BPharm 3rd Years PMY 3210

Mr Mudenda, BPharm, MSc Clin Path, MPH, SRF

School of Health Sciences
University of Zambia

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 0BJECTIVES
 At the end of this lecture, students should be able to;
 Explain the physiological and anatomical components of
the respiratory system

 Describe the aetiology of respiratory system diseases

 Classify drugs used to manage respiratory system

diseases
 Discuss the pharmacological and non-pharmacological
management of respiratory system diseases

 Apply pharmacology in the management of common

respiratory tract diseases to reduce morbidity and
mortality
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 Respiratory System
 Consists of the upper and
lower airways, the lungs, and
the thoracic cavity;

 Provides mechanism for

exchange of O2 and CO2 in
the lungs

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 Regulation of Respiratory System
 Respiration is controlled by spontaneous rhythmic discharges
from respiratory centre in medulla of CNS;

 Efferent pathways :
 Parasympathetic innervation to bronchial smooth muscle
(predominantly muscarinic M3 receptors, also M1, M2);

 Sympathetic innervation: β2-Adrenoceptors expressed in

smooth muscle, epithelium, glands and alveoli.

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 LUNG FUNCTION TESTS
 The functions of the lungs can be measured to help diagnose and
monitor various respiratory diseases.

 Forced expiratory volume (FEV)-patient inhales as deeply as

possible and then exhales forcefully and completely into a
mouthpiece connected to a spirometer.

 Forced expiratory volume in one second (FEV1)-measured in the

first second of exhalation.

 Forced vital capacity (FVC)-an assessment of the maximum volume

of air exhaled with maximum effort after maximum inspiration.
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 LUNG FUNCTION TESTS
 Peak expiratory flow rate (PEFR)-maximum flow rate that
can be forced during expiration.

 Measured using a peak flow meter.

 PEFR can be used to assess the improvement or

deterioration in the disease as well as effectiveness of
treatment.

 FEV1/FVC-ratio used to measure for capabilities of the

lungs.
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 Drugs acting on the respiratory
system
 Antiasthmatics

 Decongestants

 Antitussives

 Expectorants

 Antihistamines (H1 blockers)

 Antimicrobial agents
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BRONCHIAL ASTHMA

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 Bronchial Asthma
 A chronic disease characterized
by increased responsiveness of
trachea and bronchi to a variety
of chemical or physical stimuli;
 Affects all age groups;

 Increased airway obstruction caused

by bronchospasm and
bronchoconstriction, inflammation
and oedema of bronchioles, and
production of thick mucus that can
plug the airway.

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 Clinical Manifestations of Bronchial Asthma

 Frequent attacks of wheezing,

 Dyspnoea,

 Breathlessness,

 Chest tightness,

 Cough and

 Hypoxia in severe cases

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 Types of Bronchial Asthma
I. Antigenic (Atopic or Extrinsic) Asthma: Due to antigen-
antibody interaction on the surface of mast cells. Occurs by exposure to
allergens e.g. dust, pollen, animal hair/dander, certain types of food or drugs
e.g. Penicillins.

II. Non-antigenic (Cryptogenic or Intrinsic) Asthma: Related

to specific stimuli e.g. chest infection, exposure to cold air, exercise, emotions
or drug-induced e.g. NSAIDs-Aspirin, Brufen, Beta blockers such as
Propranolol, Opioid drugs such as Morphine, Codeine, Pethidine, etc.

III. Mixed asthma (caused by both intrinsic and extrinsic factors)

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 Pathogenesis of Bronchial Asthma
Bronchial Asthma is a complex multifactorial disease:
1. Release of mast cell mediators (Bronchoconstrictors
and inflammatory):
a)Cytoplasmic mediators; mast cell degranulation releases slow-reacting
substance of anaphylaxis-SRS-A (LTC4, LTD4), bradykinin, histamine,
5-HT, ACh and chemotatic factors.
b)Cell membrane mediators (derived from membrane phospholipids):
PAF, PGs,TXA2 and leukotrienes.

2. Mediators released from T-lymphocytes: Cytokines attract

and activate eosinophils & neutrophils to produce mediators responsible
for bronchial hyper-reactivity.

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An Asthmatic Attack

2 phases:

a) Immediate phase
consisting mainly of
bronchospasms.

b) Late or delayed
phase:
bronchospasms,
wheezing, coughing,
and inflammation.

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 Anti-Asthmatic drugs
Pharmacological management of asthma
depends upon the frequency and severity
of a patient’s symptoms.

1. Bronchodilators: prevent or reverse

bronchospasms.

2. Anti-inflammatory drugs: prevent the

inflammatory components of an asthmatic
attack (i.e. ‘mast cell stabilizers’)
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 Classification of Anti-Asthmatic drugs
Bronchodilators Anti-inflammatory drugs

1. Sympathomimetics 1. Corticosteroids
(β2-adrenergic agonists):
 Short Acting β-agonists
 Long Acting β-agonists
2. Cromolyns

2. Anticholinergics 3. Immunomodulators

3. Methyl xanthines 4. Leukotriene modifiers

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Anti-Asthmatic drugs: Bronchodilators
Drug Name Uses Dosage Adverse Effects
Sympathomimetics (β2-adrenergic agonists)
Salbutamol Acute Asthma, 2-6mg PO BD/TDS; Palpitation, Tremor,
Terbutaline Bronchospasm 2 inhalations q4— Dizziness, vertigo,
(these 2 are 6h (max 12 drowsiness,
inhalations) headache, nausea,etc
Short-acting)
Salmeterol Chronic Asthma, 2 inhalations BD Palpitations,
Formoterol Bronchospasm tachycardia, tremor,
(these 2 are nervousness,
headache, nausea,
Long-acting)
vomiting, heartburn,
etc
Albuterol Bronchospasm, 2-4 mg TID, QID Palpitations,
Exercise-induced PO; 1-2 inhalations tachycardia,
bronchospasm q4-6hr. Also given hypertension,
tremor, dizziness,
by nebulization
nervousness, nausea,
etc

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Anti-Asthmatic drugs: Bronchodilators
Drug Name Uses Dosage Adverse Effects
Methyl Xanthines
Aminophylline Relief & Individualized dose cardiac arrhythmias,
Prevention of regimen tachycardia,
Asthma; chronic tachypnea, seizures,
hyperglycemia,
bronchitis and
hypotension,
emphysema headache, insomnia,
irritability, etc
Theophylline Same as 16 mg/kg/24hr Same as
aminophylline divided doses aminophylline

Anticholinergics
Ipratropium Asthma, 2 inhalations Oropharyngyl
bromide Bronchospasm of (36µg) QID (max dryness, GI distress,
COPD, chronic 12 inhalations). dry mouth, nausea,
palpitations,
bronchitis, Also given by
dizziness, headache,
emphysema, nebulization etc
rhinorrhea 22
Anti-Asthmatic drugs: Anti-inflammatory
Drug Name Uses Dosage Adverse Effects
Glucocorticoids
Beclomethasone Asthma, Rhinitis, 2 inhalations (84– Oropharyngeal
Budesonide Post-surgery 168 g) TID, QID), irritation, fungal
Fluticasone revention of nasal Max 20 infection,
suppression of HPA
Mometasone polyps inhalations
function, stomatitis,
etc
Hydrocortisone Severe Asthma 50-100mg IV Adrenocortical
suppression,
Cushing syndrome,
Diabetes,
Hypokalemia,
Immunosupression,
Osteoporosis,
Oedema
Prednisolone Severe Asthma 40-60mg/day then Similar to
reduce dose Hydorcortisone
gradually.
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Anti-Asthmatic drugs: Anti-inflammatory
Drug Name Uses Dosage Adverse Effects
Leukotriene Receptor Antagonists
Zafirlukast Prophylaxis & 20 mg BID PO myalgia, fever,
treatment of Headache, dizziness,
chronic Asthma nausea, diarrhea,
abdominal pain, etc
Montelukast Prophylaxis & 10 mg PO nocte; Headache,
treatment of Children 6-14yrs : dizziness,
chronic Asthma 5mg chewable tab dyspepsia,
gastroenteritis,
cough, fatigue, etc
Leukotriene Synthesis Inhibitors
Zileuton Prophylaxis & 600 mg QID PO Dyspepsia, nausea,
treatment of headache, GI
chronic Asthma discomfort,
myalgia, etc

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Asthma Treatment Algorithm

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Luellmann, 2005
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STEPS ON HOW TO USE A
METERED DOSE INHALER (MDI)
 1. Remove the mouthpiece dustcap before use
 2. Shake the MDI vigorously
 3. Breathe out gently, but not fully
 4. Place the inhaler between the lips
 5. Start breathing in slowly and deeply through the mouth
 6. The canister is pressed to release the dose
 7. The breath is held for at least 10 seconds
 8. If a second dose is called for, atleast 1 minute should
elapse before repeating the inhalation procedure.
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 Nebulizers
 A nebulizer is a machine that changes liquid medicine into
a mist you can inhale

 Nebulizers are especially good for infants' or small

children's asthma medications

 They are also helpful when you have trouble using an

asthma inhaler or need a large dose of an inhaled
medication

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 Contraindications & Interactions
 Leukotriene antagonists avoided in the reversal of
bronchospasm in acute asthma attacks;
 Theophylline contraindicated in patients with arrhythmias,
hyperthyroidism, peptic ulcer and seizures;
 NSAIDs, β-blockers, Morphine, Muscarinic cholinomimetics
contraindicated in Asthma;
 Corticosteroids used cautiously in patients with compromised
immune systems, glaucoma, kidney or liver disease, convulsive
disorders, or diabetes, those taking systemic corticosteroids,
and during pregnancy;
 Concurrent use of Sympathomimetics & Sympatholytics
avoided (direct antagonism)
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 STATUS ASTHMATICUS
 A severe asthmatic attack not responding to the usual lines
of treatment;

 It is an emergency condition requiring hospitalization for;

1. Endotracheal intubation and suction of bronchial
secretions;
2.Oxygen-helium mixture inhalation;

3.IV fluids: to correct electrolyte imbalance, metabolic

acidosis and dehydration.

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 Management of status asthmaticus
Drug therapy includes:
 Prednisolone 50 mg by oral or Hydrocortisone I.V.
 Aminophylline I.V infusion
 Salbutamol inhalation (+/- Ipratropium)
 Magnesium sulphate IV infusion 1.2-2 g over 20 minutes
 Antibiotics to treat infections (if confirmed).
 Note: patients should be taught how to use a metered
dose inhaler (MDI).

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RECAP
 What are the components of the respiratory system?
 What is asthma?
 What are the types of asthma?
 Discuss the phases of an asthmatic attack
 What classes of drugs are used to treat asthma?
 What is a metered dose inhaler (MDI)?
 Explain the steps on how to use a metered dose inhaler
 Define status asthmaticus and describe its management
 What medical counseling points can you give to a patient
suffering from asthma?
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NASAL DECONGESTANTS

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 Decongestant: A drug that reduces swelling of
the nasal passages leading to opening of
clogged nasal passages and enhances drainage
of the sinuses.

 Decongestants are used for temporal relief of

nasal congestion caused by the common cold,
hay fever, sinusitis, and other respiratory
allergies.

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Mode of Action
 Nasal decongestants are sympathomimetic agents that
produce localized vasoconstriction of small blood
vessels of the nasal membranes;

 Vasoconstriction reduces swelling in the nasal

passages.

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 Nasal decongestants include:

Phenylephrine

Oxymetazoline

Pseudoephedrine

Ephedrine

Xylometazoline

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 Clinical Uses
 Decongestants are used to treat the congestion associated
with Rhinitis, Hay fever, Allergic rhinitis, Sinusitis, and
the Common Cold;

 Adjunctive therapy of middle ear infections to decrease

congestion around the eustachian tube.

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CHRONIC OBSTRUCTIVE
PULMONARY DISEASE-COPD
 COPD is a major global public health problem.

 Commonly caused by cigarette smoking.

 It is increasing in the developing world as a result of the

tobacco industry.

 COPD has been on the increase in Zambia due to Mining

and other industrial activities.

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 CLINICAL FEATURES OF COPD
 Attacks of morning cough during winter.

 Chronic cough initiated by cold.

 Progressive breathlessness.

 Reversible airway obstruction identified by an improved FEV 1

following a dose of a bronchodilator.

 Pulmonary hypertension-late complication and can lead to right-

sided heart failure (cor pulmonale) and respiratory failure.

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 PATHOGENESIS OF COPD
 There is small airways fibrosis, resulting in obstruction,
and/or destruction of alveoli and of elastin fibres in the lungs.

 This can lead to emphysema, thought to be caused by

proteases, including elastase, released during the
inflammatory response.

 Emphysema causes respiratory failure, because it destroys the

alveoli, impairing gas transfer.

 There is chronic inflammation in small airways and lung

parenchyma, characterized by increased numbers of
macrophages, neutrophils, and T-lymphocytes.
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 TREATMENT OF COPD
 Stopping smoking slows progress of COPD.

 Patients should be immunized against Influenza and Pneumococcus.

 Short-acting bronchodilators-Ipratropium and Salbutamol.

 Long-acting bronchodilators-tiotropium, salmeterol or formeterol.

 Theophylline, doxapram, hydrocortisone, prednisolone.

 Broad-spectrum antibiotics, e.g. Cefuroxime.

 Long-term oxygen therapy and mucolytic drug-Carbocisteine

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 COUGH
 Cough is an automatic protective reflex that
removes foreign material and secretions from the
bronchi and bronchioles or its an automatic
response to irritation of the airways in the lungs.

 Cough can be triggered by inflammation in the

respiratory tract, neoplasia, and undiagnosed
asthma.

 Angiotensin-Converting Enzyme Inhibitors

(ACEIs) can also trigger cough.
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 DRUGS USED FOR COUGH MX
 Antitussives-are cough suppressants-used mostly when the cause is not
known. E.g. Codeine, Dextromethorphan, Pholcodine, Methadone,
Morphine

 Expectorants-promote expulsion of bronchial secretions. E.g. Guaifenesin,

Bromhexine, Ammonium chloride, Ipecacuanha, etc

 Mucolytics-used to facilitate expectoration by reducing sputum viscosity.

E.g. Carbocisteine, Erdosteine, Mecysteine, Ambroxol, Acetylcysteine, etc

 Expectorants and mucolytics are mucokinetics. A mucokinetic drug is a drug

which aid in clearance of mucus from the airways, lungs, bronchi, and
trachea.

 Antihistamines-sedative antihistamines are used as cough suppressants. E.g.

Promethazine, Chlorpheniramine, Diphenhydramine, etc

 Antibacterials-used to treat cough due to bacterial infection. E.g.

Amoxicillin, Cephalexin, Cefuroxime, Azithromycin, etc 48
 MUCOKINETICS
 An expectorant increases bronchial secretions and mucolytics
help loosen thick bronchial secretions.

 Expectorants reduce the thickness or viscosity of bronchial

secretions thus increasing mucus flow that can be removed
more easily through coughing.

 Mucolytics break down the chemical structure of mucus

molecules. E.g. Dornase Alfa.

 The mucus becomes more thinner and can be removed through

coughing.
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 DRUGS USED FOR COUGH MX
 Decongestants can also be used to treat cough.

 Decongestants cause blood vessels in the lungs and nose to

narrow(constrict) thereby reducing congestion.

 Antitussive drugs act by depressing cough centre.

 All opioid narcotic analgesics have antitussive actions in doses

below those required for pain relief.

 Those used as cough suppressants are commonly members of the

group with minimal analgesic actions and addictive properties.

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 DRUGS USED FOR COUGH MX
 Codeine (Methylmorphine) is a weak opioid with less
addiction liability than the main opioids, and is a mild cough
suppressant.

 It decreases secretions in the bronchioles, which thickens

sputum, and inhibits ciliary activity.

 Constipation is a common side effect.

 Dextromethorphan and Pholcodine are believed to have

fewer adverse effects.

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 RECAP
 What are nasal decongestants?
 Give examples of nasal decongestants
 What is COPD?
 What are the clinical manifestations of COPD?
 What is cough?
 What are the causes of cough?
 What drugs are used to treat cough?
 Differentiate between mucolytics and expectorants
 What medical counseling points can you offer to a patient
suffering from COPD and cough?

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 Tuberculosis (TB)
 Caused by acid-fast tubercle bacilli Mycobacterium Tuberculosis
(M. tuberculosis), M. bovis, M. africanum
 Transmitted through exposure to tubercle bacilli in air-borne
droplets from people with pulmonary TB such through coughing
and sneezing
 Latent TB and Active TB-incubation period of ranges from 2 to 10
weeks

 Patients with TB have smear-positive sputum

 Risk groups include close contacts of patients with TB, casual

contacts such as work colleagues especially if they are
immunocompromised, HIV patients, diabetics, certain cancers,
advanced age, patients with silicosis, injecting drug users, etc
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 DIAGNOSIS OF TB
 An essential step in the diagnosis of TB is awareness of the
possibility of TB in people presenting with lower respiratory
tract symptoms such as chronic cough or chest infections not
responding to antibiotics.

 The preliminary diagnosis of TB is based on the symptoms and

signs in the patient, in conjunction with microscopy of sputum
(for acid-fast bacilli) followed by culture, chest radiography
and tuberculin skin test (Mantoux test).

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 Clinical manifestations
 Productive cough
 Chronic cough that lasts 3 or more weeks
 Coughing up blood (hemoptysis)
 Fever, chills,
 Night sweats
 Loss of appetite (anorexia), weight loss
 Chest pain, or pain with breathing or coughing
 Malaise (general bodily weakness, feeling unwell, illness, discomfort),
tiredness

 Combination therapy
 Treatment involves two or more drugs; (1) to minimize the risk of
resistance, (2) reduce the incidence of relapse, and (3) synergism

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AIM OF TREATMENT OF TB
 Anti-tuberculous drugs have the following purposes;
 1. to eliminate symptoms and prevent death

 2. to cure people with TB, provided the bacilli are drug

sensitive

 3. to control TB, by either preventing the development of

infectious forms or reducing the period of infectivity of people
with infectious disease

 4. to prevent relapse and reduce TB transmission

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Treatment of TB
 First line drugs
 FDCs (Fixed Dose Combinations)
 Rifampicin, Isoniazid, Ethambutol, and Pyrazinamide.
 All 4 drugs are given in the initial phase for 2 months, followed by
a further 4 months of Rifampicin and Isoniazid only in the
continuation phase.

 Second line drugs

 Streptomycin, Capreomycin, Kanamycin, Cycloserine, Ethambutol,
Amikacin, Ethionamide, Protionamide, Rifabutin, Azithromycin,
Clarithromycin, Ofloxacin, Ciprofloxacin, Levofloxacin,
Moxifloxacin, etc.

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Mechanism of action of first-line
anti-tuberculous drugs
 Rifampicin-inhibits DNA dependent RNA polymerase leading
to suppression of RNA synthesis in prokaryotic cells only-
bactericidal

 Isoniazid-inhibits synthesis of mycolic acids which are

important constituents of the mycobacterial cell wall-
bactericidal

 Ethambutol-inhibits arabinosyl transferases which is involved

in cell wall biosynthesis-bacteriostatic

 Pyrazinamide-disrupts the M. tuberculosis membrane transport

and energetics by pyrazinoic acid-bactericidal
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Major adverse effects of first-line
anti-tuberculous drugs
 Rifampicin-flu-like syndrome, hepatitis, hypersensitivity, GIT
reactions, red coloring of body fluids such as urine, sweat and tears.

 Isoniazid-hepatitis, cutaneous hypersensitivity, peripheral

neuropathy-due to depletion of Vitamin B6. Hence, give Pyridoxine
(Vitamin B6) supplementation. Other groups that can receive
Vitamin B6 include alcoholics, diabetics, poorly nourished, pregnant
women, & uraemic patients.

 Ethambutol-retrobulbar neuritis (ocular toxicity), arthralgia,

cutaneous hypersensitivity reactions,

 Pyrazinamide-hepatitis, vomiting, arthralgia, hyperuricaemia,

cutaneous hypersensitivity

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 OTHER TYPES OF TB
 Multi-drug resistant (MDR)TB-this is a form of TB which is
resistant to Rifampicin and Isoniazid. Usually treated using a
combination of 5 second-line drugs including Ethambutol

 Meningeal TB (Tuberculous meningitis)- 12 months tx

 TB of peripheral lymph nodes- 6 or 9 months tx
 Bone and joint TB- 6 months tx
 Pericardial TB- 6 months tx
 Genitourinary TB- 6 months tx

 Disseminated or Miliary or Generalized TB- 6 months tx. If there is

evidence for CNS involvement, then tx must be for 12 months same
as in Meningeal TB
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 XDR TB
 Extensively drug-resistant tuberculosis (XDR TB) is a form of
TB which is resistant to Isoniazid and Rifampicin plus any
fluoroquinolone and at least one of the three injectable second-
line drugs (i.e. Amikacin, Kanamycin, or Capreomycin)

 XDR TB is resistant to atleast four of the core anti-TB drugs

 Treatment: 9-12 months

 Fluoroquinolones-Moxifloxacin, Gatifloxacin
 Clofazimine, Ethambutol, Pyrazinamide, Prothionamide,
Kanamycin, Levofloxacin, etc

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 COMPLICATIONS OF TB
 Spinal pain, back pain, and back stiffness are the common
complications of TB
 Joint damage-tuberculous arthritis usually affects the hips and
knees
 Swelling of the membranes that cover the brain (meningitis)
 Liver or kidney problems
 Heart disorders
 Hemoptysis
 Empyema
 Miliary tuberculosis
 Bronchiectasis
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 COMPLICATIONS OF TB
 Pleurisy
 Pleural effusion
 Pneumothorax
 Aspergilloma
 Endobronchitis
 Laryngitis
 Cor pulmonale
 Cancer (Ca) of the bronchus
 Enteritis
 HIV related opportunistic infections

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 RECAP
 What is TB?
 List microorganisms that cause TB
 What are the clinical manifestations of TB?
 What groups are at risk of contracting TB?
 How is TB diagnosed?
 First-line and second line drugs used to treat TB
 Common side effects of drugs used to treat TB
 Define MDR TB and XDR TB
 Treatment of MDR TB and XDR TB
 What medical counseling points can you offer to a patient
suffering from TB?
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 Emphysema
 Emphysema is a progressive, incurable chronic lung
condition

 The air sacs (alveoli) are destroyed and oxygen uptake

is restricted due to the loss of elasticity of lung tissue

 People who smoke or live in polluted atmospheres are

possible candidates for emphysema

 People with a genetic defect (alpha 1-antitrypsin

deficiency) are also at risk

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 Types of Emphysema and
management
 Centriacinar
 Panacinar
 Distal acinar
 Irregular

 MANAGEMENT
 Corticosteroids
 Bronchodilators

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 Pneumonia
 Pneumonia is a bacterial, fungal, or viral infection that
affects one or both sides of the lungs

 Pneumonia causes the air sacs to fill up with fluids

 Often manifests as chest pain when coughing or breathing,

sweating, fever, shortness of breath, loss of appetite,
persistent dry cough

 Treated according to the causative microorganism

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 Coronavirus disease 2019
 Causative agent

 Transmission

 Clinical features

 Complications

 Preventive measures

 Treatment

 Vaccination
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 ASSIGNMENT ONE (Due 15/05/21)
 1. a. Write short notes on the types of pneumonia and include the diagnosis, causes,
clinical presentations, and complications. [5 marks]

 1. b. What are the signs and symptoms of pneumonia? [5 marks]

 1. c. Write short notes on non-pharmacological and pharmacological management of

pneumonia. [5 marks]

 2. Silicosis is one of the respiratory tract disorders. Write short notes on the diagnosis,
causes, clinical manifestations, and management of silicosis. [5 marks]

 3. Write short notes on the types of emphysema and include their causes, clinical
manifestations, and management. [10 marks]

 4. Write short notes on Sarcoidosis and include the causes, diagnosis, signs and
symptoms, stages, and treatment. [10 marks]

 5. Discuss the pathogenesis, clinical features, treatment and vaccination against

COVID-19. [10 marks]
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Reading List:
 Rang, Dale, Ritter. Rang & Dale’s Pharmacology, 6th ed., 2007.

 Goodman & Gilman; Manual of Pharmacology & Therapeutics, 2008.

 Katzung. Basic & Clinical Pharmacology, 11th ed., 2006.

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