DRUGS AFFECTING

RESPIRATORY
SYSTEM
1

ASTHMA
chronic

inflammatory airway disease

excessive tracheobronchial reactivity
SYMPTOMS
wheezing,

chest tightness, restlessness

cough,
dyspnea
Mostly

in night / early morning

2

ASTHMA 5% POPULATION
ALLERGIC
FAMILY HISTORY
HYPERSENSITIVITY
Ig

E MEDIATED
RESP INFECTIONS
DRUGS
CHEMICAL
IRRITANTS
5

TRIGGERING FACTORS
RESPIRATORY INFECTIONS
Cold Air
Fog
Wood

smoke; tobacco smoke

Emotions
Stress
Laughter
Anxiety
Exercise (dry, cold weather especially )
OCCUPATION
6

 ASPIRIN

DRUGS

NSAIDS
BETA

BLOCKERS

PRESERVATIVES
Sulfites
Benzalkonium chloride
8

CONCEPT
CONTINUAL AIRWAY INFLAMMATION

EXACERBATED

BY TRIGGERING

FACTORS

INTERACTIONS
Airway

inflammatory cells,

Inflammatory

mediators,

Cytokines,
Surface

epithelium.
10

CELLS INVOLVED
Mast

cells,

Eosinophils,
T-lymphocytes,
Macrophages,
Neutrophils,
Epithelial

cells
11

CHEMICAL MEDIATORS
HISTAMINE
LEUKOTRIENE
BRADYKININ
PLATELET ACTIVATING
PROSTAGLANDIN

FACTOR

E2, F2, D2
12

Rationale for Pharmacological

Intervention
Reduction

of mast cell degranulation

Sympathomimetic agents
Cromolyn / Nedocromil

13

Rationale for Pharmacological

Intervention
Reduction

of cholinergic influence from

vagal motor nerves
Antimuscarinic agents

Direct

relaxation of airway smooth muscle

Sympathomimetic drugs
Theophylline
14

Agents acting on Beta Adrenergic

Receptors
Albuterol
Bitolterol
Pirbuterol
Salmeterol
Terbutaline
Ephedrine
Epinephrine
Ethylnorepinephrine
Isoetherine
Isoproterenol
Metaproterenol

15

Sympathomimetic Drugs
ACTIONS
Relax

airway smooth muscle

May

Inhibit release of some mast cell

bronchoconstrictive mediators

May

inhibit microvascular leakage

May

increase mucociliary transport

16

2 receptor activation
Relaxation
Skeletal

of airway smooth muscle

muscle tremor (toxicity)

17

Beta 2 agonists
Short acting
Albuterol, Pirbuterol, Epinephrine, Terbutaline.
Route : Inhalational
Uses : Acute conditions & Symptomatic
treatment of asthma
No anti inflammatory action
Never used as sole agent
Side effects : Tachycardia, Hyperglycemia,
tremors.
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19

20

Beta 2 agonists
Long

acting : SALMETEROL

SLOW ONSET OF ACTION

LONG

DURATION OF ACTION : 12 hrs

NOT FOR ACUTE ASTHMATIC ATTACK

USED

for Maintainance
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 Anticholinergic Agent

Ipratropium bromide
Competitive blocker of muscarinic receptors

prevents bronchoconstriction.

22

Ipratropium
DOC

for beta-blocker-induced
bronchospasm

USEFUL FOR

Pt. INTOLERANT TO
BETA 2 AGONISTS

MORE

USEFUL IN ELDERLY
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MAST CELL STABILIZERS

CROMOLYN

, NEDOCROMIL

Chloride-mediated

channel effects:
Inhibition of cough
Inhibition of early response to antigens
(mast cells)
Inhibition of late response to antigens
(eosinophils)
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CROMOLYN, NEDOCROMIL
PROPHYLACTIC ANTI

INFLAMMATORY
NO

DIRECT ACTION ON AIRWAYS

NOT USEFUL IN ACUTE. ASTHMATIC

ATTACK
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 USES

: PROPHYLACTIC AGENT FOR

EXERCISE INDUCED ASTHMA

ALLERGEN INDUCED ASTHMA

SIDE

EFFECTS : THROAT IRRITATION ,

COUGH

26

METHYLXANTHINES
THEOPHYLLINE
ACTION
Mech

( AMINOPHYLLINE )

: DIRECT BROCHODILATOR

:??

27

Central Nervous System

Effects
Increased alertness; reduced fatigue
In

more sensitive individuals:

nervousness/insomnia

Very

high methylxanthine doses: medullary

stimulation, convulsions

Primary

side effect in patients requiring

aminophylline (large doses) for control of asthma:
nervousness & tremor
28

 Cardiovascular

Effects:

direct positive chronotropic

direct enhanced myocardial contractility

GIT Effects:
enhanced secretion of gastric acid and digestive

enzymes

Renal

Effects:

weak diuretics-- not therapeutically important

29

THEOPHYLLINE - USE
Relieves

airway obstruction:

In acute asthma
Reduces symptoms severity
In chronic asthma
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THEOPHYLLINE SIDE
EFFECTS
Nausea,

Headache, Insomnia, Nervousness

Seizures,

Neuromuscular irritability,

Tremor,
Arrhythmias, hypokalemia, hyperglycemia,
vomiting
IV push - seizures/cardiac
arrhythmias
31

 NO

Corticosteroids

DIRECT ACTION OVER AIRWAYS

INHIBIT INFLAMMATION
DECREASE ACTIVITY OF CELLS
DECREASES

RELEASE OF MEDIATORS
DECREASE HYPERRESPONSIVENESS
OF AIR WAYS
DECREASES MUCOSAL EDEMA
32

 Beclomethasone
Prednisone
Fluticasone
Flunisolide
Triamcinolone

33

CORTICOSTEROIDS - USES
Status

asthmaticus (Combination with Beta 2

agonists)

For

management of acutely ill patients

Patients

not adequately maintained with

bronchodilators

Patients

whose symptoms are worsening,

despite reasonable maintenance treatment

34

ROUTES
ORAL
PARENTERAL
INHALATIONAL

35

ADVERSE EFFECTS
Inhaled

topical corticosteroids: oropharyngeal

candidiasis
Hoarseness: local effect -- vocal cords
Suppression of hypothalamic-pituitary-adrenal
axis
Decreased bone density , delayed puberty
Cataract formation
High doses:
dermal thinning
glaucoma

36

Other drugs
Interruption of leukotriene
pathways
Inhibition

of 5-lipoxygenase-- Zileuton

Rationale:
Prevents leukotriene synthesis
Effective for maintenance treatment of asthma
Requires monitoring for hepatic toxicity
37

Inhibition of leukotriene D4
receptor binding
Zafirlukast
Montelukast
Less

effective than steroids

SIDE

EFFECT : BLEEDING
COMPLICATIONS
Monitor hepatic function
38

Drugs to Treat Cough

What

causes a cough?
Irritation of mucosal surface
Inflammation, hypersecretion
Solutions:
Decrease sensitivity of CNS cough center,
decrease secretions
Codeine, Hydrocodone, Hydromorphone
Dextromethorphan
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 The

Drugs
for
Allergic
Rhinitis
Problem:

Inflammation of mucous membranes

IgE-mediated
Mast cell degranulation
The

solution:
Antihistamines (eg: Diphenhydramine)
-adrenergic agents (eg:
Phenylephrine)
Steroids (eg: Beclomethasone)
Cromolyn
40

 Presents

mainly with sneezing, nasal itching,

watery rhinorrhea and congestion.

H/O
Rx
In

allergen will be there

- Oral antihistamines + decongestants.

the form of intranasal spray.

41

ANTIHISTAMINES
H1

receptor blocker
Diphenhydramine
Clorpheniramine
Loratidine
Terfenadine
Astemizole
Cetirizine
42

Alpha adrenergic agonists

Phenylephrine
Oxymetazoline
Ephedrine
Phenylpropanolamine
Tetrahydrozoline
Naphazoline
Xylometazoline
43

Drugs
to
Treat
COPD
The Problem:
Chronic, irreversible

airflow obstruction
Variety of causes
The Solutions:
2 agonists
Theophylline
Glucocorticoids
Ipratropium
44

Treatment

mainly based on
assessing any reversible
component of the disease.
To prevent the acute exacerbations.
Symptomatic
45