This simple & concise Course Note provide students with easy understood information about pharmacology of Autacoids, including:
- Histamine, histamine antagonists, & Antihitsmines
- 5-HT and antagonists
- Angiotensin, ACE inhibitors, AT-receptor blockers
- Kinins
- Prostaglandins
PHARMACOLOGY, AUTACOIDS (PHA311)
FOR STUDENTS ENROLLED IN PHARMACOLOGY PROGRAMS
AUTACOIDS - 1
Def.:
Autacoids are naturally occurring substances synthesized, released and metabolized locally within a
tissue. They have variable pharmacological actions and usually vasoactive.
Classification:
They can be classified according to their structure into:
A- Amines: as
1. Histamine
2. Serotonin
B- Peptides: as
3. Angiotensin
4. Kinins
5. Interleukins
6. Vasoactive intestinal polypeptide
C- Arachidonic (Eicosanoic) acid derivatives: as
7. Platelet activating factor (PAF)
8. Prostaglandins
1. Histamine
Def: it is a biological diamine.
Occurrence:
- Present within mast cells and basophils together with heparin.
- Non-mast cell histamine is present in gut mucosa, skin, lungs and nervous tissue.
- It is also found in stings of bees, venoms of snakes, some plants such as ergot and soya beans.
- Histamine and histamine analogues have been synthesized in the lab as betazole and Betahistine.
Storage:
Histamine is stored in the body away from its site of action to avoid its dangerous effect if present in large
concentrations. Storage occurs in specialized intracellular granules in mast cells, tissues, or neurons in the
following states:
Autacoid Pharmacology Surviving Revision
, BENHA UNIVERSITY, CREDIT HOURS SYSTEM
- Combined or bound form together with heparin and protein: released only after cell injury or
destruction.
- Labile or free form: could be released by histamine liberators.
In addition, there is very little concentration of histamine in the blood.
Release:
Histamine liberators include the following agents:
- Proteolytic enzymes as trypsin in venoms and toxins
- Drugs which are usually basic and can displace histamine from tissues as morphine, codeine,
papaverine, d-TC, atropine, trimethaphan, dextran, heparin, compound 48/80, Suxamethonium,
strychnine, polymyxins…. etc.
- Antigens or allergens via immunological reaction on mast cell membrane.
- Food stuffs as egg white, fish, shellfish, shrimps, straw berry, mango…etc.
- Surface active agents (surfactants) as bile salts and detergents
- Cell injuries, mechanical, thermal, chemical, radial…etc.
Kinetics of histamine:
1- Histamine is ineffective orally because:
- it is acetylated by intestinal flora forming acetyl histamine.
- metabolized by gut mucosa and liver.
2- Doesn’t pass BBB.
3- Fate:
- Storage
- Binding to plasma protein (histaminopexy). The hitaminopexic power of plasma is down in allergic
patients.
- Metabolism: major part of histamine is methylated, some is oxidized or acetylated.
Methyl histamine M. A. O methyl imidazole acetic acid (MIAA)
Some histamine Diamine oxidase Imidazole acetic acid (IAA)
(histaminase)
Histaminase enzyme is synthesized by placenta and increases during pregnancy.
Autacoid Pharmacology Surviving Revision
, BENHA UNIVERSITY, CREDIT HOURS SYSTEM
Dynamics of histamine:
A- Mechanism of action:
Histamine stimulates 3 types of receptors:
- H1 receptor: present on smooth muscle of intestine, bronchi and blood vessels and on sensory nerve
endings
- It is blocked by dimenhydrinate, diphenhydramine…etc.
- H2 receptor: present on gastric glands and on cardiac muscle
- It is blocked by cimetidine, ranitidine, burimamide…etc.
- H3 receptor: present on presynaptic nerves in CNS
- Blocked by thioperamide, clobenpropit & EEDQ.
B- Actions:
1- CVS:
1.1. Blood vessels (H1):
- Capillaries: dilatation and increased permeability due to shrinking of endothelial cells and exposing the
basement membrane
- Arterioles: the effect of histamine on arterioles is variable according to species; in man, dogs and cats,
dilatation; while in herbivorous animals as guinea pigs and rabbits, constriction.
- Pulmonary arteries: dilatation
- Cerebral vessels: dilatation producing headache due to pressure on the brain tissue and stretching of
perivascular nerve endings.
- Large veins: constriction.
1.2. Heart (H2): tachycardia and extrasystoles
1.3. Blood pressure: Hypotension in man, dog and cat due to dilatation of arterioles and capillaries. This
effect is reversed by: - rapid destruction of histamine in the body, - cardiovascular reflexes, -release of
norepinephrine from adrenal medulla. Hypertension occurs in herbivorous animals as guinea pigs and
rabbits.
1.4. Triple response: intradermal injection of histamine or a sting result in a “triple response” which
consists of:
- local red spot, due to capillary dilatation
- Spreading flare, arteriolar dilatation as a result of axon reflex
- Wheel of edema, due to increased capillary permeability.
Autacoid Pharmacology Surviving Revision
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