START WITH THE NAME OF

ALLAH
THE MOST BENEFICIENT,
THE MOST MERCIFUL
 AUTACOIDS

Prof. Dr. Muhammad Ashraf

Dean FBS
UVAS, Lahore

Sep 29, 2018 2

 Definition
Substances that are synthesized ,
function and degraded locally in the
tissues (local hormones or tissue
hormones)
Participate in a response to injury
Normally do not function as typical
circulating hormones
Antagonists inhibit autacoid synthesis,
release or effects on tissue receptors
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 Function

Modulate blood flow

Modulate secretions

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 Major Classes
Biogenic amines: Histamine, Serotonin
Phospholipid derived autacoids:
1. Eicosanides  Prostaglandins (PGs),
Leukotriens (LTs)
2. Platelet activating factor (PAF) 
Thromboxanes
Polypeptides: Angiotensin, Kinin
(Bradykinin, Kallidin)
Substance P, VIP
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 Biogenic amines

Histamine:
Found in skin, S/C tissue, viscera,
CNS, muscle, blood, gastric juice,
saliva, Urine, sputum, lungs
Stored in mast cell, basophils
Synthesized from Histidine by
decarboxylation
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 Release

Injury or trauma
Immune mediated (allergic reaction)
Venom, toxins
Drug mediated
 Morphine
 Curare, etc

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 Action
Cardiovascular:
1. Vasodilation
2. Decreased blood pressure
3. Increase permeability (Edema)
Lungs:
1. Bronchospasm
2. Increased secretion
GIT:
1. Increased intestinal motility
2. Increased gastric acid secretion
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 Skin:
1. Pruritis
2. Triple response
i) Red (due to capillary dilation)
ii) Weal formation (due to plasma exudate)
iii) Flare

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 Histamine receptors

H1 - smooth muscle, exocrine glands,

vascular endothelium, brain;
Coupled to phospholipase C, leading to IP3
and diacylglycerol (DAG)
H2 - parietal cells, heart, vascular smooth
muscle, mast cells, brain;
Coupled to cAMP production
H3 - presynaptic, brain, myenteric plexus
(no therapeutic applications, yet)
 Receptors
H1 – receptors 1. Mediate contraction of smooth
muscles (Bronchioles, intestine)
2. Vasodilation of small arteries
and veins
3. Capillary permeability increased
4. Pruritis

H2 – receptors 1. Mediate gastric acid secretion

2. Vasodilation

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Three mechanistically different
approaches to minimize
histamine reactions

Physiological antagonism (e.g., epinephrine)

Inhibit the release of histamine (e.g.,

cromolyn)

Pharmacological antagonism (antihistamines)

 Antihistamines
(H1 antagonist)
First generation agents
Triplennamine HCl
Mepyramine Maleate (Meprasan)
Chlorpheniramine Maleate (Piriton)
Diphenhydramine HCl (Benadryl)
Chlorpromazine HCl (Largactil)
Promethazine HCl (Phenergan)
Trimeprazine tartrate (Vallergan)
(Sedation, drowsiness is a common side effect of 1 st
generation agents)

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 H1 antagonists

Second generation agents

( Non-drowsy)
Astemizole (Hismanal)
Cetirizine (Zyrtec)
Fexofenadine (Allerga)
Terfenadine (Teldane)
Loratadine (Claritin®)

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 H2 antagonists

Cimetidine (Tagament)
Ranitidine (Zantac)
Famotidine (Nocid)
Nizatidine (Axid)

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 Therapeutic Uses
Allergic disorders
Nausea and vomiting
Ruminal disorders
Retained placenta and metritis
Post parturient paresis
Peptic ulcers ( H2 Atagonists )

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 Dosage of important
antihistamines
1. Mepyramine maleate (Meprasan)
(Anthisan)
Horse: 55 mg / 100kg b.wt.
Cattle: 1-2 mg / kg b.wt
2. Triplennamine HCl (Pyrebenzamine)
Horse & Cattle: 55 – 100 mg / 100 kg
Dog & Cat: 1 –2 mg/kg
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3. Promethazine HCl: (Phenergan)
Horse & Cattle: 55 – 100 mg/kg
Dog & Cat: 1 – 2 mg/kg
4. Antazoline HCl: (Antistin)
Small animals: 100 mg t.i.d. daily
5. Diphenhydramine HCl (Benadryl)
Horse & Cattle: 55 – 110 mg/100kg
Dog & Cat: 1 – 2 mg/kg

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 Phospholipid derived
autacoids
Prostagladins
Leukotriens
Thromboxins
1. Corticosteroids inhibit synthesis of
arachadonic acid by inhibiting
phospholipase A2
2. NSAIDs inhibit cycloxygenase enzyme
thus production of endoperoxides and
subsequently prostaglandins synthesis
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Saturday, September 29 20
 Poly peptides
Angiotensin
Kinin (Bradykinin, Kallidin)
 Angiotensinogen Renin Angiotensin-I
ACE Angiotensin-II (Octapeptide)

 Drugs Captopril,Enalapril, Lisinopril, inhibit ACE

(angiotensin converting enzyme). Used as
antihypertensive drugs. Losartan Saralasin are
receptor inhibitors.
 No specific drug in clinical use for the inhibition of
bradykinin & kallidin

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