1. Histamine and Antihistaminics

2. Case study
• A 24 year old male patient John , suffers from allergic rhinitis.
Every winter, she develops a runny nose, itchy eyes, and
sneezing.
• To relieve his symptoms, he takes an over-the-counter
antihistamine, diphenhydramine.
• John is annoyed by the unpleasant effects that accompany his
allergy medication. Every time he takes his antihistamine, he
feels drowsy and his mouth feels dry.
• He makes an appointment with his doctor who, advises him to
take loratadine. Upon taking new allergy medication, his
symptoms are relieved and he experiences no drowsiness or
other adverse effects.

3. Questions
• Why does John develop seasonal rhinitis?
• Why does diphenhydramine relieve John`s
symptoms?
• Why does diphenhydramine cause
drowsiness?
• Why doesn't loratadine cause drowsiness?

4. Histamine
• Histos: Tissue
NH2
5
H
 skin, lungs, GIT Mucosa
4
3
1
N
N
•Present mostly in mast cells:
2
•Non mast cell histamine:
Brain, Gastric Mucosa
Histamine
Histamine is a biogenic amine present in many animal and plant tissues .

5. Histamine
• Biogenic amine present in many animal and
plant tissues
• Also present in venoms and stinging
secretions
• One of the mediators involved in
inflammatory & hypersensitivity reactions.

6. Synthesis, storage & metabolism of
histamine
• Synthesized by decarboxylation of
amino acid histidine
• Histamine is present in storage
granules of mast cells & also
found in skin, lungs, liver, gastric
mucosa etc.

7. Mechanism of Action of Histamine
Histamine
H1 Receptors
↑ Ca2+
Smooth muscle contraction
Increased capillary
permeability
Vasodilation
Sensory nerve endings pain
& itching
H2 Receptors
↑ cAMP
↑ Gastric acid secretion
Blood vessels:
vasodilation
Increased capillary
permeability
H3 Receptors
(presynaptic auto
receptors)
↓ cAMP
↓ histamine release
↓secretion
Vasodilation

8. Pharmacological actions
Stimulating H1, H2, H3 Receptors
• CVS:
– Dilates arterioles, capillaries, venules,
• IV injection- decreased BP
• Intradermal- Triple response
Red spot
Wheal
Flare(Reflex
arteriolar dilatation)

9. Pharmacological actions (Contd)
• Visceral smooth muscles:
– Bronchospasm, abdominal cramps
• Secretions:
– Increased gastric secretion (H2)
– Increased nasal secretions (H1)
• Sensory Nerve Endings: Itching
• CNS:
– Wakefulness on intra Cerebroventricular Injection

10. Therapeutic Uses
• Betahistine
– To control vertigo in Meniere`s disease 8 mg tab ½
tablet QID
Histamine releasers
• stings and venom
•Ag-Ab reaction
•Drugs
 d-tubocurarine
Morphine

11. Adverse effects of histamine release
•
•
•
•
•
•
•
•
Itching, Urticaria
Flushing
Hypotension
Tachycardia
Bronchospasm
Angioedema
Wakefullness
Increased acidity (Gastric acid secretion)

12. Classification of H1 Antagonists

13. Mechanism of action
Competitive antagonism
Histamine
General formula of H1 Blocker

14. Pharmacological actions
• CNS depression: (More with first generation)
– Sedation and drowsiness
– Some have antiemetic and antiparkinsonian
effects
• Antiallergic action
• Anticholinergic actions (More with first
generation)
– Dryness of mouth , Blurring of vision
– Constipation
– Urinary retention

15. Pharmacological Actions
• Antimotion sickness effect: Dimenhydrinate,
Promethazine
• Antiemetic: Promethazine
• Antiparkinsonism: Diphenhydramine,
orphenadrine, promethazine(IV)
• Antivertigo: cinnarizine

16. Preparations & dosage (Daily)
Drug
1.
2.
3.
4.
5.
6.
7.
Dose
Diphenhydramine
Dimenhydrinate
Promethazine
Chlorpheniramine
Pheniramine
Cinnarizine
Cyprohepatidine
25-50 mg oral
25-50 mg oral
25-50 mg oral/injection
2-4 mg oral
25- 50 mg oral/im
25-150 mg oral
4 mg oral

17. Therapeutic uses
1.
2.
3.
4.
5.
6.
Allergic rhinitis & common cold
Allergic dermatitis, itching, urticaria
Wasp stings/ bite: pain and itching decreases
Mild blood transfusion reactions
Allergic conjunctivitis
Motion sickness: dimenhydrinate, promethazine
7. Morning sickness: promethazine

18. Therapeutic uses (Contd..)
8. Vertigo: cinnarizine
9. Chronic urticaria
10. Appetite stimulant: cyprohepatidine
11.Drug induced parkinsonism: Diphenhydramine,

19. Adverse effects
•
•
•
•
Sedation
Anticholinergic effects
Dermatitis on local use
Cyclizine, meclizine : teratogenicity

21. Second generation H1 Blockers
(Non Sedative:Less anticholinergic property)
•
•
•
•
•
•
•
Fexofenadine
Astemizole
Loratidine
Cetrizine
Levocetrizine
Azelastine
Terfenadine
Uses:
• Allergic rhinitis
• Allergic Dermatitis
• Allergic conjunctivitis
• Urticaria
• Common cold

22. Advantages of second generation
antihistaminics
• They have no anticholinergic side effects
• Do not cross blood brain barrier (BBB), hence
cause minimal or no drowsiness and sedation
• Do not impair Psychomotor performance

23. Drug interactions
• Increased effect of CNS depressants
• MAO inhibitors increase anticholinergic effect
of antihistaminics
• First generation antihistaminics can decrease
effectiveness of cholinesterase inhibitors used
in Alzheimer`s disease like donepezil and
rivastigmine

25. Answers
• The IgE-mediated hypersensitivity reaction is responsible for
initiation of certain inflammatory disorders, like allergic
rhinitis .
• John suffered from allergic rhinitis, with a runny nose, itchy
eyes, and sneezing.
• An environmental allergen, such as pollen, crosses the nasal
epithelium and enters the underlying tissue. There, the
allergen encounters previously sensitized mast cells and
crosslinks IgE/Fc receptor complexes on the mast cell surface.
• The mast cell degranulates and releases histamine, which
binds to H1 receptors in the nasal mucosa and local tissues.

26. Answers
• Stimulation of H1 receptors causes blood vessel
dilation and ↑es vascular permeability, leading to
edema. This swelling in the nasal mucosa is
responsible for the nasal congestion experienced
in allergic rhinitis.
• The accompanying itching, sneezing, runny
nose, etc result from the combined action of
histamine and other inflammatory
mediators, including kinins, prostaglandins etc.
• These molecules initiate the hypersecretion and
irritation characteristic of allergic rhinitis.