Untitled Quiz

Autacoids (Hormones Like Substances)

• Autacoids are hormones-like substances
• They are organic regulatory substances
• Produced in one part of an organism, and transported throughout the organism (e.g. via blood/lymph)
• Stimulate specific cells/tissues and initiate actions
• Local hormones (Autocoids): Act locally at site of synthesis/release
  • Paracrine
  • Autocrine

Forms of Chemical Signaling

• Autocrine: A cell signals itself; a ligand binds to a receptor on its own surface
• Paracrine: Cells communicate with each other over a short distance
• Endocrine: Signals are created by specialized cells and released into the bloodstream; transported to distant target cells
• Cell-cell contact signaling: Gap junctions (animals) and plasmodesmata (plants) connect neighboring cells directly through tiny channels

Paracrine Example & Synaptic Signaling

• Paracrine Example: A cell targets a cell close by (nearby cell)
• Synaptic Signaling: A specialized form of paracrine signaling, where a neurotransmitter is released into a synapse and binds to a receptor on a receiving cell

Hormones

• Circulating Hormones: Reach the bloodstream
• Local Hormones (Autocoids): Act locally first (paracrine and autocrine)

Autacoids

• Autacoids are local hormones.
• They do not circulate throughout the body.
• They act locally at the site of synthesis and release.
• They have many diverse pharmacological and physiological activities.
• They typically have a short duration of action.
• Auto = self, acos (relief or remedy)

Classification of Autacoids

• Amine-derived: Histamine (derived from amino acid histidine), Serotonin
• Peptide-derived: Angiotensin, Bradykinin
• Lipid-derived: Eicosanoids

Histamine

• A chemical messenger that mediates wide range of cellular responses.
  • Allergic and inflammatory reactions
  • Gastric acid secretion
  • Neurotransmission at parts of the brain

Histamine Locations

• Found in all types of tissues
• High concentrations in basophils and mast cells
• Component of venom and insect bites
• High concentrations in lungs, skin, and gastrointestinal tract (GIT)

Histamine Synthesis

• Histamine is stored in granules after synthesis.
• If not stored, it is rapidly inactivated by the enzyme amine oxidase.
• Produced from the amino acid histidine

Foods That Contain Histamine

• Displayed as images (no text)

Histamine Release

• Immunologically: Released from cells in response to an antibody called immunoglobulin E (IgE); secreted in response to invaders (virus, bacteria) or allergens (e.g. pollen)
• Chemically: Like morphine
• Destruction of cells: Result of cold, toxins, venom, or trauma

Histamine Mechanism of Action

• Released in response to stimuli
• Binds to various histamine receptors (H1, H2, H3, H4)
• H1 and H2 are targets for clinically useful drugs

Mechanism of Action of Histamine

• Details on effects related to H1, H2, H3, and H4 receptors (e.g., smooth muscle contraction, increased gastric acid secretion, decreased histamine release, immunomodulator, etc.)

Histamine Mechanism (additional details)

• In the stomach, converts histidine to Histamine, which stimulates the production of HCl acid
• In the brain, acts as a neurotransmitter, regulating sleep, hormonal secretion, memory formation, and brain arousal
• In the immune system, acts as a vasodilator in response to allergies/immune system responses

Actions mediated by H1 and H2 receptors

• H1 receptors: Effects on exocrine excretion, bronchial smooth muscle, intestinal smooth muscle, sensory nerve endings, skin.
• H2 receptors: Effects on stomach (stimulation of gastric acid secretion), skin, cardiovascular system

Histamine Reactions

- Local Reaction:
    - Histamine release is slow enough for it to be inactivated before it enters bloodstream
    - Causes dilation and increased permeability of capillaries, leading to protein and fluid leakage in the skin
    - Results in Lewis' Triple Response (red spot/line, redness around the line, wheal formation/edema)
- Anaphylactic Shock:
    - Rapid histamine release cannot be inactivated
    - Complete anaphylactic reaction occurs

Antihistamine

• Shown diagrammatically; antihistamine binds to receptors, inhibiting histamine effects

Histamine Antagonists

• Physiological antagonism:
  • Adrenaline
• Pharmacological antagonism:
  • H1 and H2 receptor antagonists (e.g. Nedocromil, Cromolyn, Sodium and Ketotifen)
• Immunotherapy: Inhibits antibody/antigen reaction

Histamine Receptor Blocking Agents

• First-Generation: Brompheniramine, Chlorpheniramine, Cyclizine, etc. Potential for sedation
• Second-generation: Cetirizine, Desloratadine, Fexofenadine, etc. Less sedating
• Diagram and tables provided, showing relative drowsiness potential of different drugs
  • Claritine provided as example

H1 Receptor Antagonists

• First generation:
  • Effective and inexpensive
  • Disadvantages: Crosses blood-brain barrier, causes sedation, interactions with other receptors (serotonin) contributing to side effects
  • Short duration of action
• Second generation:
  • Specific H1 blockers, less sedation
  • Longer duration of action, making daily dosing easier
• Efficacy is maximized if taken before exposure to allergen

Therapeutic Uses of Histamine Antagonists

• Allergies and inflammation: Treats symptoms like pink eye, urticaria, allergic rhinitis.
• Motion sickness and morning sickness: Effective for nausea associated with motion sickness and pregnancy.
• Sleep induction: First generation less effective because of sedation

Side Effects of Histamine Antagonists

• Sedation: Reduced with 2nd generation drugs
• Atropine-like effects: Reduced with 2nd generation drugs (e.g., dry mouth, urinary retention, blurred vision, tachycardia)

H2 Receptor Antagonists

• Competitive antagonists of histamine; fully reversible
• No effect on H1 receptors
• Mechanism: block histamine binding to H2 receptors, reduces intracellular cAMP concentrations, decreases gastric acid secretion

Mechanism of Gastric Acid Secretion

• Illustrative diagram of the steps involved, focusing on the roles of acetylcholine, histamine, prostaglandin E₂, G proteins, and protein kinase

H2 Receptor Antagonists (Therapeutic Uses)

• Used in the treatment of peptic ulcer
• Specific drugs for this use are Cimetidine, Ranitidine, Famotidine, and Nizatidine

H2 Receptor Antagonist (Therapeutic Uses) expanded

• Gastric and duodenal ulcers
• Gastroesophageal reflux disease (GERD)
• Prevent the occurrence of stress ulcers
• Prevent peptic ulcer recurrence
• Reduce acidic gastric contents aspiration during anesthesia

Side Effects related to Cimetidine

• Antiandrogenic effects: Prolonged use at high doses can decrease androgen binding to receptors, inhibit estradiol hydroxylation, and affect estrogen metabolism
  • Possible side effects for men and women
• CNS adverse effects: Dizziness, headaches, and confusion
• Drug interactions: Due to enzyme-inhibiting activity
• Hepatitis and elevated serum creatinine

Case Study

• A healthy 45-year-old physician experiences dizziness, skin redness, tachycardia, and orthostatic hypotension after eating a meal.
• Another physician at the table experiences similar symptoms.
• The menu included green salad, sautéed fish, rice, and apple pie.
• Probable diagnosis: scombroid poisoning (due to a fish containing high histamine levels after being improperly preserved). Treatment involves using histamine blockers

Answer (to the Case Study questions)

• Typical symptoms caused by histamine from improperly preserved fish.
• Maximum doses of histamine blockers (especially H1 blockers) are sufficient to control the symptoms.
• Epinephrine is unnecessary unless severe cases of hypotension or airway obstruction are apparent