2. Autacoids
These are diverse substances produced by wide variety of cells,
having intense biological activity, but act locally at the site of
synthesis and release
Types of autacoids:
• Amine autacoids
- Histamine, 5-HT (Serotonin)
• Peptide autacoids
- Plasma kinins (Bradykinin, Kallidin), Angiotensinogen
• Lipid autacoids
- Prostaglandins, Leucotrienes, PAF
5. Storage And Release
• Storage
- Mast cells and Basophils
- Non – mast cell histamine
* Stomach (ELC)
* Brain
• Release
- Immunological
- Chemical & mechanical
9. Histamine Receptors
• H1 :-
Location: Smooth muscle, exocrine glands, vascular endothelium,
brain; coupled to phospholipase C, leading to IP3 and
diacylglycerol (DAG) production
• H2 :-
Location: Parietal cells, heart, vascular smooth muscle, mast
cells, brain; coupled to cAMP production
• H3 :-
Location: Brain, myenteric plexus (no therapeutic applications,
yet)
10. MOA of Histamine
• Activation of H1 → ↑ phosphoinositol hydrolysis and ↑ in
intracellular calcium → SM contraction, ↑ in vascular
permeability and mucus secretion
• Activation of H2 → ↑ intracellular CAMP → ↑ gastric acid
secretion
• Activation of H3 → ↓ transmitter release from histaminergic
and other neurons
11. Pharmacological actions of Histamine
• CNS
- No BBB penetration
- On Intracerebrovascular injection:
* ↑ in BP, cardiac stimulation
* Vomiting, ADH release
• Heart
- Insitu heart – No prominent action
- Isolated heart - ↑ in rate & FOC
12. Pharmacological actions of Histamine Contd.
• Blood Vessels
- Dilation of smaller Bl. Vessels
- S.C. injection- heat, flushing, ↑ in HR & CO
- Rapid IV injection- ↓ BP
- Intradermal Injection: (Triple Response)
* Red Spot – Capillary dilatation
* Wheal – Exudation of fluid from capillaries and venules
* Flare – Arteriolar dilation
13. • Viceral Smooth Muscles
- Bronchoconstriction
- Abd. Cramps & colic
• Glands
- ↑ in gastric secretion
• Sensory nerve endings
- IV – itching , Pain
• Autonomic ganglia & Adrenal medulla
- Release of Adrenaline → secondary ↑ in BP
Pharmacological actions (contd.)
14. Effect of IV histamine on blood pressure
Mediated by H1 receptors on endothelium
Mediated by H2 receptors on vascular smooth muscle
17. Uses Of Histamine
No Therapeutic Use
• Diagnostic Uses:
* Secreting (Acid) capacity of stomach
* Pheocromocytoma
* Bronchial hyper-reactivity in Asthamatics
H1 Selective Histamine Analogue:
Betahistine (used to control vertigo in Meniere’s disease)
19. Antagonists of Histamine
Physiological antagonists :
Adrenaline – effects are opposite to effects of
histamine
Histamine release Inhibitors →
Mast cell stabilizers : Cromoglycate
Histamine receptor blockers :
H1 blockers and H2 blockers
21. • CNS
- Variable degree of CNS depression
• BP
- IV inj. – cause ↓ BP
• Antagonism of Histamine
- Effectively block:
* Bronchoconstriction
* Contraction of sm. Mus.
* Triple response
• Anti-allergic action
- Type- I reactions are suppressed
Pharmacological actions of
H1-Antihistamines
22. PK & SE
• PK
- A – Well absorbed
- D - Wide distribution
- M- Metabolized in liver
- E - Excreted through urine
D. O. A : 4-6 hrs 2nd Gen: 12-24 hrs
• SE
- 1st Gen;
- Sedation, Light headedness, Diminished alertness &
concentration, motor in-cordination & fatigue
- 2nd Gen;
- Dryness of mouth, Alteration of bowl movements,
Urinary hesitancy
23. Therapeutic Uses of H1- Antagonists
• Allergic Disorders
• Pruritus
• Common Cold
• Motion sickness
• Vertigo
• Preanesthetic medication
• Cough
• Parkinsonism
• Acute muscle dystonia
• As sedative, hypnotic and anxiolytic
28. Treatment of Anaphylactic Shock
• Lay the patient flat & raise the legs
• Attend to the airway
• Inj. Adrenaline
- 0.5 ml (1:1000) IM or 3-5 ml (1:10,000) Slow IV = adult
- 0.01 ml (1:1000) IM or 0.1 ml (1:10,000) Slow IV = children
• Inj. Salbutamol
- For Pts on non-selective β- blockers
• IV Fluids
- To correct hypotension
• Inj. Hydrocortisone Hemisuccinate 100mg - IV
• Antihistaminics
- Do not counter hypotension & bronchospasm
• Inj. Aminophylline IV or Nabulized Salbutamol
• Supportive Measures
- Oxygen & assisted ventilation
29. Why Adrenaline is DOC for Anaphylactic Shock ?
Epinephrine is a physiological antagonist of
histamine, not a pharmacological antagonist
α-1 = Vasoconstriction
ß-1 = Increased HR
ß-2 = Bronchodilatation