1. GUIDED BY –
Dr . Ashutosh Anand sir PRESENTED BY –
1. KOMAL SHARMA [47]
2. MEGHA GUPTA [56]
3. NIDHI SAHU [65]
4. NIKITA PRAJAPAT [68]
5. PURNIMA SINGH [84]
2. CONTENTS
• INTRODUCTION TO AUTACOIDS [HISTAMINE AND
ANTIHISTAMINE]
• SYNTHESIS , STORAGE , DISTRIBUTION OF
HISTAMINE
• RECEPTORS
• PHARMACOLOGICAL ACTION
• H1 ANTAGONISTS
• H2 ANTAGONISTS
• ADVERSE EFFECTS
• CONTAINDICATION
3. INTRODUCTION TO AUTACOIDS
o Often we get allergy from drugs , food , dust ,
pollen , bee bitting and other foregin factors .
o Came in the contact of these mediators-
1. Redness 2. Itching
5. AUTACOIDS
o Auto + coid
o Auto means ‘self ’ akos means ‘healing or therapy or remedy ’.
o Also known as local hormone .
o Responses are localised to affected site .
o Have short half life . Hence short duration of action.
o Doesn’t have any similarity with general hormones .
o Autacoids are released from secreting cells and their effect is
localised to specific tissues .
o General hormones secreted from one celland travel along
blood circulation to give their effects in distant tissues / organ .
6. CHARACTERISTICS OF AUTACOIDS
Endogenous compounds .
Autacoids involve in physiological or pathological
process.
Released during allergy /hypersensitivity ,
inflammation , injury , trauma .
Imbalance in synthesis , release or transduction
systems of autacoids.
Antigen antibody reactions.
8. INTRODUCTION TO HISTAMINE
• Natural component of mammalian tissue .
• Chemical messenger which mediates many cellular processes .
• Local action of histamine involves redness , urticaria , Edema
,inflammatory reactions .
• Histamine doesn’t have any clinical implications .
• Have modest action in anaphylaxis .
• Beta imidazolyl ethylamine derivative .
• Biologically active , secreted from mast [lungs , skin ] and non mast [brain ,
GI musosa ] cells .
Neurotransmitter and Neurohormone .
• Histamine is widely distributed in bone marrow , CSF , and some plants
[stinging nettle ]
9. • Degraded by methylation and oxidation .
• Histamine [+ve charged ] held with acidic protein and
heparin [-ve charged ] within intracellular granules .
• Increase in intracellular cyclicAMP [beta agonist ]
histamine release .
11. STORAGE OF HISTAMINE
Mast cells are predominant site of storage .
Held by intracellular granules complexed with acidic
protein and heparin (macroheparin )
In blood , histamine is present in basophils (hemopoetic
origin )
Non – mast cell (histaminocytes ) in gastric mucosa and
neurons (brain )
Replenishment of histamine in mast cell is slower
process which compared to non-mast cell .
14. IMMUNOLOGIC STIMULATION
Exposure to allergen A
Production of IgE
Bind to IgE receptors (mast cell / basophilis)
Re – exposure of allergen leads to cross linking
Degranulation of cytoplasmic granules
HISTAMINE RELEASE
15. CHEMICAL STIMULATION
Drugs (morphine , d – tubocurarine )
Degranulation of cytoplasmic granules
Replace histamine to hep-pro complex
After exocytosis , His – Hep – complex to
sodium
His displaced with na+/ ca+
HISTAMINE RELEASE
32. 1. BLOOD VESSEL
• Marked Dilation of smaller blood vessels
• Increase capillary permeability
• S.c. injection-
o Flushing
o heat
o increased heart rate
o increased CO
33. • Rapid i.v. injection – fall in BP
VASODILATION
H1
INDIRECT
Endothelial cell
‘NO’ release
H2
DIRECT
VASCULAR
SMOOTH VESSEL
34. • Intradermal injection- elicit Triple response
• RED spot- intense capillary dilation
• WHEAL – exudation of fluid from capillaries and
venules
• FLARE- arteriolar dilation mediated by axon reflex
35. 2. HEART
• Not prominent in situ
• Force of contraction –
• increased (H2 response)
40. 7. CNS
• Not penetrate BBB
• No central effect
On intracerebroventricular administration
o Rise in BP
o Cardiac stimulation
o Behavioural arousal
o Hypothermia
o Vomiting
o ADH release
43. 2. ALLERGIC PHENOMENA
• Mediate Hypersensitivity reaction
• Released from Mast cell
• Causes immediate type Hypersensitivity
• Urticaria
• Angioedema
• Bronhoconstriction
• Anaphylactic shock
AG : AB Reaction
Mast cell
HISTAMINE
44. 3. AS TRANSMITTER
• Afferent transmitter
• Sensation of pain and itching
• Nonmast cell histamine present in Brain
-wakefulness
• H1 antihistamine- sedative action
• H1 agonist – suppress appetite
• H2 & H3- Regulate body temperature, cardiovascular
function, thirst
45. 4. INFLAMMATION
• Mediator of vasodilation
• Expression of adhesion molecule- P-selectin
• Promote adhesion of Leukocytes to vascular
endothelium
• Regulate microcirculation according to local needs
46. 5. TISSUE GROWTH AND REPAIR
Regenerating tissue contain high
concentration of Histamine
Suggested to play essential role in
Growth and Repair
49. • No therapeutic use
• Past – used to test
acid secreting capacity of stomach
Bronchial hyperreactivity in asthmatics
Diagnosis of pheochromocytoma
50. BETAHISTINE
• Orally active
• H1 selective histamine analogue
• Use – Meniere’s disease
• Contraindicated –
asthmatics and ulcer patients
54. Pharmacological actions
1. ALLERGIC DISORDER :
• Do not suppress AG : AB reaction , but block
effect of released histamine are only
palliative.
• Type I hypersensitivity reactions to drugs
(except asthma and anaphylaxis) are
suppressed.
• Itching , urticaria , seasonal hay fever ,
vasomotor rhinitis.
55. 2. ANTIEMETIC , MOTION SICKNESS , MORNING SICKNESS
• Promethazine , diphenhydramine , dimenhydrinate and meclozine should be
taken one hour before starting journey.
• Promethazine can also be used in
Morning sickness
Drug induced and postoperative vomiting
Radiation sickness
3. VERTIGO :
• Cinnarazine it inhibit vestibular sensory nuclei in the inner ear , suppresses
postrotatory labyrinthe reflez, possibly by reducing stimulated influx of Ca2+
from endolymph into vestibular sensory cells.
4. DRUG INDUCED PARKINSONISM :
• Diphenhydramine
5. APPETITE STIMULANT :
• Cyprohepatidine
56. SIDE EFFECTS AND TOXICITY
• CNS - Sedation ,diminished , alertness and concentration , motor inco-
odination , fatique and tendency to fall a sleep are the most common .
• ANTICOLINERGIC – dryness of mouth , alteration of bowel moments ,
urinary hesitancy and blurring of vision
• Epigastric distress and headache
• LOCAL ACTION – contact dermatitis
• Active overdose - central excitation , tremors , hallucination , muscular
inco-odination , convulsion , flusing hypotension , fever
57. Contraindicated
1. Acute angle closure glaucoma , hypersensitivity ,
urinary obstruction.
2. Antihistaminic is not prescribed in pregnancy
60. ● The second generation antihistaminics (SGAs) may be defined as H1
receptor blocker.
● They have following properties:
•Absence of CNS depressant property.
•Higher H1 selectivity : no cholinergic side effects.
•Additional antiallergic mechanisms apart from histamine blockade:
some also inhibit late phase allergic reaction by modifying
release/action of leukotrienes, platelet activating factor (PAF) and
cytokines, etc.
● These newer drugs do not impairing psychomotor performance
(driving,etc. need not be contraindicated), produce no subjective
effects, no sleepiness,do not potentiate alcohol or benzodiazepines.
61. INDICATIONS:
1. Allergic rhinitis and conjunctivitis,hay fever,pollinosis: they
control sneezing,runny but not blocked nose,and red-
watering-itchy eyes.
2. Urticaria, dermographism,atopic eczema.
3. Acute allergic reactions to drugs and foods.
63. FEXOFENADINE :
● It is active metabolite of terfenadine.
● t1/2 is 11-16 hrs and duration of action is 24 hrs.
TERFENADINE OR TERFENADINE+CYP3A4 INHIBITORS.
(ERYTHROMYCIN ,KETOCONAZOLE etc.)
POLYMORPHIC VENTRICULAR TACHYCARDIA
DRUG WITHDRAWN
● Uses: allergic rhinitis, urticaria and other skin allergies
● Contraindicated in patients with long QT interval.
64. LORATADINE:
● Another long acting selective peripheral H1 antagonist.
● It lacks CNS depressant effects and is fast acting.
● It is partly metabolised by CYP3A4 tonan active metabolite which has
longer t1/2 of 17 hrs.
● Uses: urticaria and atopic dermatitis.
DESLORATIDINE :
● Major active metabolite of loratadine effective at half dose.
● Non interference with psychomotor performance and cardiac safety
are documented.
65. CETIRIZINE:
● metabolite of hydroxyzine.
● Affinity for peripheral H1 receptors.
● Penetrates brain poorly but mild sedation is experienced.
● It does not prolong cardiac action potential or produce arrhythmias when given
with CYP3A4 inhibitors.
● It may benefit allergic disorders by other actions as well -
it inhibits release of histamine and of cytotoxic mediators from platelets as well as
eosinophil chemotaxis during the secondary phase of allergic response.
● USES: upper respiratory allergies, pollinosis, urticaria, atopic dermatitis; also used
as adjuvant in seasonal asthma.
66. LEVOCETIRIZINE:
● It is active R(-) enantiomer of cetirizine
● It is effective at half dose and appears to produce less sedation and
other side effects.
MIZOLASTINE :
Non sedating antihistaminic effective in allergic rhinitis and urticaria by
single daily dosing despite a t1/2 of 8-10 hrs and no active metabolite
67. AZELASTINE:
● It is newer H1 blocker and has good topical activity; in addition it
inhibits histamine release and inflammatory reaction triggered by
leukotrienes and platelet activating factor (PAF).
● t1/2 is 24 hr but action lasts longer due to active metabolite.
● Given by nasal spray for seasonal and perennial allergic rhinitis it
provides quick symptomatic relief lasting 12 hrs.
● Stinging in the nose and altered taste perception are local side
effects.
.
68. EBASTINE:
● another newer SGA that rapidly gets converted into active
metabolite Carbastine having a t1/2 of 10- 16 hrs.
● Non sedating, active in nasal and skin allergies.
RUPATADINE:
● recently introduced antihistaminic , has additional PAF
antagonistic property and is indicated in allergic rhinitis.
70. Allergic disorder –
Antihistaminics do not suppress AG :AB reaction but
block the effects of released histamine .
H2 antagonist succeeds in some cases of chronic urticiria
not responding to H1 antagonist alone .
Pruritides –
Drugs chlorpheniramine , diphenhydramine remain the
firstchoice drugs for idiopathic pruritus .
Common cold –
Reduce rhinorrhoea
Motion sickness –
Promethazine ,diphenhydramine and meclozine have
prophylatic value in milder type of motion sickness should
be taken one hour before starting the journey
71. other condition –
• insect bite and ivy poisoning
• Abnormal dermographism is suppressed
• Blood / saline infusion induced rigor.
Vertigo
• Labyrinthine suppressants-
[a] antihistaminics –
cinnarazine,dimenhydrinate,diphenhydramine,promethazine.
[b] anticholinergics- atropine,hyoscine
[c] antiemetic phenothiazines-prochlorperazine
• Vasodilators – betahistine,nicotinic acid
• Diuretic s- acetazolamide, thiazide, furosemide
• Anxiolytics , antidepressants-diazepam,amitriptyline
• Corticosteroids
Parenteral PROCHLORPERAZINE is the most effective drug for controlling
violent vertigo and vomiting.
73. Adverse effects
Sedation
Diminished alertness and concentration
Light headedness
Motor incoordination
Fatigue and tendency to fall asleep
Dryness of mouth
Alteration of bowel movement
Urinary hesitancy and blurring of vision
74. H2 antagonists
• First H2 blocker Burimanide was discovered by Black in
1972.Metiamide was next but both were not found suitable for
clinical use.
• Others such as – cimetidine ,ranitidine, famotidine, roxatidine,
lafutidine and many others have been added subsequently.
• All H2 blockers are competitive antagonists of histamine at the H2
receptors but with famotidine the antagonism is partly non
competitive due to stronger binding of H2 receptors.
• The only significant in vivo action of H2 blockers is marked
inhibition of gastric secretion.
• They are used in treatment of peptic ulcer, urticaria and GERD.
![GUIDED BY –
Dr . Ashutosh Anand sir PRESENTED BY –
1. KOMAL SHARMA [47]
2. MEGHA GUPTA [56]
3. NIDHI SAHU [65]
4. NIKITA PRAJAPAT [68]
5. PURNIMA SINGH [84]](https://image.slidesharecdn.com/histamineseminar-230703103855-fca4fe5c/85/histamine-seminar-pdf-1-320.jpg)
![CONTENTS
• INTRODUCTION TO AUTACOIDS [HISTAMINE AND
ANTIHISTAMINE]
• SYNTHESIS , STORAGE , DISTRIBUTION OF
HISTAMINE
• RECEPTORS
• PHARMACOLOGICAL ACTION
• H1 ANTAGONISTS
• H2 ANTAGONISTS
• ADVERSE EFFECTS
• CONTAINDICATION](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)