[01.28a] Autacoids and Anti-Inflammatory Agents (Part 1) V2.3.pdf

Self-medicinal agent

What is the literal meaning derived from "Auto" and "Acos" that defines autacoids?

Substances released from cells in response to various stimuli to elicit local responses

What are autacoids?

Near the site of release

Where do autacoids usually act in relation to their release point?

Inflammation, hypersensitivity, behavior regulation, vasodilation

Name four diverse pharmacological activities of autacoids.

Similar to hormones

How are autacoids similar to hormones?

Bioamines, Polypeptides, Lipid-derived Substances, Nitric Oxide

What are the four main groups of autacoids mentioned in the source?

Chemical structures

According to what criteria will autacoids be discussed in this lecture?

Respiratory Module (T01.31a, 2027)

In which module will Nitric Oxide be discussed?

Amino acid

What is the basic structure common to amine autacoids?

Histamine and Antihistamines; Serotonin and Selective Serotonin Reuptake Inhibitors (SSRIs); Serotonin antagonists

What three main drug classes are included under amine autacoids?

Mediator of allergic reactions, immune responses, gastric acid secretion, sleep and wake cycle, cognitive ability, food intake

Name six known functions of histamine.

Neurotransmitter in the hypothalamus

Where does histamine function as a neurotransmitter?

Histidine

From which amino acid is histamine synthesized?

Histidine decarboxylase

What enzyme is involved in histamine synthesis?

Lung, Skin, CNS

What three organs primarily synthesize histamine?

Mast cells

Which immunologic cells are the primary producers of histamine and store it as granules?

Mast cell, ECL cell, Histaminergic neuron

What are the three major histamine-producing cells?

Dendritic cell, T-cell, Macrophages, Neutrophils, Epithelial cells

What are the five minor histamine-producing cells?

Repeated exposure to allergen

When do most allergic reactions occur?

Dilation, increased permeability of blood vessels, stimulation of sensory nerves, contraction of smooth muscles

What four effects does histamine cause during an allergic reaction?

Watery eyes, runny nose, sneezing, swelling, hives, difficulty breathing due to bronchospasms

Name six allergic symptoms histamine is responsible for.

Anaphylaxis

What life-threatening allergic reaction can result from systemic histamine release?

IgE and complement activation

What leads to histamine release from mast cells and basophils in the presence of allergens?

Vasodilation, increase in cellular permeability, irritation of peripheral neurons

What three allergy-like symptoms are caused by histamine release from mast cells and basophils?

Somatostatin and gastrin

What activates the H2-producing ECL cell in the GIT?

Gastric acid secretion

What stimulus is produced by ECL cells?

Dopamine D2, serotonin, U opioid, and N-methyl-D-aspartate receptors

What receptors lead to histamine release when activated in histaminergic neurons?

Red reaction, Wheal formation, Flare

What are the three components of the Triple Response to histamine?

Transient local vasodilation

What is a localized red reaction?

Widespread vasodilation and drop in blood pressure

What indicates a systemic red reaction?

Localized edema in the region of the red line

What is wheal formation?

Increased capillary permeability and exudation of fluid from capillaries and venules

What causes wheal formation?

Spreading redness extending beyond the red line

What is a flare?

Axon reflex

What causes a flare?

G-protein coupled receptors

What type of receptors are H-receptors?

H1, H2, H3, H4

What are the four types of H-receptors?

H1 and H4

Which two histamine receptors are involved in allergic reactions?

H2

Which histamine receptor stimulates gastric acid secretion?

Gastric parietal cells

Where are H2 receptors primarily located?

H2 antihistamines

What type of drugs are used to treat gastric acid disorders like reflux and peptic ulcers?

CNS

Where are H3 receptors primarily located?

Immune cells

Where are H4 receptors primarily located?

H1 and H4 receptors

Which two histamine receptors are considered most important and commonly found in mast cells, eosinophils, and monocytes?

Inverse agonists

Antihistamines primarily act as what type of agonists?

Competing with histamine at receptor sites to reverse histaminic responses

What is the primary mechanism of action for antihistamines?

H1 receptor

Which histamine receptor do antihistamines mainly inhibit?

Reduced vascular permeability and vasodilation

What two effects on blood vessels are reduced by H1 antihistamines during allergic reactions?

Inhibiting Nuclear Factor Kappa Beta (NF-κB) and Calcium Ion Channels

Beyond H1 receptor inhibition, how else might antihistamines modulate allergic effects peripherally?

Block effect of mast cell release via H1 and H4 receptors

What is the main overall effect of antihistamines?

Cholinergic, serotonergic, and alpha adrenergic systems

Receptors of which three systems are analogous to histamine receptors, leading to potential adverse effects?

Decreased alertness, cognition, learning, memory, and psychomotor performance

What are four CNS H1-receptor mediated adverse effects of first-generation antihistamines?

Dry mouth, urinary retention, sinus tachycardia

What are three muscarinic receptor-mediated adverse effects of first-generation antihistamines?

Increased appetite, weight gain

What are two serotonin receptor-mediated adverse effects of first-generation antihistamines?

Dizziness, postural hypotension

What are two alpha-adrenergic receptor-mediated adverse effects of first-generation antihistamines?

Increased QT interval, ventricular arrhythmias

What are two cardiac ion channel-mediated adverse effects of first-generation antihistamines?

Muscarinic receptor

Which receptor must be targeted to counter motion sickness?

Drying of the mouth and secretions

What helpful effect of muscarinic cross-reactivity can decrease vertigo?

Buclizine

Give an example of a first-generation antihistamine used as an appetite stimulant due to serotonin receptor interaction.

No operation of heavy machinery, no driving, risk of falls

What three safety warnings must patients be given when taking antihistamines affecting the CNS?

Blocking alpha-adrenergic receptors, which typically cause vasoconstriction

What is the mechanism by which first-generation antihistamines can lead to postural hypotension?

Interaction with inward potassium and sodium channels

What might explain how first-generation antihistamines lead to an increased QT interval and ventricular arrhythmias?

Alkylamines, ethanolamines, ethylenediamines, and phenothiazines

Name four chemical groups to which first-generation antihistamines belong.

Piperazine and piperidine

Which two chemical groups are more commonly associated with second-generation antihistamines, though some first-generation drugs also fall under them?

Brompheniramine, Chlorpheniramine, Dexchlorpheniramine, Pheniramine, Dimethindene, Triprolidine, Acrivastine

Name at least three examples of Alkylamine antihistamines.

Carbinoxamine, Clemastine, Dimenhydrinate, Diphenhydramine, Doxylamine, Phenyltoloxamine

Name at least three examples of Ethanolamine antihistamines.

Antazoline, Pyrilamine, Tripelennamine

Name the three Ethylenediamine antihistamines.

Promethazine, Mequitazine, Trimeprazine

Name the three Phenothiazine antihistamines.

Buclizine, Cyclizine, Meclizine, Oxatomide, Hydroxyzine, Cetirizine (I), Levocetirizine (I)

Name at least three Piperazine antihistamines, distinguishing first from second generation.

Azatadine, Cyproheptadine, Ketotifen, Loratadine (I), Desloratadine (I), Blastine (I), Ebastine (I), Terfenadine (I), Fexofenadine (I), Levocabastine (I), Mizolastine (I), Rupatadine (I)

Name at least three Piperidine antihistamines, distinguishing first from second generation.

Drowsiness/sedation

What is the significant drawback of first-generation antihistamines?

Brompheniramine, Chlorpheniramine, Clemastine, Cyproheptadine, Diphenhydramine, Doxylamine, Hydroxyzine, Promethazine

Name at least four first-generation antihistamines with a marked potential for inducing sedation.

Anticholinergic properties

What properties of first-generation antihistamines make them useful for controlling motion sickness?

Cyclizine, diphenhydramine, dimenhydrinate, hydroxyzine, meclizine, promethazine

Name at least four first-generation antihistamines often used for motion sickness.

Eliminate side effects

What was the purpose of modifying first-generation antihistamines to create second-generation ones?

Peripheral H1 receptor

For which receptor are second-generation antihistamines more selective?

Longer durations of action

What is a general characteristic of second-generation antihistamines regarding their action?

Safer, faster acting, and more potent, with a better side effect profile

What are four advantages of second-generation antihistamines?

Loratadine, Fexofenadine, Desloratadine

What are three more non-sedating second-generation antihistamines?

Acrivastine, Cetirizine, Levocetirizine

What are three second-generation antihistamines with a weak potential for producing sedation?

Derivatives of Second Generation

What are third-generation antihistamines?

Less sedation and adverse effects like CNS effects

What are two advantages of third-generation antihistamines?

Desloratadine

Which third-generation antihistamine is a metabolite of loratadine?

Fexofenadine

Which third-generation antihistamine is a metabolite of terfenadine?

Levocetirizine

Which third-generation antihistamine is an enantiomer of cetirizine?

First line for seasonal allergies

For what condition are third-generation antihistamines considered first-line?

First generation antihistamines

Which generation of antihistamines is considered the most potent and fastest acting?

Second or third generation antihistamine

Which generation of antihistamines should a patient with chronic seasonal allergies opt for?

Levocetirizine

Which specific third-generation antihistamine is allegedly non-sedating but can still cause manageable drowsiness?

Natural neurotransmitter

What type of substance is serotonin?

Tryptophan

What amino acid is converted to 5-hydroxytryptamine?

Regulation of mood and social behavior, appetite and digestion, sleep, memory, and sexual desire and function

Name at least four functions affected by serotonin.

Often used in mood-stabilizing medications (happy drugs)

Despite inconclusive evidence about depression, what type of medications often use serotonin?

5-HT1A to 5-HT4

Which HT receptors are most important for affecting mood and condition?

G-protein mediated

What is the general signaling mechanism for most 5-HT receptors?

5-HT3

Which 5-HT receptor is an exception to being G-protein mediated?

Cerebellar regulation, motor control, emesis, respiratory drive, and body temperature

What five functions are regulated by serotonergic cells in the medullary area?

GI tract

Where is most of the body's serotonin located?

Bowel function and movement

What does serotonin regulate in the GI tract?

Reducing appetite while eating

What role does serotonin play in appetite?

Contributes to the formation of blood clots

What is the function of serotonin receptors on platelets?