disease.

Depends on severity

Global
initiative for
Asthma/GINA

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 Stepwise Approach to Asthma

14 4/1/2025
 Aims of anti asthmatic drugs

To relieve acute episodes attacks of asthma

(Bronchodilators, quick relief medications)
To reduce the frequency of attacks, and nocturnal
awakenings
(Anti-inflammator drugs, prophylactic or control therapy)

15 4/1/2025
 Classification of drugs
RELIEVERS(RESCUE MEDICATIONS)

Β2-Agonist
Anti-cholinergics Agents
Methylxyhanthines
 CONROLLERS
GCs
Leukotrienes pathway inhibitors
Cromones
Anti-IgE-therapy

16 4/1/2025
 Classification…
 Bronchodilators are used both in maintenance therapy

and as needed to reverse acute attacks

 Anti-inflammatory therapy must be used in

conjunction with bronchodilators in all but the mildest

asthmatics.

17 4/1/2025
 Bronchodilators (relievers for bronchospasm)

18 4/1/2025
 Anti-inflammatory drugs (prophylactic)

19 4/1/2025
 Classification…
1. Bronchodilators are often referred to as relievers

a) Adrenergic agonists which include:

 Non selective -agonists e.g. Adrenaline

 Selective -agonists e.g. Salbutamol

b) Methylxanthines = theophylline derivatives

c) Muscranic receptor antagonists

e.g. Ipratropium bromide

20 4/1/2025
21
fig-Mechanism of bronchodilators 4/1/2025
 2. Anti-inflammatory agents

a) Steroids

e.g. Prednisolone, methyl prednisolone, triamcinolon

b) Mast cell stabilizers

e.g. Cromolyn sodium, nedocromil, ketotifen

c) Leukotriene inhibitors

i) Leukotriene synthesis inhibitor

e.g. Zileuton

ii) Leukotriene receptor antagonists

e.g. Zafrilukast and montelukast

d)Anti-IgE Therapy

22 e.g. Omalizumab 4/1/2025

23 4/1/2025
 Sympathomimetic Agents
 Includes:

 Non- selective β Agonists:-epinephrine, isoproterenol

 the selective β2-adrenoceptors, including albuterol (Ventolin,

Salbutamol), terbutaline, and salmeterol

 This class of agents has become the mainstay of modern

bronchodilator therapy

 agents are used both as needed to reverse acute episodes of

bronchospasm and prophylactically to maintain airway

patency over the long term.
 They are mostly delivered directly to the airways via inhalation.
24 4/1/2025
 β2-Agonists in Asthma
 Bronchodilators, usually given by inhalational routes
MOA
 Relaxation of Airway smooth muscle
 Non-Dilator effects
Inhibition of mast cell mediators releases

Reduction in plasma exudation

Increased mucociliary transport

Inhibition of sensory nerve activation

 Inflammatory cells express β2-receptors but these are

rapidly down regulated
25 4/1/2025
 Mechanism of action (2-agonists)
 Bronchial relaxation

 Stimulation of 2-receptor on bronchial smooth muscle

cells activates adenylate cyclase via Gs; consequently

increasing cytosolic cAMP

 Increase the conductance of Ca2+ -sensitive K+

channels in airway smooth muscle, leading to membrane

hyperpolarization and relaxation.

26 4/1/2025
 Cont’d…

 Direct 2 stimulation  stimulate

adenyl cyclase  Increase cAMP

production  increased cAMP
activate proteine kinase A(PKA) 
PKA phosphorylates myosin light
chain kinase(MLCK) 
phosphorylated MLCK  ↓affinity
for Ca calmodulin  ↓ activity of
smooth muscle actin/myosin 
bronchodilation
27 4/1/2025
 Inhibits the release of inflammatory mediators and cytokines.

 Stimulation of 2- receptor in inflammatory cells cyclic AMP

signaling cascade

 inhibits the function of mast cells, basophils, eosinophils, neutrophils,

and lymphocytes

 may also inhibit microvascular leakage and increase mucociliary

transport by increasing ciliary activity.

28 4/1/2025
Classified as

 Short-acting agonist e.g. salbutamol, terbutaline,

metaproteranol
Used for symptomatic relief of asthma

Are most effective drugs in relaxing airway smooth muscle;

Preferred treatment for rapid symptomatic relief

are administered either orally or by inhalation

Fast onset in inhalation(1-5min) and duration(2-6hrs)

Orally, maximum effect occurs within 30 minutes and

duration of action4-8 hrs

effective in prevention of exercise-induced asthma
29 4/1/2025
 Long-acting agonists e.g. salmetrol, formoterol

o The higher lipophilicity of the drugs may be

responsible for the extended effect

o Being lipophilic help partition and persists in the

membrane and only slowly dissociates from the

receptor environment

 Inhalation of salmeterol lasts over 12 hours

30 4/1/2025
o Long acting agonists

o Used for maintenance tt of chronic asthma

o Used in adjunctive therapy in patients whose asthma

is inadequately controlled by glucocorticoids

 Does not decrease airway inflammation significantly

 E.g. salmeterol-fluticasone and formoterol- budesonide

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 o LABA  given by inhalation only

 Its long duration of action makes salmeterol

particularly suitable for prophylactic use, such

as in preventing nocturnal symptoms of

asthma not used to reverse acute symptoms.

Relatively slow onset of action

32 4/1/2025
Adverse effects

 Because of being selective and local application, they have fewer side

effects

 Inhaled drugs have relatively few side effects

 The effects may include:

 muscle tremor, which results from a direct stimulation of β2 –

adrenoceptors in skeletal muscle.

 β2-Agonists also cause tachycardia and palpitations in some

patients.

 Muscle cramps, cardiac tachyarrhythmias, and metabolic

33 4/1/2025
disturbances
Oral Therapy with β- Agonists
(Carbuterol,pirbuterol,procaterol, bitolterol)

 Not generally recommended for routine use due to

adverse effects

 Situations where oral therapy is used

 In children (< 5 yrs) who can not manipulate metered-

dose inhalers (albuterol or metaproterenol syrups)

 In some severe asthma exacerbations, aerosols can

worsen cough and wheezing by causing local irritation

34 4/1/2025
 Non-selective adrenomimetics
Epinephrine

 is an effective, rapid-acting bronchodilator when injected

subcutaneously

 Maximal bronchodilation is achieved 15 minutes.

 used to manage severe acute episodes of bronchospasm

and status asthmaticus

 treating the acute vasodilation and shock as well as the

bronchospasm of anaphylaxis

35 4/1/2025
 Epinephrine

 Adverse effects

 tachycardia, arrhythmias, and worsening of

angina pectoris are troublesome.

• Contraindication: - hypertension, arrhythmia

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 Isoproterenol

 is a potent bronchodilator

 when inhaled causes maximal bronchodilation within 5

minutes

 But rarely used due to availability of effective and

selective agents

37 4/1/2025
Ephedrine

 Compared with epinephrine, ephedrine has

 a longer duration

 Can be given orally

 more pronounced central effects

 much lower potency

 currently infrequently used because of development of
more efficacious and β2-selective agents

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 2.Methylxanthines
 The three important methylxanthines are theophylline,

theobromine, and caffeine from beverages of tea,

cocoa, & coffee, respectively

 Theophylline: Not frequently used nowadays due to

the greater effectiveness of β2-agonists and

glucocorticoids.

 Its lower cost is the main reason behind its use in some

settings.

 Aminophylline: theophylline-ethylenediamine complex is

the drug preparation in the treatment of asthma.

39 4/1/2025
MOA

 Inhibits PDE enzyme, thus causing increased cytosolic levels of

cAMP
 Cardiac stimulation, Smooth muscle relaxation

 Decreased release of inflammatory mediators from mast cells

 Adenosine receptor blocker (A1 receptor)

Blockade of adenosine mediated

bronchoconstriction and histamine release

 enhancement of histone deacetylation- deactivation of

inflammatory gene transcription

 Increase diaphragmatic contraction

40 4/1/2025
Pharmacological effects of methylxanthines

 Theophylline has more smooth muscle effect but caffeine on CNS

 CNS- cortical arousal-Alertness, deferral of fatigue, nervousness,

insomnia, at very high doses (Convulsion and death)

 CVS

 Direct +ve inotropic and chronotropic effect

 inhibition of presynaptic adenosine receptors in sympathetic nerves

increasing catecholamine release (adenosine=anti adrenergic effect

???)
 increases in cAMP may result in increased influx of calcium

 GIT

41 Stimulation of secretion of both gastric acid and digestive enzymes

4/1/2025
 Cont’d
 kidney

 Weak diuretics

 may involve both increased glomerular filtration and reduced

tubular sodium reabsorption

 Smooth Muscle

 Bronchodilation: the major therapeutic action in asthma.

 Skeletal Muscle

Strengthen the contractions of isolated skeletal muscle like

diaphragm. They improve airflow in patients with dyspnea or

hypoxia
42 4/1/2025
 Cont’d

Clinical uses: anti asthmatic in patients who do not respond to

β2 agonists in acute condition
 Nowadays has less prominent role primarily because of

o the modest benefits it affords

o its narrow therapeutic window, and the required monitoring

of drug levels
Adverse effects
 It has a narrow therapeutic window and produces side effects
that can be severe, even life threatening
 GI: anorexia, nausea, vomiting, abdominal discomfort

43 4/1/2025
 CNS effects-stimulant effect causing nervousness, tremor,
insomnia, anxiety, seizure(>40μg/ml)

 CVS-Positive inotropic and chronotropic effects, vasodilation

in most blood vessels

 used with caution in patients with myocardial disease, liver

disease, and acute myocardial infarction.

 Drug interaction

 Drug that decrease theophlline levels

o Phenobarbitone, phenytoin, rifampicin,

 Drug that increase theophylline levels: Erythromycin,

cimetidine,clarithromycin, zileuton 4/1/2025

44
 3.ANTICHOLINERGICS

 Anticholinergic agents are less effective than β2-agonists

Ipratropium bromide , tiotropium

 are more selective quaternary compounds acting on M3

 are valuable for patients intolerant of inhaled β-agonist agents

 used via inhalation in the treatment of COPD and acute asthma

with albuterol.

 Ipratropium has greater effectiveness than β2-

adrenoceptor agonists in two settings:

 in psychogenic asthma, patients taking β2-adrenoceptor

45 antagonists. 4/1/2025
Tiotropium: has a high affinity for muscarinic receptors, and

dissociate very slowly than that of ipratropium

Adverse Effects

 Ipratropium is virtually devoid of the CNS side effects associated

with atropine.

 The most prevalent peripheral side effects are dry mouth,

headache, dizziness, nausea.

46 4/1/2025
 GLUCOCORTICOIDS
MOA
 Regulate responses to stress & inflammatory stimuli

 many genes are regulated by glucocorticoids acting at GRE

A. Gene repression (at low doses)

 Cytokines, adhesion molecules, Inflammatory enzymes,

Chemokines

B.Gene activation ( high doses)

 -adrenoceptor

 Annexin-1 (lipocortin-1)

 increased synthesis of annexin-1 that inhibit phospholipase A2

47 4/1/2025
….

Membrane phospholipid

Phospholipase A2 X Lipocortin-1 blocks

Arachidonic 5-lipoxygenase LTA4

acid

LTB4
LTC4 & LTD4
(chemotaxin)

Infiltration of CysLT receptor

eosinophils activation and
bronchoconstriction

48 4/1/2025
MOA

 The anti-inflammatory effects of glucocorticoids in asthma

include
Decrease synthesis and release of inflammatory mediators

(esp. that of cytokines)

Decrease infiltration and activity of inflammatory cells

Reduces bronchial hyper-reactivity

Up-regulation of -adrenoceptor number  increase

responsiveness to β2-agonist
Glucocorticoids do not directly relax airway smooth muscle
49 4/1/2025
and thus have little effect on acute bronchoconstriction
 GLUCOCORTICOIDS

 Differ in biological Half life, mineralocorticoid potency, anti-

inflammatory potency

Short Acting Corticosteroid (8-12 hrs)

1. Hydrocortisone (cortisol):-

 Prototype corticosteroid for anti-inflammatory activity

 indication: -asthma, ulcerative colitis & dermatitis

 Not indicated for fungal infection, recent ileocolostomy, & abscess

50 4/1/2025
 Intermediate acting GC (18-36 hrs)

1. Prednisone

 Clinical uses:- arthritis, asthma, COPD; Ulcerative colitis &

Crohn’s disease, Rheumatic & dermatologic disorders.

 Relative anti-inflammatory potency is 4 x cortisol

 It is a Prodrug

 Administration: Oral

51 4/1/2025
 2. Methylprednisolone
Indication:-
 Rheumatoid arthritis , Intra-articular injection,

 Ulcerative Colitis,

 alcoholic hepatitis

 Drug Interaction: Ketoconazole & some macrolide reduce

its elimination

52 4/1/2025
 3. Triamcinolone acetonide/hexacetonide
 8 x potent as prednisone

indication :-

 allergies, arthritis

 eye disease , Ulcerative Colitis

 skin diseases, respiratory diseases

53 4/1/2025
 Long acting GC
1.Betamethasone

Indication

 asthma, skin disorder, allergic or vasomotor rhinitis

 Patients with COPD usually show little or no response to

inhaled beclometasone.

54 4/1/2025
2. Dexamethasone acetate
 Indication

 Asthma

 Lupus & Rheumatoid arthritis

 Chronic allergic disorders

55 4/1/2025
Clinical use of corticosteroids in Asthma

 Corticosteroids are not effective for relief of acute

episodes of severe bronchospasm
 Inhaled corticosteroids are used for maintenance treatment
of asthma as prophylactic therapy
 Greatly enhance the therapeutic index of the drugs,

substantially diminishing the number and degree of side effects

without sacrificing clinical utility

 They differ in potency and affinity for the GR.

E.G fluticasone and budesonide having much higher affinities

than beclomethasone
56 4/1/2025
 Systemic corticosteroids.

 are used for acute asthma exacerbations and chronic severe asthma

 For the short-term (40-60mg prednisone for 5 days)

 Do not respond to β2- agonists and aerosol corticosteroid

 severe asthma may require longer treatment and slower tapering of

the dose.

 to avoid exacerbating asthma symptoms and suppressing

pituitary/adrenal function

 they should not be used for maintenance therapy unless all

other treatment options have been exhausted.

57 4/1/2025
Side effects due to prolonged use of oral corticosterids
 Adrenal suppression
 Glaucoma
 Growth retardation
 cataract
 Osteoporosis
 wasting of the muscles
 Fat distribution
 Psychosis
 Hypertension
 Cushing’s syndrome
 Hyperglycemia
 menstrual irregularities
 fluid retention
 weight gain
 susceptibility to
58 infections 4/1/2025
59 4/1/2025
 Drug interaction
 Drugs that Enhance Corticosteroid Effects

 Estrogens

 Oral contraceptives

 Antifungal agents, Antibiotics

 all of these agents inhibit cytochrome P450 enyzymes

Drugs that Reduce Corticisteroid Effects

 Antacids, Cholestyramine

 these drugs decrease the absorption of corticosteroids

 Phenytoin: induces cytochrome P450 enyzymes

60 4/1/2025
Cont’d

 Inhaled corticosteroids

o Generally well tolerated

o Are either poorly absorbed or rapidly metabolized and

inactivated
o thus have greatly diminished systemic effects relative to oral agents.

o The most frequent side effects are local

 Oral candidiasis, dysphonia, sore throat and throat irritation, and

coughing.

 Special delivery systems (e.g., devices with spacers) can minimize these

side effects.

61 4/1/2025
Leukotriene Pathway Inhibitors
 Zafirlukast and montelukast are leukotriene-receptor

antagonists.

 Zileuton is an inhibitor of 5-lipoxygenase

Pharmacokinetics

 They are rapidly absorbed orally

 They have high plasma protein binding character

 They differ in half life (zafrilukast longer) and potency

62 4/1/2025
 Mechanism of Action
Leukotriene-Receptor Antagonists
 Cysteinyl leukotrienes (cys-LTs) include LTC4, LTD4, LTE4.

 All the cys-LTs

 Are potent constrictors of bronchial smooth muscle.

 Can increase microvascular leakage, increase mucous production, and

enhance eosinophil and basophil influx into the airways
 The receptor responsible for the bronchoconstriction effect of leukotrienes is
the cys-LT1 receptor
 Zafirlukast and montelukast are selective high-affinity competitive
antagonists for the cys-LT1 receptor
 Inhibition of cys-LT-induced bronchial smooth muscle contraction and
infiltration of inflammatory cells
o relieve the symptoms of asthma.
63 4/1/2025
64 4/1/2025
Leukotriene-Synthesis Inhibitors.
 Zileuton is a potent and selective inhibitor of 5-lipoxygenase
activity and thus inhibits the formation of all 5-lipoxygenase
products.
 Thus, zileuton inhibits

 the formation of the cys-LTs

 the formation of leukotriene B4 (LTB4),a potent chemotactic

autacoids
 other eicosanoids that depend on leukotriene A4 (LTA4)
synthesis.
 Zileuton has an advantage over Cys-LT1 antagonists

 inhibit cys-LT effects regardless of the receptor subtypes

65
involved ( Cys-LT1 VS cys-LT2). 4/1/2025
Adverse effects
 Receptor antagonists

 systemic eosinophilia and avasculitis similar to Churg-Strauss

syndrome
 Zileuton

 Occasional Liver toxicity

Clinical use
 leukotriene inhibitors are effective prophylactic treatment for
mild asthma
 To control aspirin-induced asthma.

 montelukast is the most prescribed

66 4/1/2025
 taken without regard to meals and once-daily treatment
Drug interaction

 Zafirlukast may interact with warfarin and increase prothrombin

times

 Zileuton also decreases theophylline and warfarin clearance.

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 CROMOLYN SODIUM AND NEDOCROMIL

 Are Chromones

 Both administered by inhalation, poorly absorbed from GIT

 MOA: The exact MOA in asthma is not known

Inhibiting mediator release from mast cells,

suppressing the activating effects of chemotactic
peptides on human neutrophils, eosinophils, and
monocytes,
inhibiting parasympathetic and cough reflexes
 inhibiting leukocyte trafficking in asthmatic airways.
68 4/1/2025
Clinical Use

 less effective than inhaled glucocorticoids in controlling asthma

 effectively inhibit both antigen- and exercise-induced

asthma

 The drugs have no effect on airway smooth muscle tone and

are ineffective in reversing asthmatic bronchospasm;

 they are only of value when taken prophylactically.

 used for the prophylactic treatment of mild to moderate

asthma, esp children

 as added therapy, as an alternative to low dose corticosteroids

 their solutions are also useful in reducing symptoms of allergic

69 4/1/2025
rhinoconjunctivitis
Adverse effects

 Generally well tolerated; being poorly absorbed

 Include transient bronchospasm, cough or wheezing, laryngeal

edema, joint swelling and pain, angioedema, headache, rash,

and nausea

70 4/1/2025
 Anti-IgE Monoclonal Antibodies

 Omalizumab is the first "biological drug" approved for the

treatment of asthma.

 Omalizumab is a recombinant humanized monoclonal antibody

targeted against IgE.

 IgE bound to omalizumab cannot bind to IgE receptors on mast

cells and basophils, thereby preventing the allergic reaction at a

very early step in the process

 71Given SCly 4/1/2025

Mechanism of Action
 Omalizumab binds to the Fc region of the IgE antibody; thus

it is an "anti-antibody antibody."

 Omalizumab binds tightly to free IgE in the circulation to

form omalizumab-IgE complexes that have no affinity for Fc

epsilon receptor I (FcεRI) on mast cells and basophiles

 Omalizumab treatment also decreases the amount of FcεRI

expressed on basophils and mast cells

 reduce both free IgE and available FcεRIs on cell surfaces

 monocytes, lymphocytes, certain antigen-presenting cells,

72 4/1/2025
and eosinophils express Fc εRI
 Clinical Use

 indicated for adults and adolescents older than 12 years of age

with allergies and moderate-to-severe persistent asthma.

 effective in reducing the dependency on inhaled and oral

corticosteroids

 decreasing the frequency of asthma exacerbations

 other allergic disorders, such as nasal allergy

 Toxicity
 injection-site reactions (e.g., redness, stinging, bruising
73  Malignancies 4/1/2025
74 4/1/2025
 Severe acute asthma (status asthmaticus)

 Is a medical emergency requiring hospitalization.

 Treatment includes

– oxygen (in high concentration, usually 60%),

– inhalation of salbutamol given by nebuliser
– IV hydrocortisone followed by a course of oral
prednisolone .

 Additional measures occasionally used include

– nebulised ipratropium,
– intravenous salbutamol or aminophylline , and
75 antibiotics (if bacterial infection is present). 4/1/2025
 Cough
 Cough is a useful physiological mechanism

 clear the respiratory passages of foreign material and excess

secretions (useful/productive cough)

 cough may be annoying and prevent rest and sleep and

Chronic cough can contribute to fatigue, especially in elderly

patients

 unproductive/dry cough is useless

76 Related to irritantas or smoking 4/1/2025

 The cough reflex

 Involves the central and peripheral nervous systems, as well as

the smooth muscle of the bronchial tree.

 Irritation of the bronchial mucosa ⇒ Bronchoconstriction ⇒

Stimulates cough receptors (stretch receptor) in

tracheobronchial passages ⇒Afferent fibers of the vagus nerve

⇒ cough centers in the CNS (medulla)

77 4/1/2025
 Mechanism of cough

Stimulation cough receptors (throat, stretch receptors in

lungs)

Afferent impulses to cough centre (medulla)

Efferent impulses via parasympathetic & motor nerves

to diaphragm,intercostal muscles & lung

Increased contraction of diaghramatic, abdominal &

intercostal (ribs) muscles noisy expiration (cough)

78 4/1/2025
 Treatment approaches
 Two approaches of t/t

– Specific t/t: treat the cause (bacteria, virus…)

– Non-specific t/t: to relieve symptoms

 Classification of drugs
Pharyngeal demulcents: Lozenges, cough drops, linctuses
containing syrups,Glycerine,liquorice
Expectorants:
1. Mucokinetics(bronchial secretion enhancers):Soduim
or potassium citrate, potassium iodide, Ammonium chloride
2. Mucolytics: Bromhexene,Ambroxol,Acetylcystein,
Carbocisteine

79 4/1/2025
 Classification of drugs

 Anti-tussives (cough center suppressants):

a) Opoids: Codien, pholcodien

b) Non-opoids: Dextromethorphan, chlorphendianol

c) Anti-histaminics: Chlorpheniramin,
diphenhydramine,promethazine
 Adjuvant Antitussives:

 Bronchodilators: Salbutamol, terbutaline

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 Expectorants

 Stimulate the production of respiratory secretions

 Facilitate removal of mucus by increasing volume and

decreasing viscosity of bronchial secretion

 Used for the relief of productive coughs associated with:
Common cold Pertussis
Bronchitis Influenza
Laryngitis Measles
Pharyngitis

E.g. guaifenesin, iodide,NH4Cl products

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Guaifenesin

 is the only OTC expectorant recognized as safe and effective by the FDA.

MOA

 increase leaking of fluid out of the lung tissue & into the airways

 increasing the volume and reducing the viscosity of secretions in the

trachea and bronchi.

 to aid in the flow of respiratory tract secretions, allowing ciliary

movement to carry the loosened secretions upward toward the

pharynx.

 it may increase the efficiency of the cough reflex and facilitate removal of

the secretions.

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Side effect

 diarrhea, drowsiness, nausea or vomiting and stomach

pain

 Guaifenesin should be containdicated when there is

hepersensitivity reactions

 Note: NH4Cl should be avoided in pts with renal,

hepatic and heart diseases

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 MUCOLYTIC AGENTS
 Aid the clearing of the airways in high-risk respiratory patients who

are coughing up thick, tenacious secretions.

 React directly with mucus to make it more watery

 Acetylcysteine most common and effective

 Given orally or by inhalation

 breaks down di-sulfide bonds of mucoproteins

 Decrease the viscosity of mucus

 Adverse reactionsburning sensation and nausea, bronchospasm

84 Have unpleasant odor 4/1/2025

 Carbocisteine & mecysteine HCl
 These drugs act as mucolytics.

 MOA:- they reduce the viscosity of bronchial secretions by

cleaving disulphide bonds cross-linking mucus glycoprotein

molecules

 Admn:- Oral & inhalation (instillation)

 Indication :- cystic fibrosis, care of tracheostomies

 Side effect :- Gi -irritation & allergic reaction

Erdosteine – regulates mucus production.

85
- increases mucociliary transport 4/1/2025
 Antitussives
 Anti-tussive drugs are drugs that suppress cough

 Are drugs used to suppress the intensity and frequency

of coughing

 Used to treat dry, non productive cough

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 Two Types of Anti-tussives
Central anti-tussives

 Suppress the Medullary cough center

 Act within the CNS to elevate the cough threshold

 Effective and less addiction liability

 Decrease secretions in the bronchioles

 may be divided into two groups:

 Narcotic analgesics- e.g. codeine, hydrocodeine, etc

4/1/2025
87  Narcotic/Opioid derivatives-e.g. Dextromethorphan
Peripheral Antitussives

 Decrease the input of stimuli from the cough receptor in

the respiratory passage

e.g: Demulcents e.g. liquorices lozenges, honey

Local anesthetics e.g. lidocaine aerosol

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Demulcents
 Provide symptomatic relief in dry cough originating above

the larynx

 Form a protective coating over the irritated pharyngeal

mucosa

 Soother the throat (directly & also by promoting salivation)

↓afferent impulses from inflamed/irritated pharyngeal
mucosa
Given as syrups or lozenges e.g acacia, licorice, glycerin,
honey
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Opioid analgesics

 Morphine and related opioids also depress the cough reflex at

least in part by a direct effect on a cough center in the medulla.

 There is, however, no obligatory relationship between

depression of respiration and depression of coughing

 Suppression of cough by such agents appears to involve

receptors in the medulla that are less sensitive to Naloxone

than those responsible for analgesia.

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Codeine

 Codeine is indicated for the treatment of mild to moderate pain

and for its antitussive effects.

 Codeine at antitussive doses, has few side effects and has

excellent oral bioavailability 65mg vs 15mg).

 Codeine is metabolized in part to morphine, which is

believed to account for its analgesic effect.

 Codeine is rarely addictive and produces little euphoria

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pharmacokinetics

 Readily absorbed & Distributes to liver, spleen,& kidney

 Crosses BBB & Excreted in breast milk

 Metabolism is primary hepatic clearance ( CYP3A4 & CYP2D6)

 CYP2D6 polymorphisms

 Increased conversion of codeine to morphine in ultra rapid

metabolizer
 Higher risk of toxicity in 1-2% of patients
 decreased conversion of codeine to morphine poor metabolizer

 Codeine may be ineffective in 5-10% of patients

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Adverse effects-

 less intense than morphine, but at high dose it can

cause

 Vasodilation – not safe for trauma

 Suppress respiration and coughing -Contraindicated in

the case of asthma patients

 Sedation with alcohol or barbituartes

 depression, miosis, and coma

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Dextromethorphan.

 is the D-isomer of the codeine analog methorphan;

 it has no analgesic or addictive properties and does not act

through Opioid receptors.

 Although dextromethorphan is known to function as an NMDA-

receptor antagonist, its antitussive effect still is not clear

 The drug acts centrally to elevate the threshold for coughing.

 its potency is nearly equal to that of codeine.

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Clinical use

 Used as over-the-counter sale in numerous syrups and lozenges

or in combinations with antihistamines and with the

local anesthetic benzocaine

 blocks pain from throat irritation due to coughing.

Adverse effects

 Unlike codeine, dextromethorphan produces fewer subjective

and gastrointestinal side effects.

 Extremely high doses may produce CNS depression.

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 4) Antihistamines

 Added to antitussives/expectorant formulation

 Due to sedative & anticholinergic actions produce relief in

cough but lack selectivity for cough centre

 ↓secretions (anticholinergic effect)

 Suitable for allergic cough

E.g., Chlorpheniramine, diphenhydramine, promethazine

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 Mechanism of action
2.Central
1. Peripheral
 Direct Block H1 R in the CNS

 Directly prevent the production of cough which directly promote production of

which is an effect of histamine cough

receptors on sensory afferents  May bind to non histaminergic

 Indirectly block nasal mucus secretion receptors in the CNS that control

induced by histamine receptors cough excitability & mucus secretion

promotes cough & that is induced by  decrease nasal mucus secretion.

cholinergic mechanisms on pharyngeal  Induce sedation that result in

or laryngeal mechanoreceptors reduction in cough excitability

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