Pharmacology of Histamine and Kinins

These flashcards summarize key concepts regarding the pharmacology of histamine and kinins, including their roles, receptors, functions, synthesis, metabolism, and therapeutic applications.

How do kinins affect vascular permeability?

They increase permeability in small venules, leading to edema by causing separation of the junctions between endothelial cells.

What roles do H3 and H4 receptors play in the body?

H3 receptors function as autoreceptors regulating neurotransmitter release, while H4 receptors are involved in immune responses and inflammation.

How do kinins contribute to pain and inflammation?

Kinins excite sensory neurons and release neuropeptides, causing pain and increasing microvascular permeability during inflammation.

What are the four distinct classes of histamine receptors?

H1, H2, H3, and H4 receptors.

What are potential therapeutic uses for bradykinin antagonists?

They may be useful in treating inflammation-related disorders by blocking the effects of kinins.

What autacoids are released alongside histamine during allergic responses?

Leukotrienes, platelet-activating factor (PAF), and various inflammatory mediators.

In which cells is histamine primarily stored?

Histamine is primarily stored in mast cells and basophils.

How is histamine synthesized in the body?

Histamine is synthesized from histidine by the enzyme L-histidine decarboxylase.

How do kinins interact with the respiratory system?

Kinins can cause bronchospasm in asthmatic patients and contribute to symptoms of allergic rhinitis.

How do second-generation H1 receptor antagonists differ from first-generation ones?

Second-generation antagonists are less sedating and do not penetrate the blood-brain barrier, leading to fewer central nervous system side effects.

What are the pharmacological effects of H1 receptor activation?

Activation leads to bronchoconstriction, increased vascular permeability, and stimulation of sensory nerve endings.

How does histamine contribute to hypersensitivity reactions?

Histamine release from mast cells leads to allergic symptoms such as vasodilation, increased permeability, and bronchoconstriction.

What regulates histamine turnover and metabolism?

Histamine turnover and metabolism are regulated by its synthesis at non-mast cell sites and by kininase enzymes.

What is the historical significance of histamine in pharmacology?

Histamine was synthesized as a chemical curiosity before its biological significance was recognized, playing a key role in immune reactions and gastric acid secretion.

What are side effects associated with first-generation H1 receptor antagonists?

Common side effects include sedation, dry mouth, dizziness, and gastrointestinal disturbances.

How do H1 and H2 receptor agonists differ in activation?

H1 agonists primarily act on smooth muscle causing contraction, while H2 agonists stimulate gastric acid secretion.

How do H1 receptors differ from H2 receptors in function?

H1 receptors mediate smooth muscle contraction and increased vascular permeability, while H2 receptors primarily stimulate gastric acid secretion.

What role does the kallikrein-kinin system play in renal function?

Kinins regulate renal blood flow and sodium reabsorption, influencing urine volume and composition.

What is the relationship between kinins and the cardiovascular system?

Bradykinin induces vasodilation and lowers blood pressure by activating B2 receptors on endothelial cells.

Who conducted pharmacological studies on histamine historically?

Dale and Laidlaw conducted intensive pharmacological studies on histamine.

What is the significance of kininase I and II in bradykinin metabolism?

Kininase I releases the C-terminal Arg residue, converting bradykinin to B1 receptor agonists, while kininase II (ACE) degrades bradykinin activity.

How can bradykinin contribute to the therapeutic effects of ACE inhibitors?

ACE inhibitors prevent degradation of bradykinin, enhancing its beneficial effects in cardiovascular protection.

What are the roles of B1 and B2 bradykinin receptors?

B2 receptors mediate most physiological effects of bradykinin, while B1 receptors are upregulated during inflammation and bind des-Arg metabolites.

What are the therapeutic applications of H2 receptor antagonists?

H2 receptor antagonists are used to reduce gastric acid secretion in conditions like peptic ulcers and gastroesophageal reflux disease.

What enzyme synthesizes histamine from histidine?

L-histidine decarboxylase.

What physiological roles does histamine play in the human body?

Histamine is involved in allergic responses, gastric acid secretion, smooth muscle regulation, and neurotransmitter modulation.

How is bradykinin metabolized in the body?

Bradykinin is rapidly degraded by kininase II (ACE) and other enzymes such as carboxypeptidase N.

How do H1 receptor antagonists reduce allergic responses?

H1 receptor antagonists block the effects of histamine, alleviating symptoms such as itching, redness, and swelling.

What is the chemical structure of histamine?

Histamine is a hydrophilic molecule with an imidazole ring and an amino group; the pharmacologically active form is the monocationic Nγ-H tautomer.

How do bradykinin and kallidin share pharmacological properties?

Both are peptides that induce vasodilation, increased vascular permeability, and contribute to pain and inflammation.