Immunotherapy and Antihistamines Overview

Immunotherapy

• Manipulation of the immune response to treat disease
• Can involve enhancing immunity (e.g., vaccination) or suppressing immune responses (e.g., treatment of allergic or autoimmune diseases)

Antihistamines

• Block H1 histamine receptors
• Inhibit histamine-mediated vascular permeability and smooth muscle constriction
• Reduce sensory nerve stimulation (itching, sneezing, etc.)
• Histamine is produced mainly by mast cells

Antihistamines Clinical Uses:

• Type I (immediate/IgE-mediated) hypersensitivity reactions (e.g., hay fever, perennial rhinitis, acute type I allergic reactions)
• Urticaria/angioedema
• Anaphylactic reactions should be treated with i.m. adrenaline

Antihistamines Types:

• Sedative (1st generation): Chlorphenamine, diphenhydramine
• Non-sedative (2nd generation): Cetirizine, terfenadine, loratidine
• Can be given topically (e.g., nasal or eye drops) or systemically

Asthmatic Drugs

• Approximately 40 million community prescriptions per year
• Major pathogenic effect in asthma is bronchoconstriction
• Beta 2 adrenoreceptor agonists (e.g., salbutamol) and other bronchodilators are the mainstay of treatment
• In many cases, especially in children, there is an inflammatory or allergic component

Steroids

• Major class of anti-inflammatory and immunosuppressive drugs
• Commonly given by inhaler (beclometasone, budesonide, and fluticasone), topically, or systemically

Leukotriene Receptor Antagonists

• Leukotrienes are involved in inflammatory reactions
• Leukotriene receptor antagonists (Montelukast, Zafirlukast) block leukotriene effects
• Particularly helpful in exercise-induced asthma

Cromoglicate

• Stabilizes the mast cell membrane, preventing mast cell degranulation
• Mode of action is not completely understood

Asthma

• Bronchoconstriction treated with B2 agonists & others and steroids.
• Allergy or inflammation treated with leukotriene receptor antagonists and sodium cromoglicate.

Anti-inflammatory Drugs

• Block or suppress functions of non-specific inflammatory cells (monocytes, macrophages, granulocytes) or proinflammatory mediators
• May have immunosuppressive properties (inhibition of specific immune cells or their mediators)

Steroids

• Structurally related to the glucocorticoid steroid hormone, cortisol

Side Effects of Corticosteroid Drugs (Especially in Long-Term Use):

• Glucocorticoid effects: diabetes, Cushing's syndrome, adrenal suppression
• Mineralocorticoid effects: osteoporosis, hypertension
• Immunosuppressive effects: increased susceptibility to infections, impaired wound healing
• Others: emotional disturbance, enlarged sella turcica, obesity

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

• Wide group of drugs with analgesic and anti-inflammatory properties
• Main anti-inflammatory properties due to inhibition of cyclooxygenase

NSAID Mechanism of Action

• Arachidonic acid is broken down into prostaglandins by COX-1 and COX-2
• Prostaglandins from COX-1 contribute to GI mucosal protection and hemostasis
• Prostaglandins from COX-2 act as mediators of pain, inflammation, and fever

NSAIDs ADRs:

• Major side effect of (older) NSAIDs is gastrointestinal toxicity
• Newer, selective COX-2 inhibitors do not have this side effect
• COX-2 inhibitors have been found to have cardiovascular side effects

TNF (Tumor Necrosis Factor)

• Induces necrosis of tumor cells
• Has a wide range of proinflammatory actions
• Plays a central role in the pathogenesis of autoimmune diseases (rheumatoid arthritis, Crohn's disease)

TNF Functions

• Increases inflammation, cell infiltration, angiogenesis, CRP in serum, and articular cartilage degradation

TNF Antagonists:

• Infliximab: humanized monoclonal antibody against TNF
• Etanercept: TNF receptor fusion protein
• Treat severe rheumatoid arthritis and Crohn's disease
• Side effect: reactivation of latent tuberculosis

Immunosuppressive Agents:

• Corticosteroids
• Cytotoxic and anti-proliferative agents: introduced for cancer treatment
• Used to treat autoimmune diseases and inhibit organ transplant rejection

Immunological Diseases Treated with Cytotoxic Drugs:

• Organ transplant rejection
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Membranous and membranoproliferative glomerulonephritis
• Inflammatory bowel disease

Immunoglobulin (Ig)

• Intravenous immunoglobulin (IVIg) has immunomodulatory properties

Immunomodulatory Properties of Intravenous Immunoglobulin:

• Mechanism of action not fully understood
• Uses: replacement Ig therapy for antibody deficiencies, treatment of Kawasaki disease, idiopathic thrombocytopenia, Guillain-Barré syndrome

Monoclonal Antibodies:

• Rituximab: targets B-cell antigen
• Infliximab: targets TNF-α
• Omalizumab: targets IgE

Mechanisms of action of Therapeutic Monoclonal Antibodies:

• Neutralizing the target antigen
• Inducing complement-mediated or antibody dependent (NK-mediated) cytotoxicity
• Blocking cellular interactions
• Inducing apoptosis in target cells

This quiz focuses on the manipulation of the immune response through immunotherapy and the role of antihistamines in treating allergic reactions. It covers the different types of antihistamines, their clinical uses, and how they function in blocking histamine effects. Test your understanding of these crucial pharmacological concepts.