Drugs effecting

respiratory system
Dr Arfa Azhar,
MBBS, Mphil, PhD Scholar
Senior Instructor,
Department of Biological and Biomedical Sciences,
Medical College, Pakistan
INTRODUCTION
 Introduction
 Asthma is a chronic inflammatory disorder of the airways
that is characterized:
 Clinically by recurrent episodes of wheezing,
breathlessness, chest tightness, and cough, particularly at
night/early morning.
 Physiologically by widespread, reversible narrowing of the
bronchial airways and a marked increase in bronchial
responsiveness.
 7

Classification
 A heterogenous disorder.
 Atopic /extrinsic /allergic ( 70%):
o Most common type
o Environmental agent: dust, pollen, food, animal
dander
o Family history - present
o Serum IgE levels - increased
o Skin test with offending agent –wheal flare
Classification
 Non-atopic/ intrinsic /non-allergic( 30%)
 Triggered by respiratory tract infection
 Viruses - most common cause

 Drug induced asthma

 Several pharmacologic agents
 Aspirin sensitive asthma
 Increased bronchoconstrictor leukotrienes.
 11

Pathophysiology

I. Inflammation
 Chronic inflammatory state
 Involves respiratory mucosa from trachea to
terminal bronchioles, predominantly in the
bronchi.
Pathophysiology
I. Inflammation
 Activation of mast cell , infiltration of
eosinophils & T-helper type 2 (Th2)
lymphocytes
 Endogenous factors
 Atopy
 Genetic predisposition to IgE mediated type I
hypersensitivity
 The major risk factor for asthma
 Genetics
Pathophysiology
Pathophysiology
Clinical manifestations
Classification for asthma severity

Grade Symptoms Night-time

Symptoms

Mild Symptoms ≤ 2 ≤ 2 times/month

intermittent times/week

Mild Symptoms ≥ 2 ≥ 2 times/month

persistent times/week
but ≤ 1/day
Moderate Daily Symptoms ≥ 1/week
persistent

Severe Continued Symptoms Frequent

persistent Limited physical activity
DIAGNOSIS
Laboratory Diagnosis

 Pulmonary function
tests:
 Using Spirometry
 estimate degree of
obstruction
 ↓FEV1, ↓FEV1/FVC,
↓PEF.
Laboratory diagnosis
 CXR :
 hyperinflation,emphysema
 Arterial blood-gas analysis
 hypoxia & hypocarbia
 Skin hypersensitivity test
 Sputum & blood eosinophilia
 Elevated serum IgE levels
 Status asthmaticus

 Prolonged asthma attack that does not respond to typical

drug therapy
 May last several minutes to hours
 Medical emergency
CLASSFICATION
 Respiratory System Drugs

 Bronchodilators
Beta agonist e.g. salbutamol
 Anticholinergics
Mast cell stabilizers, sodium chromoglycate, Ketotifen
Corticosteroids
 Bronchodilators: β-Agonists

 Large group, sympathomimetic

 Used during acute phase of asthmatic attacks

 Quickly reduce airway constriction

 Stimulate β2-adrenergic receptors throughout the lungs

 Bronchodilators: β-Agonists

Mechanism of Action

 Begins at the specific receptor stimulated#

 Ends with the dilation of the airways

#Activation of β2 receptors activates cAMP,* which relaxes smooth

muscles of the airway and results in bronchial dilation and increased
airflow
*cAMP = cyclic adenosine monophosphate
 Bronchodilators: β-Agonists

Indications

 Relief of bronchospasm related to asthma, bronchitis, and other

pulmonary diseases

 Useful in treatment of acute attacks as well as prevention

 β-Agonists Nursing Implications
 Thorough assessment before beginning therapy

Skin color
Baseline vital signs
Respirations (should be between 12 and 24 breaths/min)
Respiratory assessment, including PO2
Sputum production
Allergies
History of respiratory problems
Other medications
 β-Agonists - Patient Education
 Patients should be encouraged to have a good state of health

 Avoid exposure to conditions that precipitate bronchospasms (allergens, smoking,

stress, air pollutants)
 Adequate fluid intake
 Compliance with medical treatment
 Avoid excessive fatigue, heat, extremes in temperature, caffeine

 Patients to get prompt treatment for flu or other illnesses

 Patients to get vaccinated against pneumonia and flu

 Check with their physician before taking any medication, including OTCs

 Teach patients to take bronchodilators exactly as prescribed

 Anticholinergics

Mechanism of Action
 Acetylcholine (ACh) causes bronchial constriction and narrowing of the
airways
 Anticholinergics bind to the ACh receptors, preventing ACh from
binding

 Result:
 bronchoconstriction is prevented
 airways dilate

 ipratropium bromide (Atrovent) and tiotropium (Spiriva)

 Slow and prolonged action
 Used to prevent bronchoconstriction
 NOT used for acute asthma exacerbations!
 Anticholinergics

Adverse effects

 Dry mouth or throat

 Nasal congestion
 Heart palpitations
 Gastrointestinal distress
 Headache
 Coughing
 Anxiety

No known drug interactions

 MAST CELL STABILIZERS
DRUGS
 Sodium cromoglycate.
 Kitotifen.
 MAST CELL STABILIZERS :
PHARMACOKINETICS
1.SODIUM CROMOGLYCATE :

 Sodium cromoglycate is not absorbed orally.

 It is absorbed as an aerosol through metered dose inhaler.
 Only a small fraction is absorbed systemically.
 Rest of the portion is rapidly excreted unchanged in urine and bile.

2.Kitotifen :

 It is absorbed orally.
 Bioavailability is 50% due to first pass metabolism.
 It is largely metabolized.
 Plasma half life is 20-22 hours.
 MAST CELL STABILIZERS
Mechanism of action
 These drugs inhibit degranulation of mast cells.
 Release of mediators like Histamine, LT<PAF<IL is inhibited.
 This action may include delayed CI channel.
 Chemo taxis of inflammatory cells is inhibited.
 Bronchial hyperactivity is reduced.
 Bronchospan due to various stimuli (allergens, irritants, cold air and ecercise)
is prevented.
 It can’t be used to prevent attacks of asthma because it does not affect the
constrictor action of histamine.
 Clinical Uses
 Sodium cromoglycate :

 1.Bronchial asthma : it is used as a long-term prophylactic in mild to moderate

asthma. Decrease in frequency and severity of attacks and improvement in lung
function is more likely in extrinsic asthma. Lasts 1-2 weeks after discontinuing.
 2.Allergic rhinitis : Sodium cromoglycate is not a nasal decongesant.
But 4times daily use as a nasal spray can produce symptomatic
improvement in 4-6 weeks.
 3.Allergic conjunctivitis : Regular use as eye drops is beneficial in some chronic
uses.
 Clinical Uses
 KTOTIFEN :

 After 6-12 weeks of use, it reduces symptoms in about 50% patients of

bronchial asthma.
 But lung function improvement is marginal.
 It also produces symptomatic relief in patients with Atopic dermatitis,
Perennial rhinitis, Conjunctivitis, Urticaria and food allergy. Thus, it is
essentially indicated in patients with multiple disorders.
 Adverse effects
Sodium cromoglycate :

 It is poorly water soluble, so poorly absorbed and systemic toxicity is

minimal. Rare side effects are :
 Headache.
 Dizziness.
 Arthralgia.
 Rashes.
 Dysuria.
 Adverse effects

Ketotifen :

Generally, this drug is well tolerated. Rare side effects are:

 Sedation.
 Dry mouth.
 Dizziness.
 Nausea.
 Weight gain.
 Corticosteroids
 Anti-inflammatory

 Uses - chronic asthma/COPD exacerbations

 Do not relieve acute asthmatic attacks

 Oral, IV (quick acting), or inhaled forms

 Inhaled forms reduce systemic effects

 May take several weeks before full
effects are seen
 Corticosteroids

Mechanism of Action

 Stabilize membranes of cells that release harmful Broncho constricting substances.

 Also increase responsiveness of bronchial smooth muscle to β-adrenergic
stimulation
 Corticosteroids - Indications

 Treatment of bronchospastic disorders that are not controlled by conventional

bronchodilators

 NOT considered first-line drugs for management of acute asthmatic attacks or

status asthmaticus
 Adverse Effects

 Pharyngeal irritation
 Coughing
 Dry mouth
 Oral fungal infections
 Systemic effects are rare because of the low doses used for inhalation therapy
 Corticosteroids
Nursing Implications – Pt Education

 Teach patients to gargle and rinse the mouth with lukewarm water
afterward to prevent the development of oral fungal infections

 If a β-agonist bronchodilator and corticosteroid inhaler are both ordered,

the bronchodilator should be used several minutes before the
corticosteroid to provide bronchodilation.
 Corticosteroids
Nursing Implications – Pt Education
 Teach patients :

 To monitor disease with a peak flow meter

 Use of a spacer device to ensure successful inhalations

 Keep inhalers and nebulizer equipment clean after uses

 Tapering doses of oral corticosteroids

 Status asthmaticus (severe
acute asthma)

 Treatment of Status asthmaticus:

 High conc. of oxygen through facemask

 Nebulised salbutamol in oxygen given immediately
 Ipratopium bromide + salbutamol nebulised in oxygen,who don’t
respond within 15-30 min
 Status asthmaticus (severe
acute asthma)
 Treatment of Status asthmaticus

 Terbutaline s.c. or i.v.

 excessive coughing or too weak to inspire adequately.
 Hydrocortisone hemisuccinate i.v. , followed by infusion.
 Endotracheal intubation & mechanical ventilation if above fails
 Prophylaxis

 Preservation of the environment, healthy life-style (smoking cessation,

physical training) – are the basis of primary asthma prophylaxis.

 These measures in combination with adequate drug therapy are

effective for secondary prophylaxis.
Anti Tuberculosis Drugs
Tuberculosis
• TUBERCULOSIS is an infectious disease caused by
Mycobacteria;
• Tuberculosis typically attacks the lungs, but can also affect other
parts of the body.

MODE OF TRANSMISSION
• It is spreaded through the air when people who have an active TB
infection cough, sneeze, or otherwise transmit respiratory fluids
through the air.
Types of tuberculosis

• Based on anatomical site

PULMONARY TB (lungs)
• MILIARY TB (Liver, kidney spleen brain)
• Based on presence of signs and symptoms
– Active TB (only shows signs and symptoms).
– Latent TB (signs and symptoms are absent-
DORMANT).
• Major portion of tubercle bacilli become intracellular(i.e
reside in macrophage),so it is inaccessible for majority of
antibiotics as they cannot penetrate easily in to the
macrophage.

Macrophage
engulfing tubercle
bacilli
When infected person coughs or sneezes, the granulomas that may be present
in sputum comes in contact with air.

Lymphocytes, fibroblasts surrounding the cluster of epitheloid cells become inactivated.

And Mycobacterium tuberculi gets free from epitheloid cells

Comes in contact with another person

New person develops TB

 Classification
First line Second line
Oral Injectable
Isoniazid ( INH/H) Amikacin
Fluoroquinolones
Rifampin ( R)
Pyrazinamide ( Z) ( ofloxacin, Kanamycin
Ethambutol ( E) levofloxacin,
moxifloxacin) Capreomycin
inj. Streptomycin
( S) Ethionamide
Cycloserine
Para-aminosalicyclic
acid ( PAS)
Rifabutin/rifapentine
 ISONIAZID

Active in acidic and alkaline MOST ACTIVE drug for treatment

medium of TB. For rapidly multiplying
mycobacterium
Inhibition of synthesis of
mycolic acid which are unique
fatty acid component of
mycobacterial cell
wall

Breakdown of cell wall

Leakage of cell contents

Cell death
 Mechanism of resistance:
1. Mutation in KatG
2. Mutation of InhA

 Pharmacokinetics:
1. Absorption: Readily absorbed through GIT.
2. Distribution: in all body fluids and tissues including CSF
3. Metabolism: Acetylation in liver
4. Excretion : renal route
 Clinical use:
1. used in combination of other antitubercular agents
2. Also used as single agent in treatment of latent TB
 Adverse Effects:
1. Fever, skin rash
2. Isoniazid induced hepatitis : jaundice, loss of apatite, nausea,
vomiting, pain stop isoniazid
3. Peripheral neuropathy due to pyridoxine deficiency 
administer pyridoxine 10mg/day
4. Less common: CNS toxicity ( memory loss, seizures etc), GIT
discomfort, anemia
 RIFAMPICIN
Active against slowly growing; both intracellular and extracellular;
bactericidal

Inhibits DNA-dependent RNA

polymerase in bacterial cells by
binding its beta-subunit

Preventing transcription to RNA

Preventing subsequent translation to

proteins

Inhibition of cell growth

10
 Pharmacokinetics
1. Absorption: well, absorbed from GIT
2. Distribution : all tissues, tubercular cavities, placenta, CSF
3. Metabolism: liver
4. Excretion: through liver into bile
 Clinical Use
1. Atypical mycobacterium
2. Leprosy ( + dapsone)
 Adverse Effects:
1. Hepatitis
2. Orange discoloration of urine, sweat, tears
3. Flu like symptoms: fever, chills, myalgia
4. Occasionally: rashes, GI disturbances, nephritis.
 Drug-Drug interactions:
1. Potent enzyme inducer ( cytochrome p450)
2. Increases elimination of : anticonvulsants, anticoagulants,
OCPs, anti- HIV drugs replace with refabutin
 Pyrazinamide

Active against bacteria in acidic environment of

macrophages ( intracellular )
Mechanism of action :
pyrazinamide

Pyrazinamidase

active

inhibits Cell membrane

metabolism and transport
Pharmacokinetics:
1. Absorption: well absorbed GIT
2. Distribution: all body tissues
3. Metabolism: liver
4. Excretion: renal
Clinical use
1. Bactericidal to TB
Adverse effects
1. Hepatotoxicity
2. Hyperuricemia  acute episodes of gout stop if
symptomatic
3. Nausea, vomiting, photosensitivity
 Ethambutol

Mechanism of action
Arabinosyl transferase
Ethambutol inhibition

Polymerization of
arabinoglycan

mycobacterial Cell wall

 Pharmacokinetics:
1. Absorption: well absorbed GIT
2. Distribution: all body tissues
3. Metabolism:liver
4. Excretion: renal ( 80%) reduce dose in renal failure, feces ( 20%)
 Clinical use
1. Bacteriostatic to TB
2. Atypical mycobacterium
 Adverse effects
1. Retrobulbar neuritis  impairment of visual aquity, red-green
colorblindness
2. Hyperuricemia  acute episodes of gout stop if symptomatic
3. Nausea, vomiting, rash, fever.
 Streptomycin

 Aminoglycoside
 Against extracellular tubercular bacteria
 Injectable

mechanism of action : binds to 30s ribosome prevents formation

of initiation complex
 Adverse effects:
1. Ototoxicity- vertigo, hearing loss
2. Nephrotoxicity- adjust dose
 Treatment of tuberculosis

• One of the main reason for threrapeutic failure has been

patients' poor compliance n after having symptomatic relief.

• WHO , therefore, has recommended DOTS(Directly Observed

Therapy for Short course) wherein the anti-TB drugs are given
under direct supervision of medical professional 3 days a week.

• This helps to ensure the right drugs are taken at the right
time for the full duration of treatment
• A Standardized recording and reporting is maintained by
health worker or medical professional. This helps to keep
track of each individual patient and to monitor overall
programme performance.

• T.B therapy normally begins with 4 1st line drugs: rifampicin

+ isoniazid + pyrizinamide + ethambutol for 2months
followed by a course of isoniazid + rifampicin for next 4
months.

• Combination of drugs ensures prevention of resistance by

mycobacteria
Recommended Doses Of First-line Anti-tuberculosis
Drugs For Adults