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Pharmacology of Respiratory
Diseases
Prepared by: Dr. Hassan Al-Tomy
Reviewed and presented by: Dr. Muna Oqal
Bronchial Asthma
Recurrent and reversible shortness of breath
Occurs when the airways of the lungs become
narrow as a result of:
– Bronchospasm
– Inflammation of the bronchial mucosa
– Edema of the bronchial mucosa
– Production of viscid mucus
Alveolar ducts/alveoli remain open, but airflow
to them is obstructed
Symptoms
– Wheezing
– Difficulty breathing
Asthma
Three categories
• Allergic
• Idiopathic
• Mixed allergic/idiopathic
COPD
Chronic obstructive pulmonary disease
• Applies to chronic bronchitis and emphysema
• Obstruction is constant
Agents Used to Treat Asthma
• Long-term control
– Antileukotrienes
– Cromolyn
– Inhaled steroids
– Long-acting beta2-agonists
• Quick relief
– Intravenous systemic corticosteroids
– Short-acting inhaled beta2-agonists
– Ipratropium
– Nedocromil
– theophylline
Aerosol delivery of drugs
– Should produce a high local concentration in the
lungs with a low systemic delivery → minimizing
side effects
– Size of the particles: critical determinant
• >10 um – deposited in the mouth & Oropharynx
• <0.5 um – inhaled, subsequently exhaled
• 1-5 um – allow deposition & most effective
Bronchodilators:
Xanthine Derivatives
• Plant alkaloids: caffeine, Theobromine, and
Theophylline
• Only Theophylline is used as a bronchodilator
– Examples:
• Aminophylline
• Theophylline
Xanthines: Action
• Smooth muscle relaxation
• Bronchodilation
• Increased airflow
Xanthines: Drug Effects
• CNS stimulation
• Cardiovascular stimulation:
– Increased force of contraction
– Increased HR
– Increased cardiac output
– Increased blood flow to the kidneys (diuretic
effect)
Xanthines: Indications
• Dilation of airways in asthmas, chronic
bronchitis, and emphysema
• Mild to moderate cases of acute asthma
• Adjunct agent in the management of COPD
Xanthines: Side Effects
• Nausea, vomiting, anorexia
• Gastroesophageal reflux during sleep
• Sinus tachycardia, extrasystole, palpitations,
ventricular dysrhythmias
• Transient increased urination
RT Implications:
Xanthine Derivatives
• Contraindications: history of PUD or GI disorders
• Cautious use: cardiac disease
• Timed-release preparations should not be
crushed or chewed (causes gastric irritation)
Bronchodilators: Beta-Agonists
• Large group, sympathomimetic.
• Used during acute phase of asthmatic attacks.
• Quickly reduce airway constriction and restore
normal airflow.
• Stimulate beta2-adrenergic receptors throughout
the lungs.
Bronchodilators: Beta-Agonists
Three types
• Nonselective adrenergics
– Stimulate alpha-, beta1- (cardiac), and beta2- (respiratory)
receptors
– Example: epinephrine
• Nonselective beta-adrenergics
– Stimulate both beta1- and beta2-receptors
– Example: Isoproterenol
• Selective beta2 drugs
– Stimulate only beta2-receptors
– Example: Salbutamol
Beta-Agonists: Mechanism of Action
• Begins at the specific receptor stimulated.
• Ends with the dilation of the airways.
– relaxes smooth muscles of the airway and results
in bronchial dilation and increased airflow
Beta-Agonists: Indications
• Relief of bronchospasm related to asthma, bronchitis,
and other pulmonary diseases.
• Useful in treatment of acute attacks as well as
prevention
• Used in hypotension and shock.
• Used to produce uterine relaxation to prevent
premature labor.
• Hyperkalemia—stimulates potassium to shift into the cell
Beta-Agonists: Side Effects
Alpha-Beta (epinephrine)
• insomnia
• restlessness
• anorexia
• vascular headache
• hyperglycemia
• tremor
• cardiac stimulation
Beta-Agonists: Side Effects
Beta1 and Beta2 (Isoproterenol)
• Cardiac stimulation
• Tremor
• Vascular headaches
• Hypotension
• Anginal pain
Beta-Agonists: Side Effects
Beta2 (Salbutamol)
• Hypotension OR hypertension
• Vascular headaches
• Tremor
RT Implications
• Monitor for therapeutic effects
– Decreased dyspnea.
– Decreased wheezing, restlessness, and anxiety.
– Improved respiratory patterns with return to normal rate and
quality.
– Improved activity tolerance.
• Decreased symptoms and increased ease of breathing.
RT Implications:
Beta-Agonist Derivatives
• Salbutamol, if used too frequently, loses its beta2-
specific actions at larger doses.
• As a result, beta1-receptors are stimulated,
causing nausea, increased anxiety, palpitations,
tremors, and increased heart rate.
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.
Anticholinergics
• Ipratropium (Atrovent) and Tiotropium
(spiriva)
• Slow and prolonged action
• Used to prevent bronchoconstriction
Anticholinergics (cont'd(
Side effects:
• Dry mouth or throat
• Gastrointestinal distress
• Headache
• Coughing
• Anxiety
Antileukotrienes
• Also called leukotriene receptor antagonists
(LRTAs).
• Newer class of asthma medications
• Three subcategories of agents.
• Leukotrienes are substances in the body that
cause inflammation, bronchoconstriction, and
mucus production.
• Result: coughing, wheezing, shortness of breath.
Antileukotrienes (cont'd(
Currently available agents
– montelukast (Singulair)
– zafirlukast (Accolate)
– zileuton (Zyflo)
Mechanism of Action
– Prevent inflammation in the lungs so asthma symptoms
are relieved
Antileukotrienes: Drug Effects
• Keep bronchial airways relaxed (open)
• Decrease mucus secretion
• Prevent vascular permeability
• Preventing inflammation
Antileukotrienes: Indications
• Prophylaxis and chronic treatment of asthma in
adults and children older than age 12.
• NOT meant for management of acute asthmatic
attacks.
• Montelukast (Singulair) is approved for use in
children ages 2 and older.
Antileukotrienes: Side Effects
Headache
Dyspepsia
Nausea
Dizziness
Insomnia
Liver dysfunction
Corticosteroids
• Anti-inflammatory.
• Used for chronic asthma.
• Do not relieve symptoms of acute asthmatic attacks.
• Oral 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
bronchoconstriction substances.
• These cells are leukocytes, or white blood cells.
• Also increase responsiveness of bronchial smooth
muscle to beta-adrenergic stimulation
Inhaled Corticosteroids
• Beclomethasone
• Fluticasone
• Budesonide
• Mometasone
Inhaled Corticosteroids:
Indications
• Treatment of bronchospastic disorders that are
not controlled by conventional bronchodilators.
• NOT considered first-line agents for management
of acute asthmatic attacks or status asthmaticus
Inhaled Corticosteroids:
Side Effects
• Pharyngeal irritation
• Coughing
• Dry mouth
• Oral fungal infections
• Systemic effects are rare because of the low
doses used for inhalation therapy
Inhaled Corticosteroids:
Nursing Implications
• Cautious use in patients with diabetes, glaucoma,
osteoporosis, PUD, renal disease, HF, edema.
• Teach patients to gargle and rinse the mouth with
water afterward to prevent the development of oral
fungal infections
Mast Cell Stabilizers
• Cromolyn (NasalCrom, Intal)
• Nedocromil (Tilade)
Mast Cell Stabilizers (cont'd(
• Indirect-acting agents that prevent the release of the
various substances that cause bronchospasm.
• Stabilize the cell membranes of inflammatory cells (mast
cells, monocytes, macrophages), thus preventing release
of harmful cellular contents.
• No direct bronchodilator activity.
• Used prophylactically.
Mast Cell Stabilizers:
Indications
• Adjuncts to the overall management of asthma.
• Used solely for prophylaxis, NOT for acute asthma
attacks.
• Used to prevent exercise-induced bronchospasm.
• Used to prevent bronchospasm associated with exposure
to known precipitating factors, such as cold, dry air or
allergens.
Mast Cell Stabilizers:
Side Effects
Coughing
Sore throat
Rhinitis
Bronchospasm
Taste changes
Dizziness
Headache
Other Respiratory Agents
Mucolytic Agents
1. Acetylcysteine
- reduce the thickness and stickiness of purulent and non-purulent
pulmonary secretions
- antidote for paracetamol poisoning
2. Carbocysteine
- act by regulating and normalizing the viscosity of secretion from
the mucus cell of respiratory tract
- decrease the size and number of mucus producing cells
3. Bromhexine
- depolymerization of mucopolysaccharides, direct effect on
bronchial glands
- liberation of lysosomal enzymes producing cells which digest
mucopolysaccharide fibers
Other Respiratory Agents
Mucokinetic & Secretolytic
1. Ambroxol
- increase respiratory tract secretions
- enhance pulmonary surfactant production
- stimulates cilia activity
Expectorant
1. Vagal stimulants: glyceryl guiacolate, salt solution
2. Direct stimulants: bromhexine, ambroxol
Antitussives
1. Narcotic antitussives: heroin, codeine, morphine
2. Non-narcotic antitussive: Dextromethorphan
THANK YOU
Mosby items and derived items © 2005,
2002 by Mosby, Inc.

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Pharmacology of Respiratory Diseases

  • 1. Pharmacology of Respiratory Diseases Prepared by: Dr. Hassan Al-Tomy Reviewed and presented by: Dr. Muna Oqal
  • 2. Bronchial Asthma Recurrent and reversible shortness of breath Occurs when the airways of the lungs become narrow as a result of: – Bronchospasm – Inflammation of the bronchial mucosa – Edema of the bronchial mucosa – Production of viscid mucus Alveolar ducts/alveoli remain open, but airflow to them is obstructed Symptoms – Wheezing – Difficulty breathing
  • 3. Asthma Three categories • Allergic • Idiopathic • Mixed allergic/idiopathic
  • 4. COPD Chronic obstructive pulmonary disease • Applies to chronic bronchitis and emphysema • Obstruction is constant
  • 5. Agents Used to Treat Asthma • Long-term control – Antileukotrienes – Cromolyn – Inhaled steroids – Long-acting beta2-agonists • Quick relief – Intravenous systemic corticosteroids – Short-acting inhaled beta2-agonists – Ipratropium – Nedocromil – theophylline
  • 6. Aerosol delivery of drugs – Should produce a high local concentration in the lungs with a low systemic delivery → minimizing side effects – Size of the particles: critical determinant • >10 um – deposited in the mouth & Oropharynx • <0.5 um – inhaled, subsequently exhaled • 1-5 um – allow deposition & most effective
  • 7. Bronchodilators: Xanthine Derivatives • Plant alkaloids: caffeine, Theobromine, and Theophylline • Only Theophylline is used as a bronchodilator – Examples: • Aminophylline • Theophylline
  • 8. Xanthines: Action • Smooth muscle relaxation • Bronchodilation • Increased airflow
  • 9. Xanthines: Drug Effects • CNS stimulation • Cardiovascular stimulation: – Increased force of contraction – Increased HR – Increased cardiac output – Increased blood flow to the kidneys (diuretic effect)
  • 10. Xanthines: Indications • Dilation of airways in asthmas, chronic bronchitis, and emphysema • Mild to moderate cases of acute asthma • Adjunct agent in the management of COPD
  • 11. Xanthines: Side Effects • Nausea, vomiting, anorexia • Gastroesophageal reflux during sleep • Sinus tachycardia, extrasystole, palpitations, ventricular dysrhythmias • Transient increased urination
  • 12. RT Implications: Xanthine Derivatives • Contraindications: history of PUD or GI disorders • Cautious use: cardiac disease • Timed-release preparations should not be crushed or chewed (causes gastric irritation)
  • 13. Bronchodilators: Beta-Agonists • Large group, sympathomimetic. • Used during acute phase of asthmatic attacks. • Quickly reduce airway constriction and restore normal airflow. • Stimulate beta2-adrenergic receptors throughout the lungs.
  • 14. Bronchodilators: Beta-Agonists Three types • Nonselective adrenergics – Stimulate alpha-, beta1- (cardiac), and beta2- (respiratory) receptors – Example: epinephrine • Nonselective beta-adrenergics – Stimulate both beta1- and beta2-receptors – Example: Isoproterenol • Selective beta2 drugs – Stimulate only beta2-receptors – Example: Salbutamol
  • 15. Beta-Agonists: Mechanism of Action • Begins at the specific receptor stimulated. • Ends with the dilation of the airways. – relaxes smooth muscles of the airway and results in bronchial dilation and increased airflow
  • 16. Beta-Agonists: Indications • Relief of bronchospasm related to asthma, bronchitis, and other pulmonary diseases. • Useful in treatment of acute attacks as well as prevention • Used in hypotension and shock. • Used to produce uterine relaxation to prevent premature labor. • Hyperkalemia—stimulates potassium to shift into the cell
  • 17. Beta-Agonists: Side Effects Alpha-Beta (epinephrine) • insomnia • restlessness • anorexia • vascular headache • hyperglycemia • tremor • cardiac stimulation
  • 18. Beta-Agonists: Side Effects Beta1 and Beta2 (Isoproterenol) • Cardiac stimulation • Tremor • Vascular headaches • Hypotension • Anginal pain
  • 19. Beta-Agonists: Side Effects Beta2 (Salbutamol) • Hypotension OR hypertension • Vascular headaches • Tremor
  • 20. RT Implications • Monitor for therapeutic effects – Decreased dyspnea. – Decreased wheezing, restlessness, and anxiety. – Improved respiratory patterns with return to normal rate and quality. – Improved activity tolerance. • Decreased symptoms and increased ease of breathing.
  • 21. RT Implications: Beta-Agonist Derivatives • Salbutamol, if used too frequently, loses its beta2- specific actions at larger doses. • As a result, beta1-receptors are stimulated, causing nausea, increased anxiety, palpitations, tremors, and increased heart rate.
  • 22. 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.
  • 23. Anticholinergics • Ipratropium (Atrovent) and Tiotropium (spiriva) • Slow and prolonged action • Used to prevent bronchoconstriction
  • 24. Anticholinergics (cont'd( Side effects: • Dry mouth or throat • Gastrointestinal distress • Headache • Coughing • Anxiety
  • 25. Antileukotrienes • Also called leukotriene receptor antagonists (LRTAs). • Newer class of asthma medications • Three subcategories of agents. • Leukotrienes are substances in the body that cause inflammation, bronchoconstriction, and mucus production. • Result: coughing, wheezing, shortness of breath.
  • 26. Antileukotrienes (cont'd( Currently available agents – montelukast (Singulair) – zafirlukast (Accolate) – zileuton (Zyflo) Mechanism of Action – Prevent inflammation in the lungs so asthma symptoms are relieved
  • 27. Antileukotrienes: Drug Effects • Keep bronchial airways relaxed (open) • Decrease mucus secretion • Prevent vascular permeability • Preventing inflammation
  • 28. Antileukotrienes: Indications • Prophylaxis and chronic treatment of asthma in adults and children older than age 12. • NOT meant for management of acute asthmatic attacks. • Montelukast (Singulair) is approved for use in children ages 2 and older.
  • 30. Corticosteroids • Anti-inflammatory. • Used for chronic asthma. • Do not relieve symptoms of acute asthmatic attacks. • Oral or inhaled forms. • Inhaled forms reduce systemic effects. • May take several weeks before full effects are seen.
  • 31. Corticosteroids: Mechanism of Action • Stabilize membranes of cells that release harmful bronchoconstriction substances. • These cells are leukocytes, or white blood cells. • Also increase responsiveness of bronchial smooth muscle to beta-adrenergic stimulation
  • 32. Inhaled Corticosteroids • Beclomethasone • Fluticasone • Budesonide • Mometasone
  • 33. Inhaled Corticosteroids: Indications • Treatment of bronchospastic disorders that are not controlled by conventional bronchodilators. • NOT considered first-line agents for management of acute asthmatic attacks or status asthmaticus
  • 34. Inhaled Corticosteroids: Side Effects • Pharyngeal irritation • Coughing • Dry mouth • Oral fungal infections • Systemic effects are rare because of the low doses used for inhalation therapy
  • 35. Inhaled Corticosteroids: Nursing Implications • Cautious use in patients with diabetes, glaucoma, osteoporosis, PUD, renal disease, HF, edema. • Teach patients to gargle and rinse the mouth with water afterward to prevent the development of oral fungal infections
  • 36. Mast Cell Stabilizers • Cromolyn (NasalCrom, Intal) • Nedocromil (Tilade)
  • 37. Mast Cell Stabilizers (cont'd( • Indirect-acting agents that prevent the release of the various substances that cause bronchospasm. • Stabilize the cell membranes of inflammatory cells (mast cells, monocytes, macrophages), thus preventing release of harmful cellular contents. • No direct bronchodilator activity. • Used prophylactically.
  • 38. Mast Cell Stabilizers: Indications • Adjuncts to the overall management of asthma. • Used solely for prophylaxis, NOT for acute asthma attacks. • Used to prevent exercise-induced bronchospasm. • Used to prevent bronchospasm associated with exposure to known precipitating factors, such as cold, dry air or allergens.
  • 39. Mast Cell Stabilizers: Side Effects Coughing Sore throat Rhinitis Bronchospasm Taste changes Dizziness Headache
  • 40. Other Respiratory Agents Mucolytic Agents 1. Acetylcysteine - reduce the thickness and stickiness of purulent and non-purulent pulmonary secretions - antidote for paracetamol poisoning 2. Carbocysteine - act by regulating and normalizing the viscosity of secretion from the mucus cell of respiratory tract - decrease the size and number of mucus producing cells 3. Bromhexine - depolymerization of mucopolysaccharides, direct effect on bronchial glands - liberation of lysosomal enzymes producing cells which digest mucopolysaccharide fibers
  • 41. Other Respiratory Agents Mucokinetic & Secretolytic 1. Ambroxol - increase respiratory tract secretions - enhance pulmonary surfactant production - stimulates cilia activity Expectorant 1. Vagal stimulants: glyceryl guiacolate, salt solution 2. Direct stimulants: bromhexine, ambroxol Antitussives 1. Narcotic antitussives: heroin, codeine, morphine 2. Non-narcotic antitussive: Dextromethorphan
  • 42. THANK YOU Mosby items and derived items © 2005, 2002 by Mosby, Inc.

Editor's Notes

  1. Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate. Aminophylline is less potent and shorter-acting than theophylline Aminophylline: competitive nonselective phosphodiesterase inhibitor[3] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha[4][5] and leukotriene[6] synthesis, and reduces inflammation and innate immunity[6]and nonselective adenosine receptor antagonist.[7]
  2. Reference ranges of theophylline in the treatment asthma vary by age, as follows: Adults: 5-15 µg/mL Children: 5-10 µg/mL The reference range of theophylline in the treatment of acute bronchospasm in adults is 10-15 µg/mL. The reference range of theophylline in the treatment of neonatal apnea is 6-11 µg/mL.
  3. PUD: peptic ulcer disease