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AUTACOIDS AND
RELATED DRUGS
Prof. Amol B Deore
MVP’s Institute of Pharmaceutical Sciences, Nashik (INDIA)
What do you mean autacoids?
These are substances produced by a wide variety of cells in the body, having intense
biological activity, but generally act locally at the site of synthesis and release. So they have
also been called ‘local hormones’.
Autacoids: This term is derived from Greek:
• autos—self, akos—healing substance or remedy.
They have short duration of action.
They usually exert their action at the site of inflammation, lesion and injury.
Autacoids are involved in a number of physiological and
pathological processes (especially reaction to injury and
immunological insult).
Some autacoids, in addition, serve as transmitters or
modulators in the nervous system, but their role at many sites
is not precisely known.
A number of useful drugs act by modifying their action or
metabolism.
The classical autacoids are—
•Histamine, 5-Hydroxytryptamine (Serotonin)
•Prostaglandins, Leukotrienes, Heparin,
Endothelins
•Bradykinin, Angiotensin
•Interleukins, TNFα,
•Platelet activating factor
Histamine and Antihistaminics
Histamine
Histamine is a biogenic amine that stimulates histamine receptor. In
mammals, histamine is found within granules of basophils and mast
cells (>90% of body stores) and within neurons of the CNS. Other
tissues rich in histamine are skin, gastric and intestinal mucosa, lungs,
liver and placenta.
When released, histamine induces complex physiological and
pathological effects, including allergic reactions, gastric acid
secretion, multiple CNS-regulated effects, smooth muscle contraction
and profound vasodilation that can lead to cardiovascular collapse.
On a general level, histamine is a chemical neurotransmitter produced by
the body during an allergic reaction, most noticeably causing skin, nose,
throat and lung irritation (itchiness, redness, swelling, rash, & cough) in
response to various allergens: insect bites or topical irritants, dust pollen,
food allergies.
These reactions are part of the inflammatory response, which is an
important part of the overall immune response.
Synthesis, storage and metabolism
Histamine is synthesize from amino acid histidine by
the action of histidine decorboxylase.
histamine is found within granules of
basophils and mast cells (>90% of body
stores) and within neurons of the CNS
(hypothalamus).
Other tissues rich in histamine are skin,
gastric and intestinal mucosa, lungs, liver and
placenta.
Mechanism of action of histamine
•Histamine released in response to the stimuli
just described exerts its effects by binding to
two types of receptors, designated H1 andH2,
located on the surfaces of cells
Histamine receptor
Pharmacological actions of
Histamine
Blood vessels-
•Histamine markedly and sharply causes dilatation of
smaller blood vessels, including arterioles, capillaries
and venules.
•On s.c. injection flushing, especially in the blush area,
heat, increased heart rate and cardiac output, with
little or no fall in BP are produced.
Heart-
•The effect of Histamine on heart mediated by H2
receptor includes positive chronotropic effect
(Increased hert rate and increased contractility),
where as the effect mediated by H1 receptors include
negative dronotropic response(Slowing down of AV
conduction).
Visceral smooth muscle-
•Histamine causes bronchoconstriction; guinea pigs and
patients of asthama are highly sensitive to this
response.
•Contractions of other smooth muscles are also
increased, e.g. gastric hypermotility, and increased
uterine contractions.
Gastric secretion:
•Histamine has dominant physiological role in
mediating secretion of HCI in the stomach.
•Histamine stored in gastric mucosa is released
locally under the influence of all stimuli that
evoke gastric secretion
Allergy (Hypersensitivity/Anaphylaxis):
•Histamine is one of the important mediators of allergic
reactions. Histamine is released from the mast cell in
response ot the antigen-antibody complex formation.
•Histamine is the cause for allergic reactions like
urticaria, angioedema, Bronchoconstriction etc.
Inflammation-
•Histamine plays an important role in
inflammatory response.
•The vasodilatation seen in acute inflammation
is as a result of release of histamine from
injured tissue.
Triple response
TRIPLE RESPONSE OF HISTAMINE
If histamine is injected intradermally or
when the skin is scratched vigorously or
due a physical trauma a triple response
will be produced. That consists of three
phases as follows: Flush, Flare and Wheal.
Localized red spot (Flush): histamine
causes immediate redness of the skin,
extending for a few (mm) around the
site of injection, which appears within
few seconds due to blood capillary
vasodilation.
Flare: histamine triggers the
sensory nerves endings that
results in itching and pains
sensation.
Wheal (edema): It occurs in 1 or 2 minutes
Histamine increases capillary permeability
and due to accumulation of plasma fluid
from capillaries. This causes formation of
edema and inflammation at the site of
injection. It may last for few minutes.
ALLERGIC REACTION
• Allergic reaction occurs when the immune system overreacts
to a harmless substance called an allergen.
• The symptoms of an allergic reaction can vary from mild to
severe. If you become exposed to an allergen for the first time,
your symptoms may be mild.
• These symptoms may get worse if you repeatedly come into
contact with the allergen.
First exposure
Allergens/ antigen/ or drug specific Antibody formation (in blood)
Re-exposure
Allergens/ antigen/ or drug + specific Antibody Antigen: Antibody reaction
Mast cells and Basophils
Degranulation and Release of Autacoids
Histamine: Flushing, Itching, Increased
capillary permeability, Oedema, vasodilation,
Hypotension, Bronchospasm, Erythema
Serotonin: Histamine like effects
Prostaglandin: Pain and inflammation
Bradykinin: Smooth muscle contraction,
Increased capillary permeability
Leukotriene: Bronchospasm, Mucus secretion
What causes an allergic reaction?
• Although the reasons why allergies develop aren’t known, there are
some substances that commonly cause an allergic reaction. People who
have allergies are typically allergic to one or more of the following:
• pet animal dander
• bee stings or bites from other insects
• certain foods, including peanuts, eggs or shellfish
• certain medications, such as penicillin or sulfa drugs
• certain plants, flowers, season, dust
• pollen grain or molds
What are the symptoms of an allergic reaction?
• The symptoms of an allergic reaction can vary from mild to severe. If you
become exposed to an allergen for the first time, your symptoms may be
mild. These symptoms may get worse if you repeatedly come into contact
with the allergen.
• Symptoms of a mild allergic reaction can include:
• hives (itchy red spots on the skin)
• itching
• nasal congestion (known as rhinitis)
• rash
• scratchy throat
• watery or itchy eyes
Severe allergic reactions can cause the following symptoms:
 abdominal cramping or pain
 pain or tightness in the chest
 diarrhea
 difficulty swallowing
 dizziness (vertigo)
 fear or anxiety
 flushing of the face
 nausea or vomiting
 heart palpitations
 swelling of the face, eyes, or
tongue
 weakness
 wheezing
 difficulty breathing
 unconsciousness
Anaphylaxis shock
• A severe and sudden allergic reaction can develop within seconds
after exposure to an allergen. This type of reaction is known
as anaphylaxis shock and results in life-threatening symptoms,
including swelling of the airway, inability to breathe, and a sudden
and severe drop in blood pressure.
• If you experience this type of allergic reaction, seek immediate
emergency help. Without treatment, this condition can result in
death within 15 minutes.
Autacoids, Histamine and Antihistaminic agents
ANTIHISTAMINIC AGENTS
•Antihistamines are drugs which treat allergic rhinitis
and other allergies.
•Antihistamines can give relief when a person has nasal
congestion, sneezing, or hives because of pollen, dust
mites, or animal allergy. They are competitive
antagonist of histamine receptors.
Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques (wheals) on
the skin that appear suddenly -- either as a result of the body's reaction to certain allergens, or
for unknown reasons
H1 receptor antagonist
Classification
1) Alkylamine derivatives
Ex. Chlorpheniramine, Dexchlorpheniramine, Bromopheniramine,
Pheniramine
2) Ethanolamine derivatives
Ex. Doxylamine, Diphenhydramine, Carbinoxamine, Phenyltoxamine,
3) Ethylenediamine derivatives
Ex. Antazoline, Pyrilamine, Tripenelamine
4) Phenothiazine derivatives
Ex. Promethazine, chlorpromazine, Prochlorperazine, fluphenazine,
Perphenazine, Thioridazine, Mesoridazine
5) Piperazines derivatives
Ex. Buclizine, Cyclizine, Meclizine, Cetrizine, Levocetrizine, Hydroxyzine
6) Piperidines derivatives
Ex. Azatadine, Loratadine, Desloratadine, Terfenadine, Fexofenadine, Cyproheptadine,
Ketotifen.
Therapeutic uses of H1 receptor antagonist
• This combination medication is used to temporarily relieve
symptoms caused by the common cold, flu, allergies, or other
breathing illnesses (such as sinusitis, bronchitis).
• Antihistamines help relieve watery eyes, itchy eyes/nose/throat,
runny nose, and sneezing.
• Decongestants help to relieve stuffy nose and ear congestion
symptoms
Autacoids, Histamine and Antihistaminic agents
Autacoids, Histamine and Antihistaminic agents
Autacoids, Histamine and Antihistaminic agents
Autacoids, Histamine and Antihistaminic agents
H2 receptor antagonist
•Ex. Ranitidine, Cimetidine, Famotidine, Roxatidine
•Histamine H2-receptor antagonists, also known as
H2-blockers, are used to treat Gastric ulcer, peptic
ulcer, duodenal ulcers and prevent their return.
•They are also used to treat gastric ulcers and for
some conditions, such as Zollinger-Ellison disease, in
which the stomach produces too much acid.
• In over-the-counter (OTC) strengths, these medicines are used to relieve
and/or prevent heartburn, acid indigestion, and sour stomach.
Autacoids, Histamine and Antihistaminic agents

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Autacoids, Histamine and Antihistaminic agents

  • 1. AUTACOIDS AND RELATED DRUGS Prof. Amol B Deore MVP’s Institute of Pharmaceutical Sciences, Nashik (INDIA)
  • 2. What do you mean autacoids? These are substances produced by a wide variety of cells in the body, having intense biological activity, but generally act locally at the site of synthesis and release. So they have also been called ‘local hormones’. Autacoids: This term is derived from Greek: • autos—self, akos—healing substance or remedy. They have short duration of action. They usually exert their action at the site of inflammation, lesion and injury.
  • 3. Autacoids are involved in a number of physiological and pathological processes (especially reaction to injury and immunological insult). Some autacoids, in addition, serve as transmitters or modulators in the nervous system, but their role at many sites is not precisely known. A number of useful drugs act by modifying their action or metabolism.
  • 4. The classical autacoids are— •Histamine, 5-Hydroxytryptamine (Serotonin) •Prostaglandins, Leukotrienes, Heparin, Endothelins •Bradykinin, Angiotensin •Interleukins, TNFα, •Platelet activating factor
  • 6. Histamine Histamine is a biogenic amine that stimulates histamine receptor. In mammals, histamine is found within granules of basophils and mast cells (>90% of body stores) and within neurons of the CNS. Other tissues rich in histamine are skin, gastric and intestinal mucosa, lungs, liver and placenta. When released, histamine induces complex physiological and pathological effects, including allergic reactions, gastric acid secretion, multiple CNS-regulated effects, smooth muscle contraction and profound vasodilation that can lead to cardiovascular collapse.
  • 7. On a general level, histamine is a chemical neurotransmitter produced by the body during an allergic reaction, most noticeably causing skin, nose, throat and lung irritation (itchiness, redness, swelling, rash, & cough) in response to various allergens: insect bites or topical irritants, dust pollen, food allergies. These reactions are part of the inflammatory response, which is an important part of the overall immune response.
  • 8. Synthesis, storage and metabolism Histamine is synthesize from amino acid histidine by the action of histidine decorboxylase.
  • 9. histamine is found within granules of basophils and mast cells (>90% of body stores) and within neurons of the CNS (hypothalamus). Other tissues rich in histamine are skin, gastric and intestinal mucosa, lungs, liver and placenta.
  • 10. Mechanism of action of histamine •Histamine released in response to the stimuli just described exerts its effects by binding to two types of receptors, designated H1 andH2, located on the surfaces of cells
  • 13. Blood vessels- •Histamine markedly and sharply causes dilatation of smaller blood vessels, including arterioles, capillaries and venules. •On s.c. injection flushing, especially in the blush area, heat, increased heart rate and cardiac output, with little or no fall in BP are produced.
  • 14. Heart- •The effect of Histamine on heart mediated by H2 receptor includes positive chronotropic effect (Increased hert rate and increased contractility), where as the effect mediated by H1 receptors include negative dronotropic response(Slowing down of AV conduction).
  • 15. Visceral smooth muscle- •Histamine causes bronchoconstriction; guinea pigs and patients of asthama are highly sensitive to this response. •Contractions of other smooth muscles are also increased, e.g. gastric hypermotility, and increased uterine contractions.
  • 16. Gastric secretion: •Histamine has dominant physiological role in mediating secretion of HCI in the stomach. •Histamine stored in gastric mucosa is released locally under the influence of all stimuli that evoke gastric secretion
  • 17. Allergy (Hypersensitivity/Anaphylaxis): •Histamine is one of the important mediators of allergic reactions. Histamine is released from the mast cell in response ot the antigen-antibody complex formation. •Histamine is the cause for allergic reactions like urticaria, angioedema, Bronchoconstriction etc.
  • 18. Inflammation- •Histamine plays an important role in inflammatory response. •The vasodilatation seen in acute inflammation is as a result of release of histamine from injured tissue.
  • 20. TRIPLE RESPONSE OF HISTAMINE If histamine is injected intradermally or when the skin is scratched vigorously or due a physical trauma a triple response will be produced. That consists of three phases as follows: Flush, Flare and Wheal.
  • 21. Localized red spot (Flush): histamine causes immediate redness of the skin, extending for a few (mm) around the site of injection, which appears within few seconds due to blood capillary vasodilation.
  • 22. Flare: histamine triggers the sensory nerves endings that results in itching and pains sensation.
  • 23. Wheal (edema): It occurs in 1 or 2 minutes Histamine increases capillary permeability and due to accumulation of plasma fluid from capillaries. This causes formation of edema and inflammation at the site of injection. It may last for few minutes.
  • 24. ALLERGIC REACTION • Allergic reaction occurs when the immune system overreacts to a harmless substance called an allergen. • The symptoms of an allergic reaction can vary from mild to severe. If you become exposed to an allergen for the first time, your symptoms may be mild. • These symptoms may get worse if you repeatedly come into contact with the allergen.
  • 25. First exposure Allergens/ antigen/ or drug specific Antibody formation (in blood) Re-exposure Allergens/ antigen/ or drug + specific Antibody Antigen: Antibody reaction Mast cells and Basophils Degranulation and Release of Autacoids Histamine: Flushing, Itching, Increased capillary permeability, Oedema, vasodilation, Hypotension, Bronchospasm, Erythema Serotonin: Histamine like effects Prostaglandin: Pain and inflammation Bradykinin: Smooth muscle contraction, Increased capillary permeability Leukotriene: Bronchospasm, Mucus secretion
  • 26. What causes an allergic reaction? • Although the reasons why allergies develop aren’t known, there are some substances that commonly cause an allergic reaction. People who have allergies are typically allergic to one or more of the following: • pet animal dander • bee stings or bites from other insects • certain foods, including peanuts, eggs or shellfish • certain medications, such as penicillin or sulfa drugs • certain plants, flowers, season, dust • pollen grain or molds
  • 27. What are the symptoms of an allergic reaction? • The symptoms of an allergic reaction can vary from mild to severe. If you become exposed to an allergen for the first time, your symptoms may be mild. These symptoms may get worse if you repeatedly come into contact with the allergen. • Symptoms of a mild allergic reaction can include: • hives (itchy red spots on the skin) • itching • nasal congestion (known as rhinitis) • rash • scratchy throat • watery or itchy eyes
  • 28. Severe allergic reactions can cause the following symptoms:  abdominal cramping or pain  pain or tightness in the chest  diarrhea  difficulty swallowing  dizziness (vertigo)  fear or anxiety  flushing of the face  nausea or vomiting  heart palpitations  swelling of the face, eyes, or tongue  weakness  wheezing  difficulty breathing  unconsciousness
  • 29. Anaphylaxis shock • A severe and sudden allergic reaction can develop within seconds after exposure to an allergen. This type of reaction is known as anaphylaxis shock and results in life-threatening symptoms, including swelling of the airway, inability to breathe, and a sudden and severe drop in blood pressure. • If you experience this type of allergic reaction, seek immediate emergency help. Without treatment, this condition can result in death within 15 minutes.
  • 31. ANTIHISTAMINIC AGENTS •Antihistamines are drugs which treat allergic rhinitis and other allergies. •Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy. They are competitive antagonist of histamine receptors. Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques (wheals) on the skin that appear suddenly -- either as a result of the body's reaction to certain allergens, or for unknown reasons
  • 32. H1 receptor antagonist Classification 1) Alkylamine derivatives Ex. Chlorpheniramine, Dexchlorpheniramine, Bromopheniramine, Pheniramine 2) Ethanolamine derivatives Ex. Doxylamine, Diphenhydramine, Carbinoxamine, Phenyltoxamine, 3) Ethylenediamine derivatives Ex. Antazoline, Pyrilamine, Tripenelamine 4) Phenothiazine derivatives Ex. Promethazine, chlorpromazine, Prochlorperazine, fluphenazine, Perphenazine, Thioridazine, Mesoridazine 5) Piperazines derivatives Ex. Buclizine, Cyclizine, Meclizine, Cetrizine, Levocetrizine, Hydroxyzine 6) Piperidines derivatives Ex. Azatadine, Loratadine, Desloratadine, Terfenadine, Fexofenadine, Cyproheptadine, Ketotifen.
  • 33. Therapeutic uses of H1 receptor antagonist • This combination medication is used to temporarily relieve symptoms caused by the common cold, flu, allergies, or other breathing illnesses (such as sinusitis, bronchitis). • Antihistamines help relieve watery eyes, itchy eyes/nose/throat, runny nose, and sneezing. • Decongestants help to relieve stuffy nose and ear congestion symptoms
  • 38. H2 receptor antagonist •Ex. Ranitidine, Cimetidine, Famotidine, Roxatidine •Histamine H2-receptor antagonists, also known as H2-blockers, are used to treat Gastric ulcer, peptic ulcer, duodenal ulcers and prevent their return. •They are also used to treat gastric ulcers and for some conditions, such as Zollinger-Ellison disease, in which the stomach produces too much acid.
  • 39. • In over-the-counter (OTC) strengths, these medicines are used to relieve and/or prevent heartburn, acid indigestion, and sour stomach.