PHARMACOLOGY UNIT THREE (3)

 PHARMACOLOGY 

UNIT THREE (3)

  

RESPIRATORY PHYSIOLOGY 

Asthma and COPD

Asthma is a chronic reversible disorder of the airflow 

COPD is a chronic, irreversible obstruction of airflow 

is directly linked to the progressive decline of lung function 

Both Condition is characterized by

• narrowing

(bronchoconstriction) 

• mucus production 
• inflammation

CAUSES

1. Genetically
2. Exercise 
3. Environmental& seasonal
4. Drugs like aspirine 
5. Smoking cigarette specially (copd)
6. Infections

Signs and symptoms

1. Shortness of breathing 
2. Cough 
3. Pain of tightness of the chest 
4. Wheezing or crackle flowing exercise 

Drugs that act on the respiratory system include

There are two categories of

1. Bronchodilators

• B2-adrenoceptor agonists
• Anticholinergic drugs
• Xanthine derivatives

1. Anti-inflammatory

agents

• Glucocorticoids
• Leukotrienes inhibitors

1. Bronchodilators

B2- Adrenergic agonists (sympathomimetic agents)

A. Non-selective B2-agonists

- Epinephrine, ephedrine, isoprotenerol

B. Selective B2-agonists

- Salbutamol(albuterol), metaproterenol, salmeterol, formaterol and etc

Mechanism of Action 

B2-Agonists causes relaxation of smooth muscle

Non-selective B2- agonists

Cause more cardiac stimulation (mediated by a 

receptor), they should be reserved for special situations

Epinephrine or adrenaline

by inhalation or subcutaneously preferred for the relief of an acute attack of bronchial  asthma 

Side effects include arrhythmia and worsening of angina pectoris, increase blood pressure, tremors etc

Contraindication: hypertension, arrhythmia

B₂- selective agonists 

They are largely replace non selective ẞ₂- agonists are effective after inhaled or oral administration 

they have a longer duration of action ►They are the most widely used sympathomimetic 

Classified as 

Short-acting agonists: used for symptomatic relief of asthma 

Long-acting agonists: used prophylactically in the treatment of the disease 

Short-Acting B₂-AR Agonists Drugs: terbutaline, albuterol, levalbuterol, 

• Used for acute inhalational treatment of bronchospasm some are also used orally (eg albuterol and metaproterenol) onset of action within 1 to 5 minutes, maximum effect within 30 minutes and 

the duration of action is 3-5 hours they are usually used on an 'as needed /PRN basis to control symptoms 

Long-Acting B₂-AR Agonists ►Drugs:-Salmeterol and formoterol slower onset of action but 

the duration of action is 8-12 hours ✓ are given regularly, twice daily, as adjunctive therapy in patients whose asthma is inadequately controlled by glucocorticoids. 

they are not used on PRN bases ✓ to prevent bronchospasm (e.g. at night or with exercise) in patients requiring long-term bronchodilator therapy

Side effects: 

Tremors; anxiety; insomnia; tachycardia; headache; hypertension; and, etc. 

Contraindications: 

Sympathomimetic are contraindicated in patients with known hypersensitivity to the drugs 

Precautions: They should be used cautiously in patients with hypertension, cardiac dysfunction, hyperthyroidism, glaucoma, diabetes, pregnancy. 

Anticholinergic agents • 

Ipratropium and tiotropium:-4° amine derivative of atropine Competitive antagonists of muscarinic (M3) effect is responsible for the bronchial relaxing effect of the drugs 

For asthma, as an addition to 

ẞ₂-adrenoceptor agonists and steroids Also useful as alternative therapies for patients intolerant of B₂-adrenoceptor agonists 15 For some patients with COPD especially long-acting drugs (e.g. tiotropium). 

bronchospasm precipitated by ẞ2-adrenoceptor 

For antagonists. 

The combination of a selective B₂ adrenergic agonist and Ipratropium should be considered in acute treatment of severe asthma exacerbations. 

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Methylxanthine drugs 

The three important methylxanthines are theophylline, theobromine, and caffeine. 

Their major source is beverages (tea, cocoa, and coffee, respectively). 

The importance of theophylline as a therapeutic agent in the treatment of asthma has diminished as the greater effectiveness of inhaled adrenoceptor agents for acute asthma and of inhaled anti- inflammatory agents for chronic asthma has been established 

►A theophylline preparation commonly used for therapeutic purposes is aminophylline 

► The metabolic products, partially demethylated xanthines (not uric acid), are excreted in the urine.

 Aminophylline

►Alertness, nervousness, insomnia, convulsion and death at very high doses ►They cause generalized vasodilatation but constrict cerebral blood vessels 

The methylxanthines stimulate secretion of both gastric acid and digestive enzymes

Anti-inflammatory 

Corticosteroids 

►Inhaled corticosteroids 

are used for maintenance treatment of asthma as prophylactic therapy

 ►Drugs of first choice in patients with any degree of persistent asthma (mild, moderate, or severe) 

Example, Beclomethasone, Fluticasone, Triamcinolone and Dipropionate

 The most frequent side effects are local :oral candidiasis, dysphonia, sore throat and throat irritation, and coughing. 

Risk can be reduced by having patients gargle water and spit after each inhaled treatment 

Systemic corticosteroids are used for the short-term treatment of asthma exacerbations that do not respond to 

B2-AR agonists and aerosol corticosteroids  

Example Prednisone and Methylprednisolone

Side effect 

adrenal suppression, growth retardation, cataracts, osteoporosis and increased susceptibility to infection 

Leukotriene inhibitors 

 ►less marked than the effects of inhaled corticosteroids 

► Principal advantage is that they are taken orally They are indicated for the prophylaxis and chronic treatment of asthma. 

An important role for leukotriene is in aspirin-induced asthma 15-10% and in exercise induces asthma 

Example, Zafirlukast and montelukast

ALLERGIC RHINITIS AND COUGH 

Rhinitis is an inflammation of the mucous membranes of the nose and is characterized by 

➤ sneezing, 

➤itchy nose/eyes, 

➤ watery rhinorrhea, and nasal congestion

Drugs for allergic rhinitis 

Antihistamines (H1-receptor blockers) like diphenhydramine, chlorpheniramine, loratadine, and fexofenadine

a- Adrenergic agonists like phenylephrine and oxymetazoline 

Corticosteroids like beclomethasone, budesonide, fluticasone, mometasone, and triamcinolone

 ► Leukotriene antagonists like montelukast

Antihistamines (H1-receptor blockers) 

► MOA 

Block H1-receptor and are useful in treating the symptoms of allergic rhinitis caused by histamine release. 

The most frequently used agents in the treatment of sneezing and watery rhinorrhea associated with allergic rhinitis 

Combinations of antihistamines with decongestants are effective when congestion is a feature of rhinitis

Side effect 

➡ sedation, 

➡ rarely, 

➡ cardiac arrhythmias, 

➡ dry eyes/mouth, 

➡ difficulty urinating

a- Adrenergic agonists 

MOA 

constrict dilated arterioles in the nasal mucosa and reduce airway resistance. 

When administered as an aerosol, these drugs have a rapid onset of action 

a-adrenergic agonist nasal formulations should be used no longer than 3 days due to the risk of rebound nasal congestion

a-adrenergic agonists 

► MOA 

constrict dilated arterioles in the nasal mucosa and reduce airway resistance. 

When administered as an aerosol, these drugs have a rapid onset of action

a-adrenergic agonist nasal formulations should be used no longer than 3 days due to the risk of rebound nasal congestion

Corticosteroids 

MOA 

These are anti-inflammatory agents 

They are effective when administered as nasal sprays 

Treatment of chronic rhinitis may not result in improvement until 1 to 2 weeks after starting therapy