histamine and antihistamines

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
N N
NH2
H
1
2
3
45
Histamine
•Present mostly in mast cells:
 skin, lungs, GIT Mucosa
•Non mast cell histamine:
Brain, Gastric Mucosa
Histamine is a biogenic amine present in many animal and plant tissues .

5. 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. 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.
• Degraded rapidly by oxidation
and methylation

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

8. Pharmacological actions
• Blood vessels:
– 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. 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 Dose
1. Diphenhydramine 25-50 mg oral
2. Dimenhydrinate 25-50 mg oral
3. Promethazine 25-50 mg oral/injection
4. Chlorpheniramine 2-4 mg oral
5. Pheniramine 25- 50 mg oral/im
6. Cinnarizine 25-150 mg oral
7. Cyprohepatidine 4 mg oral

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

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

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
• Loratadine
• Cetrizine
• Levocetrizine
• Azelastine
• Terfenadine
Uses:
• Allergic rhinitis
• Allergic Dermatitis
• Allergic conjunctivitis
• Urticaria
• Common cold

22. 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
•Additional antiallergic action – inhibits late
phase allergic reaction

23. Fexofenadine
• Active metabolite of terfenadine
• Minimal sedation
• Rapidly absorbed orally
• Half life – 11-16 hours
• Excreted unchanged in urine

24. Loratadine
• Long acting peripheral H1 antagonist
• Metabolised by CYP3A4 to an active
metabolite with longer half life - Desloratidine

25. Cetirizine
• Metabolite of hydroxyzine
• Mild sedation and somnolence
• Inhibits release of histamine and cytotoxic
mediators
• Longer lasting concentration in skin
• Half life – 7-10hours

26. Levocetirizine
• Active R(-) enantiomer of cetirizine
• Effective at half dose
• Less sedation and other side effects

27. Azelastine
• Topically used as nasal spray
• Inhibits histamine release and inflammatory
reaction triggered by LTs and PAF
• Half life – 24hours
• Allergic rhinitis symptomatic relief

28. 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

30. 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.

31. 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?

32. 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.

33. 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.

34. Thankyou