Pharmacology and Histamine Actions

Autocrine-Paracrine System

• Autocrine action involves a cell releasing a signal that acts on the same cell.
• Paracrine action involves a cell releasing a signal that acts on nearby cells.
• Endocrine action involves a cell releasing a signal that acts on distant cells via the circulatory system.

Pharmacology of Histamine

• Histamine is a chemical mediator released during allergic reactions and inflammation.
• Allergic reactions can be triggered by various factors such as bee stings, medications, pollen, plants, animal products, dust etc.
• Histamine causes inflammation by activating immune cells like neutrophils.
• Histamine also plays a role in gastric acid secretion.

Biosynthesis and Storage of Histamine

• Mast cells and basophils are responsible for the storage and release of histamine.
• Enterochromaffin cells also store and release histamine.
• Histamine release is triggered when an allergen is encountered.

Histamine Release

• IgE receptor activation leads to histamine release from mast cells.
• Allergens bind to IgE, triggering degranulation.
• Degranulation releases histamine, kinins, leukotrienes, prostaglandins, and platelet-activating factor.

Histamine Release (Additional Factors)

• Tissue injury releases histamine along with other mediators like ATP, bradykinin, and prostaglandins in inflammation.
• Venoms are also a trigger for histamine release.
• Morphine can trigger or modulate histamine release.

Modulation of Histamine

• Adrenaline is the physiological antagonist of histamine.
• H1 and H2 blockers compete with histamine at its receptors.
• Corticosteroids suppress the effects of antigen-antibody reactions and demonstrate anti-allergic and anti-inflammatory actions.

Histamine Receptor Blockers

• H1-blockers are antihistamines, which block histamine receptors.
• Diphenhydramine is a first-generation, central nervous system (CNS) penetrating, antihistamine, for treating allergies and anti-motion sickness.

H1 Receptor Blockers (Generations)

• First-generation H1-blockers are effective and inexpensive but can cause drowsiness (sedation).
• Second-generation H1-blockers have less sedation and are effective too.

Pharmacologic Actions of Histamine

• Histamine binding to receptors in the body leads to pain and itching.
• The respiratory system is also affected by histamine, causing bronchoconstriction.

Other Pharmacologic Actions of Histamine

• Histamine affects the body's sedation, anti-motion sickness, and anti-emetic systems in addition to its impact on the immune system.

Therapeutic Uses of Histamine

• Histamine-blocking agents are used to treat allergic rhinitis, allergic conjunctivitis, and urticaria.
• Treatment of anaphylaxis may require adrenaline.

Therapeutic Uses (Motion Sickness and Nausea)

• Diphenhydramine, cyclizine, dimenhydrinate, and meclizine are effective medications to prevent nausea and motion sickness symptoms.

Therapeutic Uses (Sedation/Insomnia)

• Diphenhydramine, while not specifically targeted at insomnia, can be used off-label for its sedative properties.

Therapeutic Uses (Vertigo and Meniere's Disease)

• Antihistamines are sometimes used in the treatment of vertigo and Meniere's disease.

Therapeutic Uses (Common Cold)

• Antihistamines and anticholinergic agents, can potentially help treat common cold symptoms.

Adverse Effects of Histamine Blockers

• Side effects of histamine blockers include sedation, anticholinergic manifestations, gastrointestinal (GIT) issues (nausea, constipation, diarrhea), and possible teratogenic effects.

Pharmacology of Serotonin

• Serotonin, also known as 5-hydroxytryptamine (5-HT), is an endogenous amine.
• 5-HT is derived from the amino acid tryptophan but it has no clinical drug use currently.

Serotonin Receptors & Actions

• 5-HT1A receptors in the brain are associated with mood control.
• 5-HT2A receptors are involved in platelet aggregation and other bodily functions.
• 5-HT2C receptors are involved in migraine initiation.
• 5-HT3 receptors are connected to the vomiting center.
• 5-HT4 receptors regulate gastrointestinal motility.

Serotonin Agonists

• Agonists like buspirone and triptans act on serotonin receptors specifically.

Chemotherapy-Induced Emesis

• The chemoreceptor trigger zone (CTZ) triggers nausea and vomiting.

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Fluoxetine and other SSRIs increase serotonin levels by inhibiting reuptake.
• SSRIs are antidepressants.

Pharmacology of Eicosanoids

• Eicosanoids are cell signaling molecules, including prostaglandins and leukotrienes, affecting many bodily functions.

Eicosanoid Synthesis

• Membrane lipids play a key role in eicosanoid synthesis.
• Lipoxygenase and cyclooxygenase are key enzymes in this synthesis process.

Prostaglandin Types

• COX-1 produces prostaglandins involved in normal physiological functions.
• COX-2 produces prostaglandins which are mainly involved in inflammation.

Pharmacological Uses of Prostaglandins

• Prostaglandins have various obstetric uses, including abortion and postpartum hemorrhage induction.
• They are also utilized in the treatment of peptic ulcers, open-angle glaucoma, and erectile dysfunction.

Pharmacological Antagonism of Prostaglandins

• Several medications act as prostaglandin antagonists.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs like aspirin, ibuprofen, and diclofenac are commonly used to relieve pain, reduce fever, and lower inflammation.
• Aspirin differs; it's an irreversible enzyme inhibitor.

Therapeutic Uses of NSAIDs

• NSAIDs are used to treat various inflammatory disorders, pain conditions, fever, common colds and thrombotic events.

Adverse Reactions to NSAIDs

• Adverse reactions include gastric irritation, high blood pressure, renal problems, bleeding, and hypersensitivity.

Selective COX-2 Inhibitors (Celecoxib)

• Celecoxib is a selective COX-2 inhibitor and differs from traditional NSAIDS.

Paracetamol (Acetaminophen)

• Paracetamol is an analgesic and antipyretic, working centrally to reduce fever and provide pain relief.
• It's not an anti-inflammatory agent; it does not affect prostaglandin production in most tissues.