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Principles of Pharmacology - Week 11 Seminar Notes

Topic = Drugs used to treat the respiratory system

Treatment of Allergy

Allergy Overview

  • Symptoms: Sneezing, coughing, itching, headache, nasal congestion.

  • Process: Sensitization occurs when the immune system reacts to an allergen (antigen) in the environment, such as:

    • Pollen

    • Grass

    • Dust

    • Mould

  • Mechanism:

    • Formation of IgE antibodies that attach to mast cells.

    • Subsequent exposure leads to degranulation of mast cells and release of inflammatory chemicals.

Histamine

  • Role: Histamine is released from mast cells and causes allergic symptoms.

  • Other Mediators: Prostaglandins, cytokines, leukotrienes.

Histamine Receptors

  • Function: Histamine binds to receptors in specific tissues producing allergy symptoms (itching, redness, urticaria, stuffy nose).

Types of Histamine Receptors:

  • H1 Receptors: Located in blood vessels, bronchiolar smooth muscle, intestinal smooth muscle.

  • H2 Receptors: Found in the stomach, heart, blood vessels, uterine tissue.

  • H3 and H4 Receptors: Present in neurons (CNS) and white blood cells.

  • Treatment Options:

    • Antihistamines (block histamine binding to receptors).

    • Antiallergic agents (block histamine release from mast cells).

Physiological Responses Following Histamine Release

System/Tissue

Histamine Effect

Receptor Type

Physiological Response

Blood Pressure

Decreased

H1, H2

Hypotension

Heart Rate

Increased

H2

Rapid heartbeat

Bronchioles

Constriction

H1

Breathing difficulty

Intestines

Contraction

H1

Constipation/diarrhea

Skin Capillaries

Dilation, edema

H1

Triple Response of Lewis: redness, flare, wheal

Nerves

Trigger itch-specific

H1

Itching

Gastric Acid Secretion

Increased

H2

Nausea, heartburn

Antihistamines (H1 Antagonists)

Characteristics:

  • Function: Relieve symptoms of allergic reactions AFTER histamine release.

  • Mechanism: Block histamine from binding to H1 receptors.

  • Categories:

    • First Generation:

    • Chlorphenamine (Demazin ®)

    • Dexchlorpheniramine (Polaramine ®)

    • Doxylamine (Mersyndol ®)

    • Promethazine (Phenergan ®)

    • Diphenhydramine (Benadryl ®)

    • Second Generation:

    • Cetirizine (Zyrtec ®)

    • Fexofenadine (Fexotabs ®, Telfast ®)

    • Loratadine (Claratyne ®)

Antihistamines – First Generation

  • Examples: Chlorphenamine, Dexchlorpheniramine, Doxylamine, Promethazine, Diphenhydramine.

  • Characteristics:

    • Known as sedating antihistamines.

    • Lipid-soluble, can cross the blood-brain barrier affecting CNS.

    • Associated with side effects: drowsiness, dizziness, impaired coordination, sedation.

  • Uses: Sleep aids, treatment for travel sickness.

Antihistamines – Second Generation

  • Examples: Cetirizine, Fexofenadine, Loratadine.

  • Characteristics:

    • Newer medications designed to address first-generation limitations.

    • Less lipid-soluble, limited ability to cross blood-brain barrier.

    • Referred to as non-sedating antihistamines; generally do not cause drowsiness.

  • Preferred Use: Daytime use, situations where sedation is undesirable.

Routes of Administration for Antihistamines

  • Forms: Oral, topical, nasal spray, eye drops.

Adverse Reactions:

  • Rapid heartbeat, dry mouth, epigastric distress, urinary retention.

Contraindications/Precautions:

  • Hypersensitivity, QTc interval prolongations.

  • Pregnancy, nursing mothers, newborns or premature infants.

  • CNS depression.

Mast Cell Stabilizers

Mechanism of Action:

  • Block allergic reactions by preventing mast cells from releasing their contents.

  • Example: Cromolyn sodium - a prophylactic anti-allergy drug preventing histamine release without affecting histamine receptors.

Routes of Administration:

  • Oral, intranasal, intraocular.

Adverse Effects and Contraindications:

  • Wheezing, nasal itching and burning, nausea, drowsiness.

Important Note:

  • Preventative medications most effective when taken regularly, especially before allergen exposure. Not designed for immediate relief of acute allergy symptoms; used alongside antihistamines for quick relief.

Treatment of Asthma and COPD

Respiratory Diseases:

  • Definition: Respiratory disease or obstructive airway disease characterized by restricted airflow to the lungs.

  • Examples: Chronic obstructive pulmonary disorder (COPD), which includes chronic bronchitis and emphysema.

Overview of Asthma

  • Definition: A chronic inflammatory lung disorder involving hyperreactivity of the airways and intermittent airflow obstruction.

Mechanisms of Obstruction:

  • Bronchoconstriction

  • Mucous Plugging

  • Airway Remodelling

Statistics:

  • Australia has one of the highest asthma rates in the world (1 in 9 people). In 2022, 467 people died from asthma (Australian Bureau of Statistics).

Asthma Triggers

  • Intrinsic Asthma: Triggered by stimuli such as infections, smoke or chemical fumes, cold air, exercise, strong emotion. Excess parasympathetic tone causes symptoms.

  • Extrinsic Asthma: An exaggerated IgE-mediated response to allergens such as pollen, grass, pet dander, dust mites. Mast cell degranulation releases inflammatory mediators.

Phases of Asthma Attack

Acute Phase:

  • Features bronchospasm, narrowing of the airways, and chest tightening.

  • Involves mast cell mediators.

Late Phase (60% of individuals):

  • Swelling or edema, thick mucus build-up, different immune response cells (eosinophils, basophils, neutrophils).

Classification of Drugs Used to Treat Asthma and COPD

Drug Categories:

  • Bronchodilators

  • Anti-inflammatories

  • Mast cell stabilizers

  • LT receptor antagonists

  • Anti-IgE antibody

Drugs Used in Asthma: Overview

Reliever (Blue/Grey Color):

  • Action: Relaxes tight airways for up to 4 hours.

  • Time to Work: Very quickly, in about 4 minutes.

  • When to Take: Upon symptom occurrence or before exercise as prescribed.

  • Reminder: Carry it always in case of symptoms.

Preventer (Autumn/Desert Color):

  • Action: Soothes airways, reduces swelling, and mucus.

  • Time to Work: Takes days to weeks.

  • When to Take: Every day as prescribed, even if feeling well.

  • Key Point: Crucial for maintaining asthma subsidence.

Combination Preventers:

  • Action: Acts like a preventer and relaxes airway muscles.

  • Time to Work: Fairly quickly, but improvements continue with consistent use.

  • When to Take: Every day as prescribed, even if feeling well.

  • Indicated For: Patients experiencing symptoms despite regular preventer use.

Bronchodilators: Mechanisms and Drugs

Types of Bronchodilators:

  1. Beta2 Agonists (Sympathomimetics): Short and long-acting.

  2. Muscarinic Antagonists (Parasympatholytics).

  3. Methylxanthines.

Sympathomimetic Drugs (Beta-Adrenergic Drugs):

  • Common Use: Fast-acting, safe, convenient.

  • Mechanism of Action: Stimulate beta-2 receptors in bronchial smooth muscle; stimulate adenylate cyclase, resulting in increased cAMP which decreases inflammatory mediators in mast cells.

  • Routes of Administration: Oral, injections, metered dose inhalers (MDI), nebulizer solution, rotacaps, subcutaneous, intravenous.

Adverse Effects of Sympathomimetics:

  • Inhaled: Tend to be well tolerated.

  • Oral: May cause restlessness, anxiety, hypokalemia, tremors in skeletal muscle, and rare arrhythmias.

  • Long-term Use: May lead to tolerance (down-regulation of β2 receptors).

Selective Agents:

  • Salbutamol: Short-acting, beneficial for acute attack.

  • Salmeterol: Long-acting, beneficial for maintenance therapy.

Non-selective Agents:

  • Adrenaline, Isoprenaline, Ephedrine:

    • Repeated subcutaneous/inhalation use not preferred due to increased adverse reactions.

Methylxanthine Drugs:

  • Examples: Aminophylline, Theophylline.

  • Mechanism of Action: Inhibit phosphodiesterase enzyme, resulting in increased cAMP (bronchodilation and decreased inflammatory mediators);

    • Antagonize adenosine (potent bronchoconstrictor).

  • Pharmacokinetics: Can be administered orally or intravenously; can be combined with sympathomimetics.

Adverse Effects of Methylxanthines:

  • Nausea and vomiting, flushing, vasodilation, hypotension.

  • Action is not limited to airways.

Anticholinergic Drugs:

  • Examples: Ipratropium Bromide, Tiotropium.

  • Mechanism of Action: Block acetylcholine at muscarinic (M3) receptors, reducing bronchoconstriction and respiratory secretions.

  • Characteristics: Not as potent or fast as beta-adrenergic drugs; preferred in COPD.

  • Pharmacokinetics: Administered via oral inhalation.

  • Adverse Effects: Slow absorption rate.

Anti-inflammatory Drugs

Preventer/Controller Drugs:

  • Corticosteroids: e.g., Fluticasone, Beclomethasone, Budesonide, Prednisolone.

    • Mechanism: Interfere with all stages of inflammatory and allergic response; inhibit inflammatory cells, release of mediators, production of allergic antibodies, and more.

    • Administration: Oral or parenteral (acute attacks); via inhalation for chronic treatment.

    • Adverse Effects: Fluid retention, muscle wasting, metabolic disturbances, increased susceptibility to infections.

Leukotriene Receptor Antagonists:

  • Mechanism: Inhibit leukotriene receptors, antagonizing airway smooth muscle contraction and inflammation.

  • Use: Chronic control of asthma; generally well tolerated but may cause nausea, diarrhea, rash, headache.

Cromolyn Sodium:

  • Mechanism: Interferes with degranulation of mast cells, leading to decreased mast cell mediators.

  • Use: Treat allergic conditions; administered via inhalation, topical, or eye solution.

  • Adverse Effects: Nasal stinging, headache, bad taste.

Anti-allergic Drugs

Interleukin-5 Receptor Antagonists:

  • Examples: Benralizumab, Reslizumab.

  • Mechanism: Monoclonal antibodies that reduce eosinophil production and survival.

  • Use: Severe asthma with eosinophilic phenotype; administered subcutaneously/intravenously.

  • Adverse Effects: Sore throat, myalgia, antibody development, injection site reactions.

Omalizumab (Xolair):

  • Mechanism: Binds to and inactivates IgE, reducing immune response to allergens.

  • Impact: Reduces severity and frequency of asthma attacks; administered subcutaneously, can cause pain and inflammation at injection site.

Preferred Therapy for Asthma

Mild Persistent:

  • Corticosteroid, Cromolyn, Anti-leukotriene.

Moderate Persistent:

  • Corticosteroid, Beta-2 bronchodilator.

Severe Persistent:

  • High-dose Corticosteroid, Long-acting beta-adrenergic bronchodilator.

Mild Intermittent:

  • Beta-2 bronchodilator.

Main Concepts Covered

  • COPD (including emphysema and chronic bronchitis).

  • Asthma (intrinsic and extrinsic).

  • Types of drugs used: Bronchodilators (sympathomimetics, antimuscarinics, methylxanthines), Corticosteroids, Mast cell stabilizers, Leukotriene receptor antagonists, Monoclonal antibodies.

Assignment 1 Task 2

Due Date: Friday, October 24 at 5 PM

Objective:

  • Develop reflective writing skills through the process of researching and preparing for a digital presentation on Sertraline for the treatment of depression (Assignment 2).

Requirements:

  • Short reflection demonstrating understanding and critical thinking regarding pharmacology.

  • Include:

    • Summary of what was learned about Sertraline and its pharmacology.

    • Critical analysis of knowledge development through research and presentation.

    • Connections to future academic study or professional practice.

Feedback

Depth of Reflection:

  • Strong reflections provided insights into evolving understanding of pharmacological concepts via comparisons.

Use of AI Tools:

  • AI tools should serve as partners, requiring interpretation and adaptation for original work.

Use of Sources:

  • Ensure credible sources are chosen for strength in statements, avoiding obscure or irrelevant references.

Academic Writing:

  • Maintain Australian English conventions and be cautious of formatting in references.