Histamine and Antihistamines

Flashcards covering histamine, antihistamines, and related concepts.

Histamine

A compound derived from the amino acid histidine, involved in local immune responses, vasodilation, and neurotransmission.

Antihistamines

Drugs that counteract the effects of histamine, often used to treat allergies.

Autacoid Pharmacology

The study of the pharmacological effects of autacoids, including histamine.

Histidine

Amino acid from which histamine is synthesized.

L-histidine decarboxylase

Enzyme that catalyzes the conversion of histidine to histamine.

N-methyl histamine

Metabolite of histamine formed by N-methylation.

Imidazole acetic acid (IAA)

Metabolite of histamine resulting from the action of diamine oxidase (DAO).

N-methylimidazole acetic acid (NMIAA)

Metabolite of N-methyl histamine.

Histamine N-methyl transferase

Enzyme involved in the metabolism of histamine.

Monoamine oxidase (MAO)

Enzyme involved in the metabolism of histamine and N-methyl histamine.

Diamine oxidase (DAO)

Enzyme that degrades histamine.

NMIAA

Diagnostic marker in urine when histamine is overproduced.

Mast cells

Cells that store histamine; their distribution often mirrors histamine concentration.

High turnover

Process where histamine is rapidly made and destroyed.

IgE

Antibody involved in allergic responses; cross-linking triggers histamine release from mast cells.

Kinases (tyrosine Kinases)

Proteins that become activated and lead to phosphorylation events, initiating a cascade in mast cells.

Phospholipase C (PLC)

Enzyme activated by tyrosine kinases, leading to the breakdown of membrane phospholipids.

Inositol triphosphate (IP3)

Product of phospholipase C activity that causes the release of calcium from intracellular stores.

Exocytosis

Process where granules containing histamine are released from mast cells in a calcium-dependent manner.

Negatively charged molecules

Molecule that histamine interacts with inside granules due to its positive charge.

Heparin, Chondroitin sulphate, Proteases

Substances stored in granules along with histamine.

Autoinhibition

Ability of histamine to inhibit its own further release by acting on H2 receptors.

H2 receptor

Receptor on mast cells through which histamine exerts autoinhibition.

Adenylate cyclase

Enzyme activated by the H2 receptor, leading to an increase in cAMP.

cAMP

Molecule that inhibits the release of histamine.

B2 receptor

Another receptor on mast cells that, when activated, inhibits the release of histamine.

B2 agonists

Substances that activate B2 receptors and can inhibit histamine release.

Anaphylactoid triggers

Non-antigen-specific triggers that can cause histamine release.

Morphine, Tubocurarine, Succinylcholine chloride

Examples of organic bases that can trigger histamine release.

Urticaria pigmentosa (mastocytosis)

Condition with increased mast cells in the skin, leading to itchy, colored lesions.

Systemic mastocytosis

Condition where mast cells increase in organs.

Myelogenous leukemia

Type of leukemia with increased numbers of basophils.

Gastrinoma (Zollinger-Ellison syndrome)

Condition where there is an increase in gastrin release, leading to excessive histamine release in the gut.

Urticaria

Skin rash with red, raised, itchy bumps.

Dermographism

Skin writing; a condition where the skin becomes raised when scratched.

Pruritus

Itching.

Hypotension

Low blood pressure.

Flushing

Reddening of the skin.

Oedema

Swelling.

Hives

Small, raised, itchy areas of the skin; hives.

Bronchospasm

Contraction of smooth muscles in the bronchi, leading to airway narrowing.

Triple response

Vasodilation, wheal (leakage of vessels), and flare (axon reflex).

H1, H2, H3

Histamine receptor subtypes.

7 transmembrane spanning G protein coupled receptors

Type of receptor that spans the cell membrane seven times and binds G proteins.

Diphenhydramine

H1 receptor blocker.

Cimetidine

H2 receptor blocker.

PLC, IP3, DAG

Signaling molecules associated with the H1 receptor.

cAMP

Signaling molecule associated with the H2 receptor.

G coupled Ca2+ entry

Signaling mediated by the H3 receptor.

IP3

Stimulates release of intracellular Ca2+ stores.

Myosin light chain kinase

Enzyme activated by free intracellular Ca2+ causing smooth muscle contraction.

Phospholipase A2

Causes production of eicosanoids.

H3 receptors

Modulates H1 effects.

Histamine in the heart

Increases atrial and ventricular force via H2 receptors.

H1

Activates endothelial relaxation via NO (+PG12).

H2

Activates a slower onset of direct relaxation.

Agonists

Used in bronchial hyperreactivity testing for asthmatics and by dermatologists as a positive control to test for allergen reactivity.

H1 antagonists

Used to treat mild allergies.

H2 antagonists

Used to treat peptic ulcers, dyspepsia/heart burn, and gastric reflux.

Classic H1 antagonists

H1 antagonists that are sedative, short acting, and may have significant anti-cholinergic action.

Non-sedating H1 antagonists

H1 antagonists that have low or zero CNS penetration, are long acting, and have little anticholinergic effects.

Polymorphic Ventricular Tachycardia (PVT)

May occur with astemizole and Terfenadine if these drugs are taken in high doses or in conjunction with certain macrolide antibiotics and/or certain anti-fungals.

Macrolide antibiotics and anti-fungals

Inhibit a hepatic cytochrome p450 enzyme which is required for the metabolism of astemizole and Terfenadine.

Cimetidine, Ranitidine, Famotidine, Nizatidine

H2 antagonist.

H1

Involved in allergy.

H2

Involved in acid secretion.

H3

Involved in alertness.

Gastrinoma

Increase in gastrin release resulting in excessive release of histamine from ECL cells in the guy.

Histamine In The Heart

Increase in heart rate by reducing the diastolic depolarization time at the SA node (H2 receptors).

Bronchial smooth muscle

Contraction is the dominant pathway.

Gut smooth muscle

Relaxation via increase in cAMP is a weak minor compensation (modulates H1 effects of constriction).

Anaphylactoid Triggers

Substances That Can Induce Histamine Release.

Myelogenous leukemia

Increased numbers of basophils.