💊Intro to Pharmacology Unit 8 – Respiratory & GI Pharmacotherapeutics

Key Concepts and Terminology

• Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of drugs in the body
• Pharmacodynamics focuses on the biochemical and physiological effects of drugs on the body and how they produce their therapeutic effects
• Bioavailability refers to the fraction of an administered drug that reaches systemic circulation unchanged
  • Factors influencing bioavailability include route of administration, drug formulation, and first-pass metabolism
• Half-life is the time required for the concentration of a drug in the body to decrease by half
• Therapeutic index is the ratio of the lethal dose to the therapeutic dose of a drug (LD50/ED50)
• Adverse drug reactions (ADRs) are unintended and harmful responses to a medication
• Drug-drug interactions occur when one drug alters the pharmacokinetics or pharmacodynamics of another drug

Respiratory System Overview

• The respiratory system consists of the airways, lungs, and respiratory muscles that work together to facilitate gas exchange
• The upper respiratory tract includes the nose, nasal cavity, pharynx, and larynx
• The lower respiratory tract comprises the trachea, bronchi, bronchioles, and alveoli
• Ventilation involves the movement of air in and out of the lungs through the process of inhalation and exhalation
• Gas exchange occurs in the alveoli, where oxygen diffuses into the bloodstream and carbon dioxide diffuses out
• The respiratory system is innervated by the autonomic nervous system, with the sympathetic nervous system causing bronchodilation and the parasympathetic nervous system causing bronchoconstriction
• Respiratory disorders can affect any part of the respiratory system and may be caused by infections, inflammation, or structural abnormalities

Gastrointestinal System Overview

• The gastrointestinal (GI) system consists of the alimentary canal and accessory organs that work together to digest food, absorb nutrients, and eliminate waste
• The alimentary canal includes the mouth, esophagus, stomach, small intestine, large intestine, and anus
• Accessory organs of the GI system include the salivary glands, liver, gallbladder, and pancreas
• The process of digestion begins in the mouth with mechanical and chemical breakdown of food
• The stomach secretes hydrochloric acid and digestive enzymes to further break down food
• The small intestine is the primary site of nutrient absorption, with the help of digestive enzymes from the pancreas and bile from the liver
• The large intestine absorbs water and electrolytes, and stores and eliminates fecal matter
• The GI system is regulated by hormones, the autonomic nervous system, and local reflexes

Common Respiratory Disorders and Treatments

• Asthma is a chronic inflammatory disorder characterized by airway hyperresponsiveness and reversible airflow obstruction
  • Treatment includes inhaled corticosteroids, long-acting beta-2 agonists, and short-acting beta-2 agonists for acute symptoms
• Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that includes chronic bronchitis and emphysema
  • Treatment involves bronchodilators, inhaled corticosteroids, and smoking cessation
• Pneumonia is an infection of the lungs caused by bacteria, viruses, or fungi
  • Treatment depends on the causative agent and may include antibiotics, antiviral medications, or supportive care
• Cystic fibrosis is a genetic disorder that affects the lungs and digestive system, causing thick, sticky mucus to build up
  • Treatment involves chest physical therapy, inhaled medications, and pancreatic enzyme replacement therapy
• Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition characterized by widespread inflammation in the lungs
  • Treatment includes mechanical ventilation, prone positioning, and supportive care

Common GI Disorders and Treatments

• Gastroesophageal reflux disease (GERD) occurs when stomach acid frequently flows back into the esophagus
  • Treatment includes lifestyle modifications, antacids, H2 receptor antagonists, and proton pump inhibitors (PPIs)
• Peptic ulcer disease (PUD) is characterized by open sores in the lining of the stomach or duodenum
  • Treatment involves antibiotics for Helicobacter pylori infection, PPIs, and H2 receptor antagonists
• Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis, which cause chronic inflammation of the GI tract
  • Treatment includes aminosalicylates, corticosteroids, immunomodulators, and biologic therapies
• Irritable bowel syndrome (IBS) is a functional GI disorder characterized by abdominal pain, bloating, and changes in bowel habits
  • Treatment involves dietary modifications, antispasmodics, and antidepressants
• Hepatitis is inflammation of the liver caused by viruses, alcohol, or other factors
  • Treatment depends on the underlying cause and may include antiviral medications, abstinence from alcohol, and supportive care

Pharmacokinetics and Pharmacodynamics

• Absorption is the process by which a drug moves from the site of administration into the bloodstream
  • Factors affecting absorption include the route of administration, drug formulation, and physiochemical properties of the drug
• Distribution refers to the movement of a drug from the bloodstream to various tissues and organs
  • Factors influencing distribution include blood flow, protein binding, and lipid solubility of the drug
• Metabolism is the process by which a drug is chemically altered, primarily in the liver, to facilitate its elimination
  • Cytochrome P450 enzymes play a crucial role in drug metabolism
• Excretion is the process by which a drug and its metabolites are eliminated from the body
  • The kidneys are the primary organs responsible for drug excretion, although other routes (biliary, pulmonary) may also be involved
• Pharmacodynamics involves the interaction between a drug and its target receptor or enzyme
  • Agonists bind to receptors and activate them, while antagonists bind to receptors and block their activation
• Dose-response relationships describe the relationship between the dose of a drug and its pharmacological effect
  • Therapeutic window refers to the range of doses that provide therapeutic benefit without causing unacceptable side effects

Drug Classes and Mechanisms of Action

• Bronchodilators (beta-2 agonists, anticholinergics) relax smooth muscles in the airways, increasing airflow
  • Beta-2 agonists (albuterol) activate beta-2 receptors, causing bronchodilation
  • Anticholinergics (ipratropium) block muscarinic receptors, preventing bronchoconstriction
• Corticosteroids (inhaled, oral) reduce inflammation in the airways and GI tract
  • Inhaled corticosteroids (fluticasone) are used for long-term control of asthma and COPD
  • Oral corticosteroids (prednisone) are used for acute exacerbations and IBD
• Proton pump inhibitors (omeprazole) irreversibly inhibit the H+/K+ ATPase enzyme in gastric parietal cells, reducing stomach acid production
• H2 receptor antagonists (ranitidine) block histamine-2 receptors on gastric parietal cells, decreasing acid secretion
• Antibiotics (amoxicillin, clarithromycin) are used to eradicate Helicobacter pylori infection in peptic ulcer disease
• Aminosalicylates (mesalamine) reduce inflammation in the GI tract and are used to treat IBD
• Immunomodulators (azathioprine, methotrexate) suppress the immune system and are used for IBD and other inflammatory conditions

Side Effects and Contraindications

• Beta-2 agonists can cause tremor, tachycardia, and hypokalemia
  • Contraindicated in patients with severe cardiovascular disease
• Anticholinergics may cause dry mouth, urinary retention, and constipation
  • Contraindicated in patients with narrow-angle glaucoma and urinary retention
• Corticosteroids can cause adrenal suppression, osteoporosis, and increased risk of infections
  • Contraindicated in patients with active infections and uncontrolled diabetes
• Proton pump inhibitors may cause headache, diarrhea, and vitamin B12 deficiency
  • Contraindicated in patients with a history of severe liver disease
• H2 receptor antagonists can cause confusion, headache, and diarrhea
  • Contraindicated in patients with severe renal impairment
• Antibiotics may cause gastrointestinal upset, allergic reactions, and antibiotic resistance
  • Contraindicated in patients with known drug allergies
• Aminosalicylates can cause headache, nausea, and diarrhea
  • Contraindicated in patients with salicylate hypersensitivity
• Immunomodulators may cause bone marrow suppression, liver toxicity, and increased risk of infections and malignancies
  • Contraindicated in patients with active infections and severe immunodeficiency

Clinical Applications and Case Studies

• Case 1: A 25-year-old male with a history of asthma presents with wheezing and shortness of breath
  • Treatment: Short-acting beta-2 agonist (albuterol) for acute symptoms and inhaled corticosteroid (fluticasone) for long-term control
• Case 2: A 60-year-old female with a history of COPD complains of worsening cough and dyspnea
  • Treatment: Long-acting anticholinergic (tiotropium) and inhaled corticosteroid/long-acting beta-2 agonist combination (fluticasone/salmeterol)
• Case 3: A 45-year-old male presents with burning epigastric pain and heartburn
  • Treatment: Proton pump inhibitor (omeprazole) and lifestyle modifications
• Case 4: A 30-year-old female with a history of peptic ulcer disease tests positive for Helicobacter pylori
  • Treatment: Triple therapy with a proton pump inhibitor (lansoprazole), amoxicillin, and clarithromycin
• Case 5: A 20-year-old male with a history of Crohn's disease experiences a flare-up with abdominal pain and diarrhea
  • Treatment: Oral corticosteroid (prednisone) for acute management and aminosalicylate (mesalamine) for maintenance therapy
• Case 6: A 50-year-old female with a history of IBS reports abdominal bloating and alternating constipation and diarrhea
  • Treatment: Dietary modifications (low FODMAP diet), antispasmodic (dicyclomine), and antidepressant (amitriptyline)