AUTACOIDS

 

AUTACOIDS

PREPARED BY MR. ABHIJIT DAS

The term "autacoid" is derived from the Greek words "auto," meaning self, and "akos," meaning healing. In simple terms, autacoids are self-produced molecules in the body that have healing or regulatory functions, typically acting locally on nearby cells or tissues to influence various physiological processes.

Autacoids like histamine, prostaglandins, serotonin (5HT), and bradykinin are self-produced molecules with localized effects in the body, influencing various physiological processes.

PHYSIOLOGICAL ROLE OF 5HT (SEROTONIN)

Serotonin, a neurotransmitter, plays several important physiological roles in the body, including:

1.     Mood Regulation: Serotonin is often referred to as the "feel-good" neurotransmitter because it helps regulate mood and emotions. It plays a key role in preventing feelings of depression and anxiety.

2.     Sleep Regulation: Serotonin is involved in the sleep-wake cycle. It helps regulate sleep patterns, and imbalances in serotonin levels can contribute to sleep disorders such as insomnia.

3.     Appetite Control: Serotonin is involved in regulating appetite and food intake. It helps signal feelings of fullness, and alterations in serotonin levels can impact eating behaviors.

4.     Blood Clotting: Serotonin has vasoconstrictive properties, meaning it can cause blood vessels to narrow. This can be important for blood clotting and wound healing processes.

5.     Gastrointestinal Function: Serotonin is abundant in the gastrointestinal tract, where it helps regulate gut motility, secretion, and the sensation of nausea. It plays a role in digestion and can impact gastrointestinal disorders.

5HT ANTAGONISTS

5-HT antagonists are compounds that block or inhibit the activity of serotonin (5-HT) receptors, often used to treat conditions such as nausea, migraine, and certain mental health disorders.

 

There are several types of serotonin (5-HT) receptors, categorized into seven main families (5-HT1 to 5-HT7). Each type has subtypes (e.g., 5-HT1A, 5-HT2A) with distinct functions. These receptors are located throughout the body and play roles in various physiological processes.

CLOZAPINE

MOA

Clozapine's primary mechanism of action involves blocking the 5-HT2A serotonin receptor, which contributes to its unique pharmacological profile in antipsychotic treatment.

SIDE EFFECTS

Drowsiness, constipation, low blood pressure etc.

ONDACETRON

MOA

Ondansetron's mechanism of action involves blocking serotonin (5-HT3) receptors in the central nervous system, reducing nausea and vomiting signals.

SIDE EFFECTS

Constipation, headache, diarrhea etc.

PHYSIOLOGICAL ROLE OF PROSTAGLANDIN

1.     Pain Modulation: Prostaglandins are involved in the sensitization of pain receptors (nociceptors) in response to injury or inflammation. They contribute to the perception of pain, making us aware of tissue damage or inflammation.

2.     Fever Induction: Prostaglandins, particularly PGE2 (Prostaglandin E2), can raise body temperature by acting on the hypothalamus, which is responsible for regulating body temperature. This elevation in temperature is a part of the body's defense mechanism against infections.

3.     Inflammation Mediation: Prostaglandins, such as PGE2 and PGD2, promote inflammation by causing blood vessels to dilate, increasing blood flow to the affected area, and enhancing the permeability of blood vessels. This helps immune cells reach the site of infection or injury more easily.

 

HISTAMINE

Histamine: A Brief Overview

Histamine is a small molecule in our bodies that serves as a messenger, participating in various important functions.

How Histamine is Made:

Histamine is formed from an amino acid called histidine. An enzyme called histidine decarboxylase transforms histidine into histamine by removing a specific part of the histidine molecule.

Where Histamine is Stored:

After it's synthesis, histamine isn't released immediately. It's stored in special cells called mast cells and basophils.

PHYSIOLOGICAL ROLE OF HISTAMINE

Histamine in Allergic Reactions:

1.     Vasodilation (H1 Receptor): Histamine binds to H1 receptors on the surface of blood vessels, leading to vasodilation. This widening of blood vessels increases blood flow to the affected area during allergic responses, causing redness and warmth.

2.     Bronchoconstriction (H1 Receptor): In the lungs, histamine's interaction with H1 receptors on bronchial smooth muscles triggers their contraction, causing bronchoconstriction. This can result in breathing difficulties and wheezing.

Histamine in Gastric Secretion: Histamine interacts with H2 receptors on the cells of the stomach lining. This interaction stimulates the release of gastric acid, aiding in digestion.

Histamine in the Central Nervous System (CNS):

1.     Cognitive Action (H3 Receptor): In the brain, histamine acts as a neurotransmitter and binds to H3 receptors. This receptor's activation is associated with cognitive processes such as learning, memory, and attention.

2.     Appetite Control (H1 Receptor): Histamine's interaction with H1 receptors in the brain influences appetite regulation, affecting feelings of hunger and satiety.

3.     Regulation of Sedation (H1 and H3 Receptors): H1 receptors in the brain are involved in promoting wakefulness, and their antagonism can induce drowsiness. Meanwhile, H3 receptors modulate sleep-wake cycles and contribute to regulating sedation.

In summary, histamine's physiological roles are mediated through its interactions with specific receptors:

• H1 receptors are key in allergic reactions, causing vasodilation and bronchoconstriction.
• H2 receptors play a role in gastric acid secretion in the gastrointestinal tract.
• H3 receptors influence cognitive functions, sleep-wake cycles, and sedation in the CNS.

 

ANTIHISTAMINES

H1 ANTIHISTAMINES

H1 antihistamines, also known as H1 receptor antagonists, are a class of medications that specifically target the effects of histamine at H1 receptors in the body. These receptors are primarily involved in allergic reactions and various histamine-related responses.

MOA

H1 antihistamines work by binding to H1 receptors and preventing histamine from attaching to them, thus reducing or blocking the symptoms caused by histamine release.

CLASSIFICATION

First Generation:

• Diphenhydramine (Benadryl)
• Chlorpheniramine (Chlor-Trimeton)
• Promethazine (Phenergan)
• Hydroxyzine (Atarax)

Second Generation:

• Loratadine (Claritin)
• Cetirizine (Zyrtec)
• Fexofenadine (Allegra)
• Levocetirizine (Xyzal)

Drawbacks of First-Generation H1 Antihistamines:

First-generation antihistamines come with specific drawbacks, including:

1.     Cognitive Impairment: These drugs can cause cognitive impairment, affecting memory, attention, and overall mental clarity. This can be problematic for tasks that require focus and alertness.

2.     Sedation: Sedative effects are a significant drawback of first-generation antihistamines. They can lead to drowsiness and reduced wakefulness, making activities like driving or operating machinery unsafe.

3.     Appetite Changes: First-generation antihistamines can alter appetite, often leading to an increase in food intake. This can potentially contribute to weight gain over time.