FARMAKOLOGI ANTIHISTAMIN

Summary

This lecture explores the pharmacology of antihistamines, starting with an explanation of histamine, its production, and its role in allergic reactions, tissue injury, and drug exposure. The focus then shifts to histamine receptors, particularly H1 and H2, and their functions in the body. The lecture covers both first and second-generation antihistamines, discussing their structures, mechanisms of action, and side effects. It also touches on H2 receptor blockers used in treating gastric issues like ulcers and acid reflux. The lecture provides a comprehensive understanding of how antihistamines work in the body and their clinical uses.

Takeaways

• 😀 Histamine is a small molecule produced by decarboxylation of the amino acid histidine, and it is concentrated in the skin, lungs, and gastrointestinal tract.
• 😀 Histamine is released due to three major triggers: allergic reactions, tissue injury, and exposure to drugs or foreign chemicals.
• 😀 In allergic reactions, histamine release is triggered when allergen-specific IgE antibodies bind to mast cells, causing histamine release upon subsequent exposure.
• 😀 Tissue injury leads to the release of histamine from mast cells, which affects blood vessels and nerves in the damaged area.
• 😀 Certain drugs and chemicals, such as morphine and some antibiotics, can directly displace histamine from mast cell granules.
• 😀 Histamine acts through four types of receptors (H1, H2, H3, H4), but H1 and H2 are the main targets of clinically relevant drugs.
• 😀 H1 receptors are mainly involved in inflammatory and allergic reactions, causing blood vessel dilation, broncho-constriction, and promoting wakefulness and appetite suppression.
• 😀 H2 receptors, primarily found in gastric parietal cells, regulate gastric acid secretion when activated by histamine.
• 😀 H1 receptor blockers (antihistamines) can be divided into first and second generation, with first-generation agents causing sedation and cognitive impairment.
• 😀 Second-generation antihistamines are more selective for peripheral receptors and cause fewer side effects like sedation, providing relief from allergies with less cognitive impact.
• 😀 H2 receptor antagonists block histamine's effects on gastric acid production, making them useful for treating gastric ulcers and gastroesophageal reflux disease (GERD).

Q & A

What is histamine and where is it found in the body?

Histamine is a small molecule produced by decarboxylation of the amino acid histidine. It is widely distributed throughout the body, particularly concentrated in the skin, lungs, and gastrointestinal tract. Most histamine is stored in granules within mast cells, basophils, eosinophils, and enterochromaffin-like cells in the stomach lining.

What are the three major conditions that trigger the release of histamine?

The three major conditions that trigger histamine release are: 1) Allergic reactions, where IgE antibodies produced by plasma cells activate mast cells upon re-exposure to an allergen. 2) Tissue injury, where damaged mast cells release histamine and other mediators. 3) Drugs and foreign chemicals, such as venom and certain medications, which directly displace histamine from granules.

How does histamine exert its effects in the body?

Histamine exerts its effects by binding to histamine receptors (H1, H2, H3, and H4) found on various cells in the body. The effects include dilation of blood vessels, bronchoconstriction, wakefulness promotion, and pain/itching sensations. H1 receptors are involved in allergic reactions and inflammation, while H2 receptors regulate gastric acid secretion.

What are H1 receptors and what role do they play in allergic reactions?

H1 receptors are expressed primarily on vascular endothelial cells, smooth muscle cells, and nerve endings. They mediate allergic reactions, causing blood vessels to dilate and become more permeable (leading to redness and edema). H1 activation in smooth muscle causes bronchoconstriction, while in peripheral nerve endings, it leads to pain and itching.

What are the effects of histamine binding to H2 receptors?

When histamine binds to H2 receptors, which are mainly located on gastric parietal cells, it stimulates the secretion of gastric acid. This process is important in digestion and can be targeted for managing conditions like gastric ulcers and acid reflux.

What are first-generation antihistamines, and how do they work?

First-generation antihistamines are older drugs that act as inverse agonists, binding to H1 receptors and stabilizing their inactive form to block histamine's effects. They cross the blood-brain barrier, causing sedation and impairing cognitive function. These drugs can also interact with other receptors, leading to side effects like dry mouth, blurred vision, and hypotension.

What side effects are associated with first-generation H1 antihistamines?

First-generation H1 antihistamines can cause side effects such as sedation, dry mouth, blurred vision, urinary retention, hypotension, reflex tachycardia, and increased appetite. They may also cause cognitive impairment due to their ability to cross the blood-brain barrier.

What distinguishes second-generation H1 antihistamines from first-generation ones?

Second-generation H1 antihistamines are more selective for peripheral H1 receptors and are less lipophilic, which means they do not cross the blood-brain barrier as easily. As a result, they are less likely to cause sedation and cognitive impairment while still providing effective allergy symptom relief.

What are some examples of second-generation H1 antihistamines?

Examples of second-generation H1 antihistamines include cetirizine, desloratadine, fexofenadine, loratadine, and levocetirizine. These drugs are more selective for peripheral receptors, providing effective allergy relief with fewer side effects like sedation.

What are H2 receptor antagonists, and how do they work?

H2 receptor antagonists (H2 blockers) are drugs that selectively block H2 receptors on gastric parietal cells, thereby reducing gastric acid secretion. This action helps in treating conditions like gastric ulcers and gastroesophageal reflux disease (GERD). Examples include ranitidine, famotidine, and cimetidine.

What are the common side effects of H2 receptor antagonists?

H2 receptor antagonists are generally well-tolerated with few side effects. However, the most common side effect is a headache. Some drugs, like cimetidine, may cause more significant side effects, including drug interactions and anti-androgenic effects like gynecomastia and galactorrhea.