Antihistamine Flashcards
Histamine - Definition
Histamine is a naturally occurring amine found in most tissues. Forms: Inactive (bound in granules) and active (free histamine).
Histamine - Sources
Location: Found in granules within mast cells. Also found in: Basophils and some neurons.
Histamine - Release Mechanisms
Interaction of antigen with igE antibodies on the mast cell surface
Histamine - Function in Body Epithelia
Location: Epithelia of the gut, respiratory tract, and skin. Role: Inflammatory responses to foreign substances.
Histamine - Function in Glands
Secretory Role: Involves gastric, intestinal, lachrymal, and salivary secretions.
Histamine - Mast Cells Near Blood Vessels
Role: Regulates microcirculation by releasing histamine during local inflammation.
Histamine - Local Hormone
Histamine functions as a local hormone, acting near its release site.
Histamine - Inactivation
Mechanism: Rapid inactivation by deamination and methylation.
Histamine - Effect on Smooth Muscle
Action: Generally causes contraction of smooth muscles. Exception: Arterioles, where histamine causes dilation.
Histamine - Bronchospasm
Action: Causes bronchospasm, especially in asthma and allergies.
Histamine - Effect on Blood Vessels
Vasodilation: Dilates arterioles, lowering blood pressure. Mechanism: Involves nitric oxide (NO) release from vascular endothelium.
Histamine - Capillary Permeability
Action: Increases capillary permeability, leading to edema (swelling).
Histamine - Skin Response
Effect: Causes itching (pruritus) and is involved in the flush, wheal, and flare reaction.
Histamine - Effect on Gastric Secretion
Action: Stimulates secretion of gastric acid and pepsin.
Histamine Receptors - Overview
Types: H1, H2, H3 receptors. All are G-protein-coupled receptors.
Histamine Receptors - H1
Function: Mediates pro-inflammatory effects. Involved in: Allergy symptoms like itching, bronchospasm, and vasodilation.
Histamine Receptors - H2
Function: Mediates gastric acid release. Location: Found primarily in stomach lining.
Histamine Receptors - H3
Function: Feedback inhibition for histamine and other neurotransmitters. Location: Found in the brain and nerve endings.
Methods to Counteract Histamine - Overview
- Using drugs with opposite effects (e.g., adrenaline). 2. Blocking histamine binding (receptor antagonists). 3. Using inverse agonists to block H1 receptor effects. 4. Preventing histamine release (e.g., glucocorticoids).
Physiological Antagonism
Example: Adrenaline counters histamine by activating α and β adrenoceptors.
Histamine Receptor Antagonism
Mechanism: Receptor antagonists prevent histamine from binding to its receptors.
Inverse Agonism
Mechanism: Drugs act as inverse agonists, stabilizing the H1 receptor in an inactive state.
Drugs that Prevent Histamine Release
Examples: Glucocorticoids, sodium cromoglycate. Action: Prevent release of histamine from mast cells.
Antihistamines - Definition
H1 receptor antagonists that block histamine action at H1 receptors.
Antihistamines - Mechanism of Action
Binding: Bind to H1 receptor and stabilize it in an inactive state. Effect: Block components of the triple response (flush, wheal, flare) and prevent hypotension.
Antihistamines - No Effect on H2
Limitation: H1 antihistamines do not affect H2-mediated gastric acid secretion.
Antihistamines in Asthma
Limitation: H1 antihistamines have negligible effects on asthma since cysteinyl leukotrienes are the predominant vasoconstrictors.
First-Generation Antihistamines - Overview
Characteristic: Penetrate the CNS, causing sedation. Receptors: Also block muscarinic, α1, and serotonin receptors.
First-Generation Antihistamines - Drugs
Examples: Diphenhydramine, Chlorpheniramine, Promethazine, Cyclizine.
First-Generation Antihistamines - Side Effects
CNS Effects: Sedation, dizziness, incoordination. Antimuscarinic Effects: Dry mouth, blurred vision. Precaution: Avoid operating machinery or driving due to sedation.
Second-Generation Antihistamines - Overview
Characteristic: More polar, less CNS penetration, reduced sedation. Selectivity: More selective for H1 receptors.
Second-Generation Antihistamines - Drugs
Examples: Cetirizine, Levocetirizine, Loratadine, Fexofenadine, Desloratadine.
Pharmacokinetics - Absorption
Absorption: Antihistamines are well absorbed from the gut. Availability: Some available as parenteral and topical (ophthalmic and intranasal) preparations.
Pharmacokinetics - Distribution
First-Generation: Distributed in all tissues, including the CNS. Second-Generation: Poor CNS penetration, less sedation.
Pharmacokinetics - Metabolism
First-Generation: Metabolized by CYP enzymes. Second-Generation: Cetirizine and levocetirizine are excreted primarily in urine.
Antihistamines in Children
Metabolism: Antihistamines are eliminated more rapidly in children than adults.
Antihistamines in Breastfeeding
Effect: Excreted in breast milk, causing sedation in infants.
Duration of Action
First-Generation: Duration of action is 4–6 hours. Second-Generation: Longer-acting.
Clinical Indications - Allergic Reactions
Use: Symptomatic relief in allergic reactions and anaphylaxis.
Clinical Indications - Motion Sickness
Drug Example: Promethazine is effective for motion sickness.
Clinical Indications - Common Cold
Effect: Used for symptomatic relief of rhinorrhea.
Clinical Indications - Insomnia
Use: First-generation antihistamines used due to their sedative properties.
Adverse Effects - First-Generation
Sedation: More frequent with first-generation drugs. Other Effects: Dizziness, tinnitus, and incoordination; driving should be avoided.
Adverse Effects - Antimuscarinic
Effects: Dry mouth, blurred vision, urinary retention (seen with first-generation).
Adverse Effects - Second-Generation
Tolerability: Generally well-tolerated. QT Prolongation: Terfenadine (withdrawn due to this side effect).
