Antihistamine

Question 1

Histamine - Definition

Answer 1

Histamine is a naturally occurring amine found in most tissues. Forms: Inactive (bound in granules) and active (free histamine).

Question 2

Histamine - Sources

Answer 2

Location: Found in granules within mast cells. Also found in: Basophils and some neurons.

Question 3

Histamine - Release Mechanisms

Answer 3

Interaction of antigen with igE antibodies on the mast cell surface

Question 4

Histamine - Function in Body Epithelia

Answer 4

Location: Epithelia of the gut, respiratory tract, and skin. Role: Inflammatory responses to foreign substances.

Question 5

Histamine - Function in Glands

Answer 5

Secretory Role: Involves gastric, intestinal, lachrymal, and salivary secretions.

Question 6

Histamine - Mast Cells Near Blood Vessels

Answer 6

Role: Regulates microcirculation by releasing histamine during local inflammation.

Question 7

Histamine - Local Hormone

Answer 7

Histamine functions as a local hormone, acting near its release site.

Question 8

Histamine - Inactivation

Answer 8

Mechanism: Rapid inactivation by deamination and methylation.

Question 9

Histamine - Effect on Smooth Muscle

Answer 9

Action: Generally causes contraction of smooth muscles. Exception: Arterioles, where histamine causes dilation.

Question 10

Histamine - Bronchospasm

Answer 10

Action: Causes bronchospasm, especially in asthma and allergies.

Question 11

Histamine - Effect on Blood Vessels

Answer 11

Vasodilation: Dilates arterioles, lowering blood pressure. Mechanism: Involves nitric oxide (NO) release from vascular endothelium.

Question 12

Histamine - Capillary Permeability

Answer 12

Action: Increases capillary permeability, leading to edema (swelling).

Question 13

Histamine - Skin Response

Answer 13

Effect: Causes itching (pruritus) and is involved in the flush, wheal, and flare reaction.

Question 14

Histamine - Effect on Gastric Secretion

Answer 14

Action: Stimulates secretion of gastric acid and pepsin.

Question 15

Histamine Receptors - Overview

Answer 15

Types: H1, H2, H3 receptors. All are G-protein-coupled receptors.

Question 16

Histamine Receptors - H1

Answer 16

Function: Mediates pro-inflammatory effects. Involved in: Allergy symptoms like itching, bronchospasm, and vasodilation.

Question 17

Histamine Receptors - H2

Answer 17

Function: Mediates gastric acid release. Location: Found primarily in stomach lining.

Question 18

Histamine Receptors - H3

Answer 18

Function: Feedback inhibition for histamine and other neurotransmitters. Location: Found in the brain and nerve endings.

Question 19

Methods to Counteract Histamine - Overview

Answer 19

1. 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).

Question 20

Physiological Antagonism

Answer 20

Example: Adrenaline counters histamine by activating α and β adrenoceptors.

Question 21

Histamine Receptor Antagonism

Answer 21

Mechanism: Receptor antagonists prevent histamine from binding to its receptors.

Question 22

Inverse Agonism

Answer 22

Mechanism: Drugs act as inverse agonists, stabilizing the H1 receptor in an inactive state.

Question 23

Drugs that Prevent Histamine Release

Answer 23

Examples: Glucocorticoids, sodium cromoglycate. Action: Prevent release of histamine from mast cells.

Question 24

Antihistamines - Definition

Answer 24

H1 receptor antagonists that block histamine action at H1 receptors.

Question 25

Antihistamines - Mechanism of Action

Answer 25

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.

Question 26

Antihistamines - No Effect on H2

Answer 26

Limitation: H1 antihistamines do not affect H2-mediated gastric acid secretion.

Question 27

Antihistamines in Asthma

Answer 27

Limitation: H1 antihistamines have negligible effects on asthma since cysteinyl leukotrienes are the predominant vasoconstrictors.

Question 28

First-Generation Antihistamines - Overview

Answer 28

Characteristic: Penetrate the CNS, causing sedation. Receptors: Also block muscarinic, α1, and serotonin receptors.

Question 29

First-Generation Antihistamines - Drugs

Answer 29

Examples: Diphenhydramine, Chlorpheniramine, Promethazine, Cyclizine.

Question 30

First-Generation Antihistamines - Side Effects

Answer 30

CNS Effects: Sedation, dizziness, incoordination. Antimuscarinic Effects: Dry mouth, blurred vision. Precaution: Avoid operating machinery or driving due to sedation.

Question 31

Second-Generation Antihistamines - Overview

Answer 31

Characteristic: More polar, less CNS penetration, reduced sedation. Selectivity: More selective for H1 receptors.

Question 32

Second-Generation Antihistamines - Drugs

Answer 32

Examples: Cetirizine, Levocetirizine, Loratadine, Fexofenadine, Desloratadine.

Question 33

Pharmacokinetics - Absorption

Answer 33

Absorption: Antihistamines are well absorbed from the gut. Availability: Some available as parenteral and topical (ophthalmic and intranasal) preparations.

Question 34

Pharmacokinetics - Distribution

Answer 34

First-Generation: Distributed in all tissues, including the CNS. Second-Generation: Poor CNS penetration, less sedation.

Question 35

Pharmacokinetics - Metabolism

Answer 35

First-Generation: Metabolized by CYP enzymes. Second-Generation: Cetirizine and levocetirizine are excreted primarily in urine.

Question 36

Antihistamines in Children

Answer 36

Metabolism: Antihistamines are eliminated more rapidly in children than adults.

Question 37

Antihistamines in Breastfeeding

Answer 37

Effect: Excreted in breast milk, causing sedation in infants.

Question 38

Duration of Action

Answer 38

First-Generation: Duration of action is 4–6 hours. Second-Generation: Longer-acting.

Question 39

Clinical Indications - Allergic Reactions

Answer 39

Use: Symptomatic relief in allergic reactions and anaphylaxis.

Question 40

Clinical Indications - Motion Sickness

Answer 40

Drug Example: Promethazine is effective for motion sickness.

Question 41

Clinical Indications - Common Cold

Answer 41

Effect: Used for symptomatic relief of rhinorrhea.

Question 42

Clinical Indications - Insomnia

Answer 42

Use: First-generation antihistamines used due to their sedative properties.

Question 43

Adverse Effects - First-Generation

Answer 43

Sedation: More frequent with first-generation drugs. Other Effects: Dizziness, tinnitus, and incoordination; driving should be avoided.

Question 44

Adverse Effects - Antimuscarinic

Answer 44

Effects: Dry mouth, blurred vision, urinary retention (seen with first-generation).

Question 45

Adverse Effects - Second-Generation

Answer 45

Tolerability: Generally well-tolerated. QT Prolongation: Terfenadine (withdrawn due to this side effect).