Leukotriene Pharmacology & Antihistamines — Vocabulary Flashcards

Vocabulary flashcards covering leukotriene biosynthesis, receptors, antagonists, synthesis inhibitors, and antihistamines from the lecture notes.

Arachidonic acid

Polyunsaturated fatty acid released from membrane phospholipids by phospholipase A2; substrate for COX and LOX pathways to form eicosanoids.

Phospholipase A2 (PLA2)

Enzyme that liberates arachidonic acid from membrane phospholipids, initiating eicosanoid synthesis.

5-Lipoxygenase (5-LO)

Enzyme that converts arachidonic acid to leukotriene precursors; requires FLAP for activity.

FLAP (5-Lipoxygenase Activating Protein)

Protein that facilitates 5-LO activity in leukotriene synthesis.

LTA4 (Leukotriene A4)

Unstable epoxide intermediate in leukotriene biosynthesis from which LTC4, LTD4, and LTE4 are formed.

LTC4 (Leukotriene C4)

Cysteinyl leukotriene; bronchoconstrictor; metabolizes to LTD4 and LTE4.

LTD4 (Leukotriene D4)

Potent bronchoconstrictor and inflammatory mediator; major cysteinyl leukotriene in asthma.

LTE4 (Leukotriene E4)

Stable cysteinyl leukotriene contributing to bronchoconstriction and vascular effects.

LTB4 (Leukotriene B4)

Leukotriene that acts as a strong neutrophil chemotactic factor and promotes inflammation.

Cysteinyl leukotrienes

LTC4, LTD4, and LTE4; mediators of bronchoconstriction, mucus secretion, and vascular permeability.

SRS-A (Slow-Reacting Substances of Anaphylaxis)

Historical term for the cysteinyl leukotrienes involved in anaphylactic responses.

CysLT1 receptor

Receptor for cysteinyl leukotrienes; antagonists block LTD4/LTC4/LTE4 effects.

CysLT2 receptor

Second receptor for cysteinyl leukotrienes; binds LTC4 and other LTs with different affinity.

LTB4 receptor 1 (LTB4-R1)

Receptor mediating LTB4 actions such as neutrophil chemotaxis and activation.

Zileuton

Inhibitor of 5-lipoxygenase; reduces leukotriene synthesis (LTB4 and cysteinyl LTs).

Zafirlukast

CysLT1 receptor antagonist; oral asthma medication with potential liver toxicity and CYP interactions.

Montelukast

CysLT1 receptor antagonist; once-daily oral asthma/allergic rhinitis treatment with favorable PK.

5-Lipoxygenase Activating Protein (FLAP) inhibitors

Agents like zileuton target this pathway to reduce leukotriene production.

CysLT1 receptor antagonists

Drugs (e.g., montelukast, zafirlukast) that block cysteinyl leukotriene signaling at CysLT1.

IP3 signaling (CysLT receptors)

Binding of cysteinyl leukotrienes can raise intracellular Ca2+ via IP3, promoting responses.

Inverse agonist

Drug that stabilizes the receptor in its inactive state, reducing basal activity (contrast with antagonist).

H1 receptor

Histamine receptor mediating allergic inflammation, smooth muscle contraction, vasodilation and increased permeability.

H2 receptor

Histamine receptor that stimulates gastric acid secretion.

H3 receptor

Presynaptic histamine receptor that inhibits neurotransmitter release.

H4 receptor

Histamine receptor involved in bone marrow and immune cell differentiation.

H1 inverse agonists

Antihistamines that preferentially stabilize the inactive H1 receptor state, reducing activity.

Sedating antihistamines (examples)

Promethazine, diphenhydramine, doxylamine, cyclizine, dexchlorpheniramine; effective but with CNS depression.

Non-sedating antihistamines (examples)

Cetirizine, loratadine, fexofenadine, desloratadine, levocetirizine, bilastine; less CNS sedation.

Bilastine

Newest non-sedating antihistamine with minimal CNS penetration.

Desloratadine

Active nonsedating antihistamine (metabolite of loratadine).

Pregnancy considerations (antihistamines)

Some sedating H1 blockers advised against near delivery; many are excreted in milk.

QT interval concerns (antihistamines)

Prolonged QT risk with some older drugs; third-generation options have lower risk.