Autacoids (i)

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Autacoids (i)

  1. 1. AUTACOIDS (I) HISTAMINE AND ANTI HISTAMINES
  2. 2. Aims and Objectives The term autacoid is used for a group of hormone like substances, which originate from tissues, and produce effects at the site of release.
  3. 3. Important members of this group are: I. Histamine II. 5 Hydroxytryptamine (5HT) III. Eicosanoids 1. Prostaglandins 2. Leukotrienes 3. Thromboxanes I. Kinins
  4. 4. Autacoids play an important role in the causation of inflammatory reactions, and a variety of other clinical disorders.
  5. 5. The agonists and antagonists belonging to this group of substances are of considerable clinical importance, and will, therefore, be discussed in detail. This lecture deals with Histamine and Antihistamines.
  6. 6. HISTAMINE
  7. 7. Histamine is derived from amino acid Histidine. It is found in lungs, skin and GIT. Present in high concentrations in mast cells. Also a component of venoms and secretions from insect stings.
  8. 8. In the mast cells histamine is stored in granules. The release of histamine from the granules is responsible for inflammatory and allergic reactions.
  9. 9. RECEPTORS LOCATION H1 i. Smooth muscles ii. Endothelium iii. Brain H2 i. ii. iii. iv. Gastric mucosa Cardiac muscle Mast cells Brain i. Brain H3 (Presynaptic) ii. Myenteric Plexus
  10. 10. H 1 and H 2 Receptors
  11. 11. ANTIHISTAMINES (H1 BLOCKERS)
  12. 12. FIRST GENERATION DRUGS ANTICHOLINERGIC ACTIVITY COMMENTS Carbinoxamine +++ Dimenhydrinate (Dramamine) +++ Slight to moderate sedation Diphenhydramine (Benadryl) +++ ETHANOLAMINES Marked sedation; antimotion sickness activity Marked sedation; antimotion sickness activity
  13. 13. DRUGS ANTICHOLINERGIC ACTIVITY COMMENTS + Moderate sedation Cyclizine (Marezine) - Meclizine - Slight sedation; antimotion sickness activity Slight sedation; antimotion sickness activity ETHYLAMINE DIAMINE Tripelennamine PIPERAZINE DERIVATIVES
  14. 14. DRUGS ANTICHOLINERGIC ACTIVITY COMMENTS ALKYLAMINES Brompheniramine + Slight sedation + Slight sedation; (Dimetane) Chlorpheniramine
  15. 15. DRUGS PHENOTHIAZINE DERIVATIVE Promethazine (Phenergan) MISCELLANEOUS Cyproheptadine (Periactin) ANTICHOLINERGIC ACTIVITY +++ + COMMENTS Marked sedation antiemetic; α block Moderate sedation Antiserotonin activity
  16. 16. SECOND GENERATION DRUGS PIPERIDINE Fexofenadine ANTICHOLINERGIC ACTIVITY COMMENTS - MISCELLANEOUS Longer action Loratadine - Cetrizine (Zyrtec) -
  17. 17. PHARMACOLOGICAL ACTIONS 1. Smooth Muscles i. Intestine: - Antagonism of Histamine (competitive antagonism) ii. Bronchi: - Histamine is blocked Guinea-pig can tolerate 100 times lethal dose of Histamine in the presence of a suitable dose of Antihistamine.
  18. 18. 2. Blood Pressure The initial rapid hypotensive effect is antagonized by H1 blockers. The hypotensive effect in the second phase is antagonized by H2 blockers. 3. HCl secretion: No effect
  19. 19. 4. CNS The first generation induces sedation. Central excitation is the striking effect of Poisoning. 5. Anticholinergic actions Atropine like actions. The second generation has no such effects.
  20. 20. 6. Local anesthetic action Promethazine Pyrilamine However, large doses are required. 7. Blockade of α 1 Adrenergic receptors Promethazine  Hypotension
  21. 21. 8. Other Effects i. Capillary Permeability and Edema H1 antagonists strongly block the action of Histamine, that results in increased capillary permeability and formation of edema and wheal.
  22. 22. ii. Flare and Itch: The flare component of the triple response and the itching caused by intradermal injection of histamine are two different manifestations of the action of histamine on nerve endings. H1 antagonists suppress both.
  23. 23. iii. Serotonin (5HT) Blocking Action Strong blocking effects at serotonin receptors have been demonstrated for H1 antagonist cyproheptadine. This drug is promoted as an anti serotonin agent.
  24. 24. THERAPEUTIC USES I. ALLERGIC DISORDERS 1. Pruritis (Itching) 2. Urticaria 3. Vasomotor Rhinitis 4. Allergic responses to insect bites, chemicals 5. Allergic responses to Drugs 6. Common cold
  25. 25. II. MOTION SICKNESS (Prophylaxis) Promethazine strongest in the group, because of anticholinergic effect (See Scopolamine). III. NAUSEA & VOMITING Dimenhydrinate (Drammamine) Cyclizine HCl (Marezine) Vestibular Disturbance; Meniere’s Disease
  26. 26. IV. SEDATION (CNS DEPRESSION) Diphenhydramine (Benadryl) V. ANAPHYLACTIC SHOCK 1. Edema & Itch  Blocked 2. Hypotension  Controlled to a lesser extent 3. Bronchospasm  No Effect Note: - Other substances involved.
  27. 27. SIDE EFFECTS 1. ANTIMUSCARINIC EFFECTS i) Dryness of mouth ii) Retention of urine iii) Dryness of respiratory passages. These effects are not seen with Second Generation.
  28. 28. 2. CENTRAL ACTIONS (CNS) i) Sedation (not 2nd generation). May be useful effect in some cases. ii) Other central actions. Dizziness; Tinnitus; Lassitude*; Euphoria; Tremors; Nervousness _______________________________________ * Laziness, Sluggishness
  29. 29. 3. DIGESTIVE TRACT Loss of Appetite; Epigastric distress 4. POLYMORPHIC VENTRICULAR TACHYCARDIA Terfenadine  Withdrawn 5. OTHER EFFECTS Mutagenecity; Leukopenia; Agranulocytosis
  30. 30. ACUTE POISONING • Effects strikingly resemble acute Atropine poisoning. • Central excitatory effect • Dilated pupils • Flushed face
  31. 31. • Dry mouth • Sinus tachycardia • Retention of urine • Fever • Finally coma with cardio-respiratory collapse, and death with in 2-18 hours.
  32. 32. SIDE EFFECTS
  33. 33. SIDE EFFECTS
  34. 34. QUESTIONS
  35. 35. 1. An antihistamine which has comparatively lower potential to induce drowsiness / sedation: a) b) c) d) e) Loratidine Cetrizine Acrivastine Dimenhydrinate Diphenhydramine
  36. 36. 2. A drug which belongs to second generation of antihistamines: a) b) c) d) e) Chlorpheniramine Cyclizine Meclizine Promethazine Acrivastine
  37. 37. 3. A second generation antihistamine which has been withdrawn from the market: a) b) c) d) e) Loratidine Cetrizine Terfenadine Promethazine Meclizine
  38. 38. 4. Many antihistamines (H1 Blockers) have additional non-histamine related effects: These are likely to include which one of the following? a) b) c) d) e) Muscarinic increase in the bladder tone General anesthetic effects if the drug is injected Antimotion sickness effect Increase in total peripheral resistance Insomnia

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