Autacoids (i)
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The document discusses autacoids and focuses on histamine and antihistamines. It notes that histamine is derived from the amino acid histidine and is found in tissues like lungs, skin, and the gastrointestinal tract. Histamine causes inflammatory and allergic reactions by binding to H1 and H2 receptors. Antihistamines work by blocking these histamine receptors. First generation antihistamines often have anticholinergic effects and sedation as side effects, while second generation antihistamines generally do not. Antihistamines are used to treat allergic disorders, motion sickness, nausea/vomiting, and anaphylaxis. Their side effects include dry mouth, urinary retention, sedation
Autacoids (i)
- 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. Important members of this group are: I. Histamine II. 5 Hydroxytryptamine (5HT) III. Eicosanoids 1. Prostaglandins 2. Leukotrienes 3. Thromboxanes I. Kinins
- 4. Autacoids play an important role in the causation of inflammatory reactions, and a variety of other clinical disorders.
- 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. HISTAMINE
- 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. In the mast cells histamine is stored in granules. The release of histamine from the granules is responsible for inflammatory and allergic reactions.
- 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
- 13. H 1 and H 2 Receptors
- 18. 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
- 19. DRUGS ANTICHOLINERGIC ACTIVITY COMMENTS + Moderate sedation Cyclizine (Marezine) - Meclizine - Slight sedation; antimotion sickness activity Slight sedation; antimotion sickness activity ETHYLAMINE DIAMINE Tripelennamine PIPERAZINE DERIVATIVES
- 21. DRUGS PHENOTHIAZINE DERIVATIVE Promethazine (Phenergan) MISCELLANEOUS Cyproheptadine (Periactin) ANTICHOLINERGIC ACTIVITY +++ + COMMENTS Marked sedation antiemetic; Ī± block Moderate sedation Antiserotonin activity
- 22. SECOND GENERATION DRUGS PIPERIDINE Fexofenadine ANTICHOLINERGIC ACTIVITY COMMENTS - MISCELLANEOUS Longer action Loratadine - Cetrizine (Zyrtec) -
- 23. 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.
- 24. 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
- 25. 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.
- 26. 6. Local anesthetic action Promethazine Pyrilamine However, large doses are required. 7. Blockade of Ī± 1 Adrenergic receptors Promethazine ļ Hypotension
- 27. 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.
- 28. 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.
- 29. 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.
- 32. 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
- 33. 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; Meniereās Disease
- 34. IV. SEDATION (CNS DEPRESSION) Diphenhydramine (Benadryl) V. ANAPHYLACTIC SHOCK 1. Edema & Itch ļ Blocked 2. Hypotension ļ Controlled to a lesser extent 3. Bronchospasm ļ No Effect Note: - Other substances involved.
- 35. 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.
- 36. 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
- 37. 3. DIGESTIVE TRACT Loss of Appetite; Epigastric distress 4. POLYMORPHIC VENTRICULAR TACHYCARDIA Terfenadine ļ Withdrawn 5. OTHER EFFECTS Mutagenecity; Leukopenia; Agranulocytosis
- 38. ACUTE POISONING ā¢ Effects strikingly resemble acute Atropine poisoning. ā¢ Central excitatory effect ā¢ Dilated pupils ā¢ Flushed face
- 39. ā¢ Dry mouth ā¢ Sinus tachycardia ā¢ Retention of urine ā¢ Fever ā¢ Finally coma with cardio-respiratory collapse, and death with in 2-18 hours.
- 44. SIDE EFFECTS
- 45. SIDE EFFECTS
- 46. QUESTIONS
- 47. 1. An antihistamine which has comparatively lower potential to induce drowsiness / sedation: a) b) c) d) e) Loratidine Cetrizine Acrivastine Dimenhydrinate Diphenhydramine
- 48. 2. A drug which belongs to second generation of antihistamines: a) b) c) d) e) Chlorpheniramine Cyclizine Meclizine Promethazine Acrivastine
- 49. 3. A second generation antihistamine which has been withdrawn from the market: a) b) c) d) e) Loratidine Cetrizine Terfenadine Promethazine Meclizine
- 50. 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