1. Department of Pharmacology
AUTOCOIDS BY
Mohammed Q. Mal-Allah
Department of Pharmacology
College of Medicine

2. Definition: Auto = self Coids = Remedy
or some times called Local Hormones
Why are they very important?

3. Classifications: A. Amine Autociods: 1. Histamine 2. Serotonin
B. Eicosanoids (PGs; Thromboxane ; Leukotriens)
C. Peptides Autociods:
1)Kinins
2) Renin; Angiotensins etc)
4. Endogenous peptides (Kinins; Renin; Angiotensins etc)

4. Serotonin Is serotonin as important as N.E or Histamine?
Definition and Location:
it is a neurotransmitter found in enterochromaffin cells in GIT (90%) , and in plateletes and in raphe nuclei of brain stem.
Is serotonin as important as N.E or Histamine?

6. Mechanism of action :
Interacts with 12 receptor subtypes
Why is 5-HT3 receptor differs from other HT receptors?

10. Pharmacological actions of Serotonin
CVS:
1) Blood vessels:
Potent and direct contractions on smooth muscle (via 5- HT2 ) EXCEPT : Skeletal Muscles and Heart blood vessels.
Note : 5- HT can give rise to triple action:
Decrease BP due to chemoreceptor response then increase BP due to Vasoconstriction (5-HT2), then decrease B.P due to skeletal muscle V.D
2) Platelet: Increase platelet aggregation via 5-HT2

11. GIT:
1) increase contraction of smooth muscle (via 5- HT4 stimulated the release of ACH).
What is the clinical significant?
2) Nausea and vomiting (via 5-HT3) therefore 5-HT3 antagonists are used for RX of ?
Respiration : 5-HT may produce weak bronchoconstriction.
CNS: very important.(Appetite; depression and mania; Pain; Anxiety; Schizophrenia).

14. Clinical Uses of Serotonergic Drugs:
Note1: Unlike NE or DA, serotonin its self has no clinical uses, however, its agonists and antagonists have very important therapeutic applications.
Note 2: Unlike histamine where only its antagonists are used, serotonin agonists and antagonists can be used.

15. Clin. Uses of Serotonergic Agonists:
1) Buspirone: 5-HT1A agonist used as anxiolytic agent.
2) Sumatriptan: 5-HT1D agonist for migraine (Treatment
and prophylactic).
3) Metoclopromide (Plasil): 5-HT4 agonist as prokinetic agent
(for Rx of gastroesophagial reflex). And also used for N/V via 5-HT3 antagonistic action.
4) Dexfenfuramine: Acts by stim. Release and inhib. Reuptake of serotonin.
Used as anorexic agent.
What is the effect of serotonin antagonists on appetite?

17. Clinical Uses of Serotonergic Antagonists:
1) Ondansetron & Granisetron: 5-HT3 antagonists Common
used for Rx of N/V induced by cytotoxic (chemotherapy) drugs.
2) Cyproheptadine: Both H1, 5-HT1,2 and cholinergic antagonist
used for Rx carcinoid tumor (significant increases in serotonin) and to increase appetite..
3) Ketanserin: 5-HT2/1c antagonist and a1-adrenergic blocker.
(used as antihypertensive agent)
4) Methysergide: This is an ergot alkaloid acts as 5-HT1,2
antagonist used for Rx of migraine.

23. C. Vasoactive Peptides A. Vasoconstrictors (angiotensin II;
vasopressin; endothelins and neuropeptide Y.
B. Vasodilators (Bradykinin and related
Kinins; Natriuretic Pepties; Vasoactive Intestinal Peptide; substance P; Neurotensin)

32. Vasodialtion may be due to:
I. A direct inhibitory effect of kinins on the arteriolar smooth m.
II. May be mediated by the release of vasodilator PGS(E2 & I2).

33. b. The predominant effect of kinins on veins is contraction & may be due to:
1-direct stimulation of venous smooth m .. or
2- due to the release of vasoconstrictor PGs(F2 α).

35. Ergotamine (Metograine®)

36. Bromocriptine (Parlodel®)

37. Cabergoline (Dostinex®)

38. Lysuride (Dopergin®)

39. Ergometrine (Ergonovine) (Methergin®)

40. Sumatriptan (Imigran®)

41. Captopril (Capoten®)

42. Losartan (CozAAr®)

43. Buspirone (Buspar®)

44. Tegaserod (Zelmac®)

45. Cyproheptadine (Phenergan®)

46. Pizotyline or Pizotifen (Mosegor®)

47. Ondansetron (Zofran®)

48. Granisetron (Kytril®)