Autocoids 2
Autocoids 2
Autocoids 2
Autacoids
• Endogenous compounds;
• Play an important role in the
physiological and pathological
processes;
• have very short t1/2
• have local action.
Autacoids are the substances released
from the cells in response to various types
of stimulation to elicit normal
physiological responses locally.
An imbalance in their synthesis, release or
in the transduction system contributes
significantly to pathological conditions
such as inflammation, allergy,
hypersensitivity and ischaemia-
reperfusion.
Classifications:
A. Amine Autocoids:
1. Histamine
2. Serotonin
B. Eicosanoids
1.PGs;
2.Thromboxane
3.Leukotrienes
C. Peptides Autocoids:
1.Kinins
2. Renin
3.Angiotensins etc
1.HISTAMINE
Histamine
An endogenous substance
synthesized, stored and released
Mast cells
◦ Basophils
H1 Smooth muscles, Gq
endothelium , brain
H3 Presynaptic autoreceptors Gi
and heteroreceptors, brain,
myenteric plexus, other
neuron
H4 Eosinophils, neutrophils, Gi
CD4 T -cells
Pharmacological / organ system
effects of Histamine
1.Bronchial smooth muscles
◦ bronchoconstriction mediated by H1 receptors
2.GIT
◦ significant increase in gastric acid and gastric pepsin
secretion
◦ promotes intestinal smooth muscle contraction (mediated
by H1 receptors)
Pharmacological / organ system
effects
3.Cardiovascular System
◦ ↓Systolic and diastolic blood pressure- by direct
Vasodilation of arterioles and precapillary
sphincters
Contraindications
Should not be given to asthmatics (except with extreme caution in
pulmonary function testing)
Should not be given to patients with active ulcer disease or
gastrointestinal hemorrhage
ANTIHISTAMINES/HISTAMINE
ANTAGONIST
Physiologic antagonists (agents that produce opposing effects,
acting at different receptors)
Release inhibitors
nedocromil
Anti-emetic/Anti-nausea actions
◦ Some first-generation H1 antagonists prevent motion sickness
◦ Diphenhydramine
Motion Sickness
◦ Diphenhydramine and promethazine
Side effects
GI distress
Diziness, somnolence, slured speech, & delirium
receptors:
reflex.
Respiratory system
Serotonin has a small direct stimulant effect on
bronchiolar smooth muscle in normal humans,
probably via 5-HT 2A receptors.
Ketanserin
◦ 5-HT2 receptors blocker
Ritanserin
◦ 5-HT2 antagonist
Serotonin receptor antagonists
5-HT3 antagonists
◦ Ondansetron
◦ Granisetron
◦ Dolasetron
◦ Tropisetron
Treatment of Migraine
2. EICOSANOIDS
(20 carbon atoms)
(eicosi = 20)
•Prostanoids
- Prostaglandins (PG’s)
- Thromboxane's (TX’s)
•Leukotriene's (LT’s)
•Lipoxins
PGs
Prostanoids Synthesis
Clinical importance of product of
arachidonate series
Alprostadil (PGE 1 ) may be used
for its smooth muscle relaxing effects to
maintain the ductus arteriosus patent in
some neonates awaiting cardiac surgery and
in the t/m of impotence.
Misoprostol
a PGE 1 derivative is a cytoprotective
prostaglandin
used in preventing peptic ulcer
in combination with mifepristone (RU-486)
as abortifacient.
Clinical importance of product of
arachidonate series
PGE 2 and PGF 2 are used in obstetrics
to induce labor
Thromboxane (TXA 2 )
has undesirable properties (aggregation of
platelets, vasoconstriction).
TXA 2 –receptor antagonists and synthesis
inhibitors have been developed for
cardiovascular indications
Leukotrienes biosynthesis
Lipoxins biosynthesis
Eicosanoids Antagonists
3.Peptide Autacoids
RENIN
synthesized as a preprohormone
(prorenin)
synthesized and stored in the
juxtaglomerular apparatus of the nephron
An important modulator of angiotensin
production
ANGIOTENSIN II
Plays a key role in the regulation of
◦ hypertension
Kidney
◦ Captopril, enalapril
Renin Inhibitors